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Refractive Surgery

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1. Introduction

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2. Preoperative Assessment & Patient Selection

• Unacceptably high expectations
• Dry eye syndrome
• Non-stable refractive error
• Systemic disease: SLE, rheumatoid arthritis, immunocompromise
• Ocular disease: chronic blepharitis, previous herpes simplex, glaucoma, macular degeneration

• Complete ocular examination
• Tear film osmolarity (to exclude dry eye)
• Corneal pachymetry (for residual stromal bed thickness; exclude mild keratoconus)
• Corneal topography (to exclude irregular astigmatism, keratoconus, forme fruste keratoconus)
• Corneal OCT (epithelial map)
• Corneal and whole-eye wavefront aberrometry
• Contact lens wearers: discontinue soft lenses for 2 weeks, hard/RGP lenses for at least 3 weeks before definitive keratometry

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3. Categories of Refractive Procedures

3A. Laser Corneal Procedures

LASIK (Laser In Situ Keratomileusis)

• Myopia correction: Central ablative flattening
• Hypermetropia correction: Mid-peripheral ablation (steepens centre)

• Greater postoperative comfort
• Faster visual rehabilitation
• More rapid refraction stabilization
• Milder stromal haze

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PRK (Photorefractive Keratectomy) - Surface Ablation

• Corrects myopia up to 6 D, astigmatism up to ~3 D, low-moderate hypermetropia
• Preferred in patients at higher risk of eye trauma (no flap to dislocate)
• Suitable for thin corneas
• Depth of stromal exposure: Bowman membrane

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LASEK (Laser Subepithelial Keratomileusis)

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Epi-LASIK (Epithelial LASIK)

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SMILE (Small Incision Lenticule Extraction)

• No flap whatsoever
• Corrects myopia and myopic astigmatism
• Range: spherical ~10.0 D to ~1.0 D, cylinder up to 3.0 D
• Transient light sensitivity syndrome incidence ~1% (vs 5-9% for LASIK)

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Comparison Table (from Wills Eye Manual)

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3B. Intraocular Refractive Procedures (for high refractive errors)

Phakic Intraocular Lenses (IOLs)

1. Iris clip ("lobster claw") implant - attached to iris (Artisan/Verisyse)
   • Complications: subluxation, dislocation, oval pupil, progressive endothelial cell loss, cataract, raised IOP, angle-closure glaucoma
2. Posterior chamber phakic IOL (e.g., ICL - implantable collamer lens) - placed between iris and crystalline lens
   • Complications: pupil block glaucoma, cataract formation, incorrect power

Clear Lens Exchange (Refractive Lens Exchange)

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3C. Presbyopia Correction

Intracorneal Inlays

• Refractive inlay - alters corneal curvature
• Small aperture inlay - uses the pinhole effect for extended depth of focus

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4. Correction by Refractive Error

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5. Complications

Complications of Surface Ablation (PRK / LASEK / Epi-LASIK)

• Epithelial defect (usual - takes days to heal; bandage contact lens used)
• Pain (from induced epithelial defect)
• Dislocated or poorly fitting bandage lens
• Non-healing epithelial defect
• Bacterial keratitis / corneal ulcer
• HSV reactivation

• Corneal haze (scarring in anterior stroma) - causing decreased vision, glare, monocular diplopia
  • Treatment: increase steroid frequency; severe cases - excimer PTK with mitomycin C
• Undercorrection or overcorrection
• Irregular astigmatism (central island, decentered ablation)
• Regression of refractive error
• Steroid-induced glaucoma / ocular hypertension

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Complications of LASIK

• Dry eye / neurotrophic keratopathy - by far the most common early complication; reduced corneal sensation for at least 3 months (returns to normal in 6-12 months)
• Folding, dislocation, or loss of corneal flap
• Large epithelial defect
• Diffuse lamellar keratitis (DLK) - "sands of the Sahara" - multiple fine inflammatory infiltrates at the flap interface within 5 days; treat with intensive topical antibiotic + steroids
• Infection in flap interface (bacterial keratitis)
• Central toxic keratopathy (CTK) - central stromal opacification/consolidation of unknown etiology; tends to improve over 6-12 months

• Epithelial ingrowth under flap (1-2%) - treat by lifting flap and scraping cells; ethanol or mitomycin C application possible
• Corneal haze (less common than after surface ablation)
• Irregular astigmatism (decentered ablation, flap irregularity, ectasia)
• Regression/progression of refractive error
• Chronic dry eye syndrome
• Pressure-induced stromal keratitis (PISK) - high IOP (often steroid-induced) causes fluid in the interface; IOP falsely low on central measurement, so measure peripheral to flap edge with Tono-Pen
• Corneal ectasia (0.2-0.6%) - most devastating complication
  • Risk factors: abnormal preoperative topography (forme fruste keratoconus, pellucid marginal degeneration), low preoperative corneal thickness, low residual stromal bed, high myopia, young age, high percentage of corneal tissue altered

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Workup for Post-Refractive Surgery Problems

1. Complete slit lamp examination with fluorescein staining + IOP (Tono-Pen + applanation)
2. Note: IOP may be underestimated due to reduced corneal thickness after ablation
3. Refraction - hard contact lens overrefraction corrects irregular astigmatism
4. Corneal topography/tomography if irregular astigmatism suspected
5. Corneal OCT for epithelial thickness mapping

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6. Key Tips (Kanski)

• LASIK may cause transient dry eye and glare from subepithelial haze
• Patients at occupational/recreational risk of eye trauma should be counselled for surface ablation (PRK) over LASIK
• Residual stromal bed must be ≥250 μm after ablation to prevent ectasia
• Refractive stability should be present for at least 1 year before LASIK

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The Eyelid - Comprehensive Ophthalmology Review

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1. Blepharitis

• Staphylococcal - abnormal immune response to S. aureus; associated with atopic dermatitis; causes peripheral corneal infiltrates
• Seborrhoeic - linked to generalized seborrhoeic dermatitis (scalp, nasolabial folds)

• Meibomian gland dysfunction → bacterial lipases produce free fatty acids → raised meibum melting point → gland obstruction → increased tear evaporation and instability
• Strongly associated with acne rosacea

• D. folliculorum longus (anterior) and D. folliculorum brevis (posterior)
• Collarettes at lash bases = pathognomonic of Demodex infestation

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2. Ptosis

Classification

Pseudoptosis - Causes

• Lack of globe support (artificial eye, enophthalmos, microphthalmos)
• Contralateral lid retraction (upper lid normally covers superior 2 mm of cornea)
• Ipsilateral hypotropia (lid follows globe downward; disappears on covering fellow eye)
• Brow ptosis (VII nerve palsy - diagnose by manually lifting brow)

Clinical Measurements

• MRD (margin-reflex distance): Normal ~4-5 mm; reduced in ptosis
• Ptosis grading: Mild ≤2 mm, Moderate 3 mm, Severe ≥4 mm
• Palpebral fissure height: Males 7-10 mm, Females 8-12 mm
• Levator function: Normal ≥15 mm | Good 12-14 mm | Fair 5-11 mm | Poor ≤4 mm
• Lid crease height: Males ~8 mm, Females ~10 mm
  • Absent crease → poor levator function (congenital)
  • High crease → aponeurotic defect

Causes to Always Exclude (Wills Eye Manual)

1. Horner syndrome | 2. CN III palsy | 3. Myasthenia gravis | 4. Orbital tumour | 5. Lid/conjunctival tumour | 6. CPEO (Kearns-Sayre)

Ptosis Surgery

• Levator resection - for myogenic/congenital with fair-good levator function
• Levator aponeurosis advancement - for involutional/aponeurotic ptosis
• Fasanella-Servat - for mild Horner or small aponeurotic ptosis
• Frontalis sling - for severe ptosis with poor levator function (≤4 mm)

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3. Ectropion (Lid turned outward)

Types & Treatment

• Horizontal lid laxity (>8 mm pull-distraction; no snap-back)
• Lateral canthal laxity (rounded canthus; lid moves >2 mm medially)
• Medial canthal laxity (punctum displaced; severe = reaches pupil)
• Treatment: Lateral tarsal strip procedure; medial spindle for medial ectropion

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4. Entropion (Lid turned inward)

Types

1. Horizontal lid laxity
2. Lower lid retractor attenuation (reduced lid excursion in downgaze)
3. Over-riding of pre-tarsal by preseptal orbicularis → tips lid inward
4. Orbital septum laxity + fat prolapse

• Temporary: lubricants, taping, bandage lens, botulinum toxin to orbicularis
• Surgical: Everting sutures, Wies procedure (full-thickness lid split + sutures), lower lid retractor reinsertion, tarsal strip for laxity

• Causes: trachoma, cicatrizing conjunctivitis, chemical burns, Stevens-Johnson syndrome, MMP
• Treatment: posterior lamellar lengthening with mucous membrane or hard palate graft

• Common in Asian children
• Extra skin fold pushes lashes toward cornea
• Usually resolves spontaneously; surgery if persistent corneal staining

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5. Chalazion & Hordeolum

• Histopathology: lipid-laden epithelioid cells, multinucleated giant cells, lymphocytes

• External (stye) = glands of Zeis/Moll on lid margin
• Internal = meibomian gland abscess

1. Warm compresses QID + massage
2. Topical antibiotic (hordeolum) or antibiotic-steroid ointment (chalazion)
3. Oral doxycycline 20-50 mg daily-BID for recurrent/rosacea
4. After 3-4 weeks if persistent: incision and curettage or intralesional triamcinolone (0.2-1.0 mL of 40 mg/mL mixed 1:1 with lidocaine/epi)
5. Send all excised tissue for histopathology

KEY: Recurrent chalazion at the same site in an older patient = biopsy to exclude sebaceous gland carcinoma.

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6. Eyelid Tumors

Benign

Malignant

• Lower lid > medial canthus > upper lid > lateral canthus
• Medial canthal BCC = most dangerous (orbital/sinus invasion; highest recurrence)
• Locally invasive, never metastasizes
• Features: madarosis, telangiectasia, slow growth

• Upper eyelid predominant (more meibomian glands)
• Masquerades as chalazion (nodular type) or blepharitis (spreading type)
• Yellow discolouration within tumour is highly suggestive
• Pagetoid spread (intraepithelial extension) - may be extensive
• Mortality 5-10%; worse prognosis: upper lid, size ≥10 mm, symptoms >6 months
• Histology: foamy vacuolated lipid-containing cytoplasm + hyperchromatic nuclei

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7. Miscellaneous & Congenital

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Eyelid Malignancy Red Flags

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The Orbit - Ophthalmology

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1. Orbital Anatomy

• The intraorbital optic nerve is 25 mm long, while the distance from the back of the globe to the optic canal is only 18 mm - this slack allows forward displacement of the globe (proptosis) without excessive nerve stretch
• Walls: roof (frontal bone/lesser sphenoid wing), lateral wall (zygomatic/greater sphenoid wing), floor (maxilla/zygoma/palatine), medial wall (ethmoid/lacrimal/maxilla/sphenoid) - the medial wall and floor are thinnest, most prone to fracture

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2. Approach to the Orbit: Proptosis

Assessment of Proptosis

• Axial (straight forward) → intraconal mass (within the muscle cone), e.g. cavernous haemangioma, optic nerve tumour, TED
• Non-axial (dystopia/eccentric) → extraconal mass, e.g. lacrimal gland tumour (inferomedial displacement), dermoid (superolateral), rhabdomyosarcoma (superior)

1. Asymmetrical proptosis - best detected by looking down at the patient from above and behind
2. Resistance to retropulsion (pushback of globe) - indicates firm/infiltrative mass
3. Pulsatile proptosis - suggests carotico-cavernous fistula or orbital encephalocele
4. Fundoscopy - look for optic disc swelling, choroidal folds, optociliary vessels

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3. Thyroid Eye Disease (TED)

Key Facts

• Most common cause of both unilateral and bilateral proptosis in adults
• 5x more common in women (reflects Graves' disease prevalence)
• Smoking is the major modifiable risk factor - dose-dependent; cessation reduces risk
• Radioiodine therapy for hyperthyroidism can worsen TED (give oral steroids prophylactically)
• Can occur in euthyroid and hypothyroid patients

Pathogenesis

Clinical Course

• Congestive (inflammatory) stage: Red, painful eyes; lasts 1-3 years
• Fibrotic (quiescent) stage: White eyes, fixed motility defect

Clinical Features

• Spontaneous retrobulbar pain
• Pain on attempted upgaze or downgaze
• Redness of eyelids
• Redness of conjunctiva
• Swelling of conjunctiva or plica
• Swelling of eyelid
• Chemosis

• Mild: Minor impact on daily life
• Moderate-severe: ≥1 of: moderate-severe soft tissue involvement, lid retraction ≥2 mm, diplopia, proptosis ≥3 mm above normal
• Sight-threatening: Optic neuropathy or corneal breakdown

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Five Clinical Categories

(1) Soft Tissue Involvement

• Grittiness, red eyes, lacrimation, photophobia, puffy lids, retrobulbar discomfort
• Epibulbar hyperaemia (especially over horizontal rectus insertions) - sensitive activity marker
• Periorbital oedema + chemosis + retroseptal fat prolapse into lids
• Tear insufficiency and instability

(2) Lid Retraction

• Upper lid: Müller muscle overaction (sympathetic overstimulation from high thyroid hormones); levator fibrosis
• Lower lid: Inferior rectus fibrosis pulls lower lid down
• Signs: Dalrymple's sign (upper lid retraction - above superior limbus), von Graefe's sign (lid lag on downgaze), lagophthalmos
• Lateral flare of upper lid retraction is highly specific for TED

(3) Proptosis

• Axial, bilateral (but often asymmetric) or unilateral
• Resistance to retropulsion is characteristic
• Caused by enlarged extraocular muscles + increased orbital fat volume

(4) Restrictive Myopathy (Ophthalmoplegia)

(5) Optic Neuropathy

Key pearl: Compressive optic neuropathy in TED often occurs without significant proptosis - enlarged muscles compress the apex without pushing the globe forward.

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Treatment of TED

• Stop smoking (first measure)
• Optimize thyroid function
• If radioiodine therapy planned: give concurrent oral steroids

• Lubricants, topical anti-inflammatories
• Selenium 200 μg/day for 6 months (in selenium-deficient areas)
• Head elevation to reduce periorbital oedema
• Eyelid taping for mild exposure

• IV methylprednisolone - regimen: 0.5 g weekly ×6 weeks, then 0.25 g weekly ×6 weeks. Superior outcomes and better tolerability than oral. Avoid in significant hepatic, cardiovascular, hypertensive, or diabetic disease.
• IV corticosteroids + mycophenolate sodium 0.72 g/day ×24 weeks = superior to IV steroid monotherapy (preferred at specialist centres)
• Low-dose fractionated orbital radiotherapy - second-line; maximal response by 4 months; ~40% non-responders; avoid in young patients and diabetics
• Teprotumumab (IGF-1R monoclonal antibody) - highly effective; reduces proptosis and CAS

• Urgent IV methylprednisolone (1 g/day ×3 days)
• If no response in 1-2 weeks → emergency orbital decompression surgery
• Canthotomy/cantholysis for acute pressure rise

1. Orbital decompression (for proptosis/corneal exposure) - removes orbital wall and/or fat
2. Squint surgery (for diplopia from restrictive myopathy) - after proptosis stable
3. Eyelid surgery (for retraction/lagophthalmos) - last step

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4. Orbital Cellulitis

Key Distinction: Preseptal vs Orbital (Postseptal)

Orbital Cellulitis

• Adults: S. aureus, Streptococcus spp., anaerobes
• Children: S. pneumoniae, S. aureus, S. pyogenes, H. influenzae (rare if vaccinated)
• Post-trauma: Gram-negative rods
• Dental source: mixed aggressive aerobes + anaerobes
• Immunocompromised (diabetics, HIV, chemo): Mucor/Rhizopus (zygomycosis/mucormycosis), Aspergillus

Chandler-Hubert Classification

Clinical Features

• Rapid onset: pain exacerbated by eye movement, lid swelling, proptosis, malaise
• Pyrexia (often marked)
• Painful ophthalmoplegia
• Conjunctival chemosis and injection
• Proptosis (often non-axial if abscess present)
• Reduced VA, colour vision, RAPD → suggests optic nerve compression (emergency)
• History of recent nasal/sinus/respiratory illness

Complications

• Ocular: Optic neuropathy, exposure keratopathy, raised IOP, CRAO/CRVO, endophthalmitis
• Subperiosteal abscess (medial wall most common)
• Intracranial (3-4%): Meningitis, brain abscess, cavernous sinus thrombosis

Investigation & Management

• CT orbits + paranasal sinuses + brain (with contrast) - mandatory
• CBC with differential, blood cultures, culture of nasal discharge
• Check tetanus status in trauma

• Hospital admission mandatory
• IV antibiotics until apyrexial for 4 days, then 1-3 weeks oral
  • Community: ampicillin-sulbactam (adults); supplement with metronidazole for anaerobic cover
  • Hospital/MRSA risk: add vancomycin
• Monitor optic nerve function every 4 hours (VA, colour vision, brightness comparison, pupil reactions)
• ORL (ENT) assessment for sinus drainage
• Surgical drainage of orbital/subperiosteal abscess at early stage if identified
• Deteriorating optic nerve → emergency canthotomy/cantholysis

• Occurs in diabetics (especially in DKA) and immunocompromised
• Severe pain, external ophthalmoplegia, black eschar on nasal turbinates
• Profound visual loss may occur rapidly
• Treatment: aggressive surgical debridement + IV amphotericin B (urgent)

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5. Idiopathic Orbital Inflammatory Disease (IOID / Orbital Pseudotumour)

• Acute or subacute ocular and periorbital redness, swelling, and pain
• Proptosis (congestive)
• Ophthalmoplegia (mild to severe)
• Optic nerve dysfunction (posterior orbit involvement)
• Choroidal folds
• Pyrexia in up to 50% of children (rare in adults)

• Spontaneous remission after a few weeks (best case)
• Intermittent episodes with eventual remission
• Severe prolonged disease → progressive fibrosis → "frozen orbit" (fixed ophthalmoplegia + ptosis + optic nerve involvement)

• Orbital myositis - targets one or more extraocular muscles (unlike TED: tendons are also enlarged)
• Dacryoadenitis - lacrimal gland involvement
• Tolosa-Hunt syndrome - painful ophthalmoplegia from granulomatous inflammation at superior orbital fissure/cavernous sinus

• CT: ill-defined orbital opacification, loss of definition of contents
• MRI: better soft tissue characterization
• Biopsy: required in persistent cases to exclude lymphoma, sarcoidosis, GPA, infection

1. Observation for mild disease
2. NSAIDs alone (ibuprofen) - mild disease; add PPI
3. Oral prednisolone 1.0-1.5 mg/kg/day - hallmark rapid dramatic response within 24-48 hrs (if no response, reconsider diagnosis)
4. Orbital depot steroid injection - selected cases
5. Radiotherapy - if no improvement after 2 weeks of adequate steroids

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6. Orbital Tumours

Benign

Cavernous Haemangioma (Cavernous Venous Malformation)

• Most common primary orbital tumour in adults
• Female preponderance (70%); middle-aged; growth accelerated by pregnancy
• Vascular malformation (not a true neoplasm); low-flow AVM
• Located within the muscle cone, lateral to optic nerve
• Histology: Endothelial-lined vascular channels of varying size separated by fibrous septa
• Presentation: Slowly progressive axial proptosis, diplopia; often incidental
• Imaging: Well-defined, hyperdense on CT; "progressive fill" on dynamic contrast MRI
• Treatment: Observation if asymptomatic. Surgical excision if symptomatic - well-encapsulated, relatively easy to remove

Capillary Haemangioma

• Most common orbital tumour in children/infants
• Appears shortly after birth; grows rapidly in the first year; involutes by age 5-7
• Strawberry-red, compressible; increases with crying (Valsalva)
• Can cause amblyopia (from ptosis, astigmatism, or anisometropia)
• Treatment: Oral/topical propranolol (first line); systemic steroids if propranolol contraindicated; intralesional steroid injection

Dermoid Cyst

• Choristoma derived from trapped ectoderm along embryonic fusion lines
• Superolateral orbit (frontozygomatic suture) most common site
• Smooth, non-tender, non-pulsatile; may be anchored to bone
• CT: well-defined cyst with fat density; bone remodelling
• Treatment: surgical excision (rupture causes severe granulomatous inflammation)

Pleomorphic Lacrimal Gland Adenoma (Benign Mixed-Cell Tumour)

• Most common epithelial lacrimal gland tumour
• Young to middle-aged adults; painless slow progressive proptosis (>1 year)
• Superolateral orbit → inferomedial globe displacement
• CT: well-defined mass in lacrimal gland fossa + smooth bony remodelling (not erosion)
• Treatment: Complete excision with intact pseudocapsule (biopsy/incomplete excision risks malignant transformation → adenoid cystic carcinoma)

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Malignant

Rhabdomyosarcoma (RMS) - Most Common Primary Orbital Malignancy in Children

• Most common soft tissue sarcoma of childhood; 40% in head and neck
• Mean age of onset: 7 years; 90% in children under 16
• Derived from undifferentiated mesenchymal cells
• Subtypes: Embryonal (85% of orbital RMS - best prognosis), Alveolar (worse prognosis, characteristic chromosomal translocations), Botyroid (4%), Pleomorphic

Key tip: RMS can mimic orbital cellulitis in a child - skin redness and swelling but skin is not warm.

• Rapidly progressive unilateral proptosis (days to weeks)
• Most common location: superonasal or superior orbit
• Diplopia common; pain less common; no fever
• Swelling and redness of overlying skin (not warm)

• CT: poorly-defined homogeneous mass, often with adjacent bony destruction
• MRI: poorly-defined mass

• Incisional biopsy to confirm diagnosis + histological subtype + cytogenetic analysis
• Systemic staging: chest (lung metastases), bone scan (bone metastases are common)

Orbital Lymphoma

• Most common orbital malignancy in adults (>60 years)
• MALT-type (extranodal marginal zone) B-cell lymphoma most common
• Salmon-pink "fish-flesh" conjunctival lesion
• Painless proptosis, diplopia
• Treatment: orbital radiotherapy for localized disease; systemic chemotherapy for disseminated

Lacrimal Gland Carcinoma (Adenoid Cystic Carcinoma - ACC)

• Most common malignant lacrimal gland tumour
• Pain is a key distinguishing feature from benign adenoma (perineural invasion)
• Bone erosion on CT (not smooth remodelling as in adenoma)
• Treatment: radical surgery + radiotherapy; poor prognosis

Orbital Metastases

• Adults: breast (most common, may cause enophthalmos from scirrhous reaction), lung, prostate, melanoma
• Children: neuroblastoma (bilateral orbital metastases with ecchymosis = "raccoon eyes"), Ewing's sarcoma, Wilms' tumour

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7. Orbital Trauma

Orbital Floor Fracture (Blowout Fracture)

• Mechanism: blunt trauma to orbit → sudden rise in intraorbital pressure → thin orbital floor fractures (trapdoor or open book)
• Features:
  • Enophthalmos (fat herniation into maxillary sinus)
  • Diplopia (especially on upward gaze - inferior rectus/oblique entrapment)
  • Infraorbital hypoesthesia (infraorbital nerve damage)
  • Restricted upgaze (positive forced duction)
  • Globe may appear sunken
• CT: best imaging - shows floor defect, soft tissue herniation, haemosinus
• Treatment: surgical repair if enophthalmos >2 mm, diplopia in primary or reading gaze, or large defect (>50% floor); wait 2 weeks for oedema to resolve before deciding

Orbital Haemorrhage

• Can be retrobulbar (sight-threatening); causes rapid rise in intraorbital pressure
• Presents with pain, proptosis, restricted EOM, raised IOP, visual loss, RAPD
• Emergency treatment: Lateral canthotomy + cantholysis to decompress the orbit

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Summary: Key "Most Common" Facts in Orbital Disease

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The Conjunctiva - Comprehensive Ophthalmology Review

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1. Anatomy & Histology

Anatomical Divisions

• Palisades of Vogt - radial ridges at the limbus; reservoir of corneal stem cells (limbal stem cells)
• Plica semilunaris - semilunar fold nasally; vestigial third eyelid
• Caruncle - fleshy nodule medial to plica; modified cutaneous tissue

Histology

• Epithelium: Non-keratinizing, ~5 cell layers deep; basal cuboidal → superficial polyhedral cells
• Goblet cells (mucus-secreting): within epithelium; most dense inferotemporally and in the fornices; secrete mucin (innermost layer of tear film)
• Stroma (substantia propria): Richly vascularized loose connective tissue; contains accessory lacrimal glands of Krause (fornices) and Wolfring (near superior tarsal border) - provide basal tear secretion
• CALT (Conjunctiva-Associated Lymphoid Tissue): lymphocytes, lymphatics, and follicular aggregates; mediates ocular surface immunity

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2. Clinical Signs of Conjunctival Inflammation

Symptoms

• Lacrimation, grittiness, stinging, burning
• Itching = hallmark of allergic disease
• Significant pain, photophobia, or marked foreign body sensation → suggests corneal involvement
• VA not usually affected in pure conjunctivitis

Discharge Types

Conjunctival Reaction Patterns

• Discrete, slightly elevated, translucent, rice-grain lesions
• Most prominent in the fornices
• Blood vessels run around or across the lesion (not within)
• Contain germinal centres of lymphocytes (reactive lymphoid tissue)
• Causes: viral (adenovirus, EBV, HSV), chlamydial, molluscum contagiosum, toxic (topical medications - especially brimonidine, apraclonidine, idoxuridine)

• Raised, red, polygonal lesions with a central vascular core (blood vessels run through the centre)
• Non-specific response to inflammation
• Large (>1 mm) = "giant papillae"; found on upper tarsal conjunctiva in VKC and GPC
• Causes: bacterial, allergic, chlamydial, giant papillary conjunctivitis

• True membrane - involves superficial epithelial layers; removal causes bleeding; leaves scarring
• Pseudomembrane - loosely adherent fibrinous exudate; removal is easy, no bleeding
• Both can cause scarring
• Causes: severe adenoviral EKC, gonococcal, Streptococcus, Corynebacterium diphtheriae, Stevens-Johnson syndrome, ligneous conjunctivitis

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3. Bacterial Conjunctivitis

Acute Bacterial Conjunctivitis

• Common, usually self-limiting
• Bilateral (one eye 1-2 days before the other)
• Lids stuck together on waking (mucopurulent discharge)
• Conjunctival injection; discharge initially watery, rapidly becomes mucopurulent
• Corneal punctate epithelial erosions common
• Lymphadenopathy usually absent (except with gonococcal/meningococcal)

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Gonococcal Conjunctivitis

Critical: N. gonorrhoeae can penetrate intact corneal epithelium → rapid corneal ulceration and perforation within 24-48 hrs.

• Hyperacute purulent discharge (gross, "taps open")
• Marked lid oedema and erythema
• Conjunctival chemosis
• Preauricular lymphadenopathy (present, unlike simple bacterial conjunctivitis)

• Ceftriaxone 1 g IM single dose (adults) + saline irrigation
• Treat sexual contacts
• Screen for other STIs
• Neonates: ceftriaxone 25-50 mg/kg IV/IM

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Adult Chlamydial (Inclusion) Conjunctivitis

• Males: non-gonococcal urethritis (NGU); trigger for Reiter syndrome
• Females: urethritis, PID, infertility; Fitz-Hugh-Curtis syndrome (perihepatitis) in 5-10% with PID

• Subacute onset, unilateral or bilateral
• Watery or mucopurulent discharge
• Tender preauricular lymphadenopathy (characteristic)
• Large follicles prominent in inferior fornix and upper tarsal plate
• Superficial punctate keratitis
• Perilimbal subepithelial corneal infiltrates (2-3 weeks)
• Superior corneal pannus (chronic cases)

• Giemsa staining of conjunctival scrapings: basophilic intracytoplasmic inclusion bodies
• PCR (nucleic acid amplification) - most sensitive
• Direct immunofluorescence (~90% sensitivity)

• Azithromycin 1 g single oral dose, OR
• Doxycycline 100 mg BD × 7 days
• Treat sexual partners

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Trachoma

• Surgery (for trichiasis/entropion - bilamellar tarsal rotation)
• Antibiotics (active disease and family members)
• Facial hygiene
• Environmental improvement

• Mixed follicular/papillary conjunctivitis
• Mucopurulent discharge
• Herbert's pits - limbal follicles that scar → depressions at superior limbus (pathognomonic)
• Superior corneal pannus

• Arlt's line - horizontal scar in upper tarsal plate
• Trichiasis, entropion → corneal ulceration → opacity → blindness

• Azithromycin 20 mg/kg (max 1 g) single dose - treatment of choice
• Alternatives: erythromycin 500 mg BD × 14 days; doxycycline 100 mg BD × 10 days (not in pregnancy or children <12)
• Topical tetracycline 1% ointment - less effective than oral

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Neonatal Conjunctivitis (Ophthalmia Neonatorum)

• Gonococcal: ceftriaxone IM/IV + saline irrigation
• Chlamydial: systemic erythromycin (oral) × 14 days (topical alone inadequate; prevents chlamydial pneumonia)
• HSV: IV aciclovir

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4. Viral Conjunctivitis

Adenoviral Conjunctivitis (most common = 90% of viral conjunctivitis)

Non-specific Acute Follicular Conjunctivitis

• Most common form; mild; various adenoviral serotypes
• Unilateral watery discharge, redness, irritation; fellow eye affected 1-2 days later
• Mild systemic symptoms (sore throat, common cold)

Pharyngoconjunctival Fever (PCF)

• Adenovirus serovars 3, 4, 7
• Spread by droplets; family outbreaks
• Prominent sore throat + conjunctivitis + fever
• Keratitis in ~30% but seldom severe

Epidemic Keratoconjunctivitis (EKC) - most severe

• Adenovirus serovars 8, 19, 37
• Keratitis in ~80% of cases - may be severe with marked photophobia
• Subepithelial infiltrates (SEI) develop weeks after onset - represent immune reaction - can persist months-years and impair vision
• May cause pseudomembranes, symblepharon, and long-term dry eye

• Follicular conjunctival reaction
• Preauricular lymphadenopathy
• Subconjunctival haemorrhages (especially EKC)
• Pseudomembrane formation (EKC)
• Subepithelial corneal infiltrates

• Supportive: cool compresses, lubricants
• Topical steroids/NSAIDs for severe cases (SEI, significant keratitis) - but steroids can prolong viral shedding
• Topical povidone-iodine (off-label) may shorten course
• Hand hygiene / isolate to prevent spread

Other Viral Causes

• HSV: Follicular conjunctivitis in primary infection; often unilateral; associated eyelid vesicles; treat with topical/oral aciclovir
• Molluscum contagiosum: Umbilicated lid margin lesions shed viral particles → chronic follicular conjunctivitis - treat by excision of lid lesion
• Acute haemorrhagic conjunctivitis: Enterovirus / Coxsackievirus; rapid onset; prominent subconjunctival haemorrhage; resolves in 1-2 weeks; tropical regions
• SARS-CoV-2 (COVID-19): Viral RNA in tears in ~25% of moderate-severe cases; mild follicular conjunctivitis; usually benign

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5. Allergic Conjunctivitis

Acute Allergic Conjunctivitis

• Usually in children after playing outdoors in spring/summer
• Trigger: pollen
• Acute itching + watering + dramatic chemosis (hallmark)
• Self-limiting; resolves within hours
• Treatment: cool compresses; single drop adrenaline 0.1% for extreme chemosis

Seasonal (SAC) and Perennial Allergic Conjunctivitis (PAC)

• SAC (hay fever eyes): spring/summer; tree and grass pollens
• PAC: year-round; house dust mites, animal dander, fungal allergens; milder than SAC
• Symptoms: redness, watering, itching + sneezing, nasal discharge
• Signs: conjunctival hyperaemia, mild papillary reaction, mild chemosis

1. Artificial tears (dilutes allergen)
2. Mast cell stabilizers (sodium cromoglicate, nedocromil, lodoxamide) - preventive; need days to take effect
3. Topical antihistamines (emedastine, epinastine, levocabastine) - for exacerbations
4. Dual-action agents (antihistamine + mast cell stabilizer): azelastine, ketotifen, olopatadine - rapid-acting, very effective
5. Short course topical steroids for severe acute episodes
6. Allergen immunotherapy for refractory cases

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Vernal Keratoconjunctivitis (VKC)

• Palpebral VKC (upper tarsal plate predominant)
• Limbal VKC (more common in tropical/dark-skinned individuals)

Palpebral Disease Signs:

• Diffuse velvety papillary hypertrophy on superior tarsal plate
• Macropapillae (<1 mm) - flat-topped, polygonal "cobblestones"
• Giant papillae (>1 mm) - adjacent papillae amalgamate; most characteristic
• Mucus deposition between papillae
• Whitish inflammatory infiltrates in intense disease

Limbal Disease Signs:

• Gelatinous limbal conjunctival papillae
• Horner-Trantas dots - transient white cellular collections at apices of limbal papillae (eosinophil/degenerate cell aggregates) - pathognomonic

Corneal Complications (more common with palpebral VKC):

• Superior punctate epithelial erosions with overlying mucus
• Epithelial macroerosions
• Shield ulcer - exposed Bowman membrane coated with calcium phosphate and mucus; serious; resists re-epithelialization → risk of secondary infection
• Subepithelial grey-oval scars
• Pseudogerontoxon - paralimbal band of superficial scarring resembling arcus senilis (after recurrent limbal disease)
• Keratoconus - more common in VKC; partly due to eye rubbing

• Mast cell stabilizers + antihistamines (as for SAC/PAC)
• Topical steroids (short, intensive course; rapid taper) - for acute exacerbations
• Topical ciclosporin A 0.5-2% - steroid-sparing; effective for moderate-severe disease
• Shield ulcer: mechanical debridement, therapeutic soft contact lens, topical steroids, mitomycin C; prompt treatment to prevent bacterial superinfection
• Tacrolimus ointment for lid disease

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Atopic Keratoconjunctivitis (AKC)

• More severe corneal involvement; may lead to corneal vascularization, opacity, and blindness
• Eyelid disease prominent (in contrast to VKC where lid skin is usually spared)
• Staph blepharitis commonly coexists
• Cataracts (anterior subcapsular - "shield cataract") and keratoconus more common
• Herpes simplex keratitis more common (can be bilateral)
• Progression to corneal scarring, limbal stem cell deficiency

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Giant Papillary Conjunctivitis (GPC) / Mechanically-Induced Papillary Conjunctivitis

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6. Cicatrising (Scarring) Conjunctivitides

Mucous Membrane Pemphigoid (MMP) / Ocular Cicatricial Pemphigoid (OCP)

• Papillary conjunctivitis, diffuse hyperaemia, subtle fibrosis
• Inferior fornix shortening (forniceal depth measurement important for monitoring)
• Symblepharon - adhesion between palpebral and bulbar conjunctiva
• Ankyloblepharon - adhesion at outer canthus between upper and lower lids
• Goblet cell and accessory lacrimal gland destruction → severe dry eye
• Trichiasis, aberrant lashes, lid margin keratinization
• End-stage: total symblepharon, corneal opacification (limbal stem cell failure)

• Mucosal involvement: oral blisters most common; oesophageal/laryngeal strictures
• Skin lesions (25%): tense blisters/erosions on head, neck, groin, extremities

• Dapsone - useful first-line for mild-moderate disease (~70% respond); contraindicated in G6PD deficiency
• Methotrexate - for moderate disease
• Cyclophosphamide (with systemic steroids) - for severe/rapidly progressive disease
• Biologic agents (rituximab, IVIg) for refractory cases
• Local: preservative-free lubricants; treat trichiasis/entropion; symblepharon lysis with amniotic membrane transplantation; ultimately limbal stem cell transplantation for corneal opacification

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Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN)

• Pseudomembranous or membranous conjunctivitis
• Corneal epithelial defects, ulceration
• Iritis, episcleritis

• Similar to OCP: symblepharon, trichiasis, dry eye, corneal vascularization and opacity
• Limbal stem cell deficiency

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7. Miscellaneous Conjunctival Conditions

Superior Limbic Keratoconjunctivitis (SLK)

• Hyperaemia of superior bulbar conjunctiva (radial band) - stains with rose Bengal
• Limbal papillary hypertrophy and loss of palisades superiorly
• Redundant superior bulbar conjunctiva folding across the superior limbus
• Superior punctate epithelial erosions + superior filamentary keratitis (1/3 of cases)
• Mild superior pannus
• KCS in ~50%

Subconjunctival Haemorrhage

• Bleeding under the bulbar conjunctiva; appears bright red
• Usually spontaneous (Valsalva, coughing, hypertension, anticoagulants, trauma)
• Alarming appearance but almost always benign; resolves spontaneously in 2-3 weeks
• Recurrent: check blood pressure, coagulation screen, blood glucose

Conjunctivochalasis

Pinguecula

• Yellowish-white amorphous deposit on bulbar conjunctiva, nasal > temporal; does not extend onto the cornea
• UV-related elastotic degenerative change in subepithelial stromal collagen
• Usually asymptomatic; "pingueculitis" if inflamed (treat with topical lubricants/short steroid course)

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8. Pterygium

• Cap - avascular halo-like zone at the advancing edge
• Head - apex on cornea
• Body - vascularized triangular base on the bulbar conjunctiva
• Stocker line - linear iron deposition in corneal epithelium anterior to the head (indicates slow growth)

• Small lesions - often asymptomatic
• Irritation/grittiness (dellen effect at advancing edge)
• Contact lens intolerance
• Astigmatism or visual axis obstruction (advanced lesion)
• Intermittent inflammation

• Observation if small and asymptomatic
• Lubricants, sunglasses (UV protection)
• Surgery: excision + conjunctival autograft (gold standard; lowest recurrence ~5%) or amniotic membrane transplantation
• Adjuvants to reduce recurrence: mitomycin C (intraoperative or postoperative drops); beta-irradiation
• Recurrence is the main problem (bare sclera excision alone = >50% recurrence)

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Summary: Key Diagnostic Differentiators

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The Cornea - Comprehensive Ophthalmology Review

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1. Anatomy & Physiology

• Regular lamellar arrangement of collagen fibrils (spacing maintained by proteoglycans)
• Relative dehydration (maintained by endothelial pump)
• Avascularity
• Intact epithelial barrier

Layers (anterior to posterior)

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2. Signs of Corneal Disease

Staining

• Fluorescein: Stains areas of epithelial defect (fills gaps in tight junctions; stains intercellular spaces)
• Rose Bengal: Stains devitalized/dead cells and mucus; better for filaments, dendrites, and keratoconjunctivitis sicca

Slit-lamp signs

• Keratic precipitates (KP): Inflammatory cells on endothelium
  • Fine/stellate (non-granulomatous uveitis), mutton-fat/large/greasy (granulomatous - sarcoid, TB, HSV)
• Corneal oedema: Stromal haze/thickening; epithelial bullae (advanced)
• Vascularization: Superficial (pannus - anterior stroma) or deep (interstitial keratitis)
• Infiltrate: Cellular recruitment to stroma; loss of normal lamellar clarity
• Descemetocoele: Herniation of Descemet membrane through stromal thinning; surgical emergency (risk of perforation)

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3. Dry Eye Syndrome (Keratoconjunctivitis Sicca - KCS)

Types

• Aqueous-deficient dry eye: Reduced tear production (Sjögren's syndrome, lacrimal gland disease, Riley-Day syndrome)
• Evaporative dry eye: Meibomian gland dysfunction (most common), blepharitis, lid abnormalities, contact lens wear, low blink rate

Symptoms

Corneal Signs

• Punctate epithelial erosions (PEE) - stain with fluorescein (interpalpebral distribution)
• Filaments - strands of mucus + shed epithelial cells, attached at one end; stain well with rose Bengal
• Mucous plaques - semi-transparent grey-white elevated lesions
• Thin/absent marginal tear meniscus
• Severe complications: epithelial breakdown, stromal melting, perforation, bacterial keratitis

Investigations

• Tear break-up time (BUT): Normal >10 sec; <5 sec = abnormal (measure with fluorescein)
• Schirmer's test: Filter paper strip placed at lower lid lateral fornix
  • Type I (no anaesthetic): measures basal + reflex; ≥10 mm in 5 min = normal; <5 mm = abnormal
  • Type II (with topical anaesthetic): basal secretion only
• Tear osmolarity (most sensitive/specific): >308 mOsm/L in one eye, or >8 mOsm/L difference between eyes = abnormal
• Rose Bengal / lissamine green staining - interpalpebral staining pattern (Van Bijsterveld score)
• MMP-9 point-of-care test - elevated in dry eye inflammation

Treatment

• Artificial tears (preservative-free if using >4×/day)
• Lubricating gels/ointment (nighttime)
• Treat underlying blepharitis/MGD (warm compresses, lid hygiene, doxycycline)
• Topical ciclosporin 0.05-0.1% (Restasis/Cequa) - reduces inflammation; improves tear production
• Lifitegrast (LFA-1 integrin antagonist) - anti-inflammatory
• Punctal occlusion (plugs or cautery) - retains tears
• Bandage contact lens for filamentary keratitis
• Autologous serum drops for severe/refractory cases
• Moisture chamber spectacles, humidifiers

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4. Bacterial Keratitis (Corneal Ulcer)

Pathogenesis & Risk Factors

• Contact lens wear (most important, especially extended-wear soft lenses)
• Trauma (including LASIK)
• Ocular surface disease (dry eye, lid disease, bullous keratopathy)
• Previous corneal disease
• Topical steroid use
• Immunocompromise
• Exposure keratopathy

Clinical Features

• Epithelial defect (ulcer) overlying a stromal infiltrate
• Dense white-yellow stromal infiltrate with surrounding haze
• Stromal oedema, Descemet folds
• Anterior uveitis ± hypopyon (sterile pus in anterior chamber)
• Plaque-like KPs
• Chemosis and eyelid swelling (moderate-severe)
• Descemetocoele formation and perforation (especially Pseudomonas)
• Scleritis (severe perilimbal infection)

Investigations

• 2 mm in size

• Middle to deep stroma involvement
• Within visual axis
• Chronic or atypical appearance
• Non-responsive to initial treatment

• Non-preserved topical anaesthetic (proxymetacaine 0.5%)
• Sterile No. 11 blade, 20-21G needle tip, or Kimura spatula
• Scrape margins and base
• Plate directly onto culture media
• Send smears for Gram stain, Giemsa stain, KOH (fungal), Ziehl-Neelsen (acid-fast)
• Gram stain - most rapid guide to initial therapy

Treatment

• Initial: hourly day and night for 24-48 hours, then taper
• Fluoroquinolone monotherapy (ciprofloxacin, ofloxacin, moxifloxacin, gatifloxacin) - preferred empirical treatment
• Duotherapy (cephalosporin + aminoglycoside) for aggressive disease

Note: Ciprofloxacin drops cause white corneal precipitates (drug crystallization) that can delay epithelial healing.

• Cycloplegia (atropine) for pain + prevent posterior synechiae
• IOP control if raised
• Bandage contact lens or tissue glue for imminent perforation
• Tarsorrhaphy for exposure keratopathy
• Amniotic membrane graft for persistent epithelial defect
• Steroids are generally contraindicated initially (may worsen bacterial keratitis); may be considered once infection controlled to reduce scarring

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5. Herpes Simplex Keratitis (HSK)

HSV Biology

• Enveloped double-stranded DNA virus; two subtypes
• HSV-1: Above the waist (face, lips, eyes)
• HSV-2: Venereally acquired (genital); rarely ocular (neonatal transmission)
• Latency in trigeminal ganglion (for ocular HSV)
• Reactivation triggered by: fever, UV, trauma, immunosuppression, menstruation, emotional stress

Primary HSV Infection

• Usually childhood; subclinical (or mild fever + URTI)
• May cause unilateral follicular conjunctivitis + blepharitis + vesicular lid lesions
• Dendritic corneal ulcers can occur even in the presence of maternal antibodies

Recurrent HSK - Forms

(A) Epithelial (Dendritic) Keratitis

1. Reduced VA
2. Swollen opaque epithelial cells in coarse punctate or stellate pattern
3. Central desquamation → linear-branching (dendritic) ulcer with characteristic terminal buds
4. Ulcer bed stains with fluorescein; margin cells (virus-laden) stain with rose Bengal
5. Reduced corneal sensation (highly characteristic)
6. Mild subepithelial haze
7. Steroids (inadvertent): enlargement to geographic/"amoeboid" ulcer

Key: Geographic ulcer = HSK treated with steroids alone without antiviral cover.

• Topical aciclovir 3% ointment 5× daily for 10-14 days, OR
• Ganciclovir 0.15% gel 5× daily (better tolerated)
• Do NOT use steroids alone (will enlarge ulcer)
• Debridement of infected epithelium (historical; less used now)

(B) Disciform (Endothelial/Stromal) Keratitis

• Central disc of epithelial + stromal oedema (disciform appearance)
• Descemet membrane folds (Vogt's striae)
• Wessely immune ring - deep stromal haze ring surrounding the disc (viral antigen + antibody immune complex)
• KPs on endothelium beneath the disc
• Reduced corneal sensation
• Raised IOP (not uncommon)
• Healed lesions: faint ring of stromal/subepithelial opacification + thinning

• Topical steroids (prednisolone 1% or dexamethasone 0.1%) + antiviral cover (topical aciclovir or oral aciclovir)
• Monitor IOP carefully
• Steroid intensity kept to minimum - taper over ≥4 weeks
• Long-term low-dose steroid (prednisolone 0.5% once daily) often needed to maintain remission
• Oral aciclovir (400 mg twice daily) or valaciclovir (500 mg once daily) for prophylaxis of recurrence

(C) Necrotising Stromal Keratitis

(D) Neurotrophic Keratopathy

• Impaired blink reflex + reduced tear production → epithelial breakdown
• Persistent oval epithelial defect with smooth rolled edges (typically inferior third of cornea)
• Treatment: aggressive lubrication, bandage contact lens, amniotic membrane, tarsorrhaphy, cenegermin (recombinant nerve growth factor drops)

(E) Meta-herpetic (Post-herpetic) Keratopathy

HEDS Study - Key Evidence

• Oral aciclovir prophylaxis (400 mg twice daily) reduces recurrent HSK by 45%
• Topical steroids (with antiviral cover) benefit stromal (immune) keratitis
• Topical steroids do NOT benefit epithelial (active viral) keratitis

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6. Fungal Keratitis

Risk Factors

• Trauma with vegetable/organic matter (filamentous fungi - Fusarium, Aspergillus)
• Contact lens wear (Fusarium, Candida)
• Topical steroids or antibiotics (disrupts flora)
• Immunocompromise (Candida - more common in endogenous/systemic spread)
• Tropical/agricultural regions (filamentous fungi more common)

Organisms

• Filamentous (moulds): Fusarium spp., Aspergillus spp. - associated with trauma
• Yeast: Candida spp. - associated with immunocompromise, chronic disease, contact lenses

Signs

• Typically slower onset than bacterial keratitis
• Feathery/hyphate margins (filamentous fungi)
• Satellite lesions (hyphal extensions)
• Dry, rough, raised infiltrate (unlike bacterial - which is smoother)
• Endothelial plaque
• Immune ring may develop
• Hypopyon

Investigations

• Corneal scrapings: KOH preparation (dissolves tissue; hyphae visible); Calcofluor white (fluoresces hyphae); Gram stain; Giemsa stain; cultures on Sabouraud dextrose agar (fungal media)
• Confocal microscopy (in vivo - non-invasive)
• PCR

Treatment

• Natamycin 5% (first-line for filamentous, especially Fusarium)
• Voriconazole 1% topical (excellent filamentous and Candida coverage; better corneal penetration; first-line in many centres)
• Amphotericin B 0.15% (first-line for Candida)
• Oral voriconazole for deep/severe keratitis or scleritis
• Steroids are contraindicated in active fungal keratitis
• Treatment duration typically 6-12 weeks (much longer than bacterial)

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7. Acanthamoeba Keratitis

Signs

• Severe, disproportionate pain (often out of proportion to clinical signs) - classic feature
• Slow insidious onset
• Perineural infiltrate (radial keratoneuritis) - pathognomonic; linear infiltrates tracking along corneal nerves
• Ring infiltrate (immune ring) - characteristic late sign
• Pseudodendrites (can mimic HSK dendrites but no terminal buds; stain poorly)
• Uveitis, scleritis in severe cases

Diagnosis

• Confocal microscopy - can identify cysts in vivo (doubles/trefoils of bright round structures)
• Corneal scrapings plated on non-nutrient agar with E. coli overlay (amoeba feed on bacteria)
• PCR

Treatment

• Polyhexamethylene biguanide (PHMB) 0.02% + propamidine isethionate (Brolene) 0.1% - cornerstone; hourly initially
• Or chlorhexidine 0.02% (alternative biguanide)
• Treatment for at least 12 months (to eliminate cysts)
• Steroids generally avoided initially; may be used cautiously for severe inflammation after antiamoebics started
• Corneal graft if medical treatment fails

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8. Keratoconus

Key Facts

• Progressive central/paracentral corneal stromal thinning + apical protrusion + irregular astigmatism
• Prevalence: 0.1-0.2%
• Onset: teens/twenties
• Males slightly more affected
• Bilateral (eventually in almost all; initially may present as unilateral)
• ~50% of normal fellow eyes progress to KC within 16 years
• Only ~10% have a positive family history; proposed AD with incomplete penetrance

Associations

• Systemic: Down syndrome, Ehlers-Danlos syndrome, Marfan syndrome, osteogenesis imperfecta
• Ocular: Atopy (VKC, eczema), asthma - persistent eye rubbing is a key risk factor; blue sclera, aniridia, Leber congenital amaurosis, retinitis pigmentosa

Diagnosis

• Oil-droplet reflex on direct ophthalmoscopy at arm's length (or ~50 cm)
• Scissor reflex on retinoscopy
• Vogt's striae - fine vertical lines in deep stroma (Descemet folds from stress)
• Fleischer ring - epithelial iron deposition at base of cone (best seen with cobalt blue filter)
• Munson's sign - V-shaped deformity of lower lid on downgaze (advanced)
• Rizzuti's sign - conical reflection on nasal cornea from temporal penlight
• Corneal thinning and protrusion on slit lamp
• Corneal sensation reduced

• Corneal topography/tomography (Pentacam Scheimpflug) - shows inferior steepening, asymmetric bowtie pattern; essential for diagnosis and monitoring
• Keratometry grading: Mild (<48 D), Moderate (48-54 D), Severe (>54 D)
• Pachymetry: thinning at apex

Acute Hydrops

Treatment

LASIK is absolutely contraindicated in keratoconus. Screen all refractive surgery candidates for KC first.

Pellucid Marginal Degeneration (PMD)

• Inferior crescentic corneal thinning (4-8 o'clock position) with protrusion above the thinning
• "Against-the-rule" astigmatism; "crab claw" or "butterfly" topography pattern
• Non-inflammatory; similar associations to KC
• Treatment: contact lenses; surgery for advanced cases

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9. Corneal Dystrophies

• Usually bilateral
• Primarily affect one layer of the cornea
• Slowly progressive
• Most have identified genetic mutations
• Classified by anatomical layer (IC3D classification)

Epithelial Dystrophies

Cogan (Epithelial Basement Membrane / Map-Dot-Fingerprint) Dystrophy

• Most commonly sporadic (degenerative); rare AD familial form (TGFBI gene)
• Hallmark: recurrent corneal erosions (painful, typically on waking)
• Signs on retroillumination:
  • Dot-like/microcystic lesions
  • Subepithelial map-like patterns surrounded by faint haze
  • Fingerprint-like whorled lines
  • Bleb-like/pebbled glass pattern
• Treatment: artificial tears, hypertonic saline, lubricating ointment at bedtime; epithelial debridement; anterior stromal micropuncture; excimer laser PTK

Meesmann Epithelial Dystrophy

• Rare; AD; mutations in corneal epithelial keratins (KRT3, KRT12)
• Myriad tiny uniform intraepithelial cysts centrally (sparing limbus)
• Usually asymptomatic; mild recurrent erosions in some

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Bowman Layer Dystrophies

Reis-Bücklers Dystrophy (GCD type 3)

• AD; TGFBI gene
• Histology: replacement of Bowman layer by connective tissue bands
• Severe recurrent erosions in childhood; visual impairment
• Signs: grey-white geographic subepithelial opacities, dense centrally; reticular pattern with age
• Treatment: excimer PTK; keratoplasty if severe

Thiel-Behnke Dystrophy (CBD2 / Honeycomb dystrophy)

• AD; TGFBI gene; "curly fibres" on electron microscopy
• Milder than Reis-Bücklers; honeycomb/ring network of subepithelial opacities

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Stromal Dystrophies

Descemet Membrane & Endothelial Dystrophies

Fuchs Endothelial Corneal Dystrophy (FECD)

• Most important endothelial dystrophy
• Bilateral accelerated endothelial cell loss
• More common in women; associated with slightly increased glaucoma prevalence
• Genetic: mostly sporadic; AD; TCF4 gene (most cases); COL8A2 (early-onset variant)

1. Cornea guttata - irregular warts/excrescences on Descemet membrane secreted by abnormal endothelial cells
2. Specular microscopy: tiny dark spots → "beaten metal" appearance of endothelium
3. Blurred vision, worse in the morning (nocturnal corneal oedema; dries during waking hours)
4. Central stromal oedema (thickening on pachymetry)
5. Epithelial bullae → bullous keratopathy (painful blisters; rupture = acute severe pain)
6. Subepithelial scarring + peripheral vascularization (end-stage)

• Conservative: hypertonic NaCl 5% drops/ointment; reduce IOP; hair dryer (corneal dehydration)
• Ruptured bullae: bandage contact lens, cycloplegia, antibiotic ointment, anterior stromal puncture
• Definitive: DMEK (Descemet Membrane Endothelial Keratoplasty) or DSAEK (DSAEK = Descemet Stripping Automated Endothelial Keratoplasty) - posterior lamellar transplantation; or PKP (penetrating keratoplasty)
• Promising: topical Rho-kinase inhibitor + prior transcorneal cryotherapy → stimulates endothelial proliferation
• If cataract surgery needed: consider triple procedure (phaco + IOL + DSAEK) to avoid repeated surgery

Posterior Polymorphous Corneal Dystrophy (PPCD)

• AD; usually asymptomatic
• Vesicular/band lesions on posterior Descemet; some develop corneal oedema
• Association with glaucoma; may have iris-angle abnormalities

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10. Corneal Degenerations (Non-dystrophic)

Arcus Senilis (Corneal Arcus)

• Peripheral stromal lipid deposition; separated from limbus by clear zone (lucid interval)
• In elderly: normal (arcus senilis); in young patients (<50): arcus juvenilis → screen for hyperlipidaemia (familial hypercholesterolaemia)

Band Keratopathy

• Calcium deposition in Bowman layer and superficial stroma within interpalpebral fissure
• Grey-white horizontal band with peripheral "Swiss cheese" holes (corneal nerves pass through)
• Causes: chronic uveitis (especially juvenile idiopathic arthritis), hyperparathyroidism, hypercalcaemia, chronic corneal disease, renal failure, sarcoidosis
• Treatment: EDTA chelation (topical 0.35-1.7% disodium EDTA with epithelial debridement); excimer laser PTK

Corneal Deposits

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11. Peripheral Corneal Disorders

Peripheral Ulcerative Keratitis (PUK)

• Crescentic peripheral stromal thinning with overlying epithelial defect
• Associated with systemic vasculitis (rheumatoid arthritis most common - Mooren's ulcer is idiopathic; also GPA, SLE, PAN)
• Treat systemic disease; immunosuppression (systemic steroids, methotrexate, cyclophosphamide, rituximab)

Marginal Keratitis (Catarrhal Ulcer)

• Peripheral infiltrates/ulcers at 2, 4, 8, 10 o'clock with clear interval between lesion and limbus
• Immune-mediated (staphylococcal hypersensitivity) - not infectious
• Treat underlying blepharitis + short course topical steroid-antibiotic combination

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Summary: Key Differentiating Points

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The Iris - Anatomy, Physiology & Ophthalmology

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1. Anatomy of the Iris

Overview

Macroscopic Structure

• Pupillary zone - inner zone (between pupil and collarette); contains the pupillary sphincter muscle
• Ciliary (peripheral) zone - outer zone (between collarette and iris root); contains the dilator muscle

Layers (anterior to posterior)

Pupillary Sphincter Muscle

• Circular smooth muscle at the pupillary margin (2-3 mm width)
• Innervated by parasympathetic fibers (CN III → ciliary ganglion → short ciliary nerves)
• Constricts the pupil (miosis)
• Pharmacology: constricted by pilocarpine, echothiophate; blocked by atropine, tropicamide

Pupillary Dilator Muscle

• Radially arranged in ciliary zone
• Innervated by sympathetic fibers (superior cervical ganglion → long ciliary nerves via nasociliary branch of V1)
• Dilates the pupil (mydriasis)
• Pharmacology: stimulated by phenylephrine, cocaine; blocked in Horner syndrome

Blood Supply

• Major arterial circle of the iris - at the root of the iris (formed by the long posterior and anterior ciliary arteries)
• Minor arterial circle - near the collarette (formed from branches of the major circle)
• Radially oriented blood vessels between the two circles

Nerve Supply

• Sensory: Nasociliary nerve (V1) via long and short ciliary nerves
• Motor (sphincter): Short ciliary nerves (CN III parasympathetic)
• Motor (dilator): Long ciliary nerves (sympathetic)

Colour

• Blue eyes: little stromal melanin (posterior pigment epithelium is dark in all irides - gives blue appearance by Tyndall scattering)
• Brown/dark eyes: abundant stromal melanin
• Neonates: blue at birth (stromal melanocytes not yet activated); final colour develops over first year

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2. Iris-Related Structures

The Anterior Chamber Angle

Aqueous Humour Dynamics

• Produced by ciliary body epithelium (active secretion + ultrafiltration)
• Flows from posterior chamber → through pupil → into anterior chamber
• Drainage: trabecular route (80%; Schlemm's canal → collector channels → episcleral veins) and uveoscleral route (20%; through ciliary body and suprachoroidal space)

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3. Pupil - Clinical Assessment

Normal Pupil Reflexes

Relative Afferent Pupillary Defect (RAPD / Marcus Gunn Pupil)

• Swinging flashlight test: Both pupils dilate when light moved to the affected eye (reduced afferent input from that eye)
• Indicates asymmetric afferent pathway disease (optic nerve, retina, chiasm/tract)
• Does NOT occur with pure media opacity (cataract, vitreous) unless very dense
• Causes: optic neuritis, AION, severe retinal disease, optic nerve compression

Abnormal Pupils

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4. Anterior Uveitis (Iritis/Iridocyclitis)

Classification

• Iritis = iris inflammation only
• Iridocyclitis = iris + anterior ciliary body (clinically the same)
• Anterior uveitis = encompassing term (most common form of uveitis overall)

• Acute: Rapid onset, symptomatic; resolves within 3 months
• Chronic: Persistent >3 months; often asymptomatic (insidious)
• Recurrent: Repeated episodes with intervals of quiet

Symptoms

• Pain, photophobia, consensual photophobia (pain in the affected eye when light shone in the FELLOW eye)
• Redness, tearing, decreased vision

• Decreased vision (from cataract, CME, vitreous debris, ERM)
• Floaters; may be nearly asymptomatic (especially JIA)

Signs - Slit-Lamp Examination

• Koeppe nodules - at pupillary margin; seen in both granulomatous and non-granulomatous uveitis
• Busacca nodules - in the iris stroma (mid-iris); granulomatous disease only (sarcoid, TB, leprosy)

• Ischemic: diabetic retinopathy (most common), CRVO, CRAO, ocular ischemic syndrome
• Inflammatory: chronic uveitis, Fuchs
• Tumours: retinoblastoma, melanoma

Systemic Associations of Anterior Uveitis

Key pearl: Bilateral acute recurrent alternating anterior uveitis = highly characteristic of HLA-B27 disease.

Treatment of Anterior Uveitis

• Prednisolone 1% / dexamethasone 0.1% - most effective; hourly initially, taper over 4-6 weeks
• Monitor IOP (steroid response glaucoma)

• Atropine 1% (for severe/chronic) - prevents posterior synechiae; reduces pain (ciliary spasm)
• Cyclopentolate 1% (less severe acute uveitis)

• Methotrexate (especially JIA), mycophenolate mofetil, azathioprine
• Anti-TNF biologic agents (infliximab, adalimumab) - highly effective for refractory disease

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5. Iris Abnormalities - Signs & Differential Diagnoses

Iris Heterochromia

• Congenital Horner syndrome
• Fuchs heterochromic iridocyclitis
• Chronic uveitis
• Juvenile xanthogranuloma
• Waardenburg syndrome

• Ocular melanocytosis / naevus of Ota
• Hemosiderosis / siderosis (iron from retained foreign body)
• Iris melanoma
• Diffuse iris naevus
• Retinoblastoma, leukaemia, lymphoma
• ICE syndrome
• Some cases of Fuchs heterochromic iridocyclitis

Iris Transillumination Defects

• Spoke-wheel / peripheral radial defects: Pigment dispersion syndrome (PDS)
• Patchy mid-peripheral defects: HSV/VZV anterior uveitis
• Sector defects: Trauma, focal ischemia
• Diffuse defects: Albinism, aniridia

Rubeosis Iridis (Iris Neovascularization)

• Diabetic retinopathy (most common)
• CRVO, CRAO
• Ocular ischemic syndrome
• Chronic uveitis
• Intraocular tumour (retinoblastoma, melanoma)
• Chronic retinal detachment

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6. Congenital Iris Anomalies

Aniridia

• Rare bilateral condition - absence of iris (actually a hypoplastic iris remnant present gonioscopically)
• Gene: PAX6 mutation (chromosome 11p13)
• PAX6 is adjacent to WT1 gene (Wilms tumour suppressor)

• Nystagmus and photophobia at birth (presentation)
• Variable severity of iris absence (from subtle to total)
• Foveal and/or optic nerve hypoplasia → poor vision
• Limbal stem cell deficiency → corneal vascularization + opacification ("aniridic keratopathy")
• Dry eye, tear film instability
• Cataract, lens subluxation
• Glaucoma (75%) - late childhood/adolescence; synechial angle closure; difficult to treat

Iris Coloboma

• Keyhole-shaped defect of the iris at the 6 o'clock position (inferior)
• Results from failure of embryonic fissure to close (5th-7th week)
• May involve the choroid, retina, optic nerve (complete uveal coloboma)
• Associated syndromes: CHARGE, cat-eye syndrome, trisomy 13

Persistent Pupillary Membrane

• Remnants of fetal pupillary membrane attached to the anterior lens surface or iris
• Usually regresses by birth but may persist
• Rarely affects vision; no treatment usually needed

Brushfield Spots

• Whitish/greyish spots in the peripheral iris stroma (areas of relative stromal condensation)
• Normal iris stroma surrounding = relatively thinner
• Associated with Down syndrome (trisomy 21) but can be seen in normal individuals
• Distinguish from Lisch nodules (below)

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7. Iris Lesions

Benign Iris Lesions

• Flat, small (<3 mm), discrete surface melanin deposits
• No architectural distortion of underlying stroma
• No malignant potential

• Circumscribed, flat or variably elevated pigmented lesion
• Disrupts normal iris architecture (distinguishes from freckle)
• Malignant transformation rate: up to 8% over 15 years
• Risk factors for transformation: young age (<40), inferior location, bleeding, diffuse involvement, feathery margins, ectropion uveae
• Management: lifelong observation + slit-lamp photography

• Small dome-shaped melanocytic hamartomas of iris stroma
• Bilateral; multiple; tan-coloured
• Pathognomonic of Neurofibromatosis type 1 (NF-1)
• Present in >95% of adult NF-1 patients; increases with age
• No malignant potential

• Primary (from iris pigment epithelium or iris stroma)
• Secondary (from implanted epithelium - post-trauma or surgery, or from intraocular medications such as miotics)
• Most are benign; monitoring required
• UBM (ultrasound biomicroscopy) used for diagnosis and monitoring

• Rare idiopathic granulomatous disease of early childhood
• Iris involvement → recurrent spontaneous hyphaema (highly characteristic)
• Yellowish-orange nodules on iris
• Can also cause glaucoma
• Treatment: topical/systemic steroids; subconjunctival steroid; rarely radiation

Malignant Iris Lesions

Iris Melanoma

• ~8% of uveal melanomas arise in the iris
• Best prognosis of all uveal melanomas: only ~5% develop metastasis within 10 years
• Risk factors: fair skin, light iris colour, ocular/oculodermal melanocytosis, cutaneous dysplastic naevi, chronic sun exposure, arc welding
• Presents typically in middle age (a decade earlier than ciliary body/choroidal melanoma)

• Pigmented nodule ≥3 mm diameter, ≥1 mm thick (typically inferior iris)
• Surface blood vessels (prominent)
• Ectropion uveae (pigment epithelium pulled around the pupillary margin anteriorly)
• Pupillary distortion
• Localized cataract
• Angle infiltration → glaucoma
• Extrascleral extension (rare)

• UBM - to exclude ciliary body involvement
• Fine-needle aspiration biopsy (FNAB) - before major surgery
• Systemic metastatic workup (liver function, LDH, imaging)

• Small: sector iridectomy
• Angle/ciliary body involvement: iridocyclectomy
• Radiotherapy: brachytherapy (radioactive plaque) or proton beam irradiation
• Enucleation: diffuse tumours not amenable to radiotherapy

Iris Metastasis

• Rare; fast-growing
• White, pink, or yellow mass(es)
• Most common primary: breast carcinoma (most common); lung
• Rapidly progressive hyphaema + raised IOP
• Treatment: systemic (chemotherapy/hormone therapy) ± local radiation

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8. Iridocorneal Endothelial (ICE) Syndrome

1. Progressive iris atrophy - iris holes, ectropion uveae, pseudo-polycoria
2. Chandler syndrome - corneal oedema predominates; relatively mild iris changes
3. Iris naevus (Cogan-Reese) syndrome - diffuse iris naevus with pedunculated nodules

• Unilateral, non-hereditary
• ICE (hammered silver) endothelial appearance on specular microscopy
• Peripheral anterior synechiae
• Secondary glaucoma (difficult to control)

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Summary: Key Iris Associations

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The Uvea - Anatomy, Uveitis: Complete Review

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1. Uveal Tract - Anatomy Overview

Choroid

• Highly vascular layer (the most vascular tissue in the body per unit area)
• Layers (outer to inner): Haller's layer (large vessels), Sattler's layer (medium vessels), choriocapillaris (single layer of fenestrated capillaries supplying the outer retina), Bruch's membrane (innermost; separates choriocapillaris from RPE)
• Bruch's membrane = 5 layers: RPE basement membrane / inner collagenous zone / elastin layer / outer collagenous zone / choriocapillaris endothelium basement membrane
• Blood supply: short posterior ciliary arteries (posterior choroid) and long posterior ciliary arteries (anterior choroid, iris, ciliary body)
• Venous drainage: vortex veins (4-5 exiting through sclera)

Ciliary Body

• Extends from the ora serrata to the scleral spur
• Pars plana (posterior flat portion, 3-4 mm) - surgical approach zone (pars plana vitrectomy)
• Pars plicata (anterior ridged portion, 2 mm) - contains ciliary processes (70 processes) that produce aqueous humour
• Contains ciliary muscle (3 parts: longitudinal/Brücke's, radial/oblique, circular/Müller's) - accommodation by relaxing/tightening zonular fibers
• Innervated by parasympathetics (CN III → ciliary ganglion → short ciliary nerves) and sympathetics

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2. Uveitis - Classification Framework

SUN Working Group Classification (Anatomical)

IMPORTANT (Wills): "Isolated anterior uveitis should NEVER be diagnosed without assessment of the retina."

Course Classification

• Acute: Sudden onset + limited duration (<3 months)
• Chronic: Persistent, or flaring ≤3 months after stopping therapy
• Recurrent: Repeated episodes with intervals of quiet >3 months after stopping therapy
• Uveitis controlled with medication = "suppressed" not "in remission"

Granulomatous vs. Non-Granulomatous

Key HLA Associations with Uveitis

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3. Anterior Uveitis (Iritis / Iridocyclitis)

Epidemiology

• Most common form of uveitis overall
• AAU most common: HLA-B27-related + idiopathic = largest proportion (~50% idiopathic, ~20% HLA-B27)

Symptoms

• Acute: Sudden-onset unilateral pain, photophobia, consensual photophobia (pain in the affected eye when light shone in the fellow eye), redness, tearing, decreased vision
• Chronic: Often asymptomatic or only mild; decreased vision from complications (cataract, CME, vitreous cells); floaters; common in JIA

Signs at the Slit Lamp

• Koeppe nodules = at pupillary margin; granulomatous AND non-granulomatous disease
• Busacca nodules = in iris stroma (mid-iris); granulomatous disease only (sarcoid, TB, leprosy)

Systemic Associations of Anterior Uveitis

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4. HLA-B27-Associated Uveitis

Key Features

• Recurrent, unilateral (alternating) acute non-granulomatous anterior uveitis
• Most common cause of unilateral hypopyon (Wills)
• Severe AC reaction with cell, flare, fibrin; early posterior synechiae
• More common in men

Clinical Pearl (Wills): "Over half of patients with HLA-B27-positive AAU have an underlying seronegative spondyloarthropathy, and of those, over half are diagnosed only after the onset of uveitis."

Clinical Pearl (Kanski): "Bilateral acute recurrent alternating anterior uveitis is very characteristic of HLA-B27 disease."

Associated Seronegative Spondyloarthropathies

Workup

• HLA-B27 typing
• Sacroiliac joint X-rays or CT
• ESR, CRP
• Rheumatology referral
• Swab for Chlamydia (if reactive arthritis suspected)

Treatment

• Topical prednisolone + cyclopentolate (acute episodes)
• Systemic NSAIDs for joint disease
• Anti-TNF (adalimumab, infliximab) for recurrent/vision-threatening disease

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5. Juvenile Idiopathic Arthritis (JIA) - Uveitis

JIA Classification (ILAR)

JIA Uveitis - Clinical Features

• Asymptomatic - this is the critical danger. Even 4+ cells causes no pain/redness
• Chronic bilateral non-granulomatous anterior uveitis
• White eye despite active inflammation
• Must be detected by screening slit lamp examination
• Often diagnosed late - by complications (band keratopathy, cataract, amblyopia, strabismus)

JIA Uveitis Complications

JIA Screening Protocol (RCOPHTH/BAP guidelines)

JIA Uveitis Treatment

• Topical steroids + cycloplegics (acute control)
• Methotrexate - first-line systemic agent
• Anti-TNF (adalimumab) - approved for refractory JIA uveitis; significantly improves outcomes
• Cyclosporin, mycophenolate as alternatives

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6. Fuchs Uveitis Syndrome (FUS / FHC)

Epidemiology

• Chronic non-granulomatous condition; average diagnosis age ~40 years; no gender/racial predilection
• Aetiology uncertain; rubella virus most implicated; T. gondii also suspected
• Unilateral in 90-95%

Clinical Features - The 6 Signs of FUS

Iris Features

• Fine irregular iris surface vessels (common)
• Iris nodules (30%) on pupillary border (Koeppe nodules)
• Russell bodies (tiny crystals on iris surface)
• Retroillumination shows pigment epithelial atrophy

Complications

• Cataract (PSC) - extremely common
• Glaucoma - up to 60% of involved eyes; multifactorial
• On incision into the anterior chamber → haemorrhage (Amsler sign) from angle vessels - pathognomonic

Treatment

• Steroids used sparingly (minimal benefit; poor response; steroid-induced IOP rise frequent)
• Cataract surgery - safe and effective (results good despite anterior chamber bleed)
• Glaucoma treatment as required

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7. Intermediate Uveitis (Pars Planitis / Hyalitis)

Definition & Terminology

• Primary site = vitreous; vitreous cells > AC cells; no chorioretinal disease defining it
• Pars planitis (PP) = subset of IU with snowbanking/snowballs, only if idiopathic (no systemic disease identified)
• If systemic disease found → simply "intermediate uveitis associated with [condition]"
• ~15% of all uveitis; ~20% of paediatric uveitis

Epidemiology

• Insidious onset; ages 15-40 years; bilateral (though asymmetric); minimal external inflammation
• Idiopathic (pars planitis) = >70%

Symptoms

• Painless floaters + blurred vision (no redness/photophobia)
• Younger patients may present with vitreous haemorrhage

Signs

• Snowballs - whitish focal inflammatory cell aggregates in inferior vitreous; highly characteristic
• Snowbanking - grey-white fibrovascular/exudative plaque over the inferior ora serrata and pars plana; seen only with indirect ophthalmoscopy + scleral depression (Wills)
• Peripheral retinal periphlebitis (common, especially in MS)
• Mild anterior uveitis (few cells, small KP)
• Posterior subcapsular cataract (common)
• Band keratopathy, posterior synechiae uncommon in PP

Aetiology of Intermediate Uveitis

Complications

• Cystoid macular oedema (CME) - most common cause of visual loss
• Vitreous haemorrhage (especially in children; from peripheral neovascularization)
• Epiretinal membrane (ERM)
• Tractional/exudative retinal detachment
• Secondary glaucoma, band keratopathy

Treatment

• 1st line: Periocular (sub-Tenon's) corticosteroid injection ± topical steroids
• 2nd line: Systemic corticosteroids (oral prednisone)
• Steroid-sparing: Methotrexate, mycophenolate mofetil, azathioprine
• Biologics: Anti-TNF (adalimumab/infliximab) for refractory disease
• Laser photocoagulation to peripheral neovascularization
• Pars plana vitrectomy: For severe vitreous opacities, non-clearing haemorrhage, or diagnostic purposes (lymphoma)

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8. Posterior Uveitis

Clinical Presentations

• Active lesion: whitish opacity with indistinct borders (surrounding oedema)
• Resolving lesion: borders become better defined, pigmentation
• May be focal, multifocal, geographic, or diffuse

• Active lesion: round yellow nodule
• Does NOT typically induce vitritis unless retina simultaneously involved

• Periphlebitis (venous = more common) or periarteritis
• Active: yellowish/grey-white perivascular cuffing ± haemorrhage
• Quiescent: perivascular scarring (do not mistake for active disease)

Common Causes of Posterior Uveitis

Investigations for Posterior Uveitis

• Multimodal imaging: OCT, FA/ICGA, FAF, B-scan USS
• Tailored serology: toxoplasma IgG/IgM, RPR+FTA-ABS (syphilis), IGRA/Quantiferon (TB), ACE/lysozyme (sarcoid), HIV
• Vitreous/aqueous sampling (PCR, cytology) for infections and lymphoma
• NOT a "shotgun" approach - investigations directed by clinical features

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9. Toxoplasmosis - The Most Important Posterior Uveitis

Pathogenesis

• Causative organism: Toxoplasma gondii (obligate intracellular protozoan)
• Definitive host: cat (sexual cycle in intestinal epithelium; oocysts shed in faeces)
• Intermediate hosts: mice, livestock, birds, humans
• Human infection routes: ingestion of oocysts (cat litter/contaminated water), eating undercooked meat (bradyzoite cysts in tissue), transplacental (congenital)
• Bradyzoites = dormant cysts in tissues (eye, brain, muscle); can rupture → tachyzoites → inflammation
• Most common identifiable cause of focal necrotizing retinitis (accounts for ~90%)

Clinical Features

Treatment of Toxoplasma Retinochoroiditis

• Pyrimethamine 75 mg loading dose, then 25 mg daily PLUS
• Sulfadiazine 4 g/day PLUS
• Folinic acid (leucovorin) 15 mg/day (prevents bone marrow suppression)
• Prednisolone 20-40 mg/day (started 24-48h after antiparasitic)
• Duration: 4-6 weeks

• TMP-SMX (trimethoprim-sulfamethoxazole) + folinic acid - simpler, preferred by many
• Clindamycin 300 mg QID + sulfadiazine + folinic acid
• Azithromycin, atovaquone as alternatives

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10. Panuveitis - Key Syndromes

Vogt-Koyanagi-Harada (VKH) Syndrome

• Lumbar puncture if uncertain: CSF lymphocytic pleocytosis + melanin-containing macrophages
• FA: multiple foci of RPE leakage + subretinal pooling
• FAF: hyperautofluorescence in areas of serous detachment
• ICGA: hypofluorescent spots

• High-dose systemic corticosteroids (IV methylprednisolone in acute phase)
• Long-term steroid taper + steroid-sparing agents (methotrexate, azathioprine, cyclosporin)
• Anti-VEGF for CNV complications

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Sympathetic Ophthalmia (SO)

• Exciting eye = the injured eye
• Sympathizing eye = the fellow (non-traumatized) eye that develops inflammation
• Incidence: ~0.2-0.5% after open globe injury; 0.01% after intraocular surgery
• Onset: 65% present 2 weeks to 3 months after injury; can be years later
• HLA-DR4 associated

• Diffuse lymphocytic infiltration of choroid
• Dalen-Fuchs nodules (granulomas between Bruch's and RPE)
• Melanin-containing epithelioid cells

• Exciting eye: red, irritable
• Sympathizing eye: photophobia, blurred vision, loss of accommodation
• Bilateral granulomatous anterior uveitis (mutton-fat KP)
• Multifocal choroidal infiltrates mid-periphery
• Exudative retinal detachment, vasculitis, disc swelling
• "Sunset glow" fundus (after resolution, like VKH)
• Systemic features (alopecia, vitiligo, meningismus) can occur but are uncommon

• OCT (quantify subretinal fluid)
• B-scan USS (choroidal thickening)
• FA: multiple RPE foci of leakage; subretinal pooling
• ICGA: hypofluorescent spots (active disease)
• FAF: monitor progression objectively

• Enucleation of a severely injured eye within 10-14 days historically considered protective; controversial now
• Evisceration vs enucleation debate; some prefer enucleation to prevent SO risk

• High-dose systemic steroids (main therapy)
• Steroid-sparing immunosuppressives for long-term control
• With aggressive therapy: 75% of sympathizing eyes retain VA >6/60
• Relapses in 50% of cases; long-term follow-up mandatory

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Behçet Disease

• Required: Recurrent oral ulcers (≥3 episodes in 12 months)
• Plus ≥2 of: Genital ulcers / ocular inflammation / skin lesions (erythema nodosum, pseudofolliculitis, acneiform nodules) / positive pathergy test (pustule 24-48h after sterile needle prick)

• Ocular inflammation in ~70%; more severe in men; nearly always bilateral eventually
• Classical pattern: Relapsing/remitting acute panuveitis + retinal vasculitis; may resolve spontaneously

Tip (Kanski): "A transient hypopyon in a relatively white eye is typical of Behçet disease and JIA-associated uveitis."

• Acute: Topical + systemic corticosteroids
• Posterior disease: High-dose steroids + azathioprine (first-line)
• Refractory: Anti-TNF (infliximab - excellent evidence), adalimumab
• Interferon-alpha (effective, especially in Europe)

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Sarcoidosis - Ocular

• Respiratory: cough, dyspnoea
• Löfgren syndrome = triad: erythema nodosum + bilateral hilar lymphadenopathy + polyarthralgia (good prognosis; seen in women)
• Skin: erythema nodosum, lupus pernio (violaceous indurated lesions on nose/cheeks/ears), granulomatous papules
• Systemic: fever, malaise, arthralgia, hepatosplenomegaly, hypercalcaemia, renal disease

• Chest X-ray (bilateral hilar lymphadenopathy in stage I; parenchymal infiltrates in stage II)
• ACE (serum angiotensin-converting enzyme) - elevated in ~80% of active disease
• Serum lysozyme - less sensitive/specific than ACE; combined use improves accuracy
• PPD/IGRA (to exclude TB)
• CT chest (superior to CXR)
• Conjunctival biopsy (high yield if granulomas visible)
• Tissue biopsy (lymph node, skin, lacrimal gland) for definitive diagnosis (non-caseating granuloma)

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11. Uveitis Investigations - Tailored Approach

Investigations NOT Usually Required When:

• Single episode of unilateral mild/moderate non-granulomatous AAU with no systemic features
• Systemic diagnosis already compatible with clinical features

Suggested Workup Table (Wills Eye Manual)

Serological Tests Summary

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12. Uveitis Treatment Summary

Topical

Periocular Steroids

• Sub-Tenon's triamcinolone (40 mg/mL) - anterior/intermediate/posterior uveitis; unilateral; risk of IOP rise, cataract
• Posterior sub-Tenon's or posterior juxtascleral for posterior segment

Systemic

Sustained-Release Implants

• Ozurdex (dexamethasone intravitreal implant) - 0.7 mg; 6-month duration; intermediate/posterior uveitis
• Yutiq (fluocinolone acetonide 0.18 mg) - 3-year duration
• Iluvien (fluocinolone 0.19 mg) - 36-month duration

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13. White Dot Syndromes - Brief Overview

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Summary: Uveitis Diagnosis at a Glance

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