Abstract
Purpose
Infectious keratitis, the leading cause of corneal blindness, disproportionately affects developing countries. We examined risk factors for poor presenting visual acuity in a rural Indian population.
Patients and Methods
We conducted a cross-sectional study of patients ≥16 years old with active infectious keratitis at SNC Hospital, a tertiary eye hospital in north India, from June to November 2024. Variables collected were demographics, clinical features, and anatomic findings on slit-lamp examination. Binomial logistic regression measured association of variables with best-corrected visual acuity (BCVA) ≤20/200. Significant univariable associations were incorporated into a multivariable model.
Results
Among 667 patients with keratitis (mean age: 50.3 ± 15 years), 497 (74.5%) presented with VA ≤20/200. Independent risk factors for poor VA included older age (prevalence ratio [PR] 1.01/year, 95% CI 1.00–1.01, p<0.001), bacterial infection (PR 1.12, 95% CI 1.03–1.23, p=0.009), polymicrobial infections (PR 1.13, 95% CI 1.01–1.26, p=0.027), larger epithelial defect (PR 1.38, 95% CI 1.12–1.71, p=0.042 with epithelial defect diameter >6mm), posterior stromal infiltrate (PR 1.22, 95% CI 1.09–1.36, p<0.001), endothelial plaque (PR 1.13, 95% CI 1.00–1.26, p=0.043), central infiltrate location (PR 1.26, 95% CI 1.14–1.38, p<0.001) and hypopyon (PR 1.28, 95% CI 1.18–1.39, p<0.001). Travel distance, time to presentation, and clinical risk factors were not independently associated with poor VA.
Conclusion
Anatomic features including larger epithelial defects, deep stromal infiltrates, endothelial plaque, central location, and hypopyon were the strongest predictors of poor VA. These findings highlight the utility of anatomic features for identifying eyes at risk for severe outcomes and serving as biomarkers in future clinical trials.
Keywords: corneal infection, corneal ulcer, risk stratification, biomarkers
Plain Language Summary
Eye infections that affect the cornea, the clear front part of the eye, are a major cause of blindness, especially in developing countries. This study aimed understand what factors make patients more likely to have severe vision loss when they develop corneal infections. Our team studied 667 patients with active corneal infections at SNC Chitrakoot Hospital, a hospital in north India, over six months. We collected data including patient demographics, risk factor, travel distance, and days of symptoms, and details about corneal infection, including its size, depth, location, and type. We found that several factors made severe vision loss for patients presenting with corneal infections more likely: being older, having bacterial infections or infections caused by multiple types of microbes, having larger areas of damaged tissue, having infections that went deeper into the eye, having infections located in the center of the cornea, and having pus buildup (called hypopyon) inside the eye. Surprisingly, how far patients traveled to the hospital or how long they waited before seeking treatment did not significantly affect their vision. Our study shows that ophthalmologists may be able to predict severe vision loss by carefully examining features on examination of their eye. This information can help doctors identify patients who require the most aggressive treatment and help researchers design better studies to test new treatments. The findings emphasize that anatomic factors such as location, size, and depth of the infection are the most important risk factors for vision loss compared to clinical or demographic factors.
Introduction
Infectious keratitis, or infectious corneal ulceration, is the leading etiology of corneal blindness and the fifth leading cause of blindness worldwide, causing two million cases of monocular blindness per year.1,2 It can result from bacterial, fungal, parasitic, viral, or polymicrobial infections, and presents with pain, redness, decreased vision, and photophobia.1–3 Without timely diagnosis and treatment, infectious keratitis can cause severe complications including corneal scarring, corneal perforation, or enucleation.1,4,5 If medical therapy fails, surgical management by therapeutic penetrating keratoplasty (TPK) may be required, during which diseased corneal tissue is transplanted with donor tissue.6
Infectious keratitis disproportionately affects developing countries.7,8 While the incidence of infectious keratitis is estimated to be between 2.5 and 27.6 per 100,000 in the United States, the incidence in India is estimated at up to 113 per 100,000.9,10 The higher incidence in low-resource settings has been attributed to traumatic injuries, agricultural exposures, and limited healthcare access.1,11
Major risk factors for infectious keratitis include contact lens use, trauma, ocular surface disease, prior ocular surgery, and systemic immunosuppression.1,12 Poor presenting visual acuity (VA), large infiltrate size, larger epithelial defect size, perforation at presentation, and involvement of the posterior cornea were factors associated with need for TPK.13–17 Worse presenting visual acuity, delayed presentation, and larger stromal infiltrates were associated with worse 90-day visual acuity in a study comparing US and Indian populations.18
Sociodemographic risk factors associated with keratitis have also been examined. A cohort study in a South Indian population showed that older age, female gender, and lack of education were associated with poor outcomes.14
There remains a need for detailed analyses of risk factors for severe presentations of keratitis in robust patient cohorts, especially in developing countries. This study examined clinical, anatomic, and sociodemographic risk factors for worse VA at presentation among patients with infectious keratitis presenting to Sadguru Netra Chikitsalaya (SNC) Hospital, a tertiary eye care hospital in Chitrakoot, Madhya Pradesh, India.
Methods
Study Population
We retrospectively reviewed records of patients with active infectious keratitis presenting to SNC Eye Hospital from June to November 2024. SNC Hospital serves a rural population and utilizes vision centers and screening eye camps to identify patients needing care.
Inclusion criteria were eyes from patients aged ≥ 16 years with active corneal infection diagnosed clinically or with microbiologic testing. For bilateral infections, the worse-seeing eye was analyzed.
Data Sources & Variables Collected
Data collected from the electronic medical record included demographics (age, sex, address), infection laterality, best-corrected visual acuity (BCVA), slit lamp examination findings, days from symptom onset to presentation, risk factors, and microbiology testing (Gram stain and/or KOH preparation). At SNC Chitrakoot, corneal scraping with Gram or KOH stain was used to diagnose infection; culture and PCR methods are not routinely performed at the site and were not used in this analysis. Slit lamp findings were documented via a standardized form and included epithelial defect diameter, infiltrate diameter, infiltrate stromal depth, infiltrate location relative to the limbus, and markers of severe infection including hypopyon, endothelial plaque, impending perforation/descemetocele, and frank perforation. Whether eyes were selected for TPK was also collected.
Calculation of Travel Distance
Patient addresses and the SNC Hospital address were converted to latitude and longitude coordinates via the Google Maps API and the “ggmap” R package. Straight-line distances (km) between coordinates was computed using Stata’s “geodist” command.
Classification of Infection Type
Fungal keratitis cases showed fungal organisms on KOH prep or Gram stain. Bacterial keratitis showed bacterial organisms on Gram stain. Viral keratitis cases were diagnosed clinically by a cornea specialist. Polymicrobial infections were positive for at least two of: microbiologically confirmed fungal keratitis, microbiologically confirmed bacterial keratitis, and/or clinically diagnosed viral keratitis.
Evaluation of Risk Factors for Poor Presenting VA
Poor presenting VA was defined as distance Snellen BCVA <20/200, an establishment for legal blindness that has been employed in prior studies of infectious keratitis.19,20 Univariate logistic regression was used to evaluate associations between risk factors and poor presenting VA. Binomial logistic regression was used to calculate prevalence ratio (PRs) with 95% confidence intervals (CIs). For each exposure included in the analysis, the PR quantified how the prevalence of poor presenting VA differed between levels. Significant individual risk factors were incorporated into a multivariable logistic regression model. Poisson regression with robust variance estimation was used to approximate the binomial model when the model failed to converge.
Geographic data conversion was conducted in R (v2024.09.0+375). Analyses were conducted in Stata (v18).
Results
Baseline Study Population Characteristics
About 667 eyes from 667 patients with active microbial keratitis were included. The mean patient age was 50.3 ± 15 years, and 62.2% were male (N=415). Time to presentation was 20.4 ± 27.2 days, with mean travel distance of 144.8 ± 92.1 km. Most eyes (N=494, 74.1%) presented with VA 20/200 or worse (Table 1).
Table 1.
Demographic, Clinical, and Anatomic Characteristics of Microbial Keratitis by Presenting Visual Acuity
| Overall Population (N=667) |
Presenting VA ≤20/200 (N=494) |
Presenting VA >20/200 (N=173) |
|
|---|---|---|---|
| Age (years), mean (SD) | 50.3 (15.0) | 52.4 (14.9) | 44.0 (13.7) |
| Days to Presentation, mean (SD) | 20.4 (27.2) | 22.0 (28.5) | 16.0 (22.3) |
| Travel Distance to Hospital (km), mean (SD) | 144.8 (92.1) | 144.8 (92.1) | 139.7 (90.0) |
| Affected Eye, N (%) | |||
| Left | 331 (49.6%) | 245 (49.6%) | 86 (49.7%) |
| Right | 336 (50.4%) | 249 (50.4%) | 87 (50.3%) |
| Sex, N (%) | |||
| Female | 252 (37.8%) | 193 (39.1%) | 59 (34.1%) |
| Male | 415 (62.2%) | 301 (60.9%) | 114 (65.9%) |
| Keratitis Risk Factors, N (%) | |||
| No Known Risk Factors | 247 (37.0%) | 198 (40.1%) | 49 (28.3%) |
| Vegetative Trauma | 183 (27.4%) | 127 (25.7%) | 56 (32.4%) |
| Recent Ocular Trauma | 60 (9.0%) | 42 (8.5%) | 18 (10.4%) |
| Dust Exposure | 33 (5.0%) | 21 (4.3%) | 12 (6.9%) |
| Animal Trauma | 27 (4.1%) | 18 (3.6%) | 9 (5.2%) |
| Insect Trauma | 26 (3.9%) | 18 (3.6%) | 8 (4.6%) |
| Other Trauma | 32 (4.8%) | 26 (5.3%) | 6 (3.5%) |
| Foreign Body | 22 (3.3%) | 14 (2.8%) | 8 (4.6%) |
| Steroid Use | 20 (3.0%) | 14 (2.8%) | 6 (3.5%) |
| Systemic Immunosuppression | 17 (2.6%) | 12 (2.4%) | 5 (2.9%) |
| Past Herpetic Infection | 10 (1.5%) | 7 (1.4%) | 3 (1.7%) |
| Water Exposure | 8 (1.2%) | 6 (1.2%) | 2 (1.2%) |
| Native Medication | 7 (1.1%) | 6 (1.2%) | 1 (0.6%) |
| Past Ulcer | 5 (0.8%) | 4 (0.8%) | 2 (0.6%) |
| Ocular Surgery | 3 (0.5%) | 3 (0.6%) | 0 (0.0%) |
| Diabetes Mellitus | 3 (0.5%) | 2 (0.4%) | 1 (0.6%) |
| Contact Lens Wear | 2 (0.3%) | 2 (0.4%) | 0 (0.0%) |
| Poor Contact Hygiene | 1 (0.2%) | 1 (0.2%) | 0 (0.0%) |
| Past Keratoplasty | 1 (0.2%) | 1 (0.2%) | 0 (0.0%) |
| Dacryocystitis | 1 (0.2%) | 1 (0.2%) | 0 (0.0%) |
| Trichiasis | 1 (0.2%) | 1 (0.2%) | 0 (0.0%) |
| Type of Infection, N (%) | |||
| Negative Microbiology Data | 3 (0.5%) | 1 (0.2%) | 2 (1.2%) |
| Fungal Keratitis Onlya | 320 (58.0%) | 232 (47.0%) | 88 (50.9%) |
| Bacterial Keratitis Onlyb | 177 (26.5%) | 150 (30.4%) | 27 (15.6%) |
| Viral Keratitis Onlyc | 2 (0.3%) | 2 (0.4%) | 0 (0.0%) |
| Polymicrobial Infectiond | 66 (9.9%) | 56 (11.3%) | 10 (5.8%) |
| Microbiology Data Not Available | 99 (14.8%) | 53 (10.7%) | 46 (26.6%) |
| Epithelial Defect Diameter, N (%) | |||
| No Epithelial Defect | 32 (4.8%) | 17 (3.4%) | 15 (8.7%) |
| >0 to <2mm | 121 (18.1%) | 61 (12.4%) | 60 (34.7%) |
| 2 to <6mm | 375 (56.2%) | 278 (56.3%) | 97 (56.1%) |
| ≥6mm | 139 (20.8%) | 138 (27.9%) | 1 (0.6%) |
| Infiltrate/Scar Diameter, N (%) | |||
| No Scar | 12 (1.8%) | 4 (0.8%) | 8 (4.6%) |
| >0 to <2mm | 119 (17.8%) | 62 (12.6%) | 57 (33.0%) |
| 2 to <6mm | 388 (58.2%) | 283 (57.3%) | 105 (60.7%) |
| ≥6mm | 148 (22.2%) | 145 (29.4%) | 3 (1.7%) |
| Infiltrate/Scar Stromal Depth, N (%) | |||
| Anterior 1/3 of Stroma | 241 (36.1%) | 145 (29.4%) | 96 (55.5%) |
| Middle 1/3 of Stroma | 205 (30.7%) | 150 (30.4%) | 55 (31.8%) |
| Posterior 1/3 of Stroma | 131 (19.6%) | 122 (24.7%) | 9 (5.2%) |
| Endothelial Lesion | 76 (11.4%) | 71 (14.4%) | 5 (2.9%) |
| Not Applicable | 14 (2.1%) | 6 (1.2%) | 8 (4.6%) |
| Infiltrate/Scar Location, N (%) | |||
| Central (0 to 4mm) | 390 (58.5%) | 313 (63.4%) | 96 (55.5%) |
| Mid-peripheral (4 to 8mm) | 345 (51.7%) | 259 (52.4%) | 86 (49.7%) |
| Peripheral (8 to 10mm) | 388 (58.2%) | 287 (58.1%) | 101 (58.4%) |
| Diffuse (entire cornea) | 28 (4.2%) | 27 (5.5%) | 1 (0.6%) |
| Not Applicable | 12 (1.8%) | 5 (1.0%) | 7 (4.1%) |
| Infiltrate Location Within 2mm of Limbus, N (%) | |||
| Yes | 120 (18.0%) | 101 (20.5%) | 19 (11.0%) |
| No | 547 (82.0%) | 393 (79.6%) | 154 (89.0%) |
| Hypopyon Present, N (%) | |||
| Yes | 236 (35.4%) | 218 (44.1%) | 18 (10.4%) |
| No | 431 (64.6%) | 276 (55.9%) | 155 (89.6%) |
| Impending Perforation, N (%) | |||
| Yes | 45 (6.8%) | 44 (8.9%) | 1 (0.6%) |
| No | 622 (93.3%) | 450 (91.1%) | 172 (99.4%) |
| Frank Perforation, N (%) | |||
| Yes | 52 (7.8%) | 51 (10.3%) | 1 (0.6%) |
| No | 615 (92.2%) | 443 (89.7%) | 172 (99.4%) |
| Therapeutic Keratoplasty Required, N (%) | |||
| Yes | 51 (7.7%) | 50 (10.1%) | 1 (0.6%) |
| No | 615 (92.3%) | 444 (89.9%) | 171 (99.4%) |
Notes: aFungal keratitis was microbiologically confirmed via KOH stain or Gram stain. bBacterial keratitis was microbiologically confirmed via Gram stain. cViral keratitis was clinically diagnosed by a cornea specialist. d Polymicrobial infections were positive for at least 2 of the following: microbiologically confirmed fungal keratitis, microbiologically confirmed bacterial keratitis, and/or clinically diagnosed viral keratitis.
Abbreviations: SD, standard deviation; VA, visual acuity.
Common risk factors were vegetative trauma (N=183, 27.4%), recent ocular trauma (N=60, 9.0%), dust exposure (N=33, 5.0%), animal trauma (N=27, 4.1%), and insect trauma (N=26, 3.9%), though 37% of eyes (N=247) had no identifiable risk factors. About 58% of infections were fungal keratitis only (N=320), followed by bacterial keratitis only (N=177, 26.5%), and polymicrobial infections (N=66, 9.9%). Isolated viral keratitis accounted for two infections (0.3% of cases).
Risk Factors for Poor Presenting VA
In univariable analysis, factors associated with VA ≤20/200 were increasing age (PR 1.01 per year, 95% CI 1.007–1.012, p<0.001), delayed presentation >14 days (PR 1.11, 95% CI 1.02–1.21, p=0.020), and bacterial keratitis (PR 1.16, 95% CI 1.06–1.28, p=0.001) or polymicrobial infections (PR 1.17, 95% CI 1.03–1.32, p=0.014) relative to fungal keratitis (reference group) (Table 2).
Table 2.
Patient and Eye-Level Characteristics Associated with 20/200 or Worse Presenting Visual Acuity
| Univariable log binomial regression | Multivariable log binomial regressiona | |||
|---|---|---|---|---|
| PR (95% CI) | p-value | PR (95% CI) | p-value | |
| Age, years | 1.01 (1.007–1.012) | <0.001*** | 1.01 (1.005–1.010) | <0.001*** |
| Time to Presentation | ||||
| ≤14 Days | Reference | Reference | ||
| >14 Days | 1.11 (1.02–1.21) | 0.020* | 1.05 (0.97–1.14) | 0.200 |
| Distance to Base Hospital | ||||
| ≤128 km | Reference | |||
| >128 km | 1.01 (0.93–1.11) | 0.769 | ||
| Sex | ||||
| Female | Reference | |||
| Male | 0.94 (0.86–1.03) | 0.176 | ||
| Risk Factorsb | ||||
| Vegetative Trauma | 0.91 (0.81–1.01) | 0.080 | ||
| Recent Ocular Trauma | 0.93 (0.79–1.11) | 0.436 | ||
| Dust Exposure | 0.85 (0.65–1.10) | 0.216 | ||
| Animal Trauma | 0.89 (0.68–1.17) | 0.402 | ||
| Insect Trauma | 0.93 (0.71–1.20) | 0.565 | ||
| Other Trauma | 1.13 (0.95–1.35) | 0.167 | ||
| Foreign Body | 0.85 (0.62–1.17) | 0.318 | ||
| Steroid Use | 0.94 (0.70–1.25) | 0.664 | ||
| Systemic Immunosuppression | 1.03 (0.79–1.34) | 0.845 | ||
| Past Herpetic Infection | 1.07 (0.79–1.47) | 0.652 | ||
| Water Exposure | 1.01 (0.67–1.51) | 0.974 | ||
| Native Medication | 1.15 (0.85–1.56) | 0.364 | ||
| Past Ulcer | 1.07 (0.69–1.67) | 0.750 | ||
| Diabetes Mellitus | 0.89 (0.40–1.99) | 0.785 | ||
| Type of Infection | ||||
| Fungal Keratitis Only | Reference | Reference | ||
| Bacterial Keratitis Only | 1.16 (1.06–1.28) | 0.001** | 1.12 (1.03–1.23) | 0.009** |
| Polymicrobial Keratitis | 1.17 (1.03–1.32) | 0.014* | 1.13 (1.01–1.26) | 0.027* |
| Epithelial Defect Diameter | ||||
| No Epithelial Defect | 1.05 (0.73–1.53) | 0.782 | 1.30 (0.88–1.90) | 0.187 |
| >0 to <2mm | Reference | Reference | ||
| 2 to <6mm | 1.47 (1.22–1.77) | <0.001*** | 1.24 (1.01–1.52) | 0.042* |
| >6mm | 1.97 (1.65–2.35) | <0.001*** | 1.38 (1.12–1.71) | 0.003** |
| Infiltrate/Scar Diameter | ||||
| No Scar | 0.64 (0.28–1.45) | 0.285 | 0.35 (0.09–1.40) | 0.137 |
| >0 to <2mm | Reference | Reference | ||
| 2 to <6mm | 1.40 (1.17–1.68) | <0.001*** | 1.01 (0.81–1.24) | 0.954 |
| >6mm | 1.88 (1.58–2.24) | <0.001*** | 1.14 (0.91–1.42) | 0.265 |
| Infiltrate/Scar Stromal Depth | ||||
| Anterior 1/3 of Stroma | Reference | Reference | ||
| Middle 1/3 of Stroma | 1.21 (1.06–1.38) | 0.005** | 1.08 (0.96–1.22) | 0.188 |
| Posterior 1/3 of Stroma | 1.54 (1.37–1.72) | <0.001*** | 1.22 (1.09–1.36) | <0.001*** |
| Endothelial Lesion | 1.54 (1.37–1.74) | <0.001*** | 1.13 (1.00–1.26) | 0.043* |
| Infiltrate/Scar Locationc | ||||
| Central (0 to 4mm) | 1.22 (1.11–1.34) | <0.001*** | 1.26 (1.14–1.38) | <0.001*** |
| Mid-peripheral (4 to 8mm) | 1.02 (0.93–1.11) | 0.732 | ||
| Peripheral (8 to 10mm) | 0.98 (0.90–1.07) | 0.703 | ||
| Diffuse (entire cornea) | 1.31 (1.20–1.43) | <0.001*** | 1.10 (0.99–1.23) | 0.078 |
| Infiltrate Location Within 2mm of Limbus | 1.16 (1.06–1.28) | 0.002** | 0.99 (0.90–1.09) | 0.831 |
| Hypopyon Present | 1.43 (1.32–1.54) | <0.001*** | 1.28 (1.18–1.39) | <0.001*** |
| Impending Perforation | 1.34 (1.26–1.43) | <0.001*** | 1.04 (0.95–1.13) | 0.435 |
| Frank Perforation | 1.35 (1.27–1.44) | <0.001*** | 1.05 (0.96–1.16) | 0.268 |
| Therapeutic Keratoplasty Required | 1.35 (1.27–1.44) | <0.001*** | 1.05 (0.95–1.16) | 0.358 |
Notes: aMultivariable log binomial regression model included all covariates found to be significantly associated with the outcome in univariable regression. Covariates included were age, time to presentation, type of infection, epithelial defect diameter, scar diameter, scar stromal depth, scar location, infiltrate location within 2mm of limbus, presence of hypopyon, impending perforation, frank perforation, and need for therapeutic keratoplasty. bPresence or absence of each risk factor was assessed independent of other risk factors. cPresence or absence of scar within each corneal region (central, mid-peripheral, peripheral, or diffuse) was assessed independent of scar presence in other locations. *p<0.05; **p<0.01; ***p<0.001.
Abbreviations: CI, confidence interval; PR, prevalence ratio.
Anatomic factors associated with poor presenting VA included larger epithelial defect diameter (2-< 6 mm versus 0–2 mm [reference group]: PR 1.47, 95% CI 1.22–1.77, p<0.001, and >6mm versus 0–2 mm: PR 1.97, 95% CI 1.65–2.35, p<0.001) and larger stromal infiltrate diameter (2 to <6 mm versus 0–2 mm [reference group]: PR 1.40, 95% CI 1.17–1.68, p<0.001, and >6 mm versus 0–2 mm: PR 1.88, 95% CI 1.58–2.24, p<0.001). Deeper stromal infiltrates were also associated with poorer VA. Compared to eyes with infiltrates only within the anterior one third of the stroma (reference group), eyes had higher likelihood of poor presenting VA with infiltrates in the middle one third of the stroma (PR 1.54, 95% CI 1.37–1.72, p=0.005), posterior one third of the stroma (PR 1.54, 95% CI 1.37–1.72, p<0.001), or endothelial plaque (PR 1.54, 95% CI 1.37–1.74, p<0.001). Compared to eyes without central infiltrates (reference group), infiltrates involving the central cornea (PR 1.22, 95% CI 1.11–1.34, p<0.001) or extending diffusely throughout the cornea (PR 1.31, 95% CI 1.20–1.43, p<0.001) were associated with higher risk of poor presenting VA. Eyes with infiltrate extension to within 2 mm of the limbus were also associated with higher likelihood of poorer VA on presentation (PR 1.16, 95% CI 1.06–1.28, p=0.002).
Hypopyon (PR 1.43, 95% CI 1.32–1.54, p<0.001), impending perforation (PR 1.34, 95% CI 1.26–1.43, p<0.001), frank perforation (PR 1.35, 95% CI 1.27–1.44, p<0.001), and need for therapeutic keratoplasty (PR 1.35, 95% CI 1.27–1.44, p<0.001) were all significantly associated with poor presenting VA (Table 2).
In multivariable analysis, several factors remained independently associated with poor presenting VA (Table 2). Older age (PR 1.01 per year, 95% CI 1.005–1.010, p<0.001) was associated with poor presenting VA. Both bacterial keratitis (PR 1.12, 95% CI 1.03–1.23, p=0.009) and polymicrobial infections (PR 1.13, 95% CI 1.01–1.26, p=0.027) were associated with worse presenting VA compared to fungal keratitis. Anatomically, larger epithelial defects of 2 to <6 mm (PR 1.24, 95% CI 1.01–1.52, p=0.003) and >6mm (PR 1.38, 95% CI 1.12–1.71, p=0.042) predicted worse VA compared to epithelial defects >0 to <2 mm. Posterior stromal involvement (PR 1.22, 95% CI 1.09–1.36, p<0.001), endothelial lesions (PR 1.13, 95% CI 1.00–1.26, p=0.043), central infiltrate location (PR 1.26, 95% CI 1.14–1.38, p<0.001), and the presence of hypopyon (PR 1.28, 95% CI 1.18–1.39, p<0.001) were also independent risk factors for poor presenting VA.
Discussion
This large retrospective study of infectious keratitis in India identified several anatomic, clinical, and demographic factors associated with poor presenting VA of 20/200 or worse. Anatomic risk factors were more strongly associated with poor VA than clinical or demographic risk factors, highlighting their importance as potential biomarkers to help gauge infection severity and predict clinical outcomes in keratitis. The strong associations between anatomic findings and poor presenting VA may make them useful for standardized keratitis risk assessment tools.
Anatomic Risk Factors for Worse Presenting VA
Anatomic features were more powerfully associated with poor presenting VA than any other covariates in our analysis, including well-described keratitis risk factors such as trauma and fungal infection.1,14,21 These findings indicate the importance of detailed anatomic evaluation of keratitis to triage clinical severity. Although this analysis relied on subjective clinician grading, future research can utilize imaging such as slit lamp photography and anterior segment optical coherence tomography (ASOCT) to better classify anatomic risk factors.
Central infections, which directly affect the visual axis, were associated with worse VA. The Steroids for Corneal Ulcers Trial (SCUT) demonstrated that centrally located ulcers demonstrated a benefit in 3-month VA after adjuvant corticosteroids, providing further evidence that therapies to reduce central scarring may confer visual benefits compared to treatment of peripheral scarring.22 Our work corroborates central location as an important determinant of poor keratitis outcomes.
The presence of hypopyon was associated with poorer presenting VA, indicating that measuring hypopyon may help to stratify keratitis severity. Hypopyon is an indicator of infection severity that is most frequently associated with fungal keratitis, and it has been demonstrated that up to 50% of fungal cases develop hypopyon.23–25 Objective measurement of hypopyon size on slit lamp biomicroscopy, photography, or ASOCT may aid in use of hypopyon as a biomarker in future research.
Larger epithelial defects were associated with poorer VA than smaller epithelial defects. Compared to eyes with epithelial defects 0 to <2 mm in diameter, eyes with epithelial defects 2 to <6 mm in size had 24% higher prevalence of VA ≤20/200. Eyes with epithelial defects >6 mm in diameter had 38% higher prevalence of VA 20/200 or worse, compared to epithelial defects 0 to <2 mm in diameter. Epithelial defect size is well-studied as a predictor of severe keratitis outcomes, and has been associated with higher likelihood of prolonged healing time, need for surgical intervention, and worse 3-month VA outcomes.14,17,26,27 Our finding corroborates use of epithelial defect size as a biomarker of worse presenting VA in keratitis.
Deeper stromal involvement was strongly associated with worse presenting VA. Eyes with infiltrates extending into the posterior one-third of the cornea had 22% higher prevalence of VA <20/200 compared to eyes with infiltrates in the anterior one-third of the cornea. Endothelial plaque was associated with 13% higher prevalence of VA ≤20/200 compared to isolated anterior infiltrates. In SCUT, which measured infiltrate depth via subjective slit lamp examination, subgroup analyses showed that deeper infiltrates were associated with VA improvement following exposure to adjuvant corticosteroids while parameters such as infiltrate diameter were not associated with VA improvement.22 A follow-up analysis of patients years after MUTT I showed that irregular astigmatism from post-infectious stromal thinning was strongly associated with worse long-term VA while scar depth was not associated.28 However, the authors argued that initial infection depth may predict development of irregular astigmatism and may be an important predictor of vision loss. Given the potential for novel imaging such as ASOCT to quantify infection depth, future research should evaluate the association of infection depth with longer term infection outcomes.
It is notable that larger infiltrate diameter was not associated with worse presenting VA. Larger infiltrate diameter has been associated with severe disease, worse vision, and higher rates of surgical intervention, although only a few clinical trials such as SCUT and MUT have shown an association between infiltrate diameter and trial endpoints.22,25,26,29,30 In one study using ASOCT to quantify fungal keratitis, both infiltrate width and depth were reduced from presentation to healing.31 In a separate study using ASOCT to quantify bacterial keratitis lesions, both corneal edema and stromal infiltrate thickness in the anterior-to-posterior dimension significantly decreased with infection resolution, while infiltrate width did not.32 Thus, infiltrates may be more likely to shrink in stromal depth within the anterior-to-posterior axis rather than diameter or size in the en face (X-Y) plane. Given that infiltrate diameter was not associated with poor VA while infiltrate depth remained strongly associated with poor presenting VA, future studies should evaluate the use of infiltrate depth as a sensitive biomarker for worse infection.
Clinical Risk Factors for Worse Presenting VA
Bacterial and polymicrobial infections being associated with worse VA compared to fungal keratitis is noteworthy. Fungal keratitis has been shown to have an aggressive course and lead to worse outcomes.33–35 In our study, more eyes with bacterial only infections had larger and deeper infiltrates compared to eyes with fungal only infections (Table 3). A greater percentage of polymicrobial infections also had deeper infiltrates. The poorer presenting VA associated with bacterial keratitis may be due to more severe infiltrates than those eyes with fungal keratitis. To our knowledge, this is the first study evaluating keratitis outcomes in Madhya Pradesh, where keratitis types may differ from South India, where fungal keratitis is common. Thus, both a difference in infiltrate size and geography may explain the more significant vision loss associated with bacterial infections in our analysis.
Table 3.
Demographic, Clinical, and Anatomic Characteristics of Microbial Keratitis by Infection Type
| Fungal Keratitis Onlya (N=320) |
Bacterial Keratitis Onlyb (N=177) |
Polymicrobial Infectionc (N=66) |
|
|---|---|---|---|
| Age (years), mean (SD) | 49.2 (14.1) | 51.8 (15.6) | 55.0 (15.8) |
| Days to Presentation, mean (SD) | 15.0 (14.4) | 22.3 (27.6) | 28.7 (32.5) |
| Travel Distance to Hospital (km), mean (SD) | 145.3 (87.8) | 142.7 (83.3) | 152.3 (131.9) |
| Affected Eye, N (%) | |||
| Left | 154 (48.1%) | 88 (49.7%) | 34 (51.5%) |
| Right | 166 (51.9%) | 89 (50.3%) | 32 (48.5%) |
| Sex, N (%) | |||
| Female | 126 (39.4%) | 62 (35.0%) | 24 (36.4%) |
| Male | 194 (60.6%) | 115 (65.0%) | 42 (63.6%) |
| Keratitis Risk Factors, N (%) | |||
| No Known Risk Factors | 98 (30.6%) | 79 (44.6%) | 32 (48.4%) |
| Vegetative Trauma | 106 (33.1%) | 41 (23.2%) | 15 (22.7%) |
| Recent Ocular Trauma | 34 (10.6%) | 12 (6.8%) | 9 (13.6%) |
| Dust Exposure | 21 (6.6%) | 7 (4.0%) | 1 (1.5%) |
| Animal Trauma | 14 (4.4%) | 6 (3.4%) | 0 (0.0%) |
| Insect Trauma | 16 (5.0%) | 3 (1.7%) | 1 (1.5%) |
| Other Trauma | 15 (4.7%) | 10 (5.7%) | 3 (4.6%) |
| Foreign Body | 13 (4.1%) | 6 (3.4%) | 1 (1.5%) |
| Steroid Use | 8 (2.5%) | 8 (4.5%) | 0 (0.0%) |
| Systemic Immunosuppression | 4 (1.3%) | 3 (1.7%) | 0 (0.0%) |
| Past Herpetic Infection | 0 (0.0%) | 2 (1.1%) | 3 (4.6%) |
| Water Exposure | 6 (1.9%) | 2 (1.1%) | 0 (0.0%) |
| Native Medication | 1 (0.3%) | 6 (3.4%) | 0 (0.0%) |
| Past Ulcer | 2 (0.6%) | 1 (0.6%) | 1 (1.5%) |
| Ocular Surgery | 0 (0.0%) | 3 (1.7%) | 0 (0.0%) |
| Diabetes Mellitus | 1 (0.3%) | 1 (0.6%) | 0 (0.0%) |
| Contact Lens Wear | 0 (0.0%) | 1 (0.6%) | 1 (1.5%) |
| Poor Contact Hygiene | 0 (0.0%) | 1 (0.6%) | 0 (0.0%) |
| Past Keratoplasty | 0 (0.0%) | 1 (0.6%) | 0 (0.0%) |
| Dacryocystitis | 0 (0.0%) | 1 (0.6%) | 0 (0.0%) |
| Trichiasis | 0 (0.0%) | 1 (0.6%) | 0 (0.0%) |
| Epithelial Defect Diameter, N (%) | |||
| No Epithelial Defect | 4 (1.3%) | 5 (2.8%) | 3 (4.6%) |
| >0 to <2mm | 52 (16.3%) | 29 (16.4%) | 11 (16.7%) |
| 2 to <6mm | 195 (60.9%) | 91 (51.4%) | 39 (59.1%) |
| ≥6mm | 69 (21.6%) | 52 (29.4%) | 13 (19.7%) |
| Infiltrate/Scar Diameter, N (%) | |||
| No Scar | 0 (0.0%) | 1 (0.6%) | 2 (3.0%) |
| >0 to <2mm | 43 (13.4%) | 28 (15.8%) | 9 (13.6%) |
| 2 to <6mm | 202 (63.1%) | 95 (53.7%) | 40 (60.6%) |
| ≥6mm | 75 (23.4%) | 53 (29.9%) | 15 (22.7%) |
| Infiltrate/Scar Stromal Depth, N (%) | |||
| Anterior 1/3 of Stroma | 133 (41.6%) | 47 (26.6%) | 23 (34.9%) |
| Middle 1/3 of Stroma | 101 (31.6%) | 49 (27.7%) | 19 (28.8%) |
| Posterior 1/3 of Stroma | 51 (15.9%) | 54 (30.5%) | 15 (22.7%) |
| Endothelial Lesion | 34 (10.6%) | 26 (14.7%) | 8 (12.1%) |
| Not Applicable | 1 (0.3%) | 1 (0.6%) | 1 (1.5%) |
| Infiltrate/Scar Location, N (%) | |||
| Central (0 to 4mm) | 198 (61.9%) | 98 (55.4%) | 35 (53.0%) |
| Mid-peripheral (4 to 8mm) | 174 (54.4%) | 94 (53.1%) | 34 (51.5%) |
| Peripheral (8 to 10mm) | 191 (59.7%) | 108 (61.0%) | 41 (62.1%) |
| Diffuse (entire cornea) | 9 (2.8%) | 14 (7.9%) | 2 (3.0%) |
| Not Applicable | 0 (0.0%) | 1 (0.6%) | 1 (1.5%) |
| Infiltrate Location Within 2mm of Limbus, N (%) | |||
| Yes | 50 (15.6%) | 46 (26.0%) | 16 (24.2%) |
| No | 270 (84.4%) | 131 (74.0%) | 50 (75.8%) |
| Hypopyon Present, N (%) | |||
| Yes | 129 (40.3%) | 54 (30.5%) | 28 (42.4%) |
| No | 191 (59.7%) | 123 (69.5%) | 38 (57.6%) |
| Impending Perforation, N (%) | |||
| Yes | 15 (4.7%) | 22 (12.4%) | 7 (10.6%) |
| No | 305 (95.3%) | 155 (87.6%) | 59 (89.4%) |
| Frank Perforation, N (%) | |||
| Yes | 15 (4.7%) | 28 (15.8%) | 8 (12.1%) |
| No | 305 (95.3%) | 149 (84.2%) | 58 (87.9%) |
| Therapeutic Keratoplasty Required, N (%) | |||
| Yes | 20 (6.3%) | 24 (13.6%) | 4 (6.1%) |
| No | 300 (93.8%) | 153 (86.4%) | 62 (93.9%) |
Notes: aFungal keratitis was microbiologically confirmed via KOH stain or Gram stain. bBacterial keratitis was microbiologically confirmed via Gram stain. cPolymicrobial infections were positive for at least 2 of the following: microbiologically confirmed fungal keratitis, microbiologically confirmed bacterial keratitis, and/or clinically diagnosed viral keratitis.
Abbreviation: SD, standard deviation.
Sociodemographic Risk Factors for Worse Presenting VA
Older age showed a modest association with poorer VA, where for each one-year increase in age, the prevalence of presenting VA ≤20/200 increased by 1%. Sociodemographic factors such as days to presentation and travel distance were not associated with poorer VA.
The population’s mean presentation time of 20.4 days highlights the challenge of healthcare access in rural India. Eyes with presenting VA <20/200 had greater time to presentation (22 days versus 16 days). Further, time to presentation ≥14 days had an 11% increased risk of presenting VA ≤20/200, though this was not significant in multivariable analysis. Barriers for delayed presentation in similar settings have included transportation costs, travel distance, lost wages, and lack of nearby eye care facilities.36,37 Future work should continue to explore and address sociodemographic barriers.
This study has certain limitations. SNC Hospital is a tertiary referral center, and patients in our study may represent more severe cases of keratitis, which may not be generalizable to other settings. Microbiologic confirmation with culture or PCR methods was not possible as it was not routinely performed at the site. As this was a retrospective study, it is subject to data reporting inconsistencies due to recall bias. Additionally, this analysis is focused on risk factors for presenting VA; we acknowledge that longer-term outcomes such as follow-up VA at one year, which are being collected, will be essential to thoroughly understand the risk factors associated with severe presentations of keratitis. Nonetheless, our findings highlight key anatomic and clinical features that are strongly associated with poor presenting VA in microbial keratitis.
Conclusion
In this large cross-sectional study of infectious keratitis patients presenting to a tertiary center in north India, specific anatomic features including large epithelial defect diameter, deep stromal infiltrates, central infections, and hypopyon were strongly associated with poor VA at presentation, even after accounting for several sociodemographic and clinical risk factors. In practice, structured evaluation of anatomic infection parameters can help grade keratitis severity, enable risk stratification to prioritize urgent need for therapy, and serve as clinically relevant therapeutic biomarkers for clinical trials.
Funding Statement
Funding support for this research was provided by KeraLink International and the National Eye Institute (K23EY032988, R21EY034343, R33EY034343).
Data Sharing Statement
The datasets generated and analyzed during the current study are not publicly available due to ongoing data collection and analysis but can be made available from the corresponding author on reasonable request.
Ethics Approval and Informed Consent
This study obtained ethics approval from the Johns Hopkins Institutional Review Board (ID: IRB00259376) and the SNC Hospital Research Ethics Committee (no associated ID, approved 5/2/2024). Participants gave informed consent before study entry. This study adheres to tenets of the Declaration of Helsinki.
Disclosure
The authors declare that they have no competing interests.
References
- 1.Ting DSJ, Ho CS, Deshmukh R, Said DG, Dua HS. Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye. 2021;35(4):1084–1101. doi: 10.1038/s41433-020-01339-3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Cabrera‐Aguas M, Khoo P, Watson SL. Infectious keratitis: a review. Clin Exp Ophthalmol. 2022;50(5):543–562. doi: 10.1111/ceo.14113 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Ung L, Chodosh J. Foundational concepts in the biology of bacterial keratitis. Exp Eye Res. 2021;209:108647. doi: 10.1016/j.exer.2021.108647 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Butler TKH, Spencer NA, Chan CCK, Singh Gilhotra J, McClellan K. Infective keratitis in older patients: a 4 year review, 1998–2002. Br J Ophthalmol. 2005;89(5):591–596. doi: 10.1136/bjo.2004.049072 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Khoo P, Cabrera-Aguas MP, Nguyen V, Lahra MM, Watson SL. Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation. Graefes Arch Clin Exp Ophthalmol. 2020;258(8):1745–1755. doi: 10.1007/s00417-020-04681-0 [DOI] [PubMed] [Google Scholar]
- 6.Tew TB, Chu HS, Hou YC, Chen WL, Wang IJ, Hu FR. Therapeutic penetrating keratoplasty for microbial keratitis in Taiwan from 2001 to 2014. J Formos Med Assoc. 2020;119(6):1061–1069. doi: 10.1016/j.jfma.2019.09.016 [DOI] [PubMed] [Google Scholar]
- 7.Ung L, Bispo PJM, Shanbhag SS, Gilmore MS, Chodosh J. The persistent dilemma of microbial keratitis: global burden, diagnosis, and antimicrobial resistance. Surv Ophthalmol. 2019;64(3):255–271. doi: 10.1016/j.survophthal.2018.12.003 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Ormerod LD. Causation and management of microbial keratitis in subtropical Africa. Ophthalmology. 1987;94(12):1662–1668. doi: 10.1016/s0161-6420(87)33235-x [DOI] [PubMed] [Google Scholar]
- 9.Jeng BH, Gritz DC, Kumar AB, et al. Epidemiology of ulcerative keratitis in Northern California. Arch Ophthalmol. 2010;128(8):1022–1028. doi: 10.1001/archophthalmol.2010.144 [DOI] [PubMed] [Google Scholar]
- 10.Gonzales CA, Srinivasan M, Whitcher JP, Smolin G. Incidence of corneal ulceration in Madurai district, South India. Ophthalmic Epidemiol. 1996;3(3):159–166. doi: 10.3109/09286589609080122 [DOI] [PubMed] [Google Scholar]
- 11.Stapleton F. The epidemiology of infectious keratitis. Ocular Surf. 2023;28:351–363. doi: 10.1016/j.jtos.2021.08.007 [DOI] [PubMed] [Google Scholar]
- 12.Khor WB, Prajna VN, Garg P, et al. The Asia cornea society infectious keratitis study: a prospective multicenter study of infectious keratitis in Asia. Am J Ophthalmol. 2018;195:161–170. doi: 10.1016/j.ajo.2018.07.040 [DOI] [PubMed] [Google Scholar]
- 13.Rautaraya B, Sharma S, Ali MH, Kar S, Das S, Sahu SK. A 3½-year study of bacterial keratitis from Odisha, India. Asia Pac J Ophthalmol. 2014;3(3):146–150. doi: 10.1097/APO.0b013e3182a3f301 [DOI] [PubMed] [Google Scholar]
- 14.Chidambaram JD, Venkatesh Prajna N, Srikanthi P, et al. Epidemiology, risk factors, and clinical outcomes in severe microbial keratitis in South India. Ophthalmic Epidemiol. 2018;25(4):297–305. doi: 10.1080/09286586.2018.1454964 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Titiyal JS, Negi S, Anand A, Tandon R, Sharma N, Vajpayee RB. Risk factors for perforation in microbial corneal ulcers in north India. Br J Ophthalmol. 2006;90(6):686–689. doi: 10.1136/bjo.2005.079533 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Arunga S, Kintoki GM, Mwesigye J, et al. Epidemiology of microbial keratitis in Uganda: a cohort study. Ophthalmic Epidemiol. 2020;27(2):121–131. doi: 10.1080/09286586.2019.1700533 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Prajna NV, Krishnan T, Mascarenhas J, et al. Predictors of outcome in fungal keratitis. Eye. 2012;26(9):1226–1231. doi: 10.1038/eye.2012.99 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Woodward MA, Vogt EL, Niziol LM, et al. Factors associated with vision outcomes in microbial keratitis – a multisite prospective cohort study. Ophthalmology. 2025;132:830–841. doi: 10.1016/j.ophtha.2025.02.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.US Preventive Services Task Force. Screening for impaired visual acuity in older adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2022;327(21):2123–2128. doi: 10.1001/jama.2022.7015 [DOI] [PubMed] [Google Scholar]
- 20.Przybek-Skrzypecka J, Ryk-Adamska M, Szewczuk A, et al. Severe microbial keratitis in virgin and transplanted cornea—probability of visual acuity improvement. J Clin Med. 2024;14(1):124. doi: 10.3390/jcm14010124 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Brown L, Leck AK, Gichangi M, Burton MJ, Denning DW. The global incidence and diagnosis of fungal keratitis. Lancet Infect Dis. 2021;21(3):e49–e57. doi: 10.1016/S1473-3099(20)30448-5 [DOI] [PubMed] [Google Scholar]
- 22.Srinivasan M, Mascarenhas J, Rajaraman R, et al. Corticosteroids for bacterial keratitis: the Steroids for Corneal Ulcers Trial (SCUT). Archives of Ophthalmology. 2012;130(2):143–150. doi: 10.1001/archophthalmol.2011.315 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Xu LJ, Song XS, Zhao J, Sun SY, Xie LX. Hypopyon in patients with fungal keratitis. Chin Med J. 2012;125(3):470–475. [PubMed] [Google Scholar]
- 24.Chaudhary S, Kate A, Bagga B, Mohamed A, Sharma S. Predictive factors for resolution of dematiaceous fungal keratitis. Cornea. 2022;41(6):709–713. doi: 10.1097/ICO.0000000000002825 [DOI] [PubMed] [Google Scholar]
- 25.Prajna NV, Krishnan T, Rajaraman R, et al. Predictors of corneal perforation or need for therapeutic keratoplasty in severe Fungal Keratitis: a secondary analysis of the mycotic ulcer treatment trial II. JAMA Ophthalmol. 2017;135(9):987–991. doi: 10.1001/jamaophthalmol.2017.2914 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Agarwal S, Srinivasan B, Iyer G, et al. Depth, size of infiltrate, and the microbe - The trio that prognosticates the outcome of infective keratitis. Indian J Ophthalmol. 2024;72(1):44–50. doi: 10.4103/IJO.IJO_1022_23 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Di Zazzo A, Rajan M, Dureja R, et al. Pediatric microbial keratitis: identification of clinical biomarkers for prognosis and outcome of 218 cases from 2009 to 2019. Cornea. 2022;41(9):1103–1109. doi: 10.1097/ICO.0000000000002957 [DOI] [PubMed] [Google Scholar]
- 28.Menda SA, Das M, Panigrahi A, et al. Association of postfungal keratitis corneal scar features with visual acuity. JAMA Ophthalmol. 2019;138(2):113. doi: 10.1001/jamaophthalmol.2019.4852 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Ting DSJ, Cairns J, Gopal BP, et al. Risk factors, clinical outcomes, and prognostic factors of bacterial keratitis: the Nottingham Infectious Keratitis Study. Front Med Lausanne. 2021;8:715118. doi: 10.3389/fmed.2021.715118 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Prajna NV, Lalitha P, Rajaraman R, et al. Changing azole resistance: a secondary analysis of the MUTT I randomized clinical trial. JAMA Ophthalmol. 2016;134(6):693–696. doi: 10.1001/jamaophthalmol.2016.0530 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Abdelghany AA, Alio JL, AttaAllah HR. Role of anterior segment optical coherence tomography in staging and evaluation of treatment response in infectious keratitis. Cornea. 2024;43(10):1216. doi: 10.1097/ICO.0000000000003466 [DOI] [PubMed] [Google Scholar]
- 32.Konstantopoulos A, Yadegarfar G, Fievez M, Anderson DF, Hossain P. In vivo quantification of bacterial keratitis with optical coherence tomography. Invest Ophthalmol Visual Sci. 2011;52(2):1093–1097. doi: 10.1167/iovs.10-6067 [DOI] [PubMed] [Google Scholar]
- 33.Prajna NV, Srinivasan M, Mascarenhas J, et al. Visual impairment in fungal versus bacterial corneal ulcers 4 years after successful antimicrobial treatment. Am J Ophthalmol. 2019;204:124–129. doi: 10.1016/j.ajo.2019.03.010 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology. 2017;124(11):1678–1689. doi: 10.1016/j.ophtha.2017.05.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Hsu HY, Ernst B, Schmidt EJ, Parihar R, Horwood C, Edelstein SL. Laboratory results, epidemiological features, and outcome analyses of microbial keratitis: a 15-year review from Saint Louis. Am J Ophthalmol. 2018;198:54. doi: 10.1016/j.ajo.2018.09.032 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Sengo DB, Marraca NA, Muaprato AM, García-Sanjuan S, Caballero P, López-Izquierdo I. Barriers to accessing Eye Health Services in Suburban Communities in Nampula, Mozambique. Int J Environ Res Public Health. 2022;19(7):3916. doi: 10.3390/ijerph19073916 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Kovai V, Krishnaiah S, Shamanna BR, Thomas R, Rao GN. Barriers to accessing eye care services among visually impaired populations in rural Andhra Pradesh, South India. Indian J Ophthalmol. 2007;55(5):365–371. doi: 10.4103/0301-4738.33823 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed during the current study are not publicly available due to ongoing data collection and analysis but can be made available from the corresponding author on reasonable request.