Abstract
This cases series estimates fungal keratitis prevalence among US patients with commercial insurance.
Keratitis may result from infectious or noninfectious causes and result in vision loss. In the US, nearly 1 million keratitis-related health care visits occur annually. Approximately 6% of suspected infectious keratitis cases in the US are caused by fungi, and fungal keratitis risk factors (eg, contact lens use, ocular trauma, topical corticosteroids) are well described; however, national prevalence data are scarce. We estimated fungal keratitis prevalence among commercially insured US patients.
Methods
In this case series, we used Merative MarketScan Commercial and Medicare Databases claims data submitted by health plans and large employers for more than 66 million people during January 1, 2016, through January 31, 2023. This study was reviewed by the Centers for Disease Control and Prevention (CDC) and conducted consistent with applicable federal law and CDC policy. MarketScan data are fully deidentified, so this analysis was not subject to review by the CDC institutional review board. The study followed the Appropriate Use and Reporting of Uncontrolled Case Series in the Medical Literature guideline.
Fungal keratitis was defined by ICD-10-CM code H16 for keratitis, continuous health insurance enrollment in the 14 days before and after the code, and a natamycin prescription in the continuous enrollment period. We also examined selected medications, diagnoses, and procedures among a subgroup of patients continuously enrolled 90 days before and after their first keratitis code (eTable in Supplement 1). Data were analyzed using SAS, version 9.4 statistical software (SAS Institute Inc).
Results
Among 918 949 patients with a keratitis ICD-10-CM code, 870 810 (94.8%) met 14-day continuous enrollment criteria; of those, 692 (0.8%) had a natamycin prescription (362 males [52.3%], 330 females [47.7%]; mean [SD] age, 47.5 [16.2] years). Fungal keratitis prevalence overall was 1.8 per 100 000 enrollees (Table 1). Prevalence per 100 000 enrollees was higher among males (1.9), adults 65 years or older (6.6), and patients living in the South (2.7) and rural areas (3.6). Among 184 enrollees (26.6%) with industry data, rates were highest among the oil and gas extraction, mining (2.9) and manufacturing, durable goods (2.3) industries.
Table 1. Demographic Features and Prevalence of Fungal Keratitis in Commercially Insured US Patientsa,b.
| Characteristic | No. of enrollees (%) | Prevalence per 100 000 enrolleesc |
|---|---|---|
| Total | 692 | 1.8 |
| Sex | ||
| Male | 362 (52.3) | 1.9 |
| Female | 330 (47.7) | 1.6 |
| Age group, y | ||
| <18 | 27 (3.9) | 0.3 |
| 18-44 | 238 (34.4) | 1.3 |
| 45-64 | 356 (51.4) | 3.4 |
| ≥65 | 71 (10.3) | 6.6 |
| Age, mean (SD), y | 47.5 (16.2) | NA |
| US census region of primary beneficiary’s residence | ||
| Northeast | 47 (6.8) | 0.7 |
| Midwest | 107 (15.5) | 1.4 |
| South | 484 (69.9) | 2.7 |
| West | 52 (7.5) | 0.7 |
| Unknown | 2 (0.3) | 1.3 |
| Urban or rural classification | ||
| Nonrural | 540 (78.0) | 1.5 |
| Rural | 150 (21.7) | 3.6 |
| Unknown | 2 (0.3) | 1.9 |
| Industryd (n = 184) | ||
| Oil and gas extraction, mining | 5 (2.7) | 2.9 |
| Manufacturing, durable goods | 59 (32.1) | 2.3 |
| Manufacturing, nondurable goods | 11 (6.0) | 1.1 |
| Transportation, communications, utilities | 40 (21.7) | 2.2 |
| Retail trade | 3 (1.6) | 0.5 |
| Finance, insurance, real estate | 22 (12.0) | 1.3 |
| Services | 43 (23.4) | 1.5 |
| Other industrye | 1 (0.5) | 0.7 |
Abbreviation: NA, not applicable.
International Classification of Diseases, Tenth Revision, Clinical Modification code H16 plus a prescription for natamycin in the 14 days before to 14 days after the H16 code. Natamycin prescriptions occurred a median of 3 days (range, −13 to 14 days) after the first H16 code.
Employees and dependents covered by employer-sponsored health insurance plans and retirees with employer-sponsored Medicare supplemental or Medicare Advantage plans.
Total denominator is 39 522 893 patients with any health care visit and continuous insurance enrollment in the 14 days before and 14 days after their first health care visit.
Among enrollees with data submitted to MarketScan by employers.
Other industry comprises agriculture, forestry, and fishing; construction; and wholesale, which were uncommonly represented in the dataset.
Common conditions and medications included corneal ulcer (552 [94.2%]), ophthalmic antibiotic (473 [80.7%]) or corticosteroid (255 [43.5%]), and eye and orbital injury (205 [35.0%]) (Table 2). In total, 88 (15.0%) had contact lens-associated ICD-10-CM codes, 439 (74.9%) underwent diagnostic testing, and 62 (10.6%) received a corneal transplant.
Table 2. Conditions, Procedures, and Diagnostic Tests Among 586 US Patients With Fungal Keratitis.
| Patients, No. (%) | |||
|---|---|---|---|
| On the day of keratitis diagnosis or in the 90 d before | In the 90 d after keratitis diagnosis | In the 90 d before to 90 d after keratitis diagnosis | |
| Condition or medication | |||
| Corneal ulcer | 510 (87.0) | 535 (91.3) | 552 (94.2) |
| Injury of eye and orbit | 183 (31.2) | 60 (10.2) | 205 (35.0) |
| Diabetes mellitus | 58 (9.9) | 59 (10.1) | 69 (11.8) |
| Systemic corticosteroid usea | 48 (8.2) | 133 (22.7) | 159 (27.1) |
| Glaucoma | 38 (6.5) | 49 (8.4) | 64 (10.9) |
| Corneal disorder due to contact lens | 25 (4.3) | 16 (2.7) | 37 (6.3) |
| Contact lens use | 32 (5.5) | 22 (3.8) | 51 (8.7) |
| Mycotic corneal ulcer | 14 (2.4) | 77 (13.1) | 81 (13.8) |
| Blindness or low vision | 9 (1.5) | 9 (1.5) | 16 (2.7) |
| Ophthalmic corticosteroid useb | 99 (16.9) | 204 (34.8) | 255 (43.5) |
| Ophthalmic antibioticc | 370 (63.1) | 295 (50.3) | 473 (80.7) |
| Endophthalmitis | 16 (2.7) | 26 (4.4) | 34 (5.8) |
| Perforated corneal ulcer | 2 (0.3) | 28 (4.8) | 29 (4.9) |
| Procedure | |||
| Corneal transplant | 10 (1.7) | 59 (10.1) | 62 (10.6) |
| Eye injection | 11 (1.9) | 26 (4.4) | 28 (4.8) |
| Eye surgery | 15 (2.6) | 39 (6.7) | 45 (7.7) |
| Evisceration | 0 (0.0) | 5 (0.9) | 5 (0.9) |
| Enucleation | 0 (0.0) | 2 (0.3) | 2 (0.3) |
| Diagnostic test | 242 (41.3) | 292 (49.8) | 439 (74.9) |
| Fungal culture | 152 (25.9) | 193 (32.9) | 303 (51.7) |
| Bacterial culture | 198 (33.8) | 250 (42.7) | 378 (64.5) |
| Biopsy or scraping of cornea | 146 (24.9) | 168 (28.7) | 290 (49.5) |
| Microscopy | 56 (9.6) | 83 (14.2) | 128 (21.8) |
| Susceptibility testing | 38 (6.5) | 38 (6.5) | 70 (11.9) |
| Polymerase chain reaction | 12 (2.0) | 19 (3.2) | 29 (0.0) |
A supply of prednisone, prednisolone, or methylprednisolone for 21 days or longer.
Dexamethasone, difluprednate, loteprednol, fluocinolone, fluorometholone, fluorometholone, prednisolone, or rimexolone.
Moxifloxacin, gatifloxacin, ciprofloxacin, besifloxacin, gentamicin, or tobramycin.
Discussion
We estimated that fungal keratitis prevalence may be twice as high in rural vs nonrural areas. In rural areas, disparities in access to eye care (obtaining appointments, transportation) may delay diagnosis and treatment. Fungal keratitis was more common in the South, similar to data showing that fungi accounted for more microbial keratitis cases in 2 southern cities vs other areas and consistent with the known association with tropical and subtropical climates. In low-income countries, outdoor occupation may be a risk factor for fungal keratitis. Our results support potential associations with certain industries (which may involve outdoor occupations) and with eye injuries in more than one-third of patients. The high proportion of patients prescribed ophthalmic antibiotics suggests empirical treatment for suspected bacterial keratitis before laboratory results became available. That more than 40% of patients were prescribed ophthalmic corticosteroids, which can worsen fungal keratitis, is concerning.
Industry data were only available for patients with employer-submitted data and were limited by small sample sizes, and the datasets did not contain information about occupation, race and ethnicity, laboratory results, and ophthalmic voriconazole (used for fungal keratitis treatment but not commercially available) or other compounded antifungals. Medical claims data are subject to misclassification, and diagnostic testing was not performed for all cases; thus, this analysis may underestimate contact lens use because lens fittings may be billed to vision insurance. Given the potential for poor vision outcomes and the possibility of climate change–associated geographic expansion of pathogenic fungi, monitoring fungal keratitis trends, improving rural eye care access, and promoting early diagnosis and treatment are crucial.
eTable. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) and Current Procedural Terminology (CPT) Codes Used to Identify Features of Interest
Data Sharing Statement
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Associated Data
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Supplementary Materials
eTable. International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) and Current Procedural Terminology (CPT) Codes Used to Identify Features of Interest
Data Sharing Statement