Corneal Ulcer (Ulcerative Keratitis)

Definition & Pathophysiology

• Trauma or corneal abrasion becoming secondarily infected
• Contact lens wear (especially extended-wear/overnight)
• Desiccation from incomplete lid closure (e.g., Bell's palsy → exposure keratitis)
• Immunosuppression (topical/systemic steroids, systemic immunosuppressants)

Etiology / Causative Organisms

• Pseudomonas → contact lens wearers
• Fungal → corticosteroid drop users, agricultural workers (vegetation/soil inoculation)
• HSV → most common cause requiring corneal transplant in the USA
• Acanthamoeba → contact lens wearers swimming or using tap water

Clinical Features

• Ocular pain / foreign body sensation
• Photophobia (often consensual — ciliary spasm from associated iritis)
• Redness, tearing, mucopurulent discharge
• Blurred or decreased vision (if ulcer is in the visual axis, or if uveitis is present)

• Eyelid/conjunctival erythema, mucopurulent discharge
• Corneal ulcer: round or irregular white/hazy base with heaped-up edges and stromal infiltration due to WBC infiltration
• Associated iritis: miotic pupil, ciliary flush
• Slit-lamp: flare and cells in anterior chamber
• Hypopyon (layering of inflammatory cells in the inferior anterior chamber) — indicates severe inflammation/infection

Clinical Images

Diagnosis

• Clinical — slit-lamp examination is the cornerstone
• Fluorescein staining — ulcer has "heaped-up" edges (vs. flat abrasion), with stromal edema/whitening
• Corneal scraping — should be performed in most cases; sent for:
  • Gram stain (bacteria, fungi)
  • Giemsa stain (bacteria, Acanthamoeba)
  • Calcofluor white (Acanthamoeba, fungi — requires fluorescent microscope)
  • Acid-fast stain (Mycobacteria, Nocardia)
  • Culture & sensitivity

TIP: The causative organism cannot be reliably determined from the morphological appearance of the ulcer alone. Empirical broad-spectrum treatment is started before culture results return.

Management

General Measures

• Discontinue contact lens wear immediately (mandatory)
• Protective eye shield if significant corneal thinning or perforation risk
• Emergent ophthalmology consultation — corneal ulcers can rapidly progress to permanent vision loss
• Consider hospital admission for: aggressive disease, an only eye, poor compliance

Antibiotic Treatment

• Fluoroquinolone monotherapy — ciprofloxacin or ofloxacin 1 drop every hour day and night for 24–48 h, then tapered
• Alternatively: moxifloxacin or gatifloxacin (newer-generation; better Gram-positive coverage, superior penetration)
• Duotherapy (aggressive disease or suspected streptococci): fortified cephalosporin + fortified aminoglycoside (e.g., cefuroxime 5% + gentamicin 1.5%)

TIP: Fluoroquinolones have limited activity against Gram-positive organisms, particularly Streptococcus. Ciprofloxacin drops can cause white corneal precipitates that may delay re-epithelialization.

Antifungal Treatment

• Natamycin (first-line for filamentous fungi)
• Amphotericin B or fluconazole (Candida/yeasts)
• Topical steroids are contraindicated when fungal infection is suspected

Antiviral Treatment

• HSV keratitis: Topical ganciclovir 0.15% gel (3–5×/day) or trifluridine 1% (5–9×/day × 14 days); systemic acyclovir/valacyclovir for severe or refractory cases. Avoid topical steroids (worsen HSV infection)
• HZV keratitis: Systemic therapy is standard — acyclovir 800 mg 5×/day, or valacyclovir 1000 mg 3×/day × 7–10 days. Treat within 72 hours of rash onset to reduce acute pain and ocular complications

Adjunctive

• Cycloplegics (cyclopentolate 1%, homatropine 2%, atropine 1%) — prevent posterior synechiae, reduce ciliary spasm pain
• Systemic antibiotics indicated for: N. meningitidis (life-saving — IM benzylpenicillin/ceftriaxone), N. gonorrhoeae (ceftriaxone), H. influenzae (amoxicillin-clavulanate), threatened corneal perforation (ciprofloxacin + doxycycline for anti-collagenase effect)
• Steroids (topical): controversial; reduce scarring but promote fungal/mycobacterial/HSV replication; use only after infection is controlled under specialist supervision

Complications

• Corneal perforation — may require bandage contact lens, tissue glue, or penetrating keratoplasty/patch graft
• Endophthalmitis
• Corneal scarring → permanent visual impairment
• Treatment failure — if no improvement in 24–48 h, review cultures; if still failing after a further 48 h, suspend treatment and re-scrape on broader media; consider corneal biopsy
• Consider PACK-CXL (photoactivated chromophore-enhanced collagen cross-linking) if corneal melting or antibiotic resistance is suspected

Disposition

Recent Evidence

Part 1: Gradual Loss of Vision

Differential Diagnosis by Pattern

Causes of Progressive Visual Loss (Neurology perspective)

• Glaucoma: Arcuate visual field defects; central vision spared until late; bilateral/symmetric; ↑IOP and optic disc cupping
• Chronic papilledema: Nasal defects first → progressive constriction; central vision late
• Toxic optic neuropathy: Gradual onset over weeks–months; cecocentral scotomas; prominent dyschromatopsia; optic atrophy develops late. Common culprits: ethambutol, amiodarone, linezolid
• Retinal toxins: Vigabatrin, chloroquine/hydroxychloroquine, phenothiazines, digitalis → painless progressive binocular loss

Part 2: Hyphema

Definition

Classification

Clinical Images

Etiology

Traumatic (most common)

• Blunt or penetrating trauma → rupture of iris root vessel
• Maximal visual compromise is usually at the time of injury; decreasing vision over time suggests rebleed or continued bleeding (causing IOP rise)

Spontaneous / Non-traumatic

• Iris neovascularization (rubeosis iridis) from: diabetes, central retinal vein occlusion, ocular ischemic syndrome, chronic uveitis
• Blood dyscrasias / coagulopathies
• Anticoagulant use (aspirin, warfarin, clopidogrel, NSAIDs, ethanol)
• Iris–IOL chafing (post-cataract surgery)
• Herpetic keratouveitis
• Neoplasms: iris/ciliary body melanoma, retinoblastoma, leukemia, juvenile xanthogranuloma
• Fuchs heterochromic iridocyclitis
• Post-surgical (usually self-limited)

Symptoms

• Pain, blurred vision
• History of trauma (or spontaneous — as above)
• Transient vision clouding with microhyphema (intermittent bleeds)

Workup

1. History: Mechanism/force/direction of injury; anticoagulant use; personal/family history of sickle cell disease or trait (critical — alters management); coagulopathy symptoms
2. Ocular exam: First rule out ruptured globe. Measure IOP. Document extent of hyphema (height in mm). Dilated fundus exam (no scleral depression). B-scan ultrasound if fundus view poor
3. CT orbits/brain (axial, coronal, parasagittal, 1-mm cuts) if: suspected orbital fracture, IOFB, or loss of consciousness
4. Sickledex screen (hemoglobin electrophoresis if necessary) — screen all appropriate patients
5. Spontaneous hyphema additional workup: PT/INR, PTT, CBC + platelets, bleeding time, proteins C and S; UBM (evaluate IOL haptic position, ciliary body masses); fluorescein angiogram of iris; gonioscopy (to evaluate angle neovascularization or masses)

Complications

Treatment

Activity & Environment

• Bed rest with bathroom privileges OR limited activity; elevate head of bed to 45° (blood settles inferiorly, clears trabecular meshwork, reduces IOP)
• Rigid eye shield at all times — do NOT patch (prevents recognition of sudden vision change from rebleed)
• Consider hospitalization for: noncompliant patients, bleeding diathesis, sickle cell disease/trait, severe associated ocular injuries, children at risk for amblyopia, suspected child abuse

Medications

IOP Management

1. Beta-blocker (timolol or levobunolol 0.5% b.i.d.)
2. Add alpha-agonist (brimonidine 0.1–0.2% or apraclonidine 0.5% t.i.d.) or topical CAI (dorzolamide 2% or brinzolamide 1% t.i.d.) — avoid prostaglandin analogues and miotics (increase inflammation)
3. If topical fails: acetazolamide up to 500 mg p.o. q12h (adults) or mannitol 1–2 g/kg IV over 45 min

• Beta-blocker first
• Extreme caution with all other agents: dorzolamide/brinzolamide may ↓ aqueous pH → increased sickling; alpha-agonists affect iris vasculature; avoid systemic diuretics (induce acidosis/dehydration → increased sickling)
• AC paracentesis as temporizing measure if medical management fails

Surgical Evacuation — Indications

• Corneal stromal blood staining (especially children)
• Significant visual deterioration
• Hyphema not decreasing to ≤50% by 8 days (prevents PAS)
• IOP ≥60 mmHg for ≥48 h despite maximal medical therapy (prevents optic atrophy)
• IOP ≥25 mmHg with total hyphema for ≥5 days (prevents corneal staining)
• Sickle cell: IOP ≥24 mmHg for ≥24 h, or any transient IOP ≥30 mmHg
• Children at risk for amblyopia

Follow-Up

• Daily after initial trauma: check VA, IOP, slit lamp (look for new bleeding, corneal staining, PAS, iridodialysis, lens subluxation, cataract as blood clears)
• Return immediately for sudden ↑ pain or ↓ vision (rebleed or IOP spike)
• After initial period: transition to long-acting cycloplegic (atropine 1%); taper steroids as blood/fibrin/WBCs resolve
• Protective glasses recommended after recovery

Key Clinical Points

A hyphema laying out posteriorly when the patient is supine may only become visible when sitting upright.

Rebleeding is the most feared early complication — occurs in up to 30% of cases, typically 3–5 days post-trauma, and can cause severe IOP elevation requiring surgical washout.

Sickle cell patients need a lower IOP threshold for intervention (≥24 mmHg vs. ≥30 mmHg) and require careful agent selection due to sickling risk.

Clinical Diagnosis: JIA-Associated Chronic Anterior Uveitis

The Clinical Picture

The uveitis of JIA is particularly dangerous because it is invariably asymptomatic and must generally be detected by screening with slit-lamp examination. Even during acute exacerbations with +4 aqueous cells, it is rare for patients to complain. — Kanski's Clinical Ophthalmology, p. 460

JIA: Classification (ILAR)

• Uveitis prevalence in persistent oligoarticular JIA: 16%; in extended oligoarticular: 25%
• ANA-positive in 60–70% of oligoarticular JIA → strong independent risk factor for uveitis

Ocular Findings in JIA-Associated Uveitis

Clinical Images

Slit-Lamp Findings (What the Ophthalmologist Should Look For)

Injection is usually absent even in the presence of severe uveitis. Both eyes are affected in 70% with symmetrical severity. — Kanski's Clinical Ophthalmology, p. 461

Why the Irregular Pupil?

Investigations

Ophthalmic

• Slit-lamp examination — mandatory; only way to detect and grade activity
• Measure IOP (glaucoma screening)
• Dilated fundus exam (CME, posterior involvement)

Systemic / Laboratory

Risk Stratification for Uveitis

1. Oligoarticular subtype
2. Female sex
3. ANA-positive
4. Age of onset < 7 years
5. Duration of arthritis < 4 years (uveitis most commonly develops early)

Arthritis usually antedates the diagnosis of uveitis. The irregular pupil in this child means uveitis has already been silently active long enough to form synechiae.

Ophthalmology Screening Protocol

Visual symptoms or suspicion of ocular signs (synechiae, cataract, band keratopathy) should lead to urgent ophthalmological referral and slit-lamp examination within a week.

Treatment

Ocular Management (Step-Up)

Complication-Specific Management

• Secondary glaucoma: Topical IOP-lowering agents; if refractory → trabeculectomy with mitomycin C (better outcomes with systemic anti-TNF) or Baerveldt implant
• Cataract: Surgical extraction with IOL implantation (now favoured over aphakia); outcomes generally good with controlled inflammation
• Band keratopathy: EDTA chelation
• CME: Periocular steroid injection; systemic immunosuppression
• Amblyopia: Patching therapy; optical correction

Key Points for This Patient

1. The irregular pupil = posterior synechiae — uveitis has been active and undetected
2. Slit-lamp exam urgently to grade activity, document complications, measure IOP
3. ANA test — if positive, confirms highest-risk profile
4. Refer to paediatric rheumatologist for systemic JIA management
5. Bilateral slit-lamp screening even though only one eye visibly affected — 70% of JIA uveitis is bilateral
6. Start topical steroids + cycloplegic; escalate to MTX ± adalimumab early if needed
7. Screen for amblyopia — she is still within the amblyogenic age window

Recent Evidence

• PMID 41314670 (2025 Systematic Review, RMD Open): Long-term outcomes of JIA-associated uveitis — confirms visual morbidity risk and importance of early immunomodulation
• PMID 41945858 (2026 Meta-analysis, Ocular Immunol Inflamm): Adalimumab + methotrexate combination is effective and safe for JIA-associated uveitis — supports early biologic use
• PMID 41728909 (2026 Practice Guideline, PANLAR): Recommendations for oligoarticular JIA treatment including uveitis screening

Clinical Analysis: Asymmetric Cup-Disc Ratio in a Diabetic Patient

Interpretation of the Clinical Image

• A large, pale, deeply excavated optic cup occupying the majority of the disc
• Markedly thinned neuroretinal rim (NRR), particularly inferiorly and superiorly
• Bayoneting of vessels as they exit the disc
• The cup appears to fill approximately 0.7 of the disc diameter — consistent with the reported CDR of 0.7
• No haemorrhages or diabetic changes

Q1: Significance of the Optic Disc Findings

Cup-to-Disc Ratio (CDR)

• The CDR measures the diameter of the central pale cup relative to the total disc diameter (vertical ratio is standard)
• Normal CDR: generally ≤0.5; only 2% of the population have a CDR >0.7
• The vertical CDR is more sensitive — inferior and superior NRR are lost earliest in glaucoma

This Patient's Findings

A vertical cup/disc ratio asymmetry of 0.2 or more is found in about 5% of normal individuals and in about 25% of those with glaucoma. — Kanski's Clinical Ophthalmology, p. 367

ISNT Rule (Normal NRR)

• Violation of this rule (especially inferior notching) is a key indicator of glaucomatous damage
• In this patient's left eye, inferior > superior NRR loss is the likely pattern

Q2: Provisional Diagnosis

Primary Open-Angle Glaucoma (POAG)

• Retinal nerve fibre layer (RNFL) thinning
• Glaucomatous optic nerve damage (as seen)
• Characteristic visual field loss (as damage progresses)
• Open anterior chamber angle
• Absence of secondary glaucoma or non-glaucomatous cause

Why this patient fits POAG:

• Age 65 — prevalence of POAG is ~6% in White, ~16% in Black populations >70 years
• Diabetes — associated with glaucoma risk (though longitudinal studies are mixed, clinic-based studies show higher prevalence)
• Asymptomatic — POAG is typically silent until late
• Asymmetric CDR with LE > RE — unilateral/asymmetric progression is characteristic
• CDR 0.7 LE — enlarged cup with thinned rim
• No diabetic retinopathy — rules out diabetic optic disc change (rare) as confounding cause

POAG is the most prevalent type of glaucoma in people of European and African ethnic origin. It is a chronic, progressive optic neuropathy. IOP is a key modifiable risk factor. — Kanski's Clinical Ophthalmology, p. 363

Q3: Risk Factors in This Patient

Q4: Essential Investigations

1. Applanation Tonometry (IOP measurement)

• Goldmann applanation tonometry — gold standard
• Normal range: 10–21 mmHg; however, nearly half of POAG patients have IOP ≤21 mmHg at any screening
• Intraocular pressure >21 mmHg on more than one occasion, or a circadian variation of more than 5 mmHg is significant
• Inter-eye asymmetry >5 mmHg is suspicious even within normal range
• Must be measured at different times of day (diurnal variation)

2. Visual Field Testing (Perimetry)

• Humphrey automated visual field (24-2 or 30-2 strategy) — essential
• Characteristic patterns:
  • Nasal step (earliest)
  • Paracentral scotoma
  • Arcuate scotoma (Bjerrum scotoma) — extends from blind spot superiorly or inferiorly
  • Altitudinal defect
  • Central vision spared until late in the disease

3. Gonioscopy

• To confirm open anterior chamber angle (excludes angle closure)
• Assess trabecular meshwork pigmentation
• Rule out secondary causes: peripheral anterior synechiae, pseudoexfoliation, pigment dispersion

4. Slit-Lamp Examination

• Exclude secondary glaucoma features: pseudoexfoliation material, pigment dispersion, rubeosis iridis, anterior uveitis
• Assess cornea for microcystic oedema (differentiates from PACG)

5. Central Corneal Thickness (CCT)

• Average CCT: 535–545 μm
• Thin cornea (<520 μm) → underestimates true IOP (applanation tonometry reads falsely low)
• Thin CCT is an independent risk factor for POAG development
• Essential for interpreting IOP values accurately

6. Optic Disc Documentation & Imaging

• OCT (Optical Coherence Tomography) — of the:
  • RNFL (peripapillary) — detects thinning before visual field loss
  • Ganglion cell complex (GCC) at macula — early detection
  • Optic nerve head morphology
• Stereoscopic disc photographs (baseline documentation)
• Sensitivity and specificity up to 90% compared to normative database

7. Nerve Fibre Layer Analysis

• Detects RNFL defects (inferior > superior, corresponding to superior > inferior VF loss)
• Progression analysis: widening or deepening of established defects confirms active disease

All patients with suspected glaucoma should have: complete ocular exam including visual acuity, pupillary assessment for RAPD, confrontational visual fields, slit lamp, applanation tonometry, gonioscopy, and dilated fundus examination with special attention to the optic nerve. — Wills Eye Manual, p. 552

Q5: Management

Treatment Goal

Step-Up Medical Treatment

Treatment is often started by using one type of drop in one eye (monocular therapeutic trial) with reexamination in 1–6 weeks to check for efficacy. — Wills Eye Manual, p. 555

Laser Treatment

• Selective Laser Trabeculoplasty (SLT) — first-line alternative or adjunct; IOP-lowering equivalent to argon laser; repeatable; particularly suitable for poor compliance or medication side effects
• Argon Laser Trabeculoplasty (ALT) — initial success 70–80%, declining to 50% at 2–5 years

Surgical Treatment

• Trabeculectomy (guarded filtration surgery) — with or without mitomycin C
• Tube-shunt surgery (e.g., Ahmed, Baerveldt)
• MIGS (minimally invasive glaucoma surgery) — for mild-to-moderate glaucoma: trabecular micro-bypass devices, canaloplasty, subconjunctival microstents, trabectome, endocyclophotocoagulation (ECP)
• Laser cyclophotocoagulation (diode laser) — for refractory or end-stage disease
• Cyclocryotherapy — for very advanced cases

Summary of This Case

Corneal Ulcer: Bacterial vs. Viral (HSV)

At a Glance

Morphology — The Key Differentiator

Bacterial Ulcer

• Focal white/yellow-white stromal infiltrate with overlying epithelial defect
• Dense and opaque — the slit beam cannot pass through to the iris
• Heaped-up edges; round or irregular; mucopurulent base
• Surrounding stromal oedema, Descemet folds

HSV Ulcer — Three Forms

Pathogens

Bacterial

Viral

Diagnostics

A "true" dendrite with branching epithelial ulceration and terminal end-bulbs is pathognomonic for HSV. VZV produces pseudodendrites (elevated, no bulbs, don't ulcerate centrally). — Wills Eye Manual

Treatment

Key "Don't Miss" Points

1. Decreased corneal sensation → think HSV (or VZV, Acanthamoeba, neurotrophic) — always test sensation before anaesthetic drops
2. Dendritic ulcer = HSV until proven otherwise — do NOT give steroids alone
3. Contact lens + severe pain + rapid progression = Pseudomonas — treat aggressively
4. Topical steroids + a missed fungal or HSV ulcer = catastrophic worsening
5. Necrotizing stromal HSV keratitis can look identical to bacterial keratitis → scrape and culture before committing to a diagnosis
6. VZV pseudodendrites ≠ HSV dendrites: pseudodendrites are raised (not ulcerated), have no terminal bulbs, and don't stain well with fluorescein