Lubricating drops for contact lens discomfort in adults

Abstract

Background

Contact lens discomfort is a symptom‐based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe.

Objectives

To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults.

Search methods

We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions.

Selection criteria

We included parallel‐group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication.

Data collection and analysis

We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE.

Main results

We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline.

Study characteristics

All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns.

Lubricating drops (including saline) versus no treatment

Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37‐point scale (lower is better), but the evidence is very uncertain (mean difference [MD] −5.9 points, 95% confidence interval [CI] −3.74 to −8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end‐of‐day" comfort. The trial that compared saline with no treatment provided no results for the control group.

Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low‐certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD −0.15 points, 95% CI −0.86 to 0.56; 2 RCTs; 119 participants), depth (MD −0.01 points, 95% CI −0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI −0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low‐certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI −0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI −0.39 to 0.39; 1 RCT; 73 participants).

No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision‐threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta‐analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low‐certainty evidence).

Lubricating drops versus saline

Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI −4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness.

No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision‐threatening adverse events up to four weeks of treatment. Our meta‐analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low‐certainty evidence).

Authors' conclusions

Very low‐certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low‐certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks.

Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient‐reported contact lens (dis)comfort using a validated instrument. Therefore, further well‐designed trials are needed to generate high‐certainty evidence on patient‐reported outcomes as well as on longer‐term safety outcomes.

Plain language summary

What are the benefits and harms of lubricating eye drops for contact lens discomfort?

Key messages

• Lubricating eye drops, including saline, may help to reduce contact lens discomfort in adults. The drops do not appear to cause irritation or harm to the surface of the eye. 
• Treating contact lens discomfort with lubricating drops (including saline) is a viable option. However, more studies are needed to measure their effect and to determine which drops work best with different contact lenses and wearing schedules.

What is contact lens discomfort?

Contact lens discomfort means eye irritation that is relieved when the wearer removes their contact lenses. Contact lens wearers may notice dryness, awareness of the lens in their eye, irritation, blurry vision, or a combination of these.

How is contact lens discomfort treated?

The most common way to treat contact lens discomfort is to use over‐the‐counter lubricating drops or saline drops, but eye care specialists might also change the contact lens brand, the contact lens care system, or the contact lens wearing schedule.

What did we want to find out?

We wanted to know if lubricating drops would reduce the discomfort in contact lens wearers, and whether the drops would have unwanted effects.

What did we do?

We searched for studies that compared lubricating drops against no treatment, lubricating drops against saline, or saline against no treatment in adult contact lens wearers. We compared and summarized the results of the studies and rated our confidence in the evidence based on factors such as study design and methods.

What did we find?

We found seven studies, including 463 adults, conducted in the USA, Canada, Italy, and France. Four studies compared lubricating drops with no treatment, two compared lubricating drops with saline, and one compared saline drops with no treatment.

Lubricating drops, including saline, may help reduce contact lens discomfort compared with no treatment, and lubricating drops compared with saline may not differ in their effect on contact lens discomfort. However, we are very uncertain about these results. Lubricating drops may have no effect on scratched cornea (the clear covering of the eye) and eye redness.

It appears that lubricating drops do not have unwanted effects that would stop contact lens wearers from using them.

What are the limitations of the evidence?

We only included seven studies in the review. Some studies did not use a valid instrument to measure contact lens discomfort. A valid instrument could be a questionnaire that has been tested and proven to reliably measure how a patient feels, such as the 8‐item Contact Lens Dry Eye Questionnaire (CLDEQ‐8). The studies included small numbers of contact lens wearers who used the drops for a short period of time, and only one study reported participants' race or ethnicity. Therefore, the results may not apply to all adults with contact lens discomfort. In general, this review provided useful information for patients and eye care practitioners, but more research needs to be done to improve our confidence in the results.

How up to date is this evidence?

The evidence is current to May 2024.

Summary of findings

Summary of findings 1. Lubricating drops versus no treatment.

Lubricating drops versus no treatment for contact lens discomfort
Population: participants with CL discomfort Setting: primary care clinics, eye clinics, or medical centers Intervention: lubricating drops (saline, Sensitive Eyes(R), Systane(R) Complete, Systane(R) Ultra) Comparison: no treatment
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (RCTs)	Certainty of the evidence (GRADE)	Comments
	Risk with no treatment	Risk with lubricating drops
CL discomfort at 1 to 4 weeks Assessed with: CLDEQ‐8 (0 to 37, lower is better)	Mean CL discomfort score in no treatment group was 19.56 points (SD 5.78)	—	MD−5.90 points (−8.05 to −3.74)	119 (2 RCTs)	⊕⊝⊝⊝ Very lowa	Barabino 2005 reported no outcome data for the no treatment group. McDonald 2014 (83 participants) reported changes at day 14 from baseline in "end‐of‐day comfort" using a Likert scale (0 to 5, lower is better). After reversing the sign, the MD was −0.63 (95% CI −1.57 to 0.31).
Corneal fluorescein staining Assessed with: BHVI scale (0 to 20, lower is better)	Extent Mean score in no treatment group was 1.28 points (SD 2.01).	—	MD−0.15 points (−0.86 to 0.56)	119 (2 RCTs)	⊕⊕⊝⊝ Lowb	—
	Depth Mean score in no treatment group was 0.77points (SD 1.26).	—	MD−0.01 points (−0.44 to 0.42)
	Type Mean score in no treatment group was 0.71 points (SD 1.13).	—	MD0.04 points (−0.38 to 0.46)
Conjunctival redness Assessed with: BHVI scale (0 to 4, lower is better)	Nasal region Mean score in no treatment group was 0.6 points (SD 0.78).	—	MD0.10 points (−0.29 to 0.49)	73 (1 RCT)	⊕⊕⊝⊝ Lowb	—
	Temporal region Mean score in no treatment group was 0.7 points (SD 0.78).	—	MD 0.00 points (−0.39 to 0.39)
Incident microbial keratitis	No studies reported this outcome.
Inflammatory corneal infiltrates	No studies reported this outcome.
Discontinuation during trial period	15 per 1000	21 per 1000 (3 to 165)	RR 1.42 (0.19 to 10.94)	138 (2 RCTs)	⊕⊕⊝⊝ Lowc	Pucker 2020 and Pucker 2021 reported no discontinuation in any trial group.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and the associated 95% CI). BHVI: Brien Holden Vision Institute; CI: confidence interval; CL: contact lens; CLDEQ‐8: 8‐item Contact Lens Dry Eye Questionnaire; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio; SD: standard deviation.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^a Downgraded one level for risk of bias associated with outcome measurement and reporting, one level for imprecision, and one level for inconsistency.
^b Downgraded two levels for very serious imprecision due to small sample sizes.
^c Downgraded one level for imprecision and one level for risk of bias associated with outcome measurement and reporting.

Summary of findings 2. Lubricating drops versus saline.

Lubricating drops versus saline for contact lens discomfort
Population: participants with CL discomfort Setting: primary care clinics, eye clinics, or medical centers Intervention: lubricating drops (FID114657, PVP 2%, Systane) Comparison: saline
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No. of participants (RCTs)	Certainty of the evidence (GRADE)	Comments
	Risk with saline	Risk with lubricating drops
CL discomfort at 1 to 4 weeks Assessed with: VAS (0 to 100, lower is better)	Mean score in the saline group was 29.1 points (SD 22.3).	—	MD9.50 points (−4.65 to 23.65)	39 (1 RCTs)	⊕⊝⊝⊝ Very lowa	Keir 2006 (76 participants) reported changes at day 28 from baseline in "end‐of‐day comfort" using a Likert scale (1 to 5, higher is better). After reversing the sign, MD was −0.64 (95% CI −1.91 to 0.63).
Corneal fluorescein staining	No studies reported this outcome.
Conjunctival redness	No studies reported this outcome.
Incident microbial keratitis	No studies reported this outcome.
Inflammatory corneal infiltrates	No studies reported this outcome.
Discontinuation during trial period	30 per 1000	47 per 1000 (14 to 154)	RR 1.56 (0.47 to 5.12)	269 (3 RCTs)	⊕⊕⊝⊝ Lowb	—
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and the associated 95% CI). CI: confidence interval; CL: contact lens; MD: mean difference; PVP: polyvinylpyrrolidone; RCT: randomized controlled trial; RR: risk ratio; VAS: visual analog scale.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^a Downgraded one level for risk of bias associated with outcome measurement and reporting, and two levels for very serious imprecision.
^b Downgraded one level for imprecision and one level for risk of bias associated with outcome measurement and selective reporting.

Background

Description of the condition

The Tear Film and Ocular Surface Society (TFOS) defines contact lens (CL) discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, resulting from reduced compatibility between the CL and the ocular environment, which can lead to decreased wearing time and discontinuation of CL wear" (Nichols 2013). The adverse ocular sensations associated with CL discomfort are increased perception, awareness, and feeling of the CL on the ocular surface, including symptoms of dryness, irritation, and foreign body sensation (Chalmers 2006; Nichols 2013; Vajdic 1999). CL discomfort may be accompanied by physical signs, including conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and probable meibomian gland dysfunction (Efron 2013; Efron 2016; Rueff 2021). CL discomfort can range from mild to severe ocular sensations requiring immediate CL removal and sometimes permanent discontinuation of CL wear (Pucker 2020a).

Several factors may contribute to the discomfort, including CL material, CL design, CL fit and wear schedule, CL care solution, and environmental factors. Causes of CL discomfort are typically grouped into two major subclasses: the CL, including material, design, fit and wear, and lens care; and environmental factors, including inherent or modifiable patient factors, ocular factors, and external environment (Nichols 2013). All these factors can impact CL wearers' quality of life (Dumbleton 2013). Ultimately, the material, design, and care characteristics of the ideal contact lens allow for optimal fit and wear, vision, and comfort, promoting ocular health and improving quality of life. CL discomfort differs from dry eye disease in signs and symptoms, although overlap can occur (Dumbleton 2013).

CL discomfort is not synonymous with CL dryness, CL dry eye, or CL‐induced dry eye (Nichols 2013). These conditions refer to pre‐existing dry eye disease that is exacerbated by CL wear. However, the scientific literature published before the 2013 TFOS International Workshop on CL discomfort may have used CL discomfort and CL dryness/CL dry eye/CL‐induced dry eye interchangeably (Nichols 2013).

Diagnosis of contact lens discomfort

Diagnosis of CL discomfort is typically led by patient symptomology. The 8‐item Contact Lens Dry Eye Questionnaire (CLDEQ‐8) is a validated questionnaire commonly used in clinical trials and practice (Chalmers 2012). A CLDEQ‐8 score of 12 points or more indicates a symptomatic CL wearer requiring clinical management. The scale has a clinically important difference of 3 points (Chalmers 2016). Another method for measuring CL discomfort is to use a 100‐point visual analog scale (VAS), where a change of 7 to 8 points would be considered clinically significant (Papas 2011). People experiencing CL discomfort typically report a reduction in comfortable wearing time, followed by a reduction in total wearing time, before temporarily or permanently discontinuing CL wear (Nichols 2013). Therefore, CL wearing time forms a key part of diagnosing CL discomfort.

Currently, no clinical signs form a definitive diagnosis of CL discomfort. Studies have reported various signs to be associated with symptomatic CL wear, including lid wiper epitheliopathy, the quality of meibomian gland secretions, tear instability, pre‐lens tear stability, lid parallel conjunctival folds, limbal injection, and inferior corneal staining (Stapleton 2021).

Epidemiology of contact lens discomfort

There are approximately 140 million CL wearers worldwide (Nichols 2013); however, high CL dropout—with reported rates ranging from 21.7% (Pucker 2020a) to 51% (Young 2002)—hinders growth in the number of CL wearers.

One of the earliest studies to evaluate dry eye disease in CL wearers, the Canadian Dry Eye Epidemiology Study (CANDEES), reported a prevalence of CL‐associated dry eye disease of 50.1% in respondents who were known CL wearers compared with 21.7% in non‐CL wearers (Doughty 1997). Studies in Chinese office workers reported a prevalence of dryness and discomfort in CL wearers as high as 50.4% (Uchino 2008a). In studies conducted in high school students of Asian origin (Japanese and Chinese), the reported prevalence ranged from 32.8% to 37.4% (Uchino 2008b; Zhang 2012).

The prevalence of CL discomfort may vary depending on the method used to assess symptoms and signs. It may also vary with blink pattern, ethnicity, systemic medications and disease, diet, cosmetic use, CL solution use, and social habits (Nichols 2013). Irrespective of the associated factors, it does appear that CL discomfort undergoes diurnal variation, with symptoms worsening towards the end of the day for most CL wearers (Begley 2001).

The literature contains contradictory evidence on sex‐based differences in CL discomfort. Some studies have found a higher prevalence of CL discomfort in females compared with males; specifically, Uchino and colleagues reported 35% in females and 28% in males (Nichols 2006; Uchino 2008a). However, large‐scale studies evaluating CL discomfort in around 1000 participants found no sex‐based differences in the frequency or intensity of CL discomfort between the sexes (Chalmers 2006; Young 2011).

According to the TFOS report on CL discomfort, the literature suggests that some patient‐related factors may be associated with CL discomfort, including female sex, younger age, poor tear film quantity and quality, seasonal allergies, and some systemic medications (Dumbleton 2013).

Description of the intervention

The mainstay of treatment for CL discomfort and associated dry eye is over‐the‐counter lubricating drops, some of which are designed for CLs and others for dry eye disease. Saline solutions are also available to treat CL discomfort. The US Food and Drug Administration (FDA) defines "in eye solutions" used specifically for CL discomfort as "rewetting/lubricating drops" (Premarket Notification (510K) Guidance for Contact Lens Care Products; USFDA 510k Guidance). The FDA also provides a monograph that encompasses "Ophthalmic Drug Products for Over‐The‐Counter Human Use," which includes topical demulcents and emollients used as "artificial tears" for dry eye (USFDA CFR Part 349). Historically, these artificial tears were not used for CL discomfort because they contained preservatives such as benzalkonium chloride (BAK) that could be adsorbed by the CLs and then concentrated in the post‐lens tear film with resultant corneal toxicity (Baudouin 2010). However, with the availability of new "softer" preservatives (such as Purite, a stabilized oxychloro complex), single‐use vials, and smart delivery systems that limit microbial overgrowth (Walsh 2019), manufacturers now market these products for CL discomfort as well as dry eye (Papas 2013).

The lubricating components of over‐the‐counter drops may include demulcents (such as hypromellose, dextran 70, gelatin, and polyethylene glycol (PEG)) and longer retention emollients (such as lanolin, paraffin, and mineral oil). More recent formulations have included hyaluronic acid for moisture retention, perfluorohexyloctane and omega‐3 fatty acids to supplement the lipid layer and reduce evaporation (Dogru 2011), and manuka honey (leptospermum) to provide dual effects (Hu 2022).

Other measures to improve CL discomfort include: changing CL materials, solutions, and wear schedules; modifying the local environment; mitigating topical and systemic drug effects; dietary changes; oral supplementation; lid hygiene; and warm compresses. All of these measures align with Stage 1 of TFOS Dry Eye Workshop II (Craig 2017). However, compliance can be challenging, and these remedies are often prescribed in combination, making it difficult to assess the specific effect of each component. CL discomfort may have some relationship with dry eye disease, which can be treated with prescription medications such as anti‐inflammatories, treatments for meibomian gland dysfunction, and oral supplementation (Jones 2023). However, for this review, we are only interested in evaluating the effects of lubricating drops.

How the intervention might work

Several studies suggest that lubricating drops reduce CL discomfort; however, this effect may be transient (Papas 2013; Pucker 2020b). Clinical signs related to CL discomfort, including conjunctival redness, corneal and conjunctival staining, and CL deposits, may also improve during treatment with lubricating drops (Fernandez‐Jimenez 2022; Pucker 2020b).

Disruption of the tear film has been identified as a key mechanism of CL discomfort (Craig 2013; Papas 2013). Lubricating drops may improve comfort by mitigating the biophysical and biochemical changes to the tear film associated with CL use. People experiencing CL discomfort show decreased tear film stability, increased rate of evaporation, and slower turnover of the tear film (Craig 2013). More recent research has also associated CL discomfort with higher proportions of immune cells and differential expression of tear proteins, including inflammatory cytokines (Gad 2019; Nair 2022). Lubricant drops may address CL‐related tear film disequilibria by altering stability, frictional forces, volume, viscosity, osmolarity, temperature, and hydration of the ocular surface environment, including the CL itself (Papas 2013; Pucker 2020b; Stahl 2018). The specific mechanisms of lubricating drops as an intervention in CL discomfort are only partially understood and remain of interest to clinicians, patients, and the CL industry.

Why it is important to do this review

CL discomfort affects 13% to 75% of CL wearers and is a major contributing factor to CL discontinuation (Brennan 1989; Nichols 2013; Vajdic 1999). Although many potential factors contribute to CL discomfort, one common management option adopted by practitioners and patients is over‐the‐counter lubricating drops. Little is known about what type of drop is best for CL wearers, whether these drops should be prescribed routinely before the onset of symptoms or signs, and what dosage is appropriate. Hence, there is a need for a synthesis of the evidence.

Objectives

To determine the efficacy and safety of lubricating drops for ocular discomfort associated with CL wear in adults.

Methods

Criteria for considering studies for this review

Types of studies

We included randomized controlled trials (RCTs) that allocated individuals (both eyes) to treatment groups. We considered RCTs that randomized both eyes to the same intervention but reported eye‐specific outcome data. We also considered paired‐eye design RCTs (each eye randomized to a different treatment), as lubricating drops only have a local effect. Cross‐over clinical trials were ineligible. We included eligible studies regardless of their publication status, language, or year of publication.

Types of participants

We included trials of people aged 18 years and over with discomfort or irritation related to CL use, as defined by the trial investigators. We also included trials that did not report participant age. There were no restrictions on duration of prior CL wear. We considered studies that used any type of CL material, including rigid gas‐permeable materials, except rigid gas‐permeable lenses prescribed for orthokeratology. Participants could be of any race, ethnicity, sex, or gender; with or without prior ocular or systemic health conditions. We excluded studies with only a subset of relevant participants or that recruited people using orthokeratology lenses.

Types of interventions

We planned to include trials comparing lubricating eye drops (any dosing regimen) with the following comparators.

• Placebo containing only saline or another inactive compound

• No treatment

Based on the studies identified, we decided to consider saline a type of lubricating eye drop in the comparison against no treatment. No trials used inactive components other than normal saline as control eye drops. We excluded studies that used a lubricating ointment, gel, or other non‐ophthalmic solution; and studies that assessed the effects of lubricating drops in combination with another topical intervention (e.g. steroid), systemic intervention (e.g. omega‐3 fatty acid), or behavioral intervention (e.g. warm compression).

Types of outcome measures

We considered all eligible studies regardless of the availability of outcome data.

Critical outcomes

• Mean change in participant‐reported CL discomfort from baseline to longest follow‐up between one and four weeks, measured with a validated questionnaire or a common scale. We extracted outcome data at the longest follow‐up point, up to four weeks, as reported in the trials.

We selected the timeline of one to four weeks because in clinical practice, eye care practitioners who prescribe lubricating drops typically follow patients for four weeks or less. Any symptom improvements normally occur within this time frame and then plateau, as lubricating drops have no active pharmacological agents. Further, the treatment duration in most studies involving lubricating drops is one month (Pucker 2020b).

Important outcomes

The important outcomes of this review included objective ocular examination measures, as described below.

• Mean change in corneal fluorescein staining scores from baseline to longest follow‐up between one and four weeks, as reported by the included studies

• Mean change in conjunctival redness scores (overall scores or scores for any specific quadrant) from baseline to longest follow‐up between one and four weeks, as reported by the included studies

• Adverse outcomes as reported at the end of the trials

  • Proportion of eyes or participants with incident microbial keratitis

  • Proportion of eyes or participants with one or more inflammatory corneal infiltrates, visible by slit lamp examination

  • Proportion of participants who discontinued participation in the study

Search methods for identification of studies

Electronic searches

We searched the following databases and trials registries.

• Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2024, Issue 5; Appendix 1)

• Ovid MEDLINE, Ovid MEDLINE E‐pub Ahead of Print, Ovid MEDLINE In‐Process and Other Non‐Indexed Citations, Ovid MEDLINE Daily (1946 to 12 May 2024; Appendix 2)

• Embase.com (1947 to 12 May 2024; Appendix 3)

• PubMed.gov (1946 to 12 May 2024; Appendix 4)

• Latin American and Caribbean Health Sciences Literature Database (LILACS; 1982 to 12 May 2024; Appendix 5)

• National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (clinicaltrials.gov; searched 12 May 2024; Appendix 6)

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; apps.who.int/trialsearch; searched 12 May 2024; Appendix 7)

We applied no date or language restrictions in the electronic search for trials. The last search date was 12 May 2024.

The Appendices provide details of search strategies for the different sources.

Searching other resources

We searched the reference lists of the included studies to identify additional potentially relevant trials. We contacted authors for clarification, missing data, and updated information on eligible ongoing trials. If we obtained no response within two weeks of contacting the primary investigator (or senior author of the publication), we used the available data.

Data collection and analysis

Selection of studies

The Information Specialist provided separate search results from electronic databases and trial registries. We imported these search results into web‐based software Covidence to screen for eligible studies and collect data. After Covidence had automatically removed duplicate citations, two review authors independently screened the titles and abstracts and classified each study as "yes (relevant)", "maybe (potentially relevant)", or "no (definitely not relevant)." We then retrieved full‐text reports for studies assessed as "relevant" or "potentially relevant". Two review authors independently assessed the eligibility of studies according to information presented in the full‐text reports. We resolved any discrepancies through discussion or adjudication by a third review author. We also contacted trial investigators for additional clarification where necessary. We reported reasons for exclusion at this stage in the Characteristics of excluded studies table. We recorded the study selection process in sufficient detail to complete a PRISMA flow diagram (Page 2021).

Data extraction and management

We merged multiple reports of the same study under a single study ID before data extraction. Two review authors independently extracted pertinent trial‐level characteristics, including descriptions of the participant sample, study design, treatment comparisons, and treatment outcomes from the included trials using data extraction forms developed by Cochrane Eyes and Vision US Project (CEV@US) in Covidence. We collected the following items whenever available.

• Methods: study design, total duration of study, number of study centers and location, study setting, study date, and how eyes were handled in the design and analysis of the primary study. We described how the eyes were analyzed (one or both eyes per participant) to account for data dependence.

• Participants: number of participants randomized, number lost to follow‐up/withdrawn, number analyzed, mean age, age range, sex, severity of condition, diagnostic criteria, inclusion criteria, and exclusion criteria.

• Interventions: intervention, comparison, concomitant medications (or co‐interventions), and excluded medication. For both intervention and comparison arms, we collected materials and replacement schedules of CLs and doses and frequencies of eye drop regimens. For multiarm studies, we extracted only relevant data from eligible intervention and comparator treatments. When we extracted data from more than one intervention arm, we split the data of the comparison arm in half and created separate comparisons for each intervention and the halved comparison arm, as suggested in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2023a).

• Outcomes: outcomes specified and collected and time points recorded. In studies that presented outcome data only in figures, we applied a web‐based tool to extract values from the plots (WebPlotDigitizer).

• Information about funding for the trial, notable conflicts of interest of the trial authors, trial registration ID, and trial registration date.

We resolved discrepancies through discussion within the review team. One review author entered data into RevMan 2023, and a second review author confirmed and verified the accuracy of all entries.

Assessment of risk of bias in included studies

We used the updated Cochrane risk of bias tool (RoB 2) to assess risk of bias in the reported results of all predefined outcomes (Differences between protocol and review), at the longest point between weeks one to four, as guided by the signaling questions in the following five bias domains (Higgins 2023b).

• Bias arising from the randomization process

• Bias arising from deviations from intended interventions

• Bias arising from missing outcome data

• Bias in measurement of the outcome

• Bias in selection of the reported result

We assessed the effects of intervention assignment, rather than intervention adherence. For each included trial reporting the outcome, two review authors independently judged each domain as low, high, or some concerns, providing justifications for their decisions (Sterne 2019). We resolved discrepancies through discussion or adjudication by a third review author.

Measures of treatment effect

We summarized continuous data by extracting mean differences (MDs) with standard deviations (SDs) between the treatment and the comparison arms as reported by the included studies (Higgins 2022). We derived SD using methods suggested in the Cochrane Handbook for Systematic Reviews of Interventions when the primary studies reported 95% confidence intervals (CIs) instead of SDs (Higgins 2022). We reported summary MDs and 95% CIs for continuous outcomes. When the included studies did not report change scores (differences from the baseline) but only endpoint values at the last study visit, we used the post‐intervention endpoint values for each comparison group to estimate the treatment effect as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2022). We calculated standardized mean differences (SMDs) for patient‐reported discomfort scores measured with different symptom questionnaires or scales. We interpreted treatment effects expressed in units of SMD following the rule of thumb as suggested by Cohen, which considers an SMD of 0.2 a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988).

For dichotomous outcomes, we calculated summary risk ratios (RRs) and 95% CIs (Higgins 2022).

Unit of analysis issues

The unit of analysis in this review was the individual participant randomized to each treatment group, because CL discomfort is usually a bilateral condition. We encountered no unit of analysis issues because the two trials that reported outcomes at the eye level included only one eye per person in the analysis, and no included trials had a paired‐eye design.

Dealing with missing data

We attempted to contact investigators of the included trials for missing data where necessary. We extracted available data from the published papers or from the results section of the trial registry website whenever trial authors were unable to provide requested information or did not respond after a period of two weeks. No trials reported data based on imputation; nor did we impute missing data.

Assessment of heterogeneity

We assessed clinical and methodological heterogeneity by examining characteristics of trial participants, treatment/control comparisons, and trial outcomes. To assess statistical heterogeneity, we inspected the forest plots and calculated the I² statistic, interpreting I² values according to the following thresholds (Deeks 2022).

• 0% to 40% might not be important.

• 30% to 60% may represent moderate heterogeneity.

• 50% to 90% may represent substantial heterogeneity.

• 75% to 100% represents considerable heterogeneity.

Where we detected clinical or methodological heterogeneity (based on data recorded in the Characteristics of included studies table) or considerable statistical heterogeneity, we did not report a pooled estimate. Instead, we provided a narrative or tabulated summary of the results.

Assessment of reporting biases

We assessed selective reporting of ocular symptoms guided by the signaling questions in the RoB 2 tool (Higgins 2023b). When the study protocol was available, we assessed selective outcome reporting using methods outlined in Chapter 13 of the Cochrane Handbook for Systematic Reviews of Interventions (Page 2023). Otherwise, we compared the descriptions of outcome measurements in the results section against those in the methods section of full‐text publications.

Because our review included only seven trials, we did not create funnel plots to assess possible publication bias (Egger 1997).

Data synthesis

We conducted meta‐analysis when we decided that there was no considerable clinical or methodological heterogeneity. When a meta‐analysis included fewer than three trials, we used a fixed‐effect model; otherwise we used a random‐effects model (Deeks 2022).

Subgroup analysis and investigation of heterogeneity

To investigate potential sources of heterogeneity, we planned to conduct subgroup analyses for our critical outcomes based on the following characteristics.

• CL materials (e.g. soft lenses versus rigid gas‐permeable lenses)

• Wearing schedule (e.g. daily disposable versus weekly or monthly lenses)

However, because we included only seven trials, and because most trials did not report our critical outcome, we performed no subgroup analyses.

Sensitivity analysis

To assess the robustness of the effect estimates, we planned to perform sensitivity analysis of the critical outcome by excluding studies with an overall high risk of bias. However, as we identified few eligible studies, we did not perform sensitivity analysis.

Summary of findings and assessment of the certainty of the evidence

With modifications to the planned summary of findings table (Differences between protocol and review), we included all review outcomes, as follows.

• Mean change in patient‐reported CL discomfort from baseline to longest follow‐up between one and four weeks

• Mean change in corneal fluorescein staining scores from baseline to longest follow‐up between one and four weeks

• Mean change in conjunctival redness scores from baseline to longest follow‐up between one and four weeks

• Proportion of eyes or participants with incident microbial keratitis

• Proportion of eyes or participants with one or more inflammatory corneal infiltrates

• Proportion of participants who discontinued participation in the study

Two review authors independently rated the overall certainty of evidence for each outcome as high, moderate, low, or very low based on the five GRADE considerations presented below (Schünemann 2023).

• Risk of bias

• Indirectness of evidence

• Unexplained heterogeneity or inconsistency of results

• Imprecision of results (i.e. wide CIs)

• Probability of publication bias (based on results of RoB 2 assessment)

We resolved discrepancies by discussion to achieve consensus within the review author team.

Results

Description of studies

Results of the search

Our initial search of the electronic databases on 20 April 2023 yielded 2884 records (Figure 1). We performed a top‐up search on 12 May 2024 and found an additional 294 records. After the removal of duplicates and non‐RCT publications identified by the built‐in algorithm of Covidence (Covidence), we screened 3060 records and excluded 2985 as irrelevant. We then retrieved and reviewed 75 full‐text reports (68 studies). We included seven studies (13 reports) in the review (Characteristics of included studies). Five studies had published manuscripts; one had only an unpublished manuscript, which we obtained from the corresponding author; and one trial had only posted results on ClinicalTrials.gov.

1.

PRISMA flow diagram

Included studies

Types of studies

Study design

All seven trials were parallel‐group RCTs. Three evaluated lubricating drops versus no treatment (McDonald 2014; Pucker 2020; Pucker 2021), one evaluated saline versus no treatment (Barabino 2005), and three evaluated lubricating drops versus saline (Keir 2006; Malet 2003; NCT02293538).

All studies allocated participants (rather than eyes) to treatment. All trials masked outcome assessment, but the trials comparing lubricant drops and saline to no treatment did not mask participants (Barabino 2005; McDonald 2014; Pucker 2020; Pucker 2021). Two trials reported how missing data were handled (Barabino 2005, NCT02293538). Three trials described sample size or power calculations (Malet 2003; Pucker 2020; Pucker 2021).

Setting

Three trials were conducted in the USA (McDonald 2014; Pucker 2020; Pucker 2021), one in Canada (Keir 2006), one in France (Malet 2003), and one in Italy (Barabino 2005). Three trials recruited participants from multiple centers in both university and private practice settings (McDonald 2014; Pucker 2020; Pucker 2021). Two single‐center trials recruited participants from university settings (Barabino 2005; Keir 2006). One multicenter trial provided no description of recruitment setting (Malet 2003), and one trial provided no information on the number of participating centers or the recruitment setting (NCT02293538).

Funding

Five trials reported sole sponsorship by industry (Keir 2006; McDonald 2014; NCT02293538; Pucker 2020; Pucker 2021), one trial reported partial funding by industry (Malet 2003), and one trial provided no funding details (Barabino 2005).

Types of participants

The trials recruited a total of 463 participants (all adults). The mean age of participants ranged from 25.7 years (SD 6.8) in Keir 2006 to 36.7 years (SD 10.5) in Malet 2003. The proportion of female participants ranged from 15% in Pucker 2020 to 82% in Malet 2003. Only one trial reported participant ethnicity (McDonald 2014).

Six trials included people who used soft CLs, and one permitted any CL material, with no reporting of replacement schedules (Malet 2003). Three trials included only daily disposable soft CLs (McDonald 2014; Pucker 2020; Pucker 2021), one included only biweekly replacement daily wear soft CLs (Keir 2006), one included both biweekly and monthly replacement daily wear soft CLs (NCT02293538), and one included soft hydrophilic CLs but did not report the replacement schedule (Barabino 2005).

All seven trials included only CL wearers who were experiencing discomfort or dryness associated with CL wear; two trials specifically required a clinically significant score of 12 or higher on the CLDEQ‐8 (Pucker 2020; Pucker 2021). Three trials excluded people with clinical findings of ocular surface disease or tear film instability (Barabino 2005; Malet 2003; NCT02293538). All trials excluded people with other known ocular diseases, and four trials excluded people with best‐corrected visual acuity worse than 20/30 (McDonald 2014; NCT02293538; Pucker 2020; Pucker 2021).

Interventions

Pucker 2020 evaluated Systane Complete (hydroxypropyl guar, mineral oil, propylene glycol, and sorbitol, preserved with polyquaternium), while the interventions in Pucker 2021 (a three‐arm trial) were Systane Complete and Sensitive Eyes lubricating drops. McDonald 2014 studied Systane Ultra (POLYQUAD [polyquaternium‐1], aminomethylpropanol, boric acid, hydroxypropyl guar, polyethylene glycol 400, potassium chloride, propylene glycol, purified water, sodium chloride, and sorbitol). Keir 2006 studied Systane (hydroxypropyl guar with polyethylene‐400 [macrogol 400] and propylene glycol, preserved with polyquaternium). Malet 2003 studied a polyvinylpyrrolidone (PVP)‐based drop, and NCT02293538 provided no description of the drop. The intervention in Barabino 2005 was saline.

Four trials compared lubricant drops with a control group receiving no treatment (Barabino 2005; McDonald 2014; Pucker 2020; Pucker 2021); these trials included 202 participants in total (113 in treatment arm; 55.9%). Three trials compared lubricant drops to a control of saline drops (Keir 2006; Malet 2003; NCT02293538); of 261 participants in these trials, 135 (51.7%) received lubricating drops.

Outcomes

Critical outcomes

Five trials reported changes in CL discomfort using various instruments, including the CLDEQ‐8, a VAS, and Likert scales (Keir 2006; Malet 2003; McDonald 2014; Pucker 2020; Pucker 2021). One trial did not report symptom results (NCT02293538). One trial reported changes in CL discomfort in the treatment group only (Barabino 2005).

Important outcomes

• Two trials reported corneal fluorescein staining changes (Pucker 2020, Pucker 2021).

• One three‐arm trial reported conjunctival redness changes (Pucker 2021)

• No trials reported the proportion of participants with incident microbial keratitis. Instead, McDonald 2014 and Malet 2003 reported incidents of conjunctivitis, all of which were determined as not treatment‐related.

• No trials reported the proportion of participants with inflammatory corneal infiltrates. However, Barabino 2005 reported incident findings of conjunctival hyperemia.

• All seven trials reported the number of participants who discontinued participation in the trial.

We summarized additional study outcomes that were not specified in our protocol (Caffery 2023) in Appendix 8.

Excluded studies

Of the 60 excluded studies (61 reports; Characteristics of excluded studies), 27 (45%) were excluded for ineligible study design. Nine studies (15%) included ineligible participants under the age of 18. Nine studies (15%) were excluded for ineligible interventions such as drops containing prescription compounds, and 15 studies for ineligible comparator groups such as alternative dry eye treatments (Figure 1). We categorized one trial as awaiting classification as it was documented as completed on ClinicalTrials.gov without trial results, and because we received no response from the principal investigator two weeks after trying to make contact (NCT02956083; Studies awaiting classification). There were no ongoing studies identified for this review.

Risk of bias in included studies

We assessed risk of bias for all four outcomes (Risk of bias (tables)). Detailed risk of bias assessments are available via the Open Science Foundation (osf.io/f8xjp/).

Five included trials reported CL discomfort (Keir 2006; Malet 2003; McDonald 2014; Pucker 2020; Pucker 2021). We judged two of the five trials as having some concerns due to potential biases in outcome measurement and selective reporting (Pucker 2020; Pucker 2021). We judged the other three trials at high risk of bias because of the potential risk of bias in multiple important domains (Keir 2006; Malet 2003; McDonald 2014). See the Table 10.

Risk of bias for analysis 1.1 Contact lens discomfort.

Study

Bias

Randomisation process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported results

Overall

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Subgroup 1.1.1 Postintervention value

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple" masked (Care Provider, Investigator, Outcomes Assessor)" and participants were unable to be fully masked "because there is a no treatment control group." ITT analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Some concerns

Participants in the no treatment group might report discomfort scores differentially (on CLDEQ‐4 or ‐8) from those in the other two groups because they were not masked.

Some concerns

Outcome was measured using previously validated questionnaire but outcome assessor (participants self‐reporting) was likely differed between groups CLDEQ‐4 was pre‐specified in the trial registry but CLDEQ‐4 and CLDEQ‐8 scores were reported in the results section of the trial registry and only CLDEQ‐8 scores were mentioned in the publication.

Some concerns

The trial was judged to have an overall some concerns of risk of bias due to potential risks of selective result reporting.

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple" masked (Care Provider, Investigator, Outcomes Assessor)" and participants were unable to be fully masked "because there is a no treatment control group." ITT analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Some concerns

Participants in the no treatment group might report discomfort scores differentially (on CLDEQ‐4 or ‐8) from those in the other two groups because they were not masked.

Some concerns

Outcome was measured using previously validated questionnaire but outcome assessor (participants self‐reporting) was likely differed between groups CLDEQ‐4 was pre‐specified in the trial registry but CLDEQ‐4 and CLDEQ‐8 scores were reported in the results section of the trial registry and only CLDEQ‐8 scores were mentioned in the publication.

Some concerns

The trial was judged to have an overall some concerns of risk of bias due to potential risks of selective result reporting.

Pucker 2020

Low risk of bias

The authors reported the use of blocked and stratified randomization process and "subject group assignments were concealed from the masked examiners." "There were no significant between‐group differences with respect to subject demographics or baseline clinical characteristics."

Low risk of bias

Trial registry record documented "double (Investigator, participant)" but participants were unable to be fully masked "because there is a no treatment control group."

Low risk of bias

Outcome data were available for all participants randomized.

Some concerns

Outcome was measured using previously validated questionnaire yet based on self‐reporting, which could be differential in the no treatment group.

Some concerns

Trial protocol (on trial registry website) pre‐specified the use of CLDEQ‐4 (a subset of CLDEQ‐8) but both scores were reported as outcomes in the publicaiton.

Some concerns

There were some concerns in bias associated with outcome measurement and reporting.

Subgroup 1.1.2 Change

McDonald 2014

Some concerns

It was a randomized study though details of random number generation were not provided. Nor was the process of allocation concealment reported. There was no evidence of baseline imbalance in the two groups.

Low risk of bias

This was an investigator‐masked study. Although participants were aware of their assigned intervention, the authors used appropriate analysis to estimate effects of assignment (intention‐to‐treat).

Low risk of bias

No missing outcome data.

Some concerns

The authors used Likert scale (1 to 5) to measure CL discomfort. The scale is less reliable than visual analog scale or other numerical scale, and thus we judged the trial to have some concerns in misclassification bias.

Some concerns

Study protocol was not available for evaluation. Likert Scale scores are typically analyzed as a categorical variable or proportions of participants with a score higher or lower than a certain clinically important threshold. Thus, we have concerns about how this outcome data was analyzed.

High risk of bias

The trial was judged to have high risk of bias due to potential risk of bias in randomization process, outcome measurement and reporting.

All seven trials reported numbers of participants who did not complete the trial (participant discontinuation) either in the full‐text report (published or unpublished) or on the clinical trial registry. Overall, we judged two trials at low risk of bias (2/7, 29%) and considered three to have some concerns due to unclear reporting in the randomization or allocation concealment process (Malet 2003; McDonald 2014; NCT02293538). Barabino 2005 and Keir 2006 were at high risk of bias because of concerns in multiple bias domains (Table 12).

Risk of bias for analysis 1.4 Participant discontinuation.

Study

Bias

Randomisation process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported results

Overall

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Barabino 2005

Some concerns

The authors reported that "participants were divided into two groups matched for all the variables studied" but did not provide details about random number generation. No information about baseline characteristics were reported for the control group.

Some concerns

Participants in the no treatment group were unable to be masked while a study examiner was "masked as to group assignment." Outcome data were not reported for participants in the control group besides the reportedly "no changes from baseline." However, there was probably no substantial impact on estimating treatment effects of assignment if the authors had performed the "intention‐to‐treat" effect.

Low risk of bias

The authors reported only one participant in the intervention group lost to follow‐up though no descriptions about the control group were provided.

Some concerns

"one patient in the treatment group was lost to follow‐up after the beginning of the study" A study examiner was masked to the intervention assigned though it was unclear whether he was also responsible for measuring this outcome.

Some concerns

No study protocol was available for assessment but the authors provided the count of participants lost to follow‐up for the intervention group but no information for the no treatment group.

High risk of bias

The trial was judged to have high risk of bias due to potential risks of bias in multiple important domains.

McDonald 2014

Some concerns

It was a randomized study though details of random number generation were not provided. Nor was the process of allocation concealment reported. There was no evidence of baseline imbalance in the two groups.

Low risk of bias

The study was "investigator‐masked" only and the analy was intention‐to‐treat.

Low risk of bias

Data for this outcome was available for all participants randomized.

Low risk of bias

The authors reported counts of subjects who did not complete the trial "as a result of mild infection."

Low risk of bias

No study protocol was available for assessment but the counts of participants who discontinued due to infection was reported in a standard way.

Low risk of bias

The trial was judged at an overall low risk of bias.

Domain 1: bias arising from the randomization process

Contact lens discomfort

We judged the risk of bias from the randomization process to be low in two trials that described the usage of blocked and stratified randomization and the process of allocation concealment (Pucker 2020; Pucker 2021). The other three trials did not clearly describe the generation of random sequences or concealed treatment assignment, though there was no evidence of imbalance in baseline characteristics of trial participants (Keir 2006; Malet 2003; McDonald 2014).

Corneal fluorescein staining

We judged both Pucker 2020 and Pucker 2021 at low risk of bias.

Conjunctival redness

We judged Pucker 2021 at low risk of bias.

Participant discontinuation

We judged Pucker 2020 and Pucker 2021 at low risk of bias, and we considered the other five trials had some concerns due to lack of details about the randomization and treatment assignment process.

Domain 2: bias arising from deviations from intended interventions

Contact lens discomfort

We assessed the risk of bias arising from deviations from intended interventions to be low for five trials that had documented either triple or double masking (Keir 2006; Malet 2003; McDonald 2014; Pucker 2020; Pucker 2021).

Corneal fluorescein staining

We judged both Pucker 2020 and Pucker 2021 at low risk of bias.

Conjunctival redness

We judged Pucker 2021 at low risk of bias.

Participant discontinuation

We judged all trials except Barabino 2005 at low risk of bias. The authors of Barabino 2005 described the trial as "masked", but it was unclear who was masked to the intervention; we considered this trial had some risk of bias concerns.

Domain 3: bias due to missing outcome data

Contact lens discomfort

We assessed the risk of bias due to missing outcome data as low for four trials (4/5, 80%) because outcome data were available for all or nearly all randomized participants (Keir 2006; McDonald 2014; Pucker 2020; Pucker 2021). Malet 2003 reported the number of participants who dropped out of the study, but this number did not match the results in the manuscript tables; we judged the trial to have some concerns.

Corneal fluorescein staining

We judged both Pucker 2020 and Pucker 2021 at low risk of bias.

Conjunctival redness

We judged Pucker 2021 at low risk of bias.

Participant discontinuation

We judged all but one trial (6/7, 86%) at low risk of bias because outcome data were available for nearly all participants randomized in each study. The exception was Malet 2003, where the reported number of participants who completed the trial was inconsistent (in the text and in the tables); therefore, we considered this trial had some concerns.

Domain 4: bias in outcome measurement

Contact lens discomfort

We assessed all five studies to have some concerns regarding outcome measurement. Malet 2003 used a VAS to document participants' self‐reported discomfort; Keir 2006 and McDonald 2014 used Likert scales to assess end‐of‐day comfort. These are not validated instruments for self‐reported symptoms. Although Pucker 2020 and Pucker 2021 used previously validated questionnaires, there were some concerns that the outcome measurement could be differential in the "no‐treatment" group.

Corneal fluorescein staining

We judged Pucker 2020 and Pucker 2021 at low risk of bias because both were investigator‐masked studies and participants in all comparison groups were assessed using the same examination.

Conjunctival redness

We judged Pucker 2021 at low risk of bias because it was an investigator‐masked study and participants in all comparison groups were assessed in the same manner.

Participant discontinuation

We considered there were some concerns related to participant discontinuation in two trials, primarily due to the lack of outcome data for the control group (Barabino 2005) or inconsistent reporting of the number of participants included in the final analysis (Keir 2006). The other five trials were at low risk of bias.

Domain 5: bias in selective reporting of outcome data

Contact lens discomfort

We assessed the risk of bias in selective reporting of outcome data as low in one trial (McDonald 2014), of some concern in three trials (Malet 2003; Pucker 2020; Pucker 2021), and high risk in one trial (Keir 2006). McDonald 2014 reported all outcomes specified, whereas Keir 2006 did not report the pre‐specified outcome of CL discomfort in the text, although they did provide the data in a plot (without values), possibly due to a lack of statistical significance. Pucker 2020 reported CLDEQ‐4 (a subset of CLDEQ‐8) as a pre‐specified outcome in the trial protocol found on the trial registry. However, both CLDEQ‐4 and CLDEQ‐8 are reported in the publication. Pucker 2021 pre‐specified CLDEQ‐4 in the trial registry, but CLDEQ‐4 and CLDEQ‐8 scores were reported in the results section of the trial registry, and only CLDEQ‐8 scores were mentioned in the publication. For Malet 2003, no study protocol was available for assessing the potential risk of selective reporting.

Corneal fluorescein staining

We judged both Pucker 2020 and Pucker 2021 at low risk of bias. Outcome data were analyzed and reported in a standard way.

Conjunctival redness

We judged Pucker 2021 at low risk of bias. Outcome data were analyzed and reported in a standard way.

Participant discontinuation

Because of associated concerns in measuring this outcome, we judged Barabino 2005 and Keir 2006 to have some concerns in selective result reporting (2/7, 29%). We judged the other five trials at low risk of bias.

Effects of interventions

See: Table 1; Table 2

We summarized effects of treatment on the predefined outcomes in Table 1 and Table 2. Appendix 8 presents comparison results of other participant‐reported symptom outcomes, changes in ocular surface parameters, and treatment compliance reported by the included studies.

Lubricating drops versus no treatment

Critical outcomes

Mean change in contact lens discomfort

Pucker 2021 (a three‐arm trial) contributed two pairwise comparisons and reported postintervention values and changes in CL discomfort from baseline using the CLDEQ‐8 questionnaire (scale 0 to 37, lower is better). Pucker 2020 also reported CL discomfort using the CLDEQ‐8 questionnaire. Because it was unclear whether the study authors had accounted for repeated measures in estimating SDs, we extracted postintervention values for meta‐analysis. The pooled estimate suggested lubricating drops compared with no treatment may reduce CL discomfort (MD −5.90 points, 95% CI −8.05 to −3.74; P = 0.83; I² = 0%; 2 RCTs, 119 participants; Analysis 1.1). In contrast, McDonald 2014 reported changes from baseline in "end‐of‐day comfort" using a Likert scale of 0 to 5 (higher is better). The analysis of the results suggests little or no difference between the lubrication drops and no treatment in terms of CL discomfort (MD −0.63 points, 95% CI −1.57 to 0.31; 83 participants; Analysis 1.1).

1.1. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 1: Contact lens discomfort

Overall, the certainty of the evidence for this outcome was very low. We downgraded one level for inconsistency, one level for imprecision, and one level for risk of bias associated with outcome measurement and selective reporting.

Important outcomes

Mean change in corneal fluorescein staining scores

Pucker 2020 and Pucker 2021 reported both postintervention values and changes in corneal fluorescein staining based on the Brien Holden Vision Institute (BHVI) grading scale for extent, type, and depth in five corneal regions (0‐4 scale in each of five regions, maximum 20 units per metric, with lower scores being better). However, due to similar concerns about the reported SDs, we extracted postintervention values for the pooled analysis. The pooled results suggest little or no difference between the lubricating drop and no treatment groups in corneal staining scores indicating extent (MD −0.15 points, 95% CI −0.86 to 0.56; P = 0.68; I² = 0%; 2 RCTs, 119 participants), depth (MD −0.01 points, 95% CI −0.44 to 0.42; P = 0.80; I² = 0%; 2 RCTs, 119 participants), and type (MD 0.04 points, 95% CI −0.38 to 0.46; P = 0.71; I² = 0%; 2 RCTs, 119 participants) of corneal staining (Analysis 1.2).

1.2. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 2: Corneal fluorescein staining

Overall, the certainty of the evidence for this outcome was low. We downgraded two levels for very serious imprecision due to small sample sizes.

Mean change in conjunctival redness scores

Pucker 2021 reported conjunctival redness scores based on the BHVI grading scale (0 to 4 in 0.5 increments, lower is better) for nasal and temporal bulbar conjunctival redness (Analysis 1.3). The analysis of their postintervention values suggests lubrication drops compared with no treatment have little or no effect on conjunctival redness in the nasal region (MD 0.10 points, 95% CI −0.29 to 0.49; P = 1.00; I² = 0%; 1 RCT [2 paired analyses], 73 participants) or the temporal region (MD 0.00, 95% CI −0.39 to 0.39; P = 1.00; I² = 0%; 1 RCT [2 paired analyses], 73 participants).

1.3. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 3: Conjunctival redness

Overall, the certainty of the evidence for this outcome was low. We downgraded two levels for very serious imprecision due to small sample size.

Adverse outcomes

No trials specifically reported vision‐threatening adverse events.

Proportion of participants with incident bacterial keratitis

No trials reported bacterial keratitis. However, McDonald 2014 reported two treatment‐emergent adverse events: bacterial conjunctivitis in 83 participants who received Systane Ultra lubricating drops, and one incident of herpes simplex keratitis in the no treatment group. The investigators considered both events were unrelated to the study treatment.

Proportion of participants with one or more inflammatory corneal infiltrates

No trials reported inflammatory corneal infiltrates. However, Barabino 2005 examined participants for conjunctival hyperemia, which was designated grade 0 (absent) or grade 1 (present). They reported that the proportion of participants with conjunctival hyperemia in the saline group was significantly lower at day 21 than at baseline (48.3% vs 82.8%, P < 0.05); however, there were no data reported for the control group.

Proportion of participants who discontinued participation in the study

Two trials reported participant discontinuation where the interventions were Systane Ultra lubricating drops (McDonald 2014) and saline (Barabino 2005). The pooled estimate suggests little or no differences in the risk of participant discontinuation among people receiving lubricating drops versus no treatment (RR 1.42, 95% CI 0.19 to 10.94; P = 0.74; I² = 0%; 2 RCTs, 138 participants; Analysis 1.4). Pucker 2020 and Pucker 2021 reported that no participants left the studies.

1.4. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 4: Participant discontinuation

Overall, the certainty of the evidence for this outcome was low. We downgraded one level for imprecision and one level for risk of bias associated with outcome measurement and selective reporting.

Lubricating drops versus saline

Critical outcomes

Mean change in contact lens discomfort

Two trials measured "end‐of‐day comfort" associated with CL wear (Keir 2006; Malet 2003). Keir 2006 measured change from baseline using a Likert scale of 0 to 5 (lower is better). The results suggest little or no difference in change in CL discomfort scores between Systane test drops and saline (MD −0.64 points, 95% CI −1.91 to 0.63; 76 participants; Analysis 2.1). Malet 2003 reported post‐intervention values based on a VAS of 0 to 100 (lower is better). The results suggest little or no difference in CL discomfort scores between PVP 2% lubricating drops and saline (MD 9.5 points, 95% CI −4.65 to 23.65; 39 participants; Analysis 2.1).

2.1. Analysis.

Comparison 2: Lubricants versus saline, Outcome 1: Contact lens discomfort

Overall, the certainty of the evidence on this outcome was very low. We downgraded two levels for very serious imprecision and one level for risk of bias associated with outcome measurement and selective reporting.

Important outcomes

Mean change in corneal fluorescein staining scores

No trials reported corneal fluorescein staining scores.

Mean change in conjunctival redness scores

No trials reported conjunctival redness scores.

Adverse outcomes

No trials specifically reported vision‐threatening adverse events.

Proportion of participants with incident bacterial keratitis

No trials reported bacterial keratitis. Malet 2003 reported cases of acute conjunctivitis (2 of 39 participants) and allergy (1 of 39 participants) in the PVP 2% lubricating drop group, but the investigators considered these events were unrelated to the study treatment.

Proportion of participants with one or more inflammatory corneal infiltrates

No trials reported inflammatory corneal infiltrates.

Proportion of participants who discontinued participation in the study

Three trials reported participant discontinuation, where the intervention was Systane eye drop (Keir 2006), PVP 2% lubricating drop (Malet 2003), or FID114657 lubricating drop (NCT02293538). The pooled estimate suggests little or no difference in risk of study discontinuation among people using lubricating drops versus saline (RR 1.56, 95% CI 0.47 to 5.12; P = 0.92; I² = 0%; 3 RCTs, 269 participants; Analysis 2.2).

2.2. Analysis.

Comparison 2: Lubricants versus saline, Outcome 2: Participant discontinuation

Overall, the certainty of the evidence on this outcome was low. We downgraded one level for imprecision and one level for risk of bias associated with outcome measurement and selective reporting.

Discussion

Summary of main results

This systematic review identified seven RCTs that compared lubricating drops versus no treatment or saline. Very low‐certainty evidence suggests that lubricating drops may improve CL discomfort compared with no treatment, but may have little or no effect on CL discomfort compared with saline. There is low‐certainty evidence of little or no difference in corneal fluorescein staining scores and conjunctival redness scores between people who use lubricating drops and people receiving no treatment. In addition, low‐certainty evidence suggests little or no difference in the risk of participant discontinuation over one to four weeks of treatment between lubricating drops versus no treatment and between lubricating drops versus saline.

Overall completeness and applicability of evidence

The number of included RCTs was low, which influenced the certainty of the results. While the total number of participants included in these trials (n = 463) suggested adequate sample sizes, each RCT was likely underpowered given the many different types of drops and CLs used. Further, the studies provided limited information regarding the representation of participants' race or ethnicity, types of CL materials used, wearing or replacement CL schedule, CL wear history, health, and lifestyle. This means it is unclear whether the review findings are applicable to the general population.

Specifically, the trials recruited adults in North America and Europe. Because Asians have a higher prevalence of dry eye, which could influence their experience of wearing CLs (Stapleton 2017), the review findings may not be readily generalizable to Asian adults with CL discomfort. Additionally, since CL discomfort is a symptom‐based diagnosis, there may be differences in symptom reporting associated with culture and ethnicity (Peacock 2008). Furthermore, some geographic locations may have greater environmental influences, such as pollution and climatic factors (Stapleton 2017).

The interventions in these trials included saline (versus no treatment), Systane Ultra, Systane Complete, a PVP lubricant, and an unknown lubricant (FID 114657). There were insufficient data to compare the head‐to‐head efficacy of these various lubricating drops. As CL wearers use many lubricating drop formulations, there is no evidence that one formulation is preferable to any other. Therefore, the results of this review are limited by the small number of lubricants tested and the variety of CLs and wearing schedules.

The main outcome of the studies was a change in patient‐reported CL discomfort. Also reported were corneal fluorescein staining and conjunctival hyperemia. Some trials reported adverse events and study discontinuation. Since these factors are also likely influenced by the lack of representation across the population, results related to these metrics are also uncertain.

Certainty of the evidence

The certainty of evidence on the critical and important outcomes was very low and low, due to uncertainty in the pooled estimates and considerable risk of bias associated with biased outcome measurement and selective reporting of results.

Potential biases in the review process

A Cochrane Information Specialist designed and conducted a comprehensive search of the literature published in all relevant databases. The methods of our review aligned with our published protocol (Caffery 2023). Our search was not limited by language or publication date. Two review authors independently reviewed each trial to confirm eligibility based on predefined criteria. Two review authors independently completed data extraction, with a third author adjudicating any differences. Risk of bias during the review process is considered minimal, especially as all but one review author (AP) had no conflicts of interest related to this work, and safeguards were put in place when a conflict of interest existed. The review author with two studies included in this review was not involved in reviewing or extracting data. The number of trial registration records and meeting abstracts without full publications could indicate publication bias or selective non‐reporting bias. When necessary, we contacted investigators to provide further information on study design and data, but with mixed success, leading to the uncertainty of the pooled estimates for a few outcomes.

Agreements and disagreements with other studies or reviews

A completed review of the compatibility of CLs with artificial tears and rewetting drops concluded that artificial tears and rewetting drops were effective and safe for the management of ocular surface disease in CL wearers in most situations, despite artificial tears not being FDA‐approved for this purpose (Pucker 2020b). Most studies included in this review reported minimal to no adverse events. While Pucker 2020b did not include a meta‐analysis, the conclusions were in line with ours, with no evidence of sight‐threatening adverse events related to the lubricating drops. The adverse events noted in our review were unrelated to study participation and included bacterial conjunctivitis, herpes simplex keratitis, acute conjunctivitis, and allergy. Pucker 2020b also advocated use of low‐viscosity lubricants for CLs due to the possibility of blurred vision from high‐viscosity lubricants. Although we did not evaluate vision as an outcome, using more viscous lubricating drops such as Systane Ultra and PVP 2% provided a similar level of change to end‐of‐day discomfort as saline.

The TFOS International Workshop on Contact Lens Discomfort report on management and therapy described Level II evidence for using lubricating drops for CL discomfort (Papas 2013). The report did not include a meta‐analysis, but it provided evidence that using lubricating drops for CL discomfort improved comfort on CL insertion, improved quality of vision, and reduced mucous discharge on waking compared to saline. Papas 2013 also provided an algorithm for stepwise management of CL discomfort. We did not study these treatment steps in our review. We found that end‐of‐day discomfort and overall discomfort may improve with lubricants versus no treatment. We also found low‐certainty evidence of little or no change in conjunctival redness with drops versus no treatment, and similar results with respect to end‐of‐day discomfort when comparing drops versus saline. Pucker 2020b noted decreased corneal staining, less end‐of‐day discomfort, and improved overall comfort when lubricants or rewetting drops were used to treat CL discomfort.

Rubinstein and Evans reported the contentious issue regarding preserved versus preservative‐free artificial tear drops during CL wear in a systematic review without meta‐analysis (Rubinstein 1997). They stated that the idea of adverse events from using preserved artificial tears during CL wear is not supported by the literature and may reflect the contents of care solutions rather than the preservatives. Pucker 2020b also reported that modern large molecular weight preservatives, such as polyquaternium‐1, are relatively safe for ocular use and are less expensive. We did not evaluate the impact of preserved versus non‐preserved lubricating eye drops on CL discomfort.

There is published evidence on pharmacological treatments other than lubricating drops for CL discomfort or dryness. In their review, without a meta‐analysis, Koh and colleagues found that pharmacological agents such as 3% diquafosol ophthalmic solution and ribemapide 2% ophthalmic solution offer newer ways to address dryness in CL wearers (Koh 2020). These agents lead to increased aqueous tear and mucin production, which may affect CL discomfort in some people. We did not assess alternative management options, such as changing CL materials, design, care products, or wear schedule. The TFOS report discussed how altering the CL material, water content, and wetting agents may decrease CL discomfort. It also discussed the presence of CL deposits, care products, and wearing schedules as options that can affect CL comfort (Papas 2013).

Comparison between reviews is difficult for several reasons: differences in the definition of CL discomfort, the overlap in the definitions of CL discomfort and CL dryness, differences in the intervention under review, and non‐standardized/varying tools for quantifying outcomes. However, this systematic review stands out as providing evidence for the benefits, or lack thereof, of using lubricating drops for CL discomfort.

Authors' conclusions

Implications for practice.

• Lubricating drops may reduce contact lens (CL) discomfort compared with no treatment, and may have little or no effect on CL discomfort compared with saline, but the evidence for these outcomes is very uncertain.

• Lubricating drops may have little to no effect on corneal fluorescein staining scores or conjunctival redness scores compared with no treatment.

• Compared with no treatment or saline drops, lubricating drops may have little to no effect on the risk of participant discontinuation in trials lasting one to four weeks.

• No trials reported vision‐threatening adverse events.

Implications for research.

More convincing evidence on the efficacy and safety of lubricating drops in reducing CL discomfort is needed. Future trials should:

• use validated questionnaires or instruments to quantify outcomes;

• incorporate a core outcome set (Saldanha 2018);

• involve participants from different age groups, different racial and ethnic backgrounds, and diverse geographical locations to optimize participant representativeness;

• consider particular CL types, wear schedules, and accompanying CL care systems;

• assess lubricating drops against inactive 'vehicles' to ensure proper evaluation of the non‐pharmacological active ingredients before head‐to‐head comparisons with another active drop;

• monitor participants over longer periods of time; and

• consider future studies that evaluate the effectiveness of other treatment approaches for CL discomfort such as anti‐inflammatory eyedrops and in‐office treatments.

History

Protocol first published: Issue 5, 2023

Risk of bias

Risk of bias for analysis 1.3 Conjunctival redness.

Study

Bias

Randomisation process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported results

Overall

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Subgroup 1.3.1 Nasal region

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple (Care Provider, Investigator, Outcomes Assessor)." Intention‐to‐Treat analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Low risk of bias

There were no participants who did not complete the trial (clinicaltrials.gov). Outcome measurement of participants in the three comparison groups was performed in the same way.

Low risk of bias

The data were likely measured, analyzed, and reported in a standard way.

Low risk of bias

The trial was judged to be at low risk of bias overall.

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple (Care Provider, Investigator, Outcomes Assessor)." Intention‐to‐Treat analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Low risk of bias

There were no participants who did not complete the trial (clinicaltrials.gov). Outcome measurement of participants in the three comparison groups was performed in the same way.

Low risk of bias

The data were likely measured, analyzed, and reported in a standard way.

Low risk of bias

The trial was judged to be at low risk of bias overall.

Subgroup 1.3.2 Temporal region

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple (Care Provider, Investigator, Outcomes Assessor)." Intention‐to‐Treat analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Low risk of bias

There were no participants who did not complete the trial (clinicaltrials.gov). Outcome measurement of participants in the three comparison groups was performed in the same way.

Low risk of bias

The data were likely measured, analyzed, and reported in a standard way.

Low risk of bias

The trial was judged to be at low risk of bias overall.

Pucker 2021

Low risk of bias

"Randomization included blocking and stratification by site to ensure that participants were equally distributed across study groups and sites." "The form of treatment was concealed from the participants by removing all labels and markings from the bottles." No group differences in baseline characteristics were noted.

Low risk of bias

Trial registry record documented "triple (Care Provider, Investigator, Outcomes Assessor)." Intention‐to‐Treat analysis was performed.

Low risk of bias

Outcome data were available for all participants randomized.

Low risk of bias

There were no participants who did not complete the trial (clinicaltrials.gov). Outcome measurement of participants in the three comparison groups was performed in the same way.

Low risk of bias

The data were likely measured, analyzed, and reported in a standard way.

Low risk of bias

The trial was judged to be at low risk of bias overall.

Risk of bias for analysis 2.1 Contact lens discomfort.

Study

Bias

Randomisation process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported results

Overall

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Subgroup 2.1.1 Post‐intervention value

Malet 2003

Some concerns

The authors reported that "the subjects were randomized into two treatment groups" though no details about random number generation or allocation concealment were provided. There was no evidence of baseline imbalance between the comparison groups.

Low risk of bias

Both drops used the ABAK dispenser, so it is unlikley that they could tell the difference between the drops. Also, this is a double masked study.

Low risk of bias

Outcome data was available for nearly all participants randomzied (39/45, 87%).

Some concerns

The authors used a visual analogue scale (on a scale of 0 to 100) for subjects to indicate CL discomfort (higher scores more discomfort), which was not a previously validated instrutment.

Some concerns

No study protocol was available for assessment. VAS was used to rate discomfort and the results were analyzed as reported in the Methods section.

High risk of bias

The trial was judged to have an overall high risk of bias due to potential risk of bias in multiple important domains.

Subgroup 2.1.2 Change

Keir 2006

Some concerns

"The study was conducted ...using a randomized parallel group design." However, details about allocation concealment were not reported.

Low risk of bias

Double‐masked study and "Both products were over‐labelled by an ophthalmic assistant, who also dispensed the product to the subject".

Low risk of bias

Data for nearly all participants randomized (79/81, 98%) were available.

Some concerns

A likert scale was used to "measure" participant‐reported CL discomfort at the end of day, rather than a previously validated instrument.

High risk of bias

CL discomfort was pre‐specified in the methods, the numeric results of which were not reported in the text but only provided in a plot (without values), likely due to the statistical non‐significance.

High risk of bias

There was high risk of bias associated with selective reporting of the results.

Risk of bias for analysis 2.2 Participant discontinuation.

Study

Bias

Randomisation process

Deviations from intended interventions

Missing outcome data

Measurement of the outcome

Selection of the reported results

Overall

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Authors' judgement

Support for judgement

Keir 2006

Some concerns

"The study was conducted ...using a randomized parallel group design." However, details about allocation concealment were not reported.

Low risk of bias

"Both the clinical investigator and subject were masked to the identity of the subjects’ study products at all times."

Low risk of bias

Data for the outcome were available for all participants randomized.

Some concerns

The authors reported the total number of discontinuations without breaking down into the group. Also, the initial number of participants was reportedly 81, 79 were said to complete the study. However, both table 1 and table 2 showed a total number of 80 participants with 40 in each intervention group.

Some concerns

No study protocol available for assessment. The authors did not clearly indicate to which treatment group the participants who discontinued belonged. An overall count was provided, with the number of participants completing the study incompatible with those shown in the tables.

High risk of bias

The trial was judged to have high risk of bias due to potential risk of bias in randomization process, outcome measurement and reporting.

Malet 2003

Some concerns

The authors reported that "the subjects were randomized into two treatment groups" though no details about random number generation or allocation concealment were provided. There was no evidence of baseline imbalance between the comparison groups.

Low risk of bias

Both drops used the ABAK disppenser, so it is unlikley that they could tell the difference between the drops. The authors used appropriate analysis to estimate effects of assignment.

Some concerns

Data for the outcome were available for nearly all participants randomized (39/45, 87%) but the reported numbers of participants who did not complete the study did not match between the text and the tables.

Low risk of bias

The measurement was based on the number of participants who did not show up at the last study visit.

Low risk of bias

No study protocol was available but the reporting was in accordance with the standard definition in a trial.

Some concerns

The trial was judged to have some conerns in risk of bias due to inconsistent reporting of outcome data.

NCT02293538

Some concerns

No full‐text report available. The trial registry record which described the trial as "randomized" with no additional details about random number generation or allocation concealment. Proportions of female were borderline significantly different between the two comparison groups, otherwise there was no imbalance in baseline characteristics reported on clinicaltrials.gov.

Low risk of bias

The trial was "double‐masked (participant, investigator)" and the authors used appropriate analysis to estimate effects of assignment.

Low risk of bias

Data for this outcome were available for all participants randomzied.

Low risk of bias

Counts of participants who did not complete the trial in both groups were provided. Investigators were masked to the intervention received. There was no evidence of biased outcome measurement.

Low risk of bias

No study protocol available but the result was reported in a standard fashion.

Some concerns

The trial was judged to have some concerns in risk of bias overall due to unclear reporting in the randomization process.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Contact Lenses] explode all trees
#2 ((contact or contacts) NEXT/2 (lens or lenses)):ab,ti,kw
#3 ((hydrogel* or hydrophilic* or silicone* or "gas permeable" or "gas permeables") NEXT/2 (contact or contacts)):ab,ti,kw
#4 ((hydrogel* or hydrophilic* or silicone* or "gas permeable" or "gas permeables") NEXT/2 (lens or lenses)):ab,ti,kw
#5 ((soft or disposable or disposables or daily or dailies or monthly or monthlies or weekly or weeklies or "extended wear" or "continuous wear" or hybrid* or biweek* or replacement*) NEXT/2 (contact or contacts)):ab,ti,kw
#6 ((soft or disposable or disposables or daily or dailies or monthly or monthlies or weekly or weeklies or "extended wear" or "continuous wear" or hybrid* or biweek* or replacement*) NEXT/2 (lens or lenses)):ab,ti,kw
#7 {OR #1‐#6}
#8 MeSH descriptor: [Nonprescription Drugs] explode all trees
#9 ("over‐the‐counter" or "over the counter" or OTC)
#10 ("non‐prescription" or "non‐prescriptions" or "non prescription" or "non prescriptions" or nonprescription*)
#11 MeSH descriptor: [Ophthalmic Solutions] explode all trees
#12 ("artificial tear" or "artificial tears" or "tear substitute" or "tear substitutes" or eyedrop*)
#13 ((eye or eyes or ocular* or ophthalmic* or "non prescriptive" or nonprescriptive* or wetting or rewetting or lubricating) adj2 (drop or drops or agent or agents or solution or solutions))
#14 MeSH descriptor: [Ointments] explode all trees
#15 (ointment* or lubricant*)
#16 MeSH descriptor: [Demulcents] explode all trees
#17 demulcent*
#18 MeSH descriptor: [Hypromellose Derivatives] explode all trees
#19 MeSH descriptor: [Methylcellulose] explode all trees
#20 (hypromellose or "cellulose derivative" or "cellulose derivatives" or "carboxymethylcellulose sodium" or CMC or hydroxypropylmethylcellulose or "hydroxypropyl methylcellulose" or HPMC or "hydroxyethyl cellulose" or methylcellulose or methoxyhydroxypropylcellulose or carbomer* or cellulose)
#21 "dextran 70"
#22 MeSH descriptor: [Gelatin] explode all trees
#23 (gelatin* or "HP Guar" or "Carbopol type gel")
#24 MeSH descriptor: [Polyethylene Glycols] explode all trees
#25 ("liquid polyol" or "liquid polyols" or glycerin* or "polyethylene glycol" or "polyethylene glycols" or "PEG 300" or "PEG 400" or "polysorbate 80" or "propylene glycol" or "propylene glycols" or "polyhydric alcohol" or "polyhydric alcohols").tw.
#26 MeSH descriptor: [Polyvinyls] explode all trees
#27 ("polyvinyl alcohol" or "polyvinyl alcohols" or polyvinylalcohol* or PVA)
#28 (povidone or polyvinylpyrrolidone)
#29 MeSH descriptor: [Hyaluronic Acid] explode all trees
#30 "sodium hyaluronate"
#31 MeSH descriptor: [Emollients] explode all trees
#32 emollient*
#33 MeSH descriptor: [Lanolin] explode all trees
#34 MeSH descriptor: [Paraffin] explode all trees
#35 MeSH descriptor: [Mineral Oil] explode all trees
#36 MeSH descriptor: [Fatty Acids, Omega‐3] explode all trees
#37 MeSH descriptor: [Leptospermum] explode all trees
#38 (lanolin* or paraffin*)
#39 ((castor or mineral) NEXT/2 oil*)
#40 ("omega‐3" or "omega 3")
#41 (manuka or leptospermum)
#42 {OR #8‐#41}
#43 #7 AND #42 in Trials

Appendix 2. MEDLINE (Ovid) search strategy

1. Randomized Controlled Trial.pt.
2. Controlled Clinical Trial.pt.
3. (randomized or randomised).ab,ti.
4. placebo.ab,ti.
5. drug therapy.fs.
6. randomly.ab,ti.
7. trial.ab,ti.
8. groups.ab,ti.
9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
10. exp animals/ not humans.sh.
11. 9 not 10 
12. exp Contact Lenses/
13. ((contact or contacts) adj2 (lens or lenses)).tw.
14. ((hydrogel* or hydrophilic* or silicone* or "gas perm*") adj2 (contact or contacts)).tw.
15. ((hydrogel* or hydrophilic* or silicone* or "gas perm*") adj2 (lens or lenses)).tw.
16. ((soft or disposable or disposables or daily or dailies or monthly or monthlies or weekly or weeklies or "extended wear" or "continuous wear" or hybrid* or biweek* or replacement*) adj2 (contact or contacts)).tw.
17. ((soft or disposable or disposables or daily or dailies or monthly or monthlies or weekly or weeklies or "extended wear" or "continuous wear" or hybrid* or biweek* or replacement*) adj2 (lens or lenses)).tw.
18. or/12‐17
19. exp Nonprescription Drugs/
20. ("over‐the‐counter" or "over the counter" or OTC).tw.
21. ("non‐prescription*" or "non prescription*" or "nonprescription*").tw.
22. exp Ophthalmic Solutions/
23. ("artificial tear*" or "tear substitute*" or eyedrop*).tw.
24. ((eye or eyes or ocular* or ophthalmic* or "non prescripti*" or nonprescripti* or wetting or rewetting or lubricating) adj2 (drop or drops or agent or agents or solution or solutions)).tw.
25. exp Ointments/
26. (ointment* or lubricant*).tw.
27. exp Demulcents/
28. demulcent*.tw.
29. exp Hypromellose Derivatives/
30. exp Methylcellulose/
31. (hypromellose or "cellulose derivative*" or "carboxymethylcellulose sodium" or CMC or hydroxypropylmethylcellulose or "hydroxypropyl methylcellulose" or HPMC or "hydroxyethyl cellulose" or methylcellulose or methoxyhydroxypropylcellulose or carbomer* or cellulose).tw.
32. "dextran 70".tw.
33. exp Gelatin/
34. (gelatin* or "HP Guar" or "Carbopol type gel").tw.
35. exp Polyethylene Glycols/
36. ("liquid polyol*" or glycerin* or "polyethylene glycol*" or "PEG 300" or "PEG 400" or "polysorbate 80" or "propylene glycol*" or "polyhydric alcohol*").tw.
37. exp Polyvinyls/
38. ("polyvinyl alcohol*" or polyvinylalcohol* or PVA).tw.
39. (povidone or polyvinylpyrrolidone).tw.
40. exp Hyaluronic Acid/
41. "sodium hyaluronate".tw.
42. exp Emollients/
43. emollient*.tw.
44. exp Lanolin/
45. exp Paraffin/
46. exp Mineral Oil/
47. exp Fatty Acids, Omega‐3/
48. exp Leptospermum/
49. (lanolin* or paraffin*).tw.
50. ((castor or mineral) adj2 oil*).tw.
51. (omega‐3 or omega 3).tw.
52. (manuka or leptospermum).tw.
53. or/19‐52
54. 18 and 53
55. 11 and 54

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville et al (Glanville 2006).

Appendix 3. Embase.com search strategy

#1 'randomized controlled trial'/exp
#2 'randomization'/exp
#3 'double blind procedure'/exp
#4 'single blind procedure'/exp
#5 random*:ab,ti
#6 #1 OR #2 OR #3 OR #4 OR #5
#7 'animal'/exp OR 'animal experiment'/exp
#8 'human'/exp
#9 #7 AND #8
#10 #7 NOT #9
#11 #6 NOT #10
#12 'clinical trial'/exp
#13 (clin* NEAR/3 trial*):ab,ti
#14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti
#15 'placebo'/exp
#16 placebo*:ab,ti
#17 random*:ab,ti
#18 'experimental design'/exp
#19 'crossover procedure'/exp
#20 'control group'/exp
#21 'latin square design'/exp
#22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
#23 #22 NOT #10
#24 #23 NOT #11
#25 'comparative study'/exp
#26 'evaluation'/exp
#27 'prospective study'/exp
#28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
#29 #25 OR #26 OR #27 OR #28
#30 #29 NOT #10
#31 #30 NOT (#11 OR #23)
#32 #11 OR #24 OR #31
#33 'contact lens'/exp
#34 ((contact OR contacts) NEXT/2 (lens OR lenses)):ab,ti,kw
#35 ((hydrogel* OR hydrophilic* OR silicone* OR 'gas perm*') NEXT/2 (contact OR contacts)):ab,ti,kw
#36 ((hydrogel* OR hydrophilic* OR silicone* OR 'gas perm*') NEXT/2 (lens OR lenses)):ab,ti,kw
#37 ((soft OR disposable OR disposables OR daily OR dailies OR monthly OR monthlies OR weekly OR weeklies OR 'extended wear' OR 'continuous wear' OR hybrid* OR biweek* OR replacement*) NEXT/2 (contact OR contacts)):ab,ti,kw
#38 ((soft OR disposable OR disposables OR daily OR dailies OR monthly OR monthlies OR weekly OR weeklies OR 'extended wear' OR 'continuous wear' OR hybrid* OR biweek* OR replacement*) NEXT/2 (lens OR lenses)):ab,ti,kw
#39 #33 OR #34 OR #35 OR #36 OR #37 OR #38 
#40 'non prescription drug'/exp
#41 ('over‐the‐counter' OR 'over the counter' OR OTC):ab,ti,kw
#42 ('non‐prescription*' OR 'non prescription*' OR 'nonprescription*'):ab,ti,kw
#43 'eye drops'/exp
#44 'artificial tear'/exp
#45 ('artificial tear*' OR 'tear substitute*' OR eyedrop*):ab,ti,kw
#46 ((eye OR eyes OR ocular* OR ophthalmic* OR 'non prescripti*' OR nonprescripti* OR wetting OR rewetting OR lubricating) NEXT/2 (drop OR drops OR agent OR agents OR solution OR solutions)):ab,ti,kw
#47 'ointment'/exp
#48 (ointment* OR lubricant*):ab,ti,kw
#49 'demulcent agent'/exp
#50 demulcent*:ab,ti,kw
#51 'hydroxypropylmethylcellulose'/exp
#52 'methylcellulose'/exp
#53 (hypromellose OR 'cellulose derivative*' OR 'carboxymethylcellulose sodium' OR CMC OR 'hydroxypropyl methylcellulose' OR HPMC OR 'hydroxyethyl cellulose' OR methylcellulose OR methoxyhydroxypropylcellulose OR carbomer* OR cellulose):ab,ti,kw
#54 'dextran 70'/exp
#55 'dextran 70':ab,ti,kw
#56 'gelatin'/exp
#57 (gelatin* OR 'HP Guar' OR 'Carbopol type gel'):ab,ti,kw
#58 'macrogol derivative'/exp
#59 ('liquid polyol*' OR glycerin* OR 'polyethylene glycol*' OR 'PEG 300' OR 'PEG 400' OR 'polysorbate 80' OR 'propylene glycol*' OR 'polyhydric alcohol*'):ab,ti,kw
#60 'polyvinyl derivative'/exp
#61 ('polyvinyl alcohol*' OR polyvinylalcohol* OR PVA):ab,ti,kw
#62 (povidone OR polyvinylpyrrolidone):ab,ti,kw
#63 'hyaluronic acid'/exp
#64 'sodium hyaluronate':ab,ti,kw
#65 'emollient agent'/exp
#66 emollient*:ab,ti,kw
#67 'lanolin'/exp
#68 'paraffin'/exp
#69 'liquid paraffin'/exp
#70 'mineral oil'/exp
#71 'omega 3 fatty acid'/exp
#72 'Leptospermum'/exp
#73 (lanolin* OR paraffin*):ab,ti,kw
#74 ((castor OR mineral) NEXT/2 oil*):ab,ti,kw
#75 ('omega‐3' OR 'omega 3'):ab,ti,kw
#76 (manuka OR leptospermum):ab,ti,kw
#77 #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76
#78 #39 AND #77
#79 #32 AND #78

The search filter for trials at the beginning of the Embase.com strategy is adapted from the published paper by Lefebvre et al (Lefebvre 2008).

Appendix 4. PubMed.gov search strategy

1. ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh])
2. "contact lens*"[tw] 
3. ((hydrogel*[tw] OR hydrophilic*[tw] OR silicone*[tw] OR "gas perm*"[tw]) AND (contact[tw] OR contacts[tw])) 
4. ((hydrogel*[tw] OR hydrophilic*[tw] OR silicone*[tw] OR "gas perm*"[tw]) AND (lens[tw] OR lenses[tw])) 
5. ((soft[tw] OR disposable[tw] OR disposables[tw] OR daily[tw] OR dailies[tw] OR monthly[tw] OR monthlies[tw] OR weekly[tw] OR weeklies[tw] OR "extended wear"[tw] OR "continuous wear"[tw] OR hybrid*[tw] OR biweek*[tw] OR replacement*[tw]) AND (contact[tw] OR contacts[tw])) 
6. ((soft[tw] OR disposable[tw] OR disposables[tw] OR daily[tw] OR dailies[tw] OR monthly[tw] OR monthlies[tw] OR weekly[tw] OR weeklies[tw] OR "extended wear"[tw] OR "continuous wear"[tw] OR hybrid*[tw] OR biweek*[tw] OR replacement*[tw]) AND (lens[tw] OR lenses[tw])) 
7. #2 OR #3 OR #4 OR #5 OR #6 
8. ("over‐the‐counter"[tw] OR "over the counter"[tw] OR OTC[tw])
9. ("non‐prescription*"[tw] OR "non prescription*"[tw] OR "nonprescription*"[tw])
10. ("artificial tear*"[tw] OR "tear substitute*"[tw] OR eyedrop*[tw])
11. ((eye[tw] OR eyes[tw] OR ocular*[tw] OR ophthalmic*[tw] OR "non prescripti*"[tw] OR nonprescripti*[tw] OR wetting[tw] OR rewetting[tw] OR lubricating[tw]) AND (drop[tw] OR drops[tw] OR agent[tw] OR agents[tw] OR solution[tw] OR solutions[tw]))
12. (ointment*[tw] OR lubricant*[tw])
13. demulcent*[tw]
14. (hypromellose[tw] OR "cellulose derivative*"[tw] OR "carboxymethylcellulose sodium"[tw] OR CMC[tw] OR "hydroxypropyl methylcellulose"[tw] OR HPMC[tw] OR "hydroxyethyl cellulose"[tw] OR methylcellulose[tw] OR methoxyhydroxypropylcellulose[tw] OR carbomer*[tw] OR cellulose[tw])
15. "dextran 70"[tw]
16. (gelatin*[tw] OR "HP Guar"[tw] OR "Carbopol type gel"[tw])
17. ("liquid polyol*"[tw] OR glycerin*[tw] OR "polyethylene glycol*"[tw] OR "PEG 300"[tw] OR "PEG 400"[tw] OR "polysorbate 80"[tw] OR "propylene glycol*"[tw] OR "polyhydric alcohol*"[tw])
18. ("polyvinyl alcohol*"[tw] OR polyvinylalcohol*[tw] OR PVA[tw])
19. (povidone[tw] OR polyvinylpyrrolidone[tw])
20. "sodium hyaluronate"[tw]
21. emollient*[tw]
22. (lanolin*[tw] OR paraffin*[tw])
23. ((castor[tw] OR mineral[tw]) AND (oil[tw] OR oils[tw]))
24. ("omega‐3"[tw] OR "omega 3"[tw])
25. (manuka[tw] OR leptospermum[tw])
26. #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 
27. #7 AND #26
28. #1 AND #27
29. Medline[sb]
30. #28 NOT #29

The search filter for trials at the beginning of the PubMed strategy is adapted from the published paper by Glanville et al (Glanville 2006).

Appendix 5. LILACS search strategy

("Contact Lens" OR "Contact Lenses" OR "Lentes de Contacto" OR "Lentes de Contato" OR MH:E07.632.500.276$ OR MH: VS2.006.001.009.001$ OR MH:D20.280.320.375$ OR MH:D26.255.165.320.375$ OR MH:D02.756.650.700$ OR MH:D05.750.900.850$ OR MH:D25.720.900.850$ OR MH:J01.637.051.720.900.850$ OR hydrogel$ OR hydrophilic$ OR silicone$ OR "gas permeable" OR ((soft OR disposable OR disposables OR daily OR dailies OR monthly OR monthlies OR weekly OR weeklies OR "extended wear" OR "continuous wear" OR hybrid$ OR biweek$ OR replacement$) AND (contact OR contacts OR lens OR lenses))) AND (MH:D26.530$ OR MH:VS2.002.001.006$ OR "over the counter" OR OTC OR "non prescription" OR nonprescription OR MH:D26.776.708.645$ OR MH:D27.505.954.578.645$ OR MH:D27.720.752.608$ OR "artificial tear" OR "artificial tears" OR "tear substitute" OR "tear substitutes" OR eyedrop$ OR ((eye OR eyes OR ocula$ OR ophthalmic$ OR wetting OR rewetting OR lubricating) AND (drop OR drops OR agent OR agents OR solution OR solutions)) OR MH:D26.255.640$ OR ointment$ OR lubricant$ OR MH:D27.505.954.158.515$ OR MH:D27.505.954.483.534$ OR MH:D27.505.954.796.210$ OR MH:D27.720.877.156$ OR Demulcent$ OR MH:D05.750.078.562.180.357$ OR MH:D09.698.365.180.455$ OR MH:D25.720.099.500.719$ OR MH:J01.637.051.720.099.500.719$ OR MH:D09.698.365.180.663$ OR hypromellose OR "cellulose derivative" OR "cellulose derivatives" OR "carboxymethylcellulose sodium" OR CMC OR hydroxypropylmethylcellulose OR "hydroxypropyl methylcellulose" OR HPMC OR "hydroxyethyl cellulose" OR methylcellulose OR methoxyhydroxypropylcellulose OR carbomer$ OR cellulose OR "dextran 70" OR MH:D12.776.860.476$ OR gelatin$ OR "HP Guar" OR "Carbopol type gel" OR MH:D02.033.455.250.700$ OR MH:D05.750.741$ OR MH:D25.720.741$ OR MH:J01.637.051.720.741$ OR "liquid polyol" OR "liquid polyols" OR glycerin$ OR "polyethylene glycol" OR "polyethylene glycols" OR "PEG 300" OR "PEG 400" OR "polysorbate 80" OR "propylene glycol" OR "propylene glycols" OR "polyhydric alcohol" OR "polyhydric alcohols" OR MH:D02.455.326.271.665.616$ OR MH:D02.455.326.271.884.533$ OR MH:D05.750.716.721$ OR MH:D25.720.716.721$ OR MH:J01.637.051.720.716.721$ OR "polyvinyl alcohol" OR "polyvinyl alcohols" OR polyvinylalcohol$ OR PVA OR povidone OR polyvinylpyrrolidone OR MH:D09.698.373.475$ OR "sodium hyaluronate" OR MH:D27.505.954.444.200$ OR emollient$ OR MH:D10.945.507$ OR MH:D02.455.612 OR MH:D02.455.699.500 OR MH:D10.212.302.380.410$ OR MH:D10.251.355.337$ OR MH:D10.627.430.450$ OR MH:B01.875.800.575.912.250.773.713$ OR lanolin$ OR paraffin$ OR "castor oil" OR "castor oils" OR "mineral oil" OR "mineral oils" OR "omega 3" OR manuka OR leptospermum)

Appendix 6. ClinicalTrials.gov search strategy

("contact lens" OR "contact lenses") AND ("over the counter" OR OTC OR nonprescription* OR "non prescription" OR "artificial tears" OR "tear substitute" OR eyedrop OR ((eye OR eyes OR ocular OR ophthalmic OR wetting OR rewetting OR lubricating) AND (drop OR drops OR agent OR agents OR solution OR solutions)) OR ointment OR lubricant OR Demulcent OR hypromellose OR "cellulose derivative" OR "cellulose derivatives" OR "carboxymethylcellulose sodium" OR CMC OR hydroxypropylmethylcellulose OR "hydroxypropyl methylcellulose" OR HPMC OR "hydroxyethyl cellulose" OR methylcellulose OR methoxyhydroxypropylcellulose OR carbomer OR cellulose OR "dextran 70" OR gelatin OR "HP Guar" OR "Carbopol type gel" OR "liquid polyol" OR glycerin OR "polyethylene glycol" OR "PEG 300" OR "PEG 400" OR "polysorbate 80" OR "propylene glycol" OR "polyhydric alcohol" OR "polyvinyl alcohol" OR polyvinylalcohol OR PVA OR povidone OR polyvinylpyrrolidone OR "sodium hyaluronate" OR emollient OR lanolin OR paraffin OR "castor oil" OR "mineral oil" OR "omega 3" OR manuka OR leptospermum)

Appendix 7. ICTRP search strategy

contact lens AND over the counter OR contact lens AND OTC OR contact lens AND nonprescription OR contact lens AND non prescription OR contact lens AND artificial tears OR contact lens AND tear substitute OR contact lens AND wetting OR contact lens AND rewetting OR contact lens AND lubricating OR contact lens AND drops OR contact lenses AND eyedrops OR contact lens AND agent OR contact lens AND agents OR contact lens AND solution OR contact lens AND ointment OR contact lens AND lubricant OR contact lens AND demulcent OR contact lens AND hypromellose OR contact lens AND cellulose derivative OR contact lens AND cellulose derivatives OR contact lens AND carboxymethylcellulose sodium OR contact lens AND CMC OR contact lens AND hydroxypropylmethylcellulose OR contact lens AND hydroxypropyl methylcellulose OR contact lens AND HPMC OR contact lens AND hydroxyethyl cellulose OR contact lens AND methylcellulose OR contact lens AND methoxyhydroxypropylcellulose OR contact lens AND carbomer OR contact lens AND cellulose OR contact lens AND "dextran 70" OR contact lens AND gelatin OR contact lens AND "HP Guar" OR contact lens AND carbopol type gel OR contact lens AND liquid polyol OR contact lens AND glycerin OR contact lens AND polyethylene glycol OR contact lens AND "PEG 300" OR contact lens AND "PEG 400" OR contact lens AND "polysorbate 80" OR contact lens AND propylene glycol OR contact lens AND polyhydric alcohol OR contact lens AND "polyvinyl alcohol" OR contact lens AND polyvinylalcohol OR contact lens AND PVA OR contact lens AND povidone OR contact lens AND polyvinylpyrrolidone OR contact lens AND sodium hyaluronate OR contact lens AND emollient OR contact lens AND lanolin OR contact lens AND paraffin OR contact lens AND castor oil OR contact lens AND mineral oil OR contact lens AND omega 3 OR contact lens AND manuka OR contact lens AND leptospermum OR contact lenses AND over the counter OR contact lenses AND OTC OR contact lenses AND nonprescription OR contact lenses AND non prescription OR contact lenses AND artificial tears OR contact lenses AND tear substitute OR contact lenses AND wetting OR contact lenses AND rewetting OR contact lenses AND lubricating OR contact lenses AND drops OR contact lenses AND eyedrops OR contact lenses AND agent OR contact lenses AND agents OR contact lenses AND solution OR contact lenses AND ointment OR contact lenses AND lubricant OR contact lenses AND demulcent OR contact lenses AND hypromellose OR contact lenses AND cellulose derivative OR contact lenses AND cellulose derivatives OR contact lenses AND carboxymethylcellulose sodium OR contact lenses AND CMC OR contact lenses AND hydroxypropylmethylcellulose OR contact lenses AND hydroxypropyl methylcellulose OR contact lenses AND HPMC OR contact lenses AND hydroxyethyl cellulose OR contact lenses AND methylcellulose OR contact lenses AND methoxyhydroxypropylcellulose OR contact lenses AND carbomer OR contact lenses AND cellulose OR contact lenses AND "dextran 70" OR contact lenses AND gelatin OR contact lenses AND "HP Guar" OR contact lenses AND carbopol type gel OR contact lenses AND liquid polyol OR contact lenses AND glycerin OR contact lenses AND polyethylene glycol OR contact lenses AND "PEG 300" OR contact lenses AND "PEG 400" OR contact lenses AND "polysorbate 80" OR contact lenses AND propylene glycol OR contact lenses AND polyhydric alcohol OR contact lenses AND "polyvinyl alcohol" OR contact lenses AND polyvinylalcohol OR contact lenses AND PVA OR contact lenses AND povidone OR contact lenses AND polyvinylpyrrolidone OR contact lenses AND sodium hyaluronate OR contact lenses AND emollient OR contact lenses AND lanolin OR contact lenses AND paraffin OR contact lenses AND castor oil OR contact lenses AND mineral oil OR contact lenses AND omega 3 OR contact lenses AND manuka OR contact lenses AND leptospermum

Appendix 8. Additional outcomes reported by the included studies

Other (dis)comfort measures associated with CL wear

Besides CL discomfort, the included studies also measured other patient‐reported symptom scores or metrics associated with CL wear.

• CL insertion comfort: measured on Likert Scales (0 to 5; 0 = none, 5 = worst) in Keir 2006 and McDonald 2014. Keir 2006 reported changes in CL insertion comfort in the treatment group (Systane (R)), but McDonald 2014 found similar results in the Systane(R) Ultra group and the control group.

• Overall (ocular) dryness: measured in Keir 2006 and McDonald 2014. Both trials found that participants in the lubricating drop groups had significantly less all‐day dryness compared with those in the control group. In contrast, NCT02293538 reported proportions of participants who had experienced at least a 1 unit increase in overall comfort with CLs (VAS of 0 to 10) and found that 79.4% of participants in the lubricating drops group experienced at least 1 unit increase in overall comfort after two hours of daily CL wear for two weeks compared to 84.5% of participants in the saline control group.

• Comfortable lens weartime: quantified in two trials that compared lubricating drops with no treatment (Pucker 2020; Pucker 2021) and in three trials that compared lubricating drops with saline (Keir 2006; McDonald 2014; NCT02293538). Pucker 2020 found improved lens wear time in the Systane(R) group, Pucker 2021 found no difference between the groups (Analysis 1.5). Participants in the treatment group of Keir 2006 reported a significantly longer wear time than those in the saline group (mean 9.3 hours [SD 2.9 hours] versus mean 8.0 hours [SD 3.2]; P = 0.034), whereas NCT02293538 found no differences between the lubricating drops group and the saline group (Analysis 2.3). McDonald 2014 reported that there were no statistical differences in wear time changes from baseline in the Systane(R) Ultra and the no treatment groups.

• End‐of‐study (perceived) eye comfort: reported in Pucker 2020 and Pucker 2021 as proportions of participants who self‐perceived eye comfort at the end of the two‐week trial compared to baseline as "better," "same," or "worse." In Pucker 2020, participants in the treatment group were more likely to report that their perceived eye comfort was "better" at two weeks than those in the control group. However, Pucker 2021 found "no significant difference" between the two drop groups. Both studies (Pucker 2020 and Pucker 2021), as well as McDonald 2014, also reported dry eye symptoms that were not directly associated with wearing contact lens using different instruments (Analysis 1.6).

1.5. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 5: Comfortable lens wear time (hours)

2.3. Analysis.

Comparison 2: Lubricants versus saline, Outcome 3: Comfortable lens wear time (hours)

1.6. Analysis.

Comparison 1: Lubricants versus no treatment, Outcome 6: Other dry eye symptoms

Ocular surface parameters

• Pre‐lens tear lipid layer thickness after two hours of CL wear: this measure increased in the lubricating drops group compared with the saline group of NCT02293538 (mean 59.4 nm [SD 19.30] vs mean 58.5 nm [SD 21.09]).

• Corneal punctate staining:Barabino 2005 documented the presence (Grade 1) or absence (Grade 0) of corneal punctate staining, finding no statistically significant changes between the preservative‐free 0.9% saline group and controls. Malet 2003 reported changes in the proportions of participants with corneal punctate staining from baseline through day 28. At baseline, corneal fluorescein punctate staining was observed in two participants (8.7%) in the PVP group, and one participant (6.3%) in the saline group. On day, no participants presented with punctate cornea staining in the PVP group, but three participants had corneal punctate staining in the saline group.

Compliance

• Treatment compliance: measured and reported in Pucker 2021, where participants in the artificial tear and rewetting drop groups had similar compliance rates.

Data and analyses

Comparison 1. Lubricants versus no treatment.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Contact lens discomfort	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.1.1 Postintervention value	2	119	Mean Difference (IV, Random, 95% CI)	‐5.90 [‐8.05, ‐3.74]
1.1.2 Change	1	83	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.57, 0.31]
1.2 Corneal fluorescein staining	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.2.1 Extent	2	119	Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.86, 0.56]
1.2.2 Depth	2	119	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.44, 0.42]
1.2.3 Type	2	119	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.38, 0.46]
1.3 Conjunctival redness	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
1.3.1 Nasal region	1	73	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.29, 0.49]
1.3.2 Temporal region	1	73	Mean Difference (IV, Fixed, 95% CI)	0.00 [‐0.39, 0.39]
1.4 Participant discontinuation	2	138	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [0.19, 10.94]
1.5 Comfortable lens wear time (hours)	2	119	Mean Difference (IV, Random, 95% CI)	2.41 [0.84, 3.97]
1.6 Other dry eye symptoms	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.6.1 SPEED	2	119	Mean Difference (IV, Random, 95% CI)	‐1.12 [‐2.65, 0.40]
1.6.2 Likert scale	1	83	Mean Difference (IV, Random, 95% CI)	‐0.46 [‐0.85, ‐0.07]

Comparison 2. Lubricants versus saline.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Contact lens discomfort	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.1.1 Post‐intervention value	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.1.2 Change	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
2.2 Participant discontinuation	3	269	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.47, 5.12]
2.3 Comfortable lens wear time (hours)	2	218	Mean Difference (IV, Fixed, 95% CI)	0.69 [‐0.19, 1.58]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Barabino 2005.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: April 2002 to December 2002 Unit of randomization: person Masking of participants: no Masking of outcome assessor(s): yes Masking of other trial personnel: cannot tell Was CL discomfort measured with an instrument: yes, VAS (0‐100) Duration of intervention: 21 days Duration of follow‐up: 7 days How did the study authors handle missing data?: complete case analysis Did the study authors describe power/sample size consideration?: no
Participants	Inclusion criteria Use of properly fitted soft hydrophilic contact lenses Age ≥ 18 years Frequent ocular discomfort (irritation, stinging, burning or sensation of intermittent blurred vision) in both eyes due to relative dehydration of the lenses induced by environmental factors (air conditioning, heating, long work sessions at the computer terminal) during wear Normal slit‐lamp examination Fluorescein tear film BUT ≥ 10 seconds or greater > 5 mm of wetting in 5 minutes on the Schirmer 1 test with and without anesthesia Exclusion criteria Ocular injury, infection, or inflammation within the 3 months preceding the study Concomitant ocular disease Previous ocular surgery Eyelid or eyelash abnormalities Alteration of the nasolacrimal apparatus Treatment with drugs affecting tearing Concomitant ocular therapy within the month preceding the study, except for artificial tears if followed by a washout period Neurologic or dermatologic disease affecting the health of the ocular surface Any abnormality or disorder evidenced during ophthalmic examination, such as conjunctival hyperemia (score of 2 or 3 in one or both eyes, where 0 = absent, 1 = moderately dilated conjunctival vessels, 2 = dilated conjunctival vessels and episcleral vessels, and 3 = highly dilated conjunctival and episcleral vessels) or corneal punctate staining by fluorescein (score of 2 or 3 in one or both eyes, where 0 = absent, 1 = a few punctate stains, 2 = diffuse punctate stains occupying less than half of the cornea, and 3 = diffuse punctate stains occupying more than half of the cornea). All other ocular signs were graded from 0 (absent) to 3 (severe). Patients with tearing, conjunctival discharge, or follicular or papillary conjunctivitis (score of 2 or 3 for either eye) or eyelid edema (score of 1 or more for either eye) were excluded. Baseline characteristics No treatment Age, mean (SD) or median (IQR): 35.1 (6.2) Female (%): 40 Total no. participants randomized: 20 Total no. eyes randomized: 20 Total no. eyes analyzed: 20 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 20 Saline Age, mean (SD) or median (IQR): 32.5 (8.7) Female (%): 44.8 Total no. participants randomized: 30 Total no. eyes randomized: 30 Total no. eyes analyzed: 29 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 29 Overall Age, mean (SD) or median (IQR): 33.6 (7.8) Female (%): 31 Total no. participants randomized: 50 Total no. eyes randomized: 50 Total no. eyes analyzed: 49 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 49 Group differences: NR, only age for each group was reported, post‐hoc P value > 0.05
Interventions	No treatment Active component(s): NA Dosage (no. drops, frequency): NA Intervention duration: 21 days CL materials: soft CLs CL replacement frequency (daily, weekly, biweekly, monthly, other): NR Saline Active component(s): 0.9% sodium chloride (Hydrabak, Laboratoires Thea, Clermont Ferrand, France) Dosage (no. drops, frequency): 4 times daily to both eyes Intervention duration: 21 days CL materials: soft hydrophilic CLs CL replacement frequency (daily, weekly, biweekly, monthly, other): NR
Outcomes	Overall comfort of CL wear Duration of wear Qualitative tear film analysis (Tearscope, Keeler Instruments Inc., Broomall, Pa.): lipid layer classified as thin, normal or thick, and aqueous phase classified as invisible or visible Adverse events on days 7 and 21 Ocular tolerance on instillation on days 7 and 21 (recorded in diary)
Notes	Sponsorship source: the authors have no financial interest in any of the products or instruments mentioned in this article. Country: Italy Setting: university Contact author: Stefano Barabino Institution: Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy Clinical trial registry no.: NR

Keir 2006.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: NR Unit of randomization: person Masking of participants: yes Masking of outcome assessor(s): yes Masking of other trial personnel: no; ophthalmic assistants over‐labeled then dispensed study drops to patients Was CL discomfort measured with an instrument: no, only 1 out of 6 questionsa answered on a Likert scale Duration of intervention: 1 month Duration of follow‐up: 28 daysb How did the study authors handle missing data?: NR Did the study authors describe power/sample size consideration?: NR aSymptom questionnaire: This drop makes my contact lenses more comfortable upon insertion This drop makes my contact lenses more comfortable all day long This drop makes my contact lenses feel more comfortable at the end of the day This drop makes my contact lenses less dry all day long My eyes feel less dry at the end of the day when I use this drop I can wear my contact lenses longer when I use this drop bSymptom questionnaires and report of drop use frequency completed on days 3, 7, 10, 14, 17, 21, 24, 28; bulbar conjunctival redness at baseline, 2 weeks, and 4 weeks
Participants	Inclusion criteria Current use of reusable disposable soft contact lenses (≥ 8 hours per day, five days per week) Ocular dryness symptoms resulting in discomfort when wearing lenses Comfortable lens wearing time at least 2 hours less than total wearing time Need to use rewetting drops at least some of the time during a typical day of contact lens wear Exclusion criteria Ocular disease or any clinically significant ocular signs that would contraindicate contact lens wear Baseline characteristics Saline Age, mean (SD) or median (IQR): 26.3 (6.4) Female (%): 70 Total no. participants randomized: 39 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 39 Systane(R) test Age, mean (SD) or median (IQR): 25.1 (6.8) Female (%): 72 Total no. participants randomized: 40 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 40 Overall Age, mean (SD) or median (IQR): 25.7 (6.6) Female (%): 72 Total no. participants randomized: 79 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 79 Group differences: "FDA groups of habitual lens material: more group I in the control than the treatment group (8:3); more group II in the treatment than in the control group (6:0)(Table 3).""Use of peroxide cleaning solution: 6 of 40 in treatment group vs 1 of 39 in control group (Table 4)."
Interventions	Saline Active component(s): 0.9% sodium chloride Dosage (no. drops, frequency): BID (no. drops NR) Intervention duration: 4 weeks CL materials: hydrogel and SiHy CL replacement frequency (daily, weekly, biweekly, monthly, other): biweekly Systane(R) test Active component(s): hydroxypropyl guar, propylene glycol, polyethylene glycol Dosage (no. drops, frequency): BID (no. drops NR) Intervention duration: 4 weeks CL materials: hydrogel and SiHy CL replacement frequency (daily, weekly, biweekly, monthly, other): biweekly
Outcomes	Self‐reported comfort, dryness based on the symptom questionnaire Comfortable wear time Time point: at the baseline visit and every 3 to 4 days during the study
Notes	Sponsorship source: Alcon Research Ltd Country: Canada Setting: School of Optometry, Univ of Waterloo Contact author: Y. Feng Institution: CCLR, School of Optometry, University of Waterloo, Waterloo, ON, Canada Clinical trial registry no.: NR

Malet 2003.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: November 1999 to February 2001 Unit of randomization: person Masking of participants: no Masking of outcome assessor(s): yes Masking of other trial personnel: cannot tell Was CL discomfort measured with an instrument: yes, VAS (0‐100); "the subjects marked a vertical line on the VAS at the appropriate point between the extreme left (maximum comfort) and the extreme right (maximum discomfort)." Duration of intervention: mean 28 (SD 3) days Duration of follow‐up: mean 28 (SD 3) days How did the study authors handle missing data?: cannot tell Did the study authors describe power/sample size consideration?: yes; "the number of subjects necessary for the study was calculated on the basis of a minimum clinically relevant difference between the two VAS scores in each treatment group, set at 2 cm and an estimated standard deviation of 1.5 cm (α = 5% and 1‐β% = 80%). This calculation indicated that sixteen subjects had to be enrolled in each treatment group."
Participants	Inclusion criteria: Age ≥ 18 years Good adaptation to any type of contact lenses Discomfort in the form of soreness, irritation, smarting, burning, or sensations of intermittently blurred vision Discomfort associated with contact lens wear and aggravated by environmental factors such as air conditioning, heating, and specific working conditions (e.g. prolonged use of visual display unit) "For subjects using topical ocular treatments, inclusion in the clinical trial was preceded by an 8‐day wash‐out period" Exclusion criteria No appreciable anomaly on slit‐lamp examination, particularly conjunctival hyperemia or folliculo‐papillary conjunctivitis Clinical score > 1 on corneal staining with fluorescein Criteria corresponding to dry eye (BUT > 10 seconds; Schirmer test without anesthesia > 5 mm in 5 minutes) Ocular infection, traumatic injury, inflammation, or laser treatment within 3 months preceding the study Eye surgery during the previous year Baseline characteristics Saline Age, mean (SD) or median (IQR): 33.9 (9.1) Female (%): 81.3 Total no. participants randomized: 20 Total no. eyes randomized: NR Total no. eyes analyzed: 16 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): 6% Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 16 PVP 2% Age, mean (SD) or median (IQR): 38.7 (11.2) Female (%): 82.6 Total no. participants randomized: 25 Total no. eyes randomized: NR Total no. eyes analyzed: 23 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): 4% Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 23 Overall Age, mean (SD) or median (IQR): 36.7 (10.5) Female (%): 82% Total no. participants randomized: 45 Total no. eyes randomized: NR Total no. eyes analyzed: 39 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): 5% Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 39 Group differences: none as described in Table 1
Interventions	Saline Active component(s): 0.9% NaCl Dosage (no. drops, frequency): 1 to 6 drops/day Intervention duration: 28 days CL materials: any CL replacement frequency (daily, weekly, biweekly, monthly, other): any PVP 2% Active component(s): 2% PVP Dosage (no. drops, frequency): 1 to 6 drops/day Intervention duration: 28 days CL materials: any CL replacement frequency (daily, weekly, biweekly, monthly, other): any
Outcomes	Primary efficacy endpoint: change in overall comfort of CL wear Assessed by VAS (scale 0 to 100) "marked a vertical line on the VAS at the appropriate point between the extreme left (maximum comfort) and the extreme right (maximum discomfort) Recorded at day 0 and day 28 visits and in the participant's diary on day 7, day 14, and day 21 Effect of the hydrating solutions on the eye surface According to the following signs: conjunctival hyperemia, chemosis, lacrimation, conjunctival secretions, palpebral edema, folliculo‐papillary conjunctivitis, and fluorescein staining corneal punctations; the assessment consisted of 4 grades (0 = absent, 1 = slight, 2 = moderate, 3 = severe) with the exception of conjunctival hyperemia (scored as 0 = absent, 1= conjunctival vessels moderately dilated, 2 = both conjunctival and episcleral vessels dilated, 3 = both conjunctival and episcleral vessels very dilated) Assessed at day 0 and day 28 visits Tolerability of the products on instillation The investigator recorded any sensations of irritation, burning, smarting, dryness, or presence of a foreign body. Assessed 15 min after instillation of the ocular hydrating agent, at the end of the visit by the investigator
Notes	Sponsorship source: "This study was supported in part by Laboratoires Thea." Country: France Setting: multicenter (N = 15) Contact author: Dr. Florence Malet Institution: Clinique Ophtalmologique, Hôpital Pellegrin CHU Clinical trial registry no.: NR Comments: few participants from each site. Number of participants lost to follow‐up does not match numbers in the Results section/Tables: "Of the 45 subjects (25 in the PVP group and 20 in the NaCl group), six did not undergo evaluation at D28. In the PVP group, three subjects were lost to follow‐up, and one discontinued the study prematurely owing to acute conjunctivitis; and in the NaCl group, two subjects were lost to follow‐up."

McDonald 2014.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: April 2010 to November 2010 Unit of randomization: person Masking of participants: no Masking of outcome assessor(s): yes Masking of other trial personnel: cannot tell Was CL discomfort measured with an instrument: yes (unvalidated questionnaire, Likert scale (5‐point) Duration of intervention: 2 weeks Duration of follow‐up: 2 weeks How did the study authors handle missing data?: NR Did the study authors describe power/sample size consideration?: no
Participants	Inclusion criteria Age ≥ 18 years Best‐corrected distance visual acuity with contact lenses of 20/30 or better in each eye Ocular dryness (symptomatic for end‐of‐day dryness) as a result of wearing daily disposable soft contact lenses Exclusion criteria Cardiovascular disease, hypertension, diabetes, or cystic fibrosis Participation in any other ophthalmic drug or device clinical trial within 30 days of enrollment. Any systemic or ocular disease or disorder (except refractive disorders or dry eye disease), complicating factor, or structural abnormality that would negatively affect the conduct or outcome of the study Recent use of medications that could confound study results Baseline characteristics No treatment Age, mean (SD) or median (IQR): 30.7 (8.6) Female (%): 76 Total no. participants randomized: 45 Total no. eyes randomized: 90 Total no. eyes analyzed: 90 White (%): 84 Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 45 Systane(R) Ultra Age, mean (SD) or median (IQR): 31.3 (10.6) Female (%): 57 Total no. participants randomized: 44 Total no. eyes randomized: 88 Total no. eyes analyzed: 88 White (%): 84 Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 44 Overall Age, mean (SD) or median (IQR): 31.0 (9.6) Female (%): 66 Total no. participants randomized: 89 Total no. eyes randomized: 178 Total no. eyes analyzed: 178 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR):NR Number of persons (or eyes) analyzed at baseline: 89 Group differences: both groups had a greater proportion of women, and this difference was more pronounced in the control group (Systane Ultra group: 43% male, 57% female; control group: 24% male, 76% female).
Interventions	No treatment Active component(s): NA Dosage (no. drops, frequency): NA Intervention duration: NA CL materials: NA CL replacement frequency (daily, weekly, biweekly, monthly, other): NA Systane(R) Ultra Active component(s): Polyethylene glycol 400 (0.4%), propylene glycol (0.3%), hydroxypropyl guar Dosage (no. drops, frequency): 1 to 2 drops, into each eye 10 minutes before lens insertion and after lens removal Intervention duration: 2 weeks CL materials: habitual CL replacement frequency (daily, weekly, biweekly, monthly, other): daily disposable
Outcomes	Changes in (subjective) comfort/acceptability in the intervention group versus the control group Changes from baseline for all comfort variables Safety outcomes, included visual acuity, biomicroscopy examination (slit lamp), and adverse events Time points of assessment: 14 days
Notes	Sponsorship source: Alcon Research Ltd., Fort Worth, TX Country: USA Setting: not specified, likely private practice(s) and Southern College of Optometry, Memphis, TN Contact author: Marguerite McDonald Institution: Ophthalmic Consultants of Long Island Clinical trial registry no.: NCT01132287 Comments: while the ethics was approved in the USA and 3/4 authors are in private practice there (the other author being an employee of the sponsor), the location and settings are not specified in the article or on the clinical trials website, apart from that it is a multicenter trial. Original enrollment 96, actual enrollment 92 (clinicaltrials.gov), no. reported 89 persons.

NCT02293538.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: November 2014 to July 2015 Unit of randomization: person Masking of participants: yes Masking of outcome assessor(s): yes Masking of other trial personnel: cannot tell Was CL discomfort measured with an instrument: yes, VAS(0‐10); "the participant rated both eyes together by providing one single rating." Duration of intervention: 14 days Duration of follow‐up: 14 days How did the study authors handle missing data?: complete case analysis; "analysis of comfort was done with "Intention to treat participants with non‐missing observations." Did the study authors describe power/sample size consideration?: no
Participants	Inclusion criteria Informed consent Stable, tear lipid layer thickness ≤ 75 nm without contact lenses Successful use of biweekly or monthly replacement soft contact lenses in both eyes for ≥ 5 days/week during the 2 months prior to Visit 1 Vision correctable to 20/25 Snellen (feet) or better at distance with habitual contact lenses at Visit 1 Willingness to wear lenses 5 days a week, 8 hours a day for at least 2 days during the study Symptoms of contact lens discomfort Other protocol‐defined inclusion criteria may apply Exclusion criteria Routinely sleeping in lenses Any active eye inflammation or condition that contraindicates contact lens wear Any systemic diseases that could prevent successful contact lens wear Use of systemic or ocular medications that contraindicate lens wear Fit with only 1 contact lens Unwillingness to discontinue use of cosmetics (such as eyeliner, mascara, or eye shadow) or facial creams on or around the eyelids on Day 1 and Day 14 of the study Pregnancy, breastfeeding, or unwillingness to use adequate birth control throughout the study Baseline characteristics Saline Age, mean (SD) or median (IQR): 34.3 (12.25) Female (%): 78.4 Total no. participants randomized: 74 Total no. eyes randomized: 148 Total no. eyes analyzed: 144 White (%): NR Hispanic (%): Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 74 FID114657 Age, mean (SD) or median (IQR): 38.3 (12.36) Female (%): 90.3 Total no. participants randomized: 72 Total no. eyes randomized: 144 Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 72 Overall Age, mean (SD) or median (IQR): 36.2(12.43) Female (%): 84.2 Total no. participants randomized: 146 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 146 Group differences: NR, but post‐hoc analysis showed the control group had more men (21.6% vs 9.7%; P = 0.0483)
Interventions	Saline Active component(s): none Dosage (no. drops, frequency): 1 to 2 drops instilled in each eye 10 minutes prior to inserting a new pair of habitual contact lenses and after removing them, daily for 2 weeks Intervention duration: 14 days CL materials: soft CL CL replacement frequency (daily, weekly, biweekly, monthly, other): commercially marketed biweekly or monthly replacement soft contact lenses as prescribed by eye care practitioner, brand and power FID114657 Active component(s): not specified Dosage (no. drops, frequency): 1 to 2 drops instilled in each eye 10 minutes prior to inserting a new pair of habitual contact lenses and after removing them, daily for 2 weeks. Intervention duration: 14 days CL materials: soft CL replacement frequency (daily, weekly, biweekly, monthly, other): commercially marketed biweekly or monthly replacement soft contact lenses as prescribed by eye care practitioner, brand and power
Outcomes	Primary study outcome Mean pre‐lens tear lipid layer thickness after 2 hours of lens wear on day 1 Secondary study outcomes Mean comfortable lens wear time Percentage of participants who experienced ≥ 1 unit increase from baseline score to day 14 for overall comfort with lenses Mean change from baseline in comfortable lens wear time Mean pre‐lens tear lipid layer thickness after 2 hours of lens wear on day 14 Time points: baseline (day 0) and day 14
Notes	Sponsorship source: Alcon Research Country: USA Setting: NR Contact author: NR except "study director: clinical Manager, Pharmaceuticals, Global Medical Affairs, Alcon Research" Institution: Alcon Research Ltd Clinical trial registry no.: NCT02293538

Pucker 2020.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: November 2018 to March 2019 Unit of randomization: person Masking of participants: no Masking of outcome assessor(s): yes Masking of other trial personnel: yes; "the patients who are randomized to Systane Complete will be masked to the brand of the artificial tears. There will be a masked examiner who does not know the subject's study group." Was CL discomfort measured with an instrument: yes, CLDEQ‐4 (subset of CLDEQ‐8) Duration of intervention: 2 weeks Duration of follow‐up: 2 weeks How did the study authors handle missing data?: NA Did the study authors describe power/sample size consideration?: yes; "a 4‐ point difference in CLDEQ‐4 scores was considered to be a clinically meaningful improvement in contact lens comfort. Sample size calculations determined that 19 subjects per group were needed to determine if there were no significant differences in contact lens comfort between the Systane Complete (artificial tear group) and no treatment groups at the two‐week visit (power = 90%; alpha = 0.05). The sample size was inflated by 20% to account for any potential attrition; this yielded a final sample size of 46 subjects."
Participants	Inclusion criteria Age ≥ 18 years Use of daily disposable contact lenses 20/30 Snellen visual acuity or better Symptomatic CLDEQ‐8 scores (≥ 12) Exclusion criteria Other contact lens modalities and wear schedules (e.g. biweekly and monthly replacement contact lenses, gas‐permeable contact lenses) Use of non‐compliant daily disposable contact lenses Baseline characteristics No treatment Age, mean (SD) or median (IQR): 28.8 (11.2) Female (%): 21% Total no. participants randomized: 24 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 21% Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 24 Systane(R) Complete Age, mean (SD) or median (IQR): 32.7 (13.1) Female (%): 9% Total no. participants randomized: 22 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 23% Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 22 Overall Age, mean (SD) or median (IQR): 30.7 (12.2) Female (%): 15% Total no. participants randomized: 46 Total no. eyes randomized: NR Total no. eyes analyzed: NR White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): NR Duration of dry eye known, mean (SD) or median (IQR):NR Number of persons (or eyes) analyzed at baseline: 46 Group differences: "With the exception of self‐reported ocular allergies being more common in the treatment group compared to the no treatment group (p = 0.02), there were no significant between‐group differences with respect to subject demographics or baseline clinical characteristics (All p > 0.11; Tables 1 and 2). There were also no significant between‐group differences with regards to contact lens wearing experience, wearing habits, satisfaction with contact lens comfort, or satisfaction with vision in contact lenses (All p > 0.19; Table 3)."
Interventions	No treatment Active component(s): NA Dosage (no. drops, frequency): NA Intervention duration: NA CL materials: NA CL replacement frequency (daily, weekly, biweekly, monthly, other): NA Systane(R) Complete Active component(s): Propylene glycol, mineral oil, hydroxypropyl guar Dosage (no. drops, frequency): 2 times per day in each eye; 10 minutes before and directly after contact lens wear Intervention duration: 2 weeks CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): daily disposable
Outcomes	Primary outcome: contact lens symptoms as measured with: CLDEQ‐8 scores (clinicaltrials.gov); and CLDEQ‐4 scores (clinicaltrials.gov and publication). Secondary outcomes End‐of‐day eye comfort as measured with SPEED Corneal staining Schirmer's I test without anesthetic Tear BUT Time point: baseline and at 2 weeks
Notes	Sponsorship source: industry Disclosure: "the authors have received financial research support from Alcon Research, LLC. (All), Allergan (CL), Bausch + Lomb (ADP), Contamac (ADP), Euclid (ADP), EyeGate Pharmaceuticals, Inc. (ADP), EpiTech (ADP), Optikal Care Inc. (ADP), Paragon Vision Sciences, (ADP), PentaVision (ADP), and Transitions (CL) in the past three years." Country: USA Setting: University setting (University of Alabama, Birmingham and Southern College of Optometry) and private clinic (Lindenhurst Eye Physicians & Surgeons, PC) Contact author: Andrew Pucker Institution: University of Alabama at Birmingham Clinical trial registry no.: NCT03682809

Pucker 2021.

Study characteristics
Methods	Study design: parallel‐group RCT Study year: May 2019 to October 2019 Unit of randomization: person Masking of participants: no; "the subjects cannot be fully masked because there is a no treatment control group." Masking of outcome assessor(s): yes Masking of other trial personnel: yes (care provider, investigator, outcome assessor) Was CL discomfort measured with an instrument: yes, CLDEQ‐8 (publication); CLDEQ‐4 (trial registry; "the CLDEQ‐4 is a contact lens specific symptoms survey; range = 0‐18 with 18 being most symptomatic.") Duration of intervention: 2 weeks Duration of follow‐up: 2 weeks How did the study authors handle missing data?: cannot tell Did the study authors describe power/sample size consideration?: yes; "this study used a minimum sample size of 69 participants to ensure that both outcomes (corneal health as judged by corneal staining and CL comfort as judged by CLDEQ‐8 scores) were adequately powered."
Participants	Inclusion criteria: Age ≥ 18 years Use of daily disposable CLs for any length of time (though participants had to wear their CLs for the duration of the study 20/30 visual acuity or better Clinically significant CLDEQ‐8 scores (≥ 12) "Sufferers of non‐autoimmune‐based dry eye disease were allowed to participate." "Participants were included if they had non‐visually significant corneal scarring." "Participants using artificial tears were included if they agreed to cease use of the drops at least one day before starting and during the study." Exclusion criteria Non‐compliance with CL usage instructions (CLs not discarded on schedule) Use of reusable CLs Conditions known to alter the tear film (e.g. eye lid abnormalities, herpetic eye disease, Sjogren's syndrome, rheumatoid arthritis) Ocular surgery in the past year History of major ocular trauma/scarring Active eye disease Use of eye medication or medication that affects the eyes Pregnancy or breastfeeding Baseline characteristics No treatment Age, mean (SD) or median (IQR): 31.3 (12.9) Female (%): 73% Total no. participants randomized: 24 Total no. eyes randomized: 24 Total no. eyes analyzed: 24 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 21% Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 24 Systane(R) Complete Age, mean (SD) or median (IQR): 29.8 (10.8) Female (%): 73% Total no. participants randomized: 25 Total no. eyes randomized: 25 Total no. eyes analyzed: 25 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 4% Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 25 Rewetting drop (Sensitive Eyes(R)) Age, mean (SD) or median (IQR): 29.8 (11.3) Female (%): 73% Total no. participants randomized: 24 Total no. eyes randomized: 24 Total no. eyes analyzed: 24 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 8% Duration of dry eye known, mean (SD) or median (IQR): NR Number of persons (or eyes) analyzed at baseline: 24 Overall Age, mean (SD) or median (IQR): 30.3 (11.5) Female (%): 73% Total no. participants randomized: 73 Total no. eyes randomized: 73 Total no. eyes analyzed: 73 White (%): NR Hispanic (%): NR Screen time used, mean (SD) or median (IQR): NR Smoking (%): NR Dry eye diagnosis told by clinicians (%): 11% Duration of dry eye known, mean (SD) or median (IQR):NR Number of persons (or eyes) analyzed at baseline: 73 Group differences: "No significant baseline differences were found between the three groups with regard to patient‐reported dry eye, ocular allergies, or artificial tear or rewetting drop usage (all p ≥ 0.12; Table 1). No significant baseline differences were found between the three groups with regard to CL comfort (CLDEQ‐8), dry eye symptoms (SPEED), or ocular surface testing (all p ≥ 0.28; Table 2). CL comfort, vision, and CL wear habits were not significantly different between groups at baseline (Table 3; all p ≥ 0.31)."
Interventions	No treatment Active component(s): NA Dosage (no. drops, frequency): "one drop directly before CL use, two drops while wearing the CLs (spaced by at least two hours), and one drop directly after CL use; no other time of day restrictions were placed on drop usage." Intervention duration: 2 weeks CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): daily disposable Systane(R) Complete Active component(s): Systane Ultra and Systane Balance Dosage (no. drops, frequency): "one drop directly before CL use, two drops while wearing the CLs (spaced by at least two hours), and one drop directly after CL use; no other time of day restrictions were placed on drop usage." Intervention duration: 2 weeks CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): daily disposable Rewetting drop (Sensitive Eyes(R)) Active component(s): over‐the‐counter artificial tears Dosage (no. drops, frequency): "one drop directly before CL use, two drops while wearing the CLs (spaced by at least two hours), and one drop directly after CL use; no other time of day restrictions were placed on drop usage." Intervention duration: 2 weeks CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): daily disposable
Outcomes	Primary study outcome Difference in ocular surface damage as measured by the Brien Holden Vision Institute (BHVI) Grading Scale Secondary study outcome Dry eye disease, as measured by the CLDEQ‐4 Time points: baseline and 2 weeks
Notes	Sponsorship source: industry; "Alcon Research, LLC supported this investigator‐initiated study" Country: USA Setting: hospital and clinic based (university hospital and private practice) Contact author: Andrew Pucker Institution: University of Alabama at Birmingham, Birmingham, AL, USA Clinical trial registry no.: NCT03848221

BID: twice daily; BUT: break‐up time; CL: contact lens; CLDEQ: Contact Lens Dry Eye Questionnaire; IQR: interquartile range; NA: not applicable; NaCl: sodium chloride; NR: not reported; PVP: polyvinylpyrrolidone; RCT: randomized controlled trial; SD: standard deviation; SiHy: silicone hydrogel; SPEED: Standardized Patient Evaluation of Eye Dryness questionnaire; VAS: visual analog scale.

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
ACTRN12619000274178	Ineligible design: cross‐over trial.
ACTRN12619000773134	Ineligible design: cross‐over trial.
Asharlous 2016	Ineligible design: non‐RCT.
Berry 1998	Ineligible design: non‐RCT.
Caffery 1990	Ineligible design: cross‐over trial.
Calvão‐Santos 2011	Ineligible population: asymptomatic CL wearers.
Carracedo 2018	Ineligible population: asymptomatic CL wearers.
ChiCTR2200066298	Ineligible population: asymptomatic CL wearers.
ChiCTR2300069668	Ineligible comparator: active comparator.
CTRI/2022/07/043793	Ineligible design: non‐RCT.
CTRI/2022/07/043860	Ineligible design: non‐RCT.
Downie 2018	Ineligible intervention.
Dumbleton 2008	Ineligible population.
Efron 1991	Ineligible design: cross‐over trial.
Gonzalez 2018	Ineligible intervention.
Guillon 2013	Ineligible design: cross‐over trial.
Guthrie 2015	Ineligible comparator: active comparator.
ISRCTN11194798	Ineligible design: cross‐over trial.
ISRCTN16230269	Ineligible design: cross‐over trial.
Itoi 1995	Ineligible population: asymptomatic CL wearers.
Jeon 2021	Ineligible comparator: active comparator.
JPRN‐JRCT1031230239	Ineligible design: cross‐over trial.
JPRN‐UMIN000010975	Ineligible intervention.
JPRN‐UMIN000011397	Ineligible intervention.
JPRN‐UMIN000024064	Ineligible intervention.
JPRN‐UMIN000031169	Ineligible design: non‐RCT.
Kading 2010	Ineligible comparator.
Liu 2020	Ineligible population: orthokeratology lens wearers.
NCT00469573	Ineligible design: non‐RCT.
NCT00570843	Ineligible comparator: active comparator.
NCT00691197	Ineligible comparator: active comparator.
NCT00761202	Ineligible population; ineligible comparator: active comparator.
NCT01051804	Ineligible comparator: active comparator.
NCT01105624	Ineligible intervention.
NCT01267656	Ineligible design: non‐RCT.
NCT01384851	Ineligible design: cross‐over trial.
NCT01543061	Ineligible design: cross‐over trial.
NCT01747616	Ineligible population: asymptomatic CL wearers.
NCT01844388	Ineligible comparator: active comparator.
NCT03050125	Ineligible design: cross‐over trial.
NCT03994406	Ineligible intervention.
NCT04175340	Ineligible comparator: active comparator.
NCT04297618	Ineligible intervention.
NCT04963543	Ineligible design: non‐RCT.
NCT05290727	Ineligible design: cross‐over trial.
NCT05505292	Ineligible intervention.
NCT05741216	Ineligible comparator: active comparator.
NCT05814367	Ineligible design: cross‐over trial.
NCT05902364	Ineligible comparator: active comparator.
NCT05932225	Ineligible comparator: active comparator.
NCT06131476	Ineligible design: cross‐over trial.
Nichols 2016	Ineligible comparator: active comparator.
Ogami 2021	Ineligible intervention.
Ozkan 2004	Ineligible design: cross‐over trial.
Ozkan 2005	Ineligible design: cross‐over trial.
Rohit 2016	Ineligible design: cross‐over trial.
Rohit 2017	Ineligible design: cross‐over trial.
Sasai 2009	Ineligible comparator: active comparator.
Tavazzi 2020	Ineligible comparator: active comparator.
Xu 2023	Ineligible population: asymptomatic CL wearers.

CL: contact lens; RCT: randomized controlled trial.

Characteristics of studies awaiting classification [ordered by study ID]

NCT02956083.

Methods	Study design: parallel‐group RCT Study year: July 2014 to July 2015 Unit of randomization: person Masking of participants: yes Masking of outcome assessor(s): no Masking of other trial personnel: cannot tell Was CL discomfort measured with an instrument: yes, CLDEQ Duration of intervention: 1 month Duration of follow‐up: 1 month Did the study authors report how missing data were handled?: NR Did the study authors describe power/sample size consideration?: NR
Participants	Inclusion criteria Age ≥ 21 years CL‐associated discomfort Exclusion criteria No CL discomfort Active inflammation or infection of the anterior segment of the eyes Group differences: NR
Interventions	Saline Active component(s): saline Dosage (no. drops, frequency): NR Intervention duration: 1 month CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): NR Systane(R) Balance Active component(s): propylene glycol 0.6% Dosage (no. drops, frequency): NR Intervention duration: 1 month CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): NR Systane(R) Contacts Active component(s): hydroxypropyl methycellulose Dosage (no. drops, frequency): NR Intervention duration: 1 month CL materials: NR CL replacement frequency (daily, weekly, biweekly, monthly, other): NR
Outcomes	CL discomfort Fluorescein tear BUT Time point: 1 month
Notes	Sponsorship source: University of the Incarnate Word Country: USA Setting: university Contact author: Srihari Narayanan, OD, PhD Institution: University of the Incarnate Word Clinical trial registry no.: NCT02956083 Comments: trial completed but no results posted on ClinicalTrials.gov.

BUT: break‐up time; CL: contact lens; CLDEQ: contact lens dry eye questionnaire; NR: not reported; RCT. randomized controlled trial

Differences between protocol and review

• For other review outcomes defined as important rather than critical, we also applied the risk of bias tool (RoB 2) to assess outcome‐level risk of bias. This change from the protocol allowed for the consistent application of the same risk of bias tool throughout the review process (Caffery 2023).

• In addition to two review outcomes specified in the protocol, we added all other review outcomes to the summary of findings tables.

• In addition to three trials comparing lubricating drops to no treatment, we included one study comparing saline to no treatment.

Contributions of authors

All authors were involved in conceptualization, screening search results, data extraction, data verification, data analysis and interpretation, risk of bias assessment, and writing the review. The only exception was AP, who did not participate in data extraction, verification, analysis/interpretation, or risk of bias assessment due to concerns of potential conflicts of interest.

Sources of support

Internal sources

• None, Other

  No internal source of support.

External sources

• Public Health Agency, UK

  The HSC Research and Development (R&D) Division of the Public Health Agency funds the Cochrane Eyes and Vision editorial base at Queen's University Belfast (up to the end of March 2023).

• Queen's University Belfast, UK

  Gianni Virgili, Co‐ordinating Editor for Cochrane Eyes and Vision's work is funded by the Centre for Public Health, Queen's University of Belfast, Northern Ireland (up to the end of March 2023).

• National Eye Institute, National Institutes of Health, USA

  Cochrane Eyes and Vision US Project, supported by grant UG1EY020522 (PI: Tianjing Li, MD, MHS, PhD)

Declarations of interest

BC: none known.
AP: Dr. Pucker has received research support from Alcon Research, LLC, Art Optical, ScienceBased Health, and the National Eye Institute. Dr. Pucker has served as a consultant for Alcon Research, LLC, Bausch and Lomb, Contamac, CooperVision, EpiTech, EyeGate Pharmaceuticals Inc., Euclid Systems, Hanall Biopharma, Kala Pharmaceuticals, Lexitas Pharma Services, Nevakar Inc., and Optikal Care Inc. Dr. Pucker is currently an employee of Lexitas Pharma Services. Lexitas Pharma Services did not have active artificial tear or rewetting drop studies during the conduct of this work. Dr. Pucker has received research and consulting fees related to articles included in this review. Dr. Pucker was not allowed to comment on these works, and he was not allowed to be the first or last author of this article to help mitigate his conflicts of interest.
NC‐E: none known
CJO: none known
BH: Dr. Harkness has served as a consultant for Valley Contax, Inc. 
NC: Dr. Carnt reported receiving an Independent Medical Education Grant for Healthy Contact Lens Wear Australian Roadshow from Alcon Research, LLC; payment to institution.
SL: reports a grant (UG1 EY020522) from the National Eye Institute, National Institutes of Health, USA; payment to institution. Dr. Liu is Managing Editor of Cochrane Review Group but was not involved in the editorial process for this review.
AN: none known.

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