Trachoma

Definition & Causative Agent

Epidemiology

• The WHO estimates ~6 million people have been blinded by trachoma; ~1.3 million currently have preventable blindness from it.
• Hyperendemic zones: northern and sub-Saharan Africa, Middle East, drier parts of the Indian subcontinent, and Southeast Asia.
• In hyperendemic areas, prevalence is nearly 100% by age 2-3 years. Children are the primary reservoir for active infection; adults suffer the blinding sequelae.
• Transmission occurs via contact with ocular/nasal discharge, direct person-to-person spread, and through eye-seeking flies (Musca sorbens) acting as mechanical vectors.
• The WHO Neglected Tropical Diseases roadmap 2021-2030 targets global elimination of blinding trachoma as a public health problem by 2030. - Harrison's 22E, p. 1518

Pathogenesis

Clinical Manifestations

Active (Inflammatory) Phase

• Mixed follicular/papillary conjunctivitis with mucopurulent discharge (in children <2 years the papillary component may dominate)
• Superior epithelial keratitis and pannus formation (superficial corneal vascularization from the superior limbus downward)
• Inflammatory leukocytic infiltration of the cornea

Cicatricial (Scarring) Phase

• Linear or stellate conjunctival scars (mild) or broad confluent scars - the classic "Arlt line" (severe)
• Herbert pits: shallow depressions at the superior limbus left by resolved limbal follicles - pathognomonic of trachoma
• Trichiasis: inward turning of eyelashes abrading the cornea
• Entropion (cicatricial): inward rotation of the eyelid margin
• Progressive corneal ulceration, scarring, and opacification leading to blindness
• Dry eye: goblet cell and lacrimal gland duct destruction causes xerosis and secondary bacterial corneal ulcers
• Seasonal co-epidemics with H. influenzae conjunctivitis worsen inflammatory damage in endemic communities

Clinical Photographs

WHO Grading System (SAFE-related classification)

• Kanski's Clinical Ophthalmology 10e, p. 192

Diagnosis

1. Lymphoid follicles on the upper tarsal conjunctiva
2. Typical conjunctival scarring
3. Vascular pannus (most marked at the superior limbus)
4. Limbal follicles or their sequelae (Herbert pits)

• Giemsa staining of conjunctival smears: intracytoplasmic chlamydial inclusions in 10-60% of active cases
• NAATs (PCR) are most sensitive and specific - can detect chlamydial DNA even when cultures are negative, suggesting persistent infection is more common than previously recognized
• NAATs remain prohibitively expensive for most endemic regions
• Harrison's 22E, p. 1518; Park's Textbook of Preventive and Social Medicine

Treatment

Individual Treatment

• All sexual partners and family members should be treated simultaneously to prevent re-infection.
• A single course is not always sufficient; communities may need annual treatment cycles.

Surgical Treatment

• Bilamellar tarsal rotation for cicatricial entropion and trichiasis - aims to relieve lid inversion and maintain full lid closure, preventing ongoing corneal abrasion.

The WHO SAFE Strategy (Control Framework)

Mass vs. Selective Treatment

• Mass (blanket) treatment: indicated when moderate-to-severe trachoma prevalence is >5% in children under 10 - tetracycline 1% ointment twice daily for 5 consecutive days/month for 6 months, or 60 consecutive days. Azithromycin mass drug administration is now preferred.
• Selective treatment: used in low-to-medium prevalence communities - screen first, treat only those with active disease.
• Park's Textbook of Preventive and Social Medicine, p. 1135-1168; Kanski's Clinical Ophthalmology 10e, p. 192

Key Points Summary

Recent evidence note: A 2025 systematic review and meta-analysis (PMID: 40860538) examined the prevalence and risk factors for active trachoma among children aged 1-9 in low-income African countries, reconfirming that young children in resource-poor settings remain the highest-burden group and that socioeconomic and hygiene factors remain key drivers - consistent with textbook guidance.

Corneal Ulcer

Definition

Pathophysiology

1. Epithelial barrier disruption (by trauma, desiccation, hypoxia, direct microbial invasion, or desquamation)
2. Microorganisms gain access to the corneal stroma
3. Inflammatory cell recruitment causes stromal necrosis and tissue loss
4. Progressive thinning may lead to descemetocoele (posterior bulging of Descemet membrane) and perforation

Etiology & Risk Factors

Common Organisms

Key Risk Factors

Symptoms

• Pain (often severe; disproportionately severe pain suggests Acanthamoeba or Pseudomonas)
• Photophobia
• Foreign body sensation
• Redness and lid swelling
• Mucopurulent or purulent discharge
• Decreased visual acuity (especially if ulcer is in the visual axis)
• Acute contact lens intolerance

Signs

• Focal white/gray stromal opacity (infiltrate) with overlying epithelial defect - the hallmark finding. An examiner using a slit beam cannot see clearly through an infiltrate/ulcer to the iris (unlike stromal edema or mild scars which are more transparent)
• Stromal edema, folds in Descemet membrane
• Anterior uveitis: cells and flare, keratic precipitates
• Hypopyon (sterile layered pus in anterior chamber) - common in moderate-to-severe disease
• Circumcorneal injection (ciliary flush)
• Chemosis and eyelid swelling (moderate-severe)
• Descemetocoele (bulging of Descemet membrane) in severe thinning
• Posterior synechiae, raised IOP in severe cases
• Wills Eye Manual, p. 199; Kanski's Clinical Ophthalmology 10e, p. 227

Clinical Photographs

Types of Corneal Ulcer

1. Bacterial Keratitis

• Presentation: rapid onset, pain, mucopurulent discharge
• Hallmark: focal well-defined white/yellow-white infiltrate with epithelial defect
• Pseudomonas: particularly aggressive, may cause rapid perforation
• S. aureus: focal, fairly well-defined infiltrate
• Streptococci: often aggressive

2. Fungal Keratitis

• Filamentous fungi (tropics, agricultural trauma): gray-white stromal infiltrate with indistinct fluffy margins, satellite lesions, feathery branch-like extensions, ring infiltrate
• Candida (temperate climates, pre-existing ocular disease): yellow-white densely suppurative infiltrate, mimics bacterial ulcer
• Key feature: infiltrate often extends beyond the epithelial defect
• Can penetrate intact Descemet membrane and cause endophthalmitis without obvious perforation
• Diagnosis frequently delayed - always maintain high suspicion

3. Acanthamoeba Keratitis

• Classic history: soft contact lens wearer + exposure to water (swimming, hot tub, tap water for lens cleaning)
• Pain out of proportion to early clinical findings
• Early: pseudodendrites, epitheliitis, subepithelial microcysts, radial keratoneuritis (perineural infiltrates) - pathognomonic
• Late (3-8 weeks): ring-shaped stromal infiltrate
• Bacteria cultures are negative; does not respond to antibiotics or antivirals
• Often mimics HSV keratitis early - always consider Acanthamoeba in contact lens wearers with apparent HSV

Investigations

Corneal Scraping (when to do it)

• 2 mm in size

• Middle to deep stromal involvement
• Within the visual axis
• Chronic or atypical in appearance

• Instill preservative-free topical anaesthetic (e.g., proxymetacaine 0.5%)
• Use No. 11 scalpel blade, 20-21G hypodermic needle tip, or Kimura spatula
• Remove loose mucus/necrotic tissue first
• Scrape margins and base of lesion

Culture Media (routine)

• Blood agar - general bacteria
• Chocolate agar - Neisseria, Haemophilus
• Sabouraud dextrose agar - fungi
• Brain-heart infusion (BHI) - enrichment broth

Stains

Other

• Confocal microscopy: in vivo identification of organisms; especially useful for Acanthamoeba; not widely available outside tertiary centres
• Corneal biopsy: for suspected fungal keratitis with no improvement after 3-4 days and no growth on culture after 1 week
• Kanski's Clinical Ophthalmology 10e, p. 228

Management

General Measures (All Ulcers)

1. Discontinue contact lens wear immediately
2. Cycloplegic drop (e.g., cyclopentolate 1% TID; atropine 1% BID-TID if hypopyon present) - for comfort and to prevent posterior synechiae
3. Obtain cultures before starting antibiotics
4. Emergent ophthalmology referral
5. Avoid topical steroids until infection is controlled

Bacterial Keratitis - Treatment Algorithm (Wills Eye)

Note: Moxifloxacin and besifloxacin have slightly better Gram-positive coverage. Gatifloxacin and ciprofloxacin have slightly better Pseudomonas and Serratia coverage.

Fungal Keratitis - Treatment

• Start hourly for 48 hours, then reduce as signs permit
• Systemic antifungals for severe cases: voriconazole 400 mg BID x1 day then 200 mg BID; itraconazole 200 mg OD; fluconazole 200 mg BID
• Tetracycline (doxycycline 100 mg BID) for anticollagenase effect if significant thinning
• Therapeutic keratoplasty (penetrating or deep anterior lamellar) when medical therapy fails or post-perforation

Acanthamoeba Keratitis - Treatment

• PHMB (polyhexamethylene biguanide) 0.02% + propamidine isethionate (Brolene) 0.1% topically - intensive initially then tapered over months
• Treatment is prolonged (often >6 months)
• Does not respond to standard antibiotics or antivirals

Surgical Options for Corneal Ulcer Complications

Recent evidence note: A 2025 systematic review (PMID: 39257085) found that amniotic membrane grafts are effective for managing persistent epithelial defects following infective corneal ulcers and keratitis, consistent with Kanski's guidance on this technique.

Differential Diagnosis Summary

• Kanski's Clinical Ophthalmology 10e, p. 226-233; Wills Eye Manual, p. 199-215; Tintinalli's Emergency Medicine, p. 191