Abstract
Background
Millions of people in Germany wear contact lenses every day. Deficient contact lens hygiene can lead to corneal infection. Contact lens–associated keratitis usually has a highly acute presentation and can cause long-term visual loss.
Methods
This review is based on pertinent publications retrieved by a selective search in PubMed, as well as on relevant meta-analyses, Cochrane reviews, and reports by national and international health care authorities.
Results
23–94% of contact lens wearers report associated discomfort and eye problems. The annual incidence of contact lens–associated keratitis is 2–4/10 000. It is due to bacteria in 90% of cases, and much less commonly to acanthamoebae and fungi. The pathogens generally arrive with the contact lens on the surface of the eye and can penetrate into the corneal tissue because the tear film under the lens is not swept away from the ocular surface by the eyelids, and corneal epithelial changes are often present as well. Corneal infiltration that is diagnosed early is often self-limited, but advanced bacterial infection usually requires intense topical antibiotic treatment. Some severe infections can only be eradicated by emergency corneal transplantation; this is the case in 20–30 % of fungal and acanthamoebic infections.
Conclusion
The wearing of contact lenses, particularly soft ones, is associated with a risk of microbial keratitis if proper contact lens hygiene is not exercised. Contact lens–associated keratitis very rarely causes permanent damage to eyesight (0.6 cases per 10 000 contact lens wearers per year). The use of contact lenses always calls for meticulous care.
cme plus
This article has been certified by the North Rhine Academy for Continuing Medical Education. Participation in the CME certification program is possible only over the internet: cme.aerzteblatt.de. The deadline for submission is 06 October 2023.
Estimates for 2021 put the number of people in Germany using contact lenses to correct refractive errors at 3.7 million, of which 45% regularly and 55% occasionally wear contact lenses (1, 2). In a survey conducted in 2005, 81% of contact lens wearers reported using soft contact lenses, whereas only 12% used rigid gas permeable (“hard”) contact lenses to correct their refractive error, while 7% of respondents did not respond (3). In the US, the number of contact lens wearers rose from 32 million in 2002 to 40.9 million in 2014 (4).
Eye problems due to long-term and frequent use of mostly soft contact lenses are comparatively common. For example, depending on study design, 23–94% of contact lens wearers reported discomfort or eye problems associated with contact lens wear (5). Furthermore, in a survey of nearly 1000 contact lens wearers, almost one-third reported having visited a physician at least once due to painful red eye (4). On the other hand, contact lens wear is responsible for 52–65% of new cases of microbial keratitis (6). Thus, the risk for microbial keratitis is 80 times higher for contact lens wearers compared to non–contact lens wearers (7). This means that, alongside injury, contact lens wear is the main risk factor for the development of the normally rare microbial keratitis. In both cases, avoidable factors are responsible for one-third each of the observed corneal infections (7). For example, the incidence of contact lens–associated keratitis was reported to be 0.4–4 per 10,000 wearers of rigid gas permeable contact lenses, 2–4 per 10,000 wearers of soft contact lenses that are taken out overnight, and 20 per 10,000 wearers of “overnight” contact lenses (8). In addition, there are several factors associated with the use of contact lenses that can increase the risk of microbial keratitis (table 1).
Table 1. Risk factors for the development of microbial keratitis in contact lens wear.
| Risk factor | Risk increase | References |
| Excessive or overnight wear of contact lenses | 3.4- To 15-fold | (9, 10) |
| Deficient hygiene/water contact/no hand-washing | 3.6- To 11-fold | (9– 13) |
| Swimming with contact lenses | 5-Fold | (14) |
| Smoking | 3- To 5.2-fold | (10, 11) |
| Male sex | 1.5-Fold | (7, 13, 15) |
| Scant experience with contact lenses | 4.4-Fold | (10, 13) |
| Young age (< 24 years) | 3.5-Fold | (7, 13, 15) |
| Low socioeconomic status | 2.7-Fold | (7, 13, 15) |
| Hyperopia | 1.8-Fold | (10, 13) |
| Ordering contact lenses online | 4.8-Fold | (10, 13) |
In a survey of almost 1000 contact lens wearers, only 1% reported following all directions relating to contact lens wear and hygiene. In this survey, 50% of respondents occasionally left their contact lenses in overnight, 55% only refilled rather than renewed the disinfection solution, 50% used their contact lenses and 82% their contact lens case longer than recommended, 85% showered and 61% went swimming with their contact lenses, 35% used tap water to clean their lenses, and 17% stored their contact lenses in tap water (4).
Contact lens–associated microbial keratitis is usually caused by bacteria. Infections due to fungi or acanthamoebae are significantly less frequent, but are often far more severe when they do occur. In approximately 11–14% of affected individuals, permanent loss of visual acuity occurs after severe bacterial keratitis (16), whereas this is the case in 30% of individuals affected by Acanthamoeba keratitis (17). In addition, over the course of the disease, at least 20% of cases of Acanthamoeba keratitis require corneal transplantation, which seems to be even more common in fungal keratitis at a figure of at least 30% (18). This emergency transplantation, known as “keratoplasty à chaud,” accounts for a significantly larger proportion of corneal transplants in countries designated as lower and middle income countries (LMIC) compared to industrialized nations (19, 20).
According to estimates in the US, contact lenassociated eye problems annually account for 1 million visits to a phyiscian’s office and 58,000 emergency presentations (21). However, the overall risk for loss of visual acuity as a result of wearing contact lenses is low and no higher than that seen after laser correction of refractive errors. For example, laser in situ keratomileusis (Lasik) causes a reduction in visual acuity in 66 of 100,000 treated individuals. According to estimates, a comparable loss of visual acuity occurs in wearers of soft daily disposable contact lenses after 103 years of wear (22).
At the Eye Center, Medical Center, University of Freiburg, Germany, a total of 35 patients with microbial contact lens–associated keratitis were treated in 2021, with these cases representing a selection of severe cases that had already been unsuccessfully treated by office-based ophthalmologists. Of these patients, 74% could be treated in the outpatient setting, while 26% required inpatient treatment. Of those treated as inpatients, 50% required surgical management (table 2).
Table 2. Contact lens–associated microbial keratitis at the Eye Center, Medical Center, University of Freiburg in 2021 (n = 35).
| Type of contact lens used | |
| Soft contact lens | 69% (n = 24) |
| Rigid gas permeable lens | 3% (n = 1) |
| Unknown | 28% (n = 10) |
| Type of treatment | |
| Outpatient | 74% (n = 26) |
| Inpatient | 26% (n = 9) |
| Treatment measures for inpatient treatment | |
| Intensive topical treatment only | 13% (n = 4) |
| Thermocautery | 13% (n = 4) |
| Amniotic membrane transplantation | 3% (n = 1) |
Pathogenesis
In order for microbial keratitis to develop, at least two conditions always need to be fulfilled. Firstly, there needs to be an alteration or defect in the epithelial cell layer of the cornea, and secondly, pathogens need to be present in sufficient numbers. It is assumed for contact lens–associated keratitis that a sufficient number of pathogens come into contact with the contact lens on the surface of the eye. Therefore, in order to detect the pathogen, those affected should always also bring the contact lens in question as well as the the associated contact lens case to their examination if microbial keratitis is suspected. Pathogens isolated in the laboratory from worn contact lenses reveal microorganisms on the ocular surface as well as bacteria in the aqueous, predominantly Gram-negative environment (23). This is confirmed by the fact that Pseudomonas aeruginosa is by far the most common cause of bacterial contact lens–associated keratitis (24). Pseudomonas are able to adhere to the contact lens material (25) and, under the right conditions, form a biofilm—that is to say, a protective mucous layer with sometimes very high pathogen concentrations (26). This biofilm can weaken not only the immunological defense mechanism but also the effect of antibiotics. The longer a contact lens remains on the ocular surface, the more cell debris, toxins, and antigenic structures are able to accumulate (27), which can promote an infectious event. In addition, contact lens wear results in reduced turnover of corneal epithelial cells, which gives bacteria and other pathogens more time to adhere to the cells and thus penetrate the epithelial layer (28).
Another important role in pathogen defense at the ocular surface is played by the tear film with antimicrobial properties, by which foreign bodies as well as pathogens are regularly cleared from the ocular surface during blinking, which can no longer take place to the same extent when contact lenses are worn (29).
Clinical presentation and treatment
The healthy cornea is transparent since it is free of blood and lymph vessels. Only at the edge of the cornea, the cornea limbus, can blood and lymph vessels be found. The cornea is constantly able to maintain this transparency due to deviant immune responses, also referred to as “immune privilege”: A specific cytokine and cell environment prevents the destruction of non-regenerative tissue (30). In the case of irritation of the superficial corneal epithelial cells, for example due to contact lenses, injury, or pathogens, the epithelial cells start to secrete cytokines. This leads to leukocyte migration, which presents clinically as corneal infiltrates (31). A clinical distinction is made between erosion (absence of an epithelial cell layer and intact corneal stroma without infiltration), a corneal ulcer (defects in the epithelium as well as the underlying stroma), and a corneal infiltrate (cellular infiltration caused by pathogens or toxins in the presence of an intact or absent epithelium).
Bacteria are by far the most common cause of microbial keratitis in Europe. Fungal or Acanthamoeba infections, in contrast, are far rarer. In Europe, contact lens–associated keratitis has been found to be caused by bacteria in 91–100% of cases, fungi in 3–7%, and acanthamoebae in 1–5% (32). Due to the heterogeneous nature of the disease, all of the mentioned studies are generally not randomized controlled trials, but rather case-control studies (evidence level III) or observational studies (evidence level IV).
Bacterial keratitis
Those affected by bacterial contact lens–associated keratitis generally develop, within a few days, symptoms that can rapidly worsen. Due to corneal infiltration, loss of visual acuity rapidly ensues accompanied by characteristically strong light sensitivity. Slit lamp microscopic examination usually reveals a dense, whitish-yellow, circumscribed, sometimes ring-shaped infiltrate. Likewise, depending on severity, a correspondingly strong anterior chamber reaction is detected in the aqueous humor. It is not uncommon to also see hypopyon (usually sterile pus producing a fluid level in the anterior chamber; see Figure 1) early on. Untreated, this leads to lytic processes in the corneal stroma and consequently to the development of a corneal ulcer and even perforation.
Figure 1.
Clinical presentation of bacterial contact lens–associated keratitis
a) Dense paracentral microbial infiltrates that could be treated with intensive topical antibiotic therapy.
b) Dense ulcerative leukocytic infiltration of the corneal stroma with frank hypopyon (pus producing a fluid level in the anterior chamber) in migratory endophthalmitis. In general, the pus formation is a cytotoxic reaction to the corneal infection, and in these cases ultrasound of the eyeball always needing to be performed to exclude vitreous involvement.
Source: Department of Ophthalmology, Freiburg University Hospital, Germany
If bacterial keratitis is present, treatment should, if possible, be provided under inpatient conditions, given that the required intensive treatment regimen is difficult to provide in the home setting, even with good adherence. Treatment initially comprises intensive (every 15 min) topical antibiotic therapy with two different broad-spectrum antibiotics (for example, moxifloxacin and tobramycin). If pathogen detection is carried out, the choice of antibiotic can be adjusted to the antibiogram. If there is a lot of necrotic tissue or dense infiltration, the infected area of the cornea can be treated by means of thermocautery to directly eliminate the pathogens via heat exposure and improve antibiotic penetration (33). In such situations, corneal crosslinking, in which the cornea is first soaked with riboflavin and then irradiated with high-energy UV-A light following mechanical debridement of necrotic tissue, can have a comparable effect (34). Following this, it is not uncommon for a corneal ulcer to persist, necessitating an amniotic membrane graft to cover the ulcer. If it is not possible to control the infection with these measures, often the only option remaining is corneal transplantation, which involves the excision of all infiltrated corneal tissue. This is always a high-risk procedure due to the presence of a strong inflammatory response and the increased risk of rejection (32% versus 21% rejections in normal-risk transplants) and reduced graft survival (63% versus 87% clear graft survival in normal-risk transplants) (35).
Acanthamoeba keratitis
Acanthamoebae are ubiquitously occurring amoebae found primarily in watery environments. A distinction is made for these amoebae between trophozoites, the vegetative life form, and cysts, the resistant permanent form. In over 85% of cases, Acanthamoeba infection of the cornea is associated with mostly soft contact lens wear (14, 18). The onset of Acanthamoeba keratitis is generally significantly slower compared to bacterial keratitis. Characteristically, affected individuals report severe pain early on in the course of the disease, although opthalmologic findings are comparatively unremarkable (moderate conjunctival injection, epithelial disarray). In such cases, one often speaks of a ‘dirty epithelium,” which should prompt suspicion of Acanthamoeba early on. At this stage, is not uncommon to mistake findings for herpes simplex keratitis (36), which can have serious consequences for the subsequent course, since the topical steroids often used in herpes simplex keratitis can mitigate Acanthamoeba infection. This can lead to delayed diagnosis and, consequently, to further corneal spread of Acanthamoeba. If untreated, an almost pathognomonic infiltration around the stromal corneal nerves develops in the further course (optic perineuritis), and finally also a ring infiltrate (Figure 2), although the infiltration appears far more subtle than in Pseudomonas aeruginosa infection. If the acanthamoebae have spread as far as the corneal margin, the sclera may become involved (37). A survey of German eye clinics revealed that of 120 cases of Acanthamoeba keratitis, almost 50% were initially misinterpreted as herpes simplex keratitis, 25% as bacterial keratitis, and 4% as mycotic keratitis (38). On average, the time to correct diagnosis is 2.8 months. Today, the infection is hardly ever detected by pathogen culture, but instead by polymerase chain reaction (PCR) on swab material. Correct diagnosis as early as possible is crucial for the treatment of Acanthamoeba keratitis. This is due to the fact that the further and deeper the amoebae have spread in the corneal tissue, the less amenable they are to drug therapy.
Figure 2:
Clinical presentation of contact lensassociated Acanthamoeba keratitis: In the early weeks, pathognomonic perineuritis of the stromal corneal nerves may develop (a, see arrows). In the late stage, one sees a ring infiltrate (b) that usually requires emergency corneal transplantation in order to get the infection under control
Source: Eye Center, Medical Center, University of Freiburg, Germany
Therapy, which should be delivered in an inpatient setting, consists of the following intensive (every 15 min) treatment with topical drops (39):
Topical antibiotic (for example, moxifloxacin or tobramycin)
Topical diamidine derivative (propamidine isethionate 0.1% or hexamidine 1%)
Topical disinfectant (for example, polyhexamethylene biguanide 0.02%)
Complementary topical or systemic voriconazole as appropriate. Topical steroids (for example, dexamethasone) can still be added in the further course.
Due to the environmental resistance of amoebic cysts, recurrences can occur even after many months, making thorough education and very good compliance important on the part of affected individuals. If medical therapy is unable to achieve an improvement, the only option remaining in approximately 20% of cases is keratoplasty à chaud to eliminate all amoebae capable of division (40). Here, again, the prognosis after transplantation is limited (47% vs. 21% rejection in normal-risk grafts and 73% vs. 87% clear graft survival in normal-risk transplants) (35), and topical follow-up with the abovementioned drugs needs to be continued for many months post transplantation. Despite all treatment measures, approximately one-third of patients experience a permanent reduction in visual acuity in the long term (38).
Fungal keratitis
Fungal infection of the cornea leads to corresponding findings and symptoms significantly more slowly than does bacterial keratitis. The most common pathogens include Candida species (spp.), Aspergillus spp., and Fusarium spp. Filamentous fungi (Aspergillus and Fusarium) are more common in contact lens wearers.
Distinguishing the clinical picture from bacterial keratitis is not always straightforward. Often, the infiltrates or ulcerations are initially less dense, irregularly circumscribed, and not infrequently exhibit a number of small satellite infiltrates. They often also appear less purulent yellowish than whitish-gray and, over time, develop characteristic, sometimes slightly raised feather-like extensions (figure 3).
Figure 3.
Clinical course of contact lensassociated fungal keratitis:
a) Initially, the whitish infiltration of the cornea is usually clinically indistinguishable from bacterial keratitis (figure 1).
b) Despite intensive antimycotic treatment, the infiltration continues to increase accompanied by deep ulceration.
Source: Department of Ophthalmology, Freiburg University Hospital, Germany
With regard to the application of topical antimycotics (voriconazole or natamycin primarily for filamentous fungi, amphotericin primarily for Candida), one needs to bear in mind that some of these agents are unable to penetrate the intact corneal epithelium, meaning that this may need to be removed each time for the duration of treatment.
Unfortunately, since there are no topical antifungal preparations available on the European market for the treatment of fungal keratitis, azole and amphotericin B eye drops need to be made-up in the pharmacy, or natamycin needs to be imported from the USA via the international pharmacy. Despite intensive topical and in some cases systemic treatment, a surgical approach is often unavoidable in fungal keratitis. In 30% of cases, emergency corneal transplantation becomes necessary in order to completely clear the focus of infection and preserve the affected eye.
Summary
Of the nearly four million contact lens wearers in Germany, estimates suggest that more than one million complain of significant eye problems over the course of use. Every year, approximately 800–1600 people develop contact lens–associated, visual acuity-threatening microbial keratitis. The most important risk factor is poor hygiene, mostly when handling soft contact lenses.
In general, infections are initially treated topically with eye drops. In some cases, acute surgical measures such as thermocautery, corneal crosslinking, or corneal transplantation may become necessary.
Even in the case of successful conservative treatment, 11–30% of patients, depending on the pathogen and the severity of the infection, are left with vision-impairing corneal scarring, which may require further vision rehabilitation.
Therefore, it is absolutely crucial that contact lens wearers exercise the necessary care and hygiene in order to avoid serious sequelae to their eyesight.
eTable. Criteria for distinguishing between sterile infiltration and microbial keratitis in contact lens–associated keratitis (from [31]).
| Sterile infiltrate | Microbial keratitis | |
| Clinical presentation | ||
| Etiology | Inflammation (toxins, antigens) | Infection (pathogen) |
| Photophobia | Mild | Severe |
| Visual acuity | Usually unchanged | Usually reduced |
| Epiphora | Mild | Moderate to severe |
| Pain | Mild | Moderate to severe |
| Eyelid edema | None | Common |
| Injection | Moderate, localized | Severe, generalized |
| Localization | Mostly peripheral | Mid-peripheral, all over |
| Size | 0.1–2 mm | > 1 mm |
| Infiltration | Focally circumscribed | Diffuse, irregular, with mucus/pus formation |
| Anterior stroma | All stroma depths possible | |
| Epithelium | Closed/disrupted | Epithelial defect |
| Anterior chamber reaction | None to mild | From moderate to hypopyon (pus producing a fluid level in the anterior chamber) |
| Symptoms after contact lens abstinence | Improved | Further worsened |
| Treatment | ||
| Topical antibiotics | Monopreparation (e.g., moxifloxacin) 5 times/day in epithelial defects | Intensive treatment with drops (every 15–30 min for 24– 48 h) with two antibiotics (e.g., moxifloxacin and tobramycin) |
| Topical steroids | Dexamethasone 3–4 times daily | In epithelial defects: subconjunctival beta- methasoneAfter epithelial closure: dexamethasone 5 times/daily |
| Cycloplegia | Not necessary | E.g., tropicamide 2 times daily |
| Surgical measures | Not necessary | If necessary, debridement, thermocautery,amnion membrane transplantation, crosslinking, corneal transplantation |
| Follow-up | Outpatient every 1–2 days | Inpatient treatment |
| Prevention | Risk-factor modification | Risk-factor modification |
| Prognosis | ||
| Scarring | None to mild peripheral scarring | Always |
| Recurrence | Not rare depending on risk profile | Rare depending on risk profile |
| Vision | No impairment | Significant visual loss common |
eFigure.
Sterile infiltration (arrows) of the cornea in contact lens–associated keratitis, which is often self-limiting if contact lens abstinence is observed.
Source: Department of Ophthalmology, University Hospital Freiburg, Germany
Questions on the article in issue 40/2022:
Contact lens–associated Keratitis—an Often Underestimated Risk
The submission deadline is 06 October 2023. Only one answer is possible per question. Please select the answer that is most appropriate.
Question 1
What percentage of cases of contact lens–associated microbial keratitis is caused by bacteria?
Approximately 15%
Approximately 35%
Approximately 50%
Approximately 75%
Approximately 90%
Question 2
Approximately how often do contact lens wearers who leave their lenses in overnight develop contact lens–associated keratitis?
0.4–4 Per 10,000 contact lens wearers
2–4 Per 10,000 contact lens wearers
20 Per 10,000 contact lens wearers
80 Per 10,000 contact lens wearers
150 Per 10,000 contact lens wearers
Question 3
Infection of the cornea by which parasite results in permanent visual loss in approximately 30% of cases?
Naegleria
Entamoeba dispar
Iodamoeba buetschlii
Acanthamoeba
Entamoeba gingivalis
Question 4
Which pathogen is most commonly responsible for bacterial contact lens–associated keratitis?
Streptococcus pyogenes
Pseudomonas aeruginosa
Haemophilus influenzae
Staphylococcus aureus
Group B Streptococcus
Question 5
Which of the following responses takes place in the case of irritation of the superficial corneal epithelial cells?
Cytokine release by epithelial cells
Cytokine release by endothelial cells
Lysozyme release by Bowman’s membrane
Lysozyme release by endothelial cells
Interleukin release by Bowman’s membrane
Question 6
Which symptom is typical of contact lens–associated keratitis?
Altered color vision
Light sensitivity
Migraine
Dry eye
Auras
Question 7
What is meant by hypopyon?
Accumulation of pus in the posterior chamber of the eye
Optic disc swelling
Reduced internal pressure in the anterior chamber of the eye
Accumulation of pus in the anterior chamber of the eye
Undersupply of retinal cells
Question 8
With regard to contact lens wear, what represents a risk factor for microbial keratitis?
Hand-washing
Myopia
Advanced age
Ordering contact lenses online
Female sex
Question 9
Severe pain is a common early symptom of Acanthamoeba infection. This is usually accompanied by which relatively unremarkable ophthalmologic finding?
“Opaque epithelium”
“Foggy epithelium”
“Cloudy epithelium”
“Dirty epithelium”
“Muddy epithelium”
Question 10
In some cases of Acanthamoebic keratitis, keratoplasty remains the only therapeutic option for complete pathogen elimination. With this approach, how high is the rejection rate compared to the 21% seen in normal-risk patients?
25%
47%
62%
74%
93%
Acknowledgments
Translated from the original German by Christine Rye.
Footnotes
Conflict of interest statement The authors declare that no conflict of interests exists.
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