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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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Contents Overview (from Kanski Chapter 2)

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1. Blepharitis

Introduction

Anterior Blepharitis

• Staphylococcal: Abnormal cell-mediated response to S. aureus cell wall components. More common in atopic dermatitis. Associated with peripheral corneal infiltrates and red eyes.
• Seborrhoeic: Strongly associated with generalized seborrhoeic dermatitis (scalp, nasolabial folds, behind ears, sternum).

Posterior Blepharitis (Meibomian Gland Dysfunction - MGD)

• Caused by meibomian gland dysfunction and altered secretions
• Bacterial lipases produce free fatty acids → raised melting point of meibum → gland obstruction, tear film instability
• Loss of tear film phospholipids (surfactants) → increased tear evaporation and osmolarity
• Associated with acne rosacea

Demodex Blepharitis

• Demodex folliculorum longus - anterior blepharitis
• Demodex folliculorum brevis - posterior blepharitis
• Collarettes (partially digested epithelial cells, keratin, mite waste/eggs at lash bases) - pathognomonic sign of Demodex infestation

Symptoms & Diagnosis

• Bilateral, symmetrical; no visual disturbance
• Burning, grittiness, mild photophobia, crusting (more common in anterior), stinging (more common in posterior)
• Poor correlation between symptom severity and clinical signs

Treatment

• Lid hygiene (warm compresses + lid scrubs) - cornerstone of treatment
• Topical antibiotics (for staphylococcal component)
• Topical/systemic steroids (short course for severe inflammation)
• Oral tetracyclines (doxycycline) - for MGD/rosacea-associated disease
• Tea tree oil - for Demodex (off-label)
• Artificial tears for associated dry eye

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2. Ptosis

Classification

Pseudoptosis

• Lack of globe support (artificial eye, microphthalmos, phthisis bulbi, enophthalmos)
• Contralateral lid retraction (compare lid levels; normal upper lid covers superior 2 mm of cornea)
• Ipsilateral hypotropia (upper lid follows globe downwards; disappears on covering the normal eye)
• Brow ptosis (seventh nerve palsy or dermatochalasis - diagnose by manually elevating the brow)

Clinical Evaluation

• Mild: up to 2 mm
• Moderate: 3 mm
• Severe: 4 mm or more

• Males: 7-10 mm | Females: 8-12 mm
• Upper lid normally rests ~2 mm below upper limbus; lower lid ~1 mm above lower limbus

• Normal: ≥15 mm | Good: 12-14 mm | Fair: 5-11 mm | Poor: ≤4 mm
• Measured by blocking frontalis action with thumb, then measuring excursion from full downgaze to full upgaze

• Males: ~8 mm | Females: ~10 mm
• Absent crease → poor levator function (congenital)
• High crease → aponeurotic defect (involutional)

• Pupils - exclude Horner syndrome (miosis + ptosis) and third nerve palsy (mydriasis + EOM defect)
• Chin-up head posture or brow elevation (compensatory)
• Amblyopia assessment in children

Important Causes to Exclude (Wills Eye Manual)

1. Horner syndrome
2. Third cranial nerve palsy (complete, partial, or aberrant regeneration)
3. Myasthenia gravis
4. Orbital tumour
5. Eyelid/conjunctival tumour
6. Chronic progressive external ophthalmoplegia (CPEO; especially Kearns-Sayre syndrome)

Ptosis Surgery

• Levator resection - for myogenic/congenital ptosis with fair-good levator function
• Levator aponeurosis repair/advancement - for aponeurotic (involutional) ptosis
• Fasanella-Servat (tarso-Müller's resection) - for mild Horner ptosis or small aponeurotic ptosis
• Brow suspension (frontalis sling) - for severe ptosis with poor levator function (poor levator function <4 mm)

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3. Ectropion

Types

Involutional (Age-Related) - Most Common

• Horizontal lid laxity - lid can be pulled ≥8 mm from globe and fails to snap back without blinking
• Lateral canthal tendon laxity - rounded lateral canthus; lower lid can be pulled medially >2 mm
• Medial canthal tendon laxity - inferior punctum displaced laterally; if severe, may reach the pupil

• Generalized ectropion → lateral tarsal strip procedure (shortens and reattaches lower canthal tendon to lateral orbital rim)
• Medial ectropion → medial spindle (conjunctival diamond excision), often combined with tarsal strip
• Pentagon excision is an alternative for focal disease

Cicatricial Ectropion

Paralytic (Facial Nerve Palsy) Ectropion

• Lubricants, taping at night
• Lateral tarsorrhaphy (temporary or permanent)
• Eyelid weighting (gold/platinum implant in upper lid) for lagophthalmos

Mechanical Ectropion

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4. Entropion

Involutional (Age-Related) Entropion - Most Common

• Irritation
• Punctate epithelial erosions
• In severe/long-standing cases: pannus formation and ulceration

1. Horizontal lid laxity (stretched canthal tendons + tarsal plate)
2. Vertical lid instability - attenuation/dehiscence of lower lid retractors (reduced lower lid excursion in downgaze)
3. Over-riding of pre-tarsal by preseptal orbicularis on lid closure → tips lid margin inwards
4. Orbital septum laxity with fat prolapse

• Lubricants, taping, bandage contact lens
• Orbicularis chemodenervation with botulinum toxin

• Transverse everting sutures - quick, lasts months; useful in frail/confused patients
• Wies procedure - full-thickness horizontal lid splitting + everting sutures; durable correction
• Lower lid retractor reinsertion - direct advancement of retractors; reserved for recurrence
• Lateral canthal sling (tarsal strip) - addresses co-existing horizontal laxity

Cicatricial Entropion

• Cicatrizing conjunctivitis
• Trachoma (most common worldwide cause)
• Chemical burns
• Stevens-Johnson syndrome / mucous membrane pemphigoid

Congenital Entropion

• Epiblepharon (most common in Asian children) - extra skin fold pushes lashes toward cornea; usually resolves spontaneously; surgery if causing persistent corneal staining

Trichiasis

• Epilation (temporary)
• Electrolysis, cryotherapy, or argon laser (for permanent ablation)

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5. Chalazion and Hordeolum (Wills Eye Manual, 6.2)

Definitions

• Chalazion: Focal sterile chronic granulomatous lipogranuloma of the meibomian gland (or Zeis gland), caused by retained sebaceous secretions. Obstruction leads to lipid leakage → giant cell reaction.
• Hordeolum (stye):
  • External (stye proper): acute infection/abscess of the glands of Zeis (or Moll) on the lid margin
  • Internal: acute infection/abscess of the meibomian gland
  • Both usually caused by Staphylococcus species

Chalazion Histopathology (Kanski)

• Extracellular fat deposits
• Lipid-laden epithelioid cells
• Multinucleated giant cells
• Lymphocytes

Associations

• Blepharitis (very common)
• Acne rosacea (multiple/recurrent chalazia)
• Bortezomib therapy (within 3 months of starting)

Clinical tip: A recurrent chalazion at the same site in an older patient should be biopsied to exclude malignancy (sebaceous gland carcinoma masquerading as chalazion).

Treatment

Caution: Intralesional steroid can cause permanent skin depigmentation/atrophy (especially in dark-skinned individuals). Rare risk of retrograde intra-arterial injection causing central retinal artery occlusion.

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6. Miscellaneous Acquired Eyelid Disorders

Dermatochalasis

Floppy Eyelid Syndrome

• Extremely lax upper eyelids that evert spontaneously during sleep
• Strong association with obstructive sleep apnoea and obesity
• Causes papillary conjunctivitis from mechanical trauma against pillow
• Treatment: protective eye shield, lateral tarsorrhaphy, or horizontal lid tightening

Blepharochalasis

Upper Lid Retraction

• Thyroid eye disease (most common) - fibrosis/overaction of Müller's muscle
• Contralateral ptosis (Hering's law)
• Aberrant 3rd nerve regeneration
• Parinaud syndrome (dorsal midbrain - bilateral upper lid retraction + upgaze palsy)
• Local anaesthetic injection

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7. Eyelid Tumors

Benign Tumors

Malignant Tumors

Basal Cell Carcinoma (BCC)

• Most common malignant eyelid tumor - 90% of all cases
• Most common in elderly, fair-skinned individuals; chronic sun exposure is the main risk factor
• Lower eyelid most common site, followed by medial canthus, upper eyelid, lateral canthus
• Medial canthal BCCs are most dangerous - prone to orbital/sinus invasion and higher recurrence
• Slow-growing, locally invasive, non-metastasizing
• Madarosis (lash loss) commonly seen

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Sebaceous Gland Carcinoma (SGC)

• Rare, slow-growing, potentially lethal
• Mostly elderly women; upper eyelid predominance (meibomian glands more numerous in upper lid)
• Arises from meibomian glands (most common), glands of Zeis, or caruncle

• Yellowish material within tumour - highly suggestive
• Nodular SGC: Hard nodule in upper tarsal plate with yellow discolouration → often mistaken for chalazion
• Spreading SGC: Diffuse lid margin thickening + lash loss → often mistaken for blepharitis
• Pagetoid spread (intraepithelial extension) - not uncommon; difficult to clear
• Madarosis common

• Upper lid involvement
• Tumour size ≥10 mm
• Symptoms duration >6 months

Clinical tip: SGC can be confused with chronic/recurrent localized meibomian gland inflammation. Always suspect in recurrent "chalazion" or unilateral "blepharitis" in an older patient.

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Squamous Cell Carcinoma (SCC)

• Second most common malignant eyelid tumor (~5%)
• Locally invasive; may metastasise to regional lymph nodes and beyond
• Lower lid and medial canthus most common sites
• Arise from actinic keratoses or de novo
• Predispositions: xeroderma pigmentosum, immunosuppression

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Melanoma

• Rare on the eyelids but potentially lethal
• Half of lid melanomas are non-pigmented (amelanotic) - may be missed
• Features suggesting melanoma: recent onset, change in pigmented lesion, irregular margins, asymmetric shape, color change, multiple colors, diameter >6 mm
• Lentigo maligna = melanoma in situ in sun-damaged skin (Hutchinson's freckle); malignant transformation in 3-10%

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8. Congenital Malformations

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Summary: Eyelid Malignancy Red Flags

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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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