Real-World Treatment Patterns and Clinical Outcomes with Cyclosporine 0.1% in Semifluorinated Alkane for Dry Eye Disease

Abstract

Purpose

To evaluate real-world clinical outcomes and treatment patterns associated with long-term use of cyclosporine 0.1% in semifluorinated alkane (SFA) (VEVYE^®, Harrow Inc, Nashville, TN, USA) in patients with dry eye disease (DED), focusing on patient-reported symptoms, and corneal staining.

Methods

This retrospective, real-world evidence, observational study analyzed electronic medical records from 55 patients with DED treated with cyclosporine 0.1% in SFA (CsA/SFA) for at least six months. Patient-reported symptoms were assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Corneal fluorescein staining was evaluated using the Oxford grading scale. All outcomes were compared from baseline to the most recent follow-up visit using paired statistical tests, with a two-sided p-value of less than 0.05 considered statistically significant.

Results

The cohort comprised 48 female and 7 male patients. Mean SPEED scores decreased from 12.53 ± 7.17 to 8.36 ± 5.77, representing a clinically and statistically relevant 33.2% reduction (p < 0.001). Mean Oxford staining scores demonstrated clinically and statistically relevant decreases from 1.11 ± 0.83 to 0.49 ± 0.54 in the right eye (55.7% reduction; p < 0.001) and from 1.14 ± 0.84 to 0.59 ± 0.65 in the left eye (48.0% reduction; p < 0.001).

Conclusion

CsA/SFA was associated with clinically and statistically significant improvements in both patient-reported symptoms and corneal staining over six months, with concordant improvements in subjective and objective outcome measures. These findings support its use as an effective therapeutic option for moderate DED.

Introduction

Dry eye disease (DED) is a common, chronic, and multifactorial disorder of the ocular surface characterized by tear film instability, hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities.¹ Affecting millions worldwide, DED is one of the leading causes of eye clinic visits and carries a substantial economic burden, with US direct healthcare costs estimated at $3.8 billion and total societal costs exceeding $55 billion annually in 2011.^2,3 The economic burden as well as the overall prevalence of DED has steadily increased in the last decade, especially after the COVID-19 pandemic, during which its global prevalence ranged between 51.8% and 70.2%.^4–6 Meanwhile, a longitudinal study involving 150 faculty suggested that the prevalence of DED, which was 54.1% before the pandemic, increased to as much as 94.6% after the second wave of COVID-19,⁷ with these observations bearing a strong correlation to the increased use of digital devices.⁸ These studies highlight the significantly elevated burden of DED, which bears a strong association with several factors in the domains of mental, physical, and social health.⁹

Although DED is traditionally subclassified into aqueous-deficient dry eye (ADDE), evaporative dry eye (EDE), and mucin-deficient dry eye (MDDE), the three subtypes show considerable overlap, with most patients demonstrating a mixed pathology or “hybrid” form of the disease leading to the formation of a “vicious circle of DED”.¹⁰ It is now well established that tear film instability and tear hyperosmolarity are key drivers of ocular surface inflammation, which plays a causal role in manifestation of the vicious circle of DED and deterioration of patients’ quality of vision and subsequent quality of life.^11,12

Beyond symptoms such as dryness, burning, irritation, and fluctuating vision, ocular surface inflammation contributes to clinically significant adverse effects, including reduced quality of vision, contact lens intolerance, and increased error in biometric measurements, prior to cataract surgery.¹³ Untreated DED can negatively affect keratometry, leading to inaccurate intraocular lens (IOL) calculations and postoperative refractive aberrations. Therefore, treating the clinical signs of DED and optimizing the ocular surface before cataract surgery reduces postoperative variability, improves refractive accuracy, and ultimately patient satisfaction.^14,15

Immunomodulatory therapy targeting T-cell–mediated inflammation is often used for the management of moderate to severe DED. Cyclosporine A (CsA), a calcineurin inhibitor, suppresses T-cell activation and reduces IL-2–mediated inflammatory signaling.^16,17 While cyclosporine emulsions have long been a mainstay therapy, limitations such as poor bioavailability, delayed onset of action, and frequent burning or stinging upon instillation can reduce patient compliance and clinical efficacy.^18–23

Semifluorinated alkane (SFA)-based CsA eyedrops, currently marketed as VEVYE^® cyclosporine ophthalmic solution 0.1% (Harrow Inc, Nashville, TN, USA) (CsA/SFA) in the US and Vevizye^® (Laboratoires Théa, Clermont-Ferrand, France) in the EU, represent a significant paradigm shift in the management of DED and overcome several challenges associated with traditional CsA eyedrops. Perfluorobutylpentane (PFBP), the SFA in CsA/SFA, exhibits surface-active and physicochemical properties that allow for dissolution of therapeutically relevant levels of cyclosporine (CsA). This results in a clear, non-emulsified, water-free, preservative-free eye drop with improved bioavailability, enhanced corneal penetration, longer precorneal residence time, earlier symptom and staining improvement, and significantly better tolerability.^24–28 Clinical studies have shown significant improvement in both objective and subjective measures of DED with CsA/SFA, as well as the PFBP vehicle alone, alongside a favorable safety and tolerability profile.^26–33

The purpose of this real-world analysis is to evaluate clinical outcomes and treatment patterns associated with long-term use of CsA/SFA, focusing on patient-reported symptoms using the SPEED questionnaire, and corneal staining via the Oxford scale in patients with established DED.

Methods

Study Design and Patient Selection

This investigation was a single-center, retrospective, real-world evidence (RWE), observational study conducted from January 2024 to August 2025. Electronic medical records (EMR) were analyzed to identify consecutive eligible patients diagnosed with DED who were prescribed and treated with CsA/SFA.

Inclusion criteria required patients to have been treated with the study medication CsA/SFA for a duration of at least six months and to have complete data records for key clinical assessments at both baseline and the most recent follow-up visit. Patients were excluded if they had incomplete baseline or follow-up data, received less than six months of CsA/SFA treatment, had active ocular infection or ocular surface disease unrelated to dry eye that could confound assessment, or had changes in other prescription dry eye therapies during the follow-up period. A total of 55 patients were included in the final analysis. All assessments were conducted by trained clinical staff as part of routine care. Outcomes were compared between baseline (pre-treatment) and the most recent follow-up visit.

Outcome Measures

Patient-reported symptoms of ocular discomfort and dryness were quantitatively assessed using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. The SPEED questionnaire is a validated dry eye questionnaire and yields a cumulative score ranging from 0 to 28, where a higher score indicates greater symptom severity and frequency. Objective assessment of ocular surface damage was performed by evaluating corneal fluorescein staining using the Oxford grading scale. This scale ranges from 0 (no staining) to 5 (most severe staining). Importantly, this study included only patients presenting with baseline corneal staining scores ranging from 0 to 3; no patients with grades 4 or 5 were included in the analysis. All Oxford corneal staining assessments were performed by a single examiner as part of routine clinical care, thereby eliminating inter-examiner variability; because grading was performed by a single examiner, inter-rater agreement was not applicable.

Statistical Analysis

Baseline and most-recent-follow-up values were compared for all outcomes (SPEED score and Oxford corneal staining) using paired t-tests. Because SPEED and Oxford corneal staining scores are ordinal and discrete, normality of the within-patient difference scores was not assumed; paired t-tests were therefore accompanied by nonparametric Wilcoxon signed-rank tests as a concordant sensitivity analysis. Data are reported as means ± SD with 95% confidence intervals, and within-patient mean changes with 95% CIs alongside p-values. All analyses included the 55 patients meeting the inclusion and exclusion criteria. All 55 had complete baseline and follow-up data for the analyzed outcomes, as incomplete data were an exclusion criterion, so no imputation was required. The association between change in SPEED and change in mean Oxford staining was assessed with Pearson and Spearman correlations. No a priori power calculation was performed. A two-sided p < 0.05 was considered significant.

Results

A total of 55 patients were identified and included in the analysis, consisting of 48 female and 7 male patients. Baseline demographic and clinical characteristics are summarized in Table 1.

Table 1.

Baseline Demographic and Clinical Characteristics (n = 55)

Characteristic	Value
Sex, n (%)
Female	48 (87.3%)
Male	7 (12.7%)
Duration on CsA/SFA, months
Mean ± SD	8.5 ± 2.7
Median (range)	8 (6–17)
Baseline SPEED score, mean ± SD	12.53 ± 7.17
Baseline Oxford staining, mean ± SD
Right eye (OD)	1.11 ± 0.83
Left eye (OS)	1.14 ± 0.84
Baseline staining severity, worse eye, n (%)a
Grade 0	8 (14.5%)
Grade >0 to 1	22 (40.0%)
Grade >1 to 2	22 (40.0%)
Grade >2 to 3	3 (5.5%)

Notes: ^aWorse eye denotes the higher (more severe) of the two eyes’ baseline Oxford corneal staining grade; percentages are of n = 55. Oxford increments include half-grades.

Treatment with CsA/SFA resulted in a statistically significant improvement in patient-reported symptoms. The mean SPEED score decreased from 12.53 ± 7.17 (SD) at baseline to 8.36 ± 5.77 (SD) at the most recent follow-up, representing a 33.2% decrease from baseline (p < 0.001).

Objective clinical signs, as measured by the Oxford Grading System for corneal staining, also showed a statistically significant reduction following treatment. The mean staining score in the right eye (OD) decreased from 1.11 ± 0.83 (SD) at baseline to 0.49 ± 0.54 (SD) at follow-up, representing a 55.7% decrease (p < 0.001).

The mean staining score in the left eye (OS) decreased from 1.14 ± 0.84 (SD) at baseline to 0.59 ± 0.65 (SD) at follow-up, representing a 48.0% decrease (p < 0.001). Baseline and follow-up values with 95% confidence intervals and within-patient mean changes are presented in Table 2. Change in symptom score (SPEED) did not correlate with change in corneal staining (Pearson r = 0.08, p = 0.55; Spearman ρ = 0.06, p = 0.65).

Table 2.

Clinical Outcomes from Baseline to Most Recent Follow-Up

Outcome	Baseline Mean ± SD (95% CI)	Follow-Up Mean ± SD (95% CI)	Mean Change (95% CI)	Reduction	p-valuea
SPEED (n = 55)	12.53 ± 7.17 (10.59–14.47)	8.36 ± 5.77 (6.80–9.92)	4.16 (2.42–5.91)	33.2%	<0.001
Oxford staining, OD (n = 55)	1.11 ± 0.83 (0.88–1.33)	0.49 ± 0.54 (0.34–0.64)	0.62 (0.40–0.83)	55.7%	<0.001
Oxford staining, OS (n = 55)	1.14 ± 0.84 (0.91–1.36)	0.59 ± 0.65 (0.41–0.77)	0.55 (0.33–0.76)	48.0%	<0.001

Notes: ^ap-values are from paired t-tests; nonparametric Wilcoxon signed-rank tests were concordant for all outcomes (all p < 0.001). Percentage reduction = (baseline mean − follow-up mean)/baseline mean. Change in SPEED did not correlate with change in mean Oxford staining (Pearson r = 0.08, p = 0.55; Spearman ρ = 0.06, p = 0.65).

Discussion

This retrospective study evaluates the long-term treatment pattern for a CsA/SFA and demonstrates significant improvement in patient-reported symptoms as well as corneal staining scores. The primary findings included a clinically and statistically significant 33.2% reduction in mean SPEED symptom scores and a 48–56% decrease in corneal staining, reflecting objective surface healing over a six-month period. Clinically and statistically significant improvements were observed in both patient-reported symptoms (p < 0.001) and corneal staining (p < 0.001), suggesting consistent improvements across both subjective and objective outcome measures.

The clinical utility of CsA/SFA is supported by the observed improvements in corneal staining scores over the six-month study period. For cataract and refractive surgeons, this may have important clinical implications, particularly in the context of preoperative optimization of the ocular surface, where significant clearing of central corneal staining is essential for accurate keratometry and optimal surgical outcomes.^14,15

Previously published studies indicate that CsA/SFA compares favorably with traditional cyclosporine formulations. Interestingly, CsA/SFA is the first and only US Food and Drug Administration approved cyclosporine formulation indicated for the treatment of the signs and symptoms of dry eye disease. Previous-generation cyclosporine formulations are indicated for increased tear production in dry eye disease. Prior literature suggests that cyclosporine A 0.05% emulsion (Restasis, AbbVie, Chicago, IL, USA) may require up to several months to achieve maximal therapeutic effect, with pivotal trials demonstrating significant increases in tear production at 6 months.³⁴ In contrast, cyclosporine A 0.09% solution (Cequa, Sun Pharma, Princeton, NJ, USA) demonstrated increased tear production at 3 months in pivotal studies and has demonstrated early efficacy with improvement in signs and symptoms as early as 4 weeks in a single open-label study, in patients inadequately controlled on CsA 0.05%.²⁰ Similarly, clinical trials with CsA/SFA have reported statistically and clinically meaningful improvements as early as 15 days, with pooled analyses showing that 56.8% of patients responded with clinically relevant corneal staining improvement by day 15.^28,30,31,33 Lifitegrast 5% ophthalmic solution (Xiidra, Bausch and Lomb, Bridgewater, NJ, USA) has also demonstrated symptom improvement as early as 2 weeks (day 14) in a Phase 3 trial.^35,36

Although onset of action was not specifically evaluated in the present study, the favorable outcomes observed in our cohort are consistent with these previously reported clinical benefits.

In a Phase II, randomized, vehicle-controlled trial (207 patients, four arms over 16 weeks), CsA/SFA produced a significantly greater reduction in total corneal fluorescein staining than open-label cyclosporine A 0.05% emulsion, with earlier onset (by day 14), and fewer treatment-emergent adverse events.²⁶ Notably, the PFBP vehicle alone reduced corneal staining comparably to cyclosporine A 0.05% emulsion, indicating an intrinsic therapeutic contribution of the vehicle to ocular surface healing; the authors attributed this to PFBP’s low surface tension, which allows it to spread and form a protective ocular-surface layer.^26,37 This hypothesis has also been confirmed in vivo, where a statistically significant improvement in the tear fluid lipid layer grade was observed immediately after administration of a single drop of the PFBP vehicle.³⁷ Moreover, administration of PFBP twice daily to healthy rabbits over a period of 7 days also improved and maintained the tear film lipid layer grade, with the lipid layer grade remaining consistently at or above Grade 3 (~50–80 nm) throughout the test period.³⁷ These properties of the PFBP vehicle explain the significant symptomatic relief observed even with the vehicle itself in clinical trials.^26,31–33

Another advantage of the PFBP vehicle is its ability to enhance drug bioavailability and potentiate the anti-inflammatory effect of CsA. Ex vivo and in vivo studies have shown several-fold higher corneal bioavailability of CsA with the PFBP vehicle than with conventional CsA emulsions, such as cyclosporine A 0.05% emulsion and Ikervis (ciclosporin A 0.1%, Santen, Osaka, Japan).^25,38 These findings are attributed to the longer precorneal retention time³⁸ and surface-active properties of PFBP, which enable it to spread rapidly and cover a larger area of the cornea,³⁷ thus maximizing corneal exposure to the drug and enhancing drug penetration.^27,38

Clinically, both CsA/SFA and a longer-chain semifluorinated alkane, perfluorohexyloctane (PFHO; Miebo, Bausch and Lomb, Bridgewater, NJ, USA), are approved for the treatment of the signs and symptoms of dry eye disease, but their mechanisms of action differ. CsA/SFA is an anti-inflammatory cyclosporine formulation delivered in a water-free semifluorinated alkane vehicle, whereas PFHO is a water-free, semifluorinated alkane alone that primarily targets tear film evaporation by stabilizing the lipid layer. Studies by Agarwal et al demonstrated that, like PFHO, PFBP rapidly spreads across the corneal surface with a contact angle approaching zero and produces a statistically significant improvement in tear film lipid layer grade within 30 minutes of a single instillation, although the improvement was more sustained after instillation of PFHO.³⁷ Given the well-established role of the lipid layer in reducing aqueous tear evaporation, reinforcement of the lipid layer by PFBP may help reduce tear evaporation in DED patients with a compromised tear film. This mechanism may contribute, at least in part, to the improvement in corneal staining and symptomatic relief observed with the PFBP vehicle alone in clinical studies.^26,31–33

However, a recent in vitro study found that shorter chain SFAs, such as PFBP/CsA found in CsA/SFA, did not significantly inhibit the evaporation of saline, whereas perfluorohexyloctane ophthalmic solution was observed to reduce evaporation by approximately 80%.³⁹ A comprehensive review summarized preclinical and clinical evidence supporting a dual role of PFBP as both a tear film stabilizer and an effective drug delivery vehicle for cyclosporine (CsA). Improvements in lipid layer thickness may help explain the early clinical benefit observed as early as 2 weeks in the ESSENCE clinical trials.²⁷ These findings are aligned with concepts discussed in the recently published Tear Film and Ocular Surface Society (TFOS) DEWS III Management and Therapy report, which states that the spreading and residence properties of semifluorinated alkane-based formulations may enhance ocular surface residence and bioavailability compared with traditional CsA emulsions (eg, 0.05% and 0.1%). The report also notes that improvements in lipid layer parameters have been observed in association with these vehicles, which may contribute to reduced tear evaporation.⁴⁰ The TFOS DEWS III report further recognizes CsA/SFA as a treatment option for both the signs and symptoms of DED within its evidence-based prescribing algorithm.⁴⁰

In the present study, patients were required to have used CsA/SFA for at least 6 months, although onset of action was not specifically evaluated. Improvements in both symptoms and corneal staining were observed within this 6-month period. These findings are consistent with the ESSENCE-2 open-label extension, a phase 3 study in which 202 patients who completed ESSENCE-2 received CsA/SFA twice daily for an additional 52 weeks.²⁹ Statistically significant improvements over baseline were observed across all prespecified endpoints: corneal staining improved early and remained stable, tear production increased progressively, and symptom scores reached their lowest levels by one year.²⁹ Tolerability was favorable, with only one treatment-related discontinuation and high patient-reported satisfaction, supporting the durability of the benefits seen in the present cohort.²⁹ These long-term data stand in contrast to real-world discontinuation rates of 70.8% for cyclosporine 0.05% emulsion and 64.4% for lifitegrast at 12 months, where instillation-site reactions and delayed onset of efficacy are considered the primary drivers of nonadherence.⁴¹ Compared with CsA/SFA, a greater incidence of adverse effects has been reported with cyclosporine 0.05% (17%),³¹ and 22% of patients receiving cyclosporine 0.09% reported instillation-site pain.^20,41

Implications for Clinical Practice

Our findings broadly support the use of CsA/SFA as a safe and effective therapeutic option for the treatment of DED in patients with an inadequate response to artificial tears alone, including patients unable to tolerate treatment because of side effects. The early onset of action documented in other studies and sustained efficacy over 6 months observed in this study suggest that patients can expect both rapid symptomatic relief and sustained healing of the ocular surface.

The clinically and statistically significant improvements in symptoms and corneal staining observed in this cohort have notable implications for specific clinical contexts. Ocular surface disease, particularly corneal staining, can adversely impact biometry measurements and surgical outcomes, with irregular astigmatism and higher-order aberrations contributing to suboptimal postoperative visual results.^42,43 The American Society of Cataract and Refractive Surgery has identified corneal staining as the single most critical sign to normalize prior to cataract refractive surgery.⁴⁴ Recent evidence demonstrates that optimization of the ocular surface with treatments that reduce corneal staining can significantly improve refractive accuracy and patient satisfaction. One study, for example, demonstrated an increase from 36% to 70% of eyes achieving a spherical equivalent within ±0.25 D after treating the ocular surface.⁴⁴ Our results demonstrate that, due to the marked reduction in corneal staining achieved with CsA/SFA, this formulation may find application in optimizing the ocular surface prior to refractive or cataract surgery.

Clinically and statistically significant improvements were observed in both corneal staining and patient-reported symptom scores (both p < 0.001). Improvements in both signs and symptoms are noteworthy, as sign–symptom discordance has historically complicated the assessment of DED treatments and limited patient satisfaction. These findings suggest that improvement in ocular surface health with CsA/SFA may be accompanied by clinically meaningful symptom improvement, which may support long-term treatment adherence.

Limitations and Future Directions

As a real-world observational study, the lack of a concurrent control group limits the ability to definitively attribute all observed improvements exclusively to CsA/SFA, though the magnitude and consistency of the observed effects are closely aligned with findings from previous randomized controlled trials. The 6-month follow-up period, while adequate to demonstrate sustained efficacy, does not fully encompass the long-term disease-modifying potential of therapy or the durability of treatment responses beyond this timeframe. Additionally, discontinuation rates were not formally recorded as a study endpoint, and clinical benefit or adverse events were not captured in patients who discontinued treatment prior to the 6-month assessment, potentially due to cost, treatment-related side effects, inadequate therapeutic response, or other factors. Future studies incorporating extended follow-up periods would be valuable in determining whether the improvements observed at 6 months are maintained, further enhanced, or attenuated with continued therapy.

Additionally, this cohort may not fully represent the broader DED patient population, particularly patients with predominantly evaporative DED or those with concomitant systemic autoimmune conditions, such as Sjögren’s syndrome. As such, the generalizability of these findings to these patient subgroups warrants further investigation. Finally, while the SPEED questionnaire is a validated tool for assessing DED symptoms, the inclusion of additional patient-reported outcome measurements and quality-of-life assessments would enable a more comprehensive evaluation of treatment effects on daily functioning and visual performance. In addition, only two measures, the SPEED questionnaire and Oxford corneal staining, were consistently documented across the cohort; other objective ocular surface tests (eg, tear osmolarity) were not uniformly available in this retrospective dataset and could not be analyzed. Lastly, the sample size was modest and insufficient for subgroup analyses (eg, by baseline severity or DED subtype).

Future research should prioritize the identification of predictive biomarkers to inform patient selection for CsA/SFA eyedrop therapy and to optimize treatment duration and dosing strategies. Such investigations may also benefit from head-to-head comparative studies evaluating the efficacy of CsA/SFA relative to other emerging and novel DED therapies. Additionally, studies exploring combination treatment approaches that leverage complementary mechanisms of action may provide synergistic benefits for patients with refractory disease.

Conclusion

This real-world study demonstrates that cyclosporine 0.1% ophthalmic solution in semifluorinated alkane, perfluorobutylpentane, represents a clinically meaningful advancement in dry eye disease management, addressing key unmet needs in both efficacy and tolerability. The significant reductions in SPEED scores and corneal staining over a 6-month period are consistent with this formulation’s efficacy in improving both subjective symptoms and objective signs of DED. Improvements were observed in both corneal staining and patient-reported symptoms over the treatment period. As the therapeutic landscape of DED therapy continues to evolve with emerging agents targeting diverse aspects of disease pathology, SFA-based CsA formulation highlights how innovative drug delivery strategies can enhance both the efficacy and tolerability of already established therapeutic compounds. These findings should be interpreted in light of the study’s retrospective, single-center design and the exclusion of patients with the most severe baseline staining (Oxford grades 4–5). Overall, findings from this real-world cohort support the integration of CsA/SFA into evidence-based treatment strategies for DED, providing clinicians with an effective option to achieve rapid, sustained, and clinically significant improvements in both the signs and symptoms of dry eye disease.

Abbreviations

ADDE, aqueous-deficient dry eye; CsA, cyclosporine A; DED, dry eye disease; EDE, evaporative dry eye; EMR, electronic medical records; FDA, US Food and Drug Administration; IOL, intraocular lens; IRB, institutional review board; MDDE, mucin-deficient dry eye; OD, oculus dexter; OS, oculus sinister; PFBP, perfluorobutylpentane; PFHO, perfluorohexyloctane; RWE, real-world evidence; SD, standard deviation; SFA, semifluorinated alkane; SPEED, Standard Patient Evaluation of Eye Dryness.

Ethics Approval and Informed Consent

This retrospective study was conducted in accordance with the Declaration of Helsinki. Sterling IRB reviewed the study and determined that IRB approval was not required due to the retrospective, de-identified nature of the data. Given the retrospective design and use of de-identified data, the requirement for individual informed consent was waived.

Disclosure

Alice Epitropoulos is a paid consultant of Harrow Inc and received a grant from Harrow Inc to complete this investigator-initiated study. She reports royalties for sale of EpiGlare tester from EpiGlare Tester (Hilco & Eye Care & Cure); consulting fees from EyePromise, Ocubio, Harrow, Dompe, Bausch & Lomb, Alcon; travel support from Bausch & Lomb; patents from EpiGlare tester, (4 US patents + European patent US6783239; US8690332; USD782341S1; European Patent (granted 2019) to device launched at AAO 2015); pending patent for novel artificial tear to Meibomian Gland Solutions, LLC; leadership or fiduciary roles from EnergizeCare, ASCRS; stock or stock options from TEKv Therapeutics and EyePromise (PRN). She also serves as a consultant to EyeCool Therapeutics, EyePromise, Horizon, Tarsus, SUN, OTX, Ocubio, Imprimis/Harrow, Dompe, Biotissue, Bausch & Lomb, Abbvie, Alcon, Aerie in the dry eye space. Richard Lindstrom is a consultant and member of the Board of Directors for Harrow. Richard Costine is an employee of Harrow, which owns commercial rights to Vevye in the United States. The authors report no other conflicts of interest in this work.