Diagnostic approach
Clinical management depends on the etiology and the aggravating factors. The diagnosis must first distinguish infectious from non-infectious causes.
History
- History of the illness: duration of symptoms, pain often absent in neurotrophic forms, discharge.
- Ocular history: surgery (refractive, cataract, graft, retinal detachment), epithelial/stromal dystrophies, recurrent erosions, herpes, endothelial dystrophy (ulcer over a bulla).
- General history: diabetes, Sjögren syndrome and connective-tissue diseases, immunosuppression, malnutrition, alcoholism, trigeminal involvement (surgery, tumor, radiotherapy).
- Trauma: foreign body, chemical or vegetal agent. Contact lenses: type, overnight wear, hygiene and compliance.
- Medications: self-administered anesthetics, NSAIDs, corticosteroids, aminoglycosides, antivirals, preserved eye drops. Late corneal perforation after photorefractive keratectomy under topical NSAID (diclofenac) illustrates the iatrogenic risk [5].
Clinical examination
- General state: rosacea, skin lesions in the V territory, neurological disorders.
- Eyelids & adnexa: static and dynamic lid position, lagophthalmos, quality and frequency of blinking, trichiasis, entropion, floppy eyelid, blepharitis/meibomitis, examination of the tarsal conjunctiva.
- Corneal sensation to be tested before any instillation and before tonometry (cotton-wisp test; Cochet-Bonnet esthesiometer).
- Tear film: Schirmer test, break-up time (BUT), superficial punctate keratitis, filaments.
- Slit lamp — the ulcer: size, shape, location, appearance of the edges, microcysts (examine both eyes).
- Stroma: thinning (pachymetry / OCT); endothelium: precipitates, guttata; anterior chamber: flare, hypopyon.
Anterior-segment OCT quantifies stromal thinning and defect depth over time (screening for a descemetocele). In vivo confocal microscopy assesses sub-basal nerve density — useful for the diagnosis and follow-up of neurotrophic keratitis — and looks for Acanthamoeba cysts or fungal filaments.
Given the morbidity of infectious ulcers, a corneal scraping for direct examination, cultures and PCR (HSV/adenovirus/Acanthamoeba as appropriate) is performed at the slightest doubt. When smears are negative but the picture is suggestive, a corneal biopsy may unmask an infection partly treated by empiric therapy. A systemic inflammatory work-up is requested only when the context is suggestive.
Etiologies & Mackie staging
The etiology of the sterile ulcer is frequently multifactorial: identifying all contributing factors is decisive.
| Category | Orienting features |
|---|---|
| Infectious (to exclude first) | Bacterial (focal infiltrate, purulent discharge); fungal (vegetal trauma, satellite lesions); Acanthamoeba (contact lenses, intense pain, ring ulcer); herpes simplex (dendrites, hypoesthesia); herpes zoster (dermatome, pseudodendrites). |
| Neurotrophic | Corneal hypo-/anesthesia: post-herpetic (HSV, VZV), trigeminal involvement (surgery/tumor, neuroma, radiotherapy), diabetes, refractive surgery, topical anesthetic abuse. Ulcer with raised edges, oval, often inferior, painless. |
| Severe dry eye | Sjögren syndrome, GVHD, filaments; aseptic central keratolysis. To be sought in the fellow eye. |
| Exposure | Lagophthalmos, facial palsy, exophthalmos, lid malocclusion. |
| Mechanical | Entropion, trichiasis, distichiasis, tarsal foreign body, contact keratopathy. |
| Iatrogenic | Anesthetics, topical NSAIDs, aminoglycosides, antivirals, prolonged corticosteroids, preservatives (benzalkonium chloride), mitomycin C, radiotherapy. |
| Peripheral immunological | Mooren ulcer, pseudo-Mooren, peripheral ulcerative keratitis of connective-tissue disease (rheumatoid arthritis, granulomatosis with polyangiitis), ocular rosacea. |
| Pre-existing corneal abnormality | Basement-membrane dystrophies, recurrent erosions, limbal deficiency (aniridia, burn), bullae on endothelial decompensation. |
| Nutritional | Vitamin A deficiency (deprivation, malabsorption: celiac disease, cystic fibrosis, cholestasis, bariatric surgery). |
| Factitious | Psychological/psychiatric disorder, to consider in an atypical, treatment-resistant picture. |
Stage I — epithelial involvement: superficial punctate keratitis, irregularity, epithelial edema, superficial neovascularization, without loss of substance. Stage II — persistent epithelial defect with smooth, raised edges, with stromal reaction, without deep ulceration. Stage III — stromal ulcer with melting, risk of descemetocele and perforation. This classification guides therapeutic escalation and remains the reference [13].