Vitreous Substitutes - Types and Indications

What is the Vitreous?

Classification of Vitreous Substitutes

1. Gases (air and expansile gases)
2. Perfluorocarbon liquids (PFCLs)
3. Silicone oils (including combinations)

1. GASES

A. Air

• Least effective tamponade due to short duration
• Non-toxic, absorbed rapidly
• No special precautions for anesthesia

• Fluid-air exchange at the end of vitrectomy
• Macular hole surgery (small holes)
• Short-term tamponade after simple retinal detachment repair
• Descemet's membrane detachment (anterior segment use)

B. Sulfur Hexafluoride (SF₆)

• Expansile gas - expands to approximately twice its injected volume by absorbing surrounding gases
• Typically used as a 20-25% concentration (non-expansile) or pure (expansile)
• In the anterior segment: used in non-expansile concentration after DSAEK/endothelial keratoplasty to press the lamellar graft against the posterior cornea; also used to treat Descemet's membrane detachments after cataract surgery

• Rhegmatogenous retinal detachment (pneumatic retinopexy) - superior breaks
• Primary vitrectomy for uncomplicated retinal detachment
• Macular hole repair

• Post-DSEK/DSAEK to assist graft adherence (non-expansile concentration)
• Descemet's membrane detachment

C. Perfluoropropane (C₃F₈)

• Longest-lasting of the commonly used gases
• Expands to ~4 times injected volume
• Available in concentrations of 12-16% (non-expansile)

• Giant retinal tears (GRT)
• Complex retinal detachment with PVR (proliferative vitreoretinopathy) - as an alternative to silicone oil for moderately severe cases
• Macular hole surgery (especially large holes, high myopia)
• Inferior retinal breaks (when patient can maintain prone positioning)
• Cases requiring longer tamponade than SF₆ provides but shorter than silicone oil

Critical anesthesia point: Patients with any intraocular gas (SF₆ or C₃F₈) must NOT receive nitrous oxide (N₂O) during general anesthesia. N₂O rapidly diffuses into the gas bubble, causing dangerous expansion and acute elevation of IOP, which can result in vision loss. This restriction continues for the duration of the gas bubble (up to 2 months for C₃F₈).

Complications of Gases (All Types)

• Elevated intraocular pressure (IOP)
• Corneal edema
• Posterior subcapsular cataract
• Subretinal gas if injected under the retina
• Optic nerve damage from IOP spikes
• Positional requirements (face-down positioning) can be burdensome

2. PERFLUOROCARBON LIQUIDS (PFCLs)

• Perfluoro-n-octane (C₈F₁₈)
• Perfluorodecalin
• Perfluoroperhydrophenanthrene

• Immiscible with water; clear, colorless
• High density - sink posteriorly, push detached retina back
• Chemically inert but toxic to the retina with prolonged exposure
• Strictly intraoperative use only - must be removed at the end of surgery

• Giant retinal tears (GRT) - excellent for unfolding the inverted retina; considered gold standard intraoperatively for GRT
• Posterior dislocated lens fragments or IOL - to float the nucleus/IOL forward
• Subretinal proliferation removal
• Stabilizing the posterior pole during complex membrane peeling
• Reattaching the posterior retina while working anteriorly
• Combined traction-rhegmatogenous retinal detachments

3. SILICONE OIL (SO)

Standard Silicone Oil (Lighter than Water)

• Floats on aqueous - provides tamponade of superior retinal breaks
• 1000 cs (lower viscosity): easier to inject/remove, slightly higher emulsification risk
• 5000 cs (higher viscosity): more resistant to emulsification, harder to remove
• Must be surgically removed (usually after 3-6 months)

• Complex retinal detachment with severe PVR (grade C or higher) - the most common indication
• Giant retinal tears (GRT) especially when the patient cannot maintain face-down positioning
• Tractional retinal detachment (e.g., from proliferative diabetic retinopathy)
• Pediatric retinal detachments (unable to cooperate with positioning requirements of gas)
• HIV retinopathy / CMV retinitis with associated retinal detachment
• Ocular trauma with retinal detachment
• Cases where re-operation is anticipated
• Phthisis-prone eyes
• Inferior retinal breaks that cannot be treated adequately with gas
• When the patient cannot fly (gas bubbles expand at altitude)

• Glaucoma (most common serious complication): emulsified droplets block trabecular meshwork
• Cataract (posterior subcapsular and nuclear)
• Corneal edema and band keratopathy (from emulsified oil in the anterior chamber, especially in aphakic eyes)
• Emulsification of oil over time
• Retinal toxicity (long-term)
• Hypotony after removal
• Inferior oil keratopathy in aphakes

Heavy Silicone Oil (HSO) / SO-PFA Combinations

• Density slightly greater than vitreous/aqueous
• FDA/CE approved combinations (e.g., Oxane HD - silicone oil + perfluorohexyloctane)
• Different refractive index than standard SO

• Inferior retinal detachment with PVR
• Inferior giant retinal tears
• Cases where inferior tamponade is needed but patient cannot position face-down
• Lower retinal breaks not amenable to conventional SO or gas

• Risk of superior oil keratopathy
• Different emulsification profile
• Less clinical data compared to standard SO

COMPARISON TABLE

SPECIAL CONSIDERATIONS

Posturing Requirements

• Gas (air, SF₆, C₃F₈): Patients need face-down positioning to bring the gas bubble to tamponade superior or posterior breaks. Duration depends on the gas used.
• Standard SO: Patients should lie on their back (face up) so oil floats to tamponade superior breaks.
• Heavy SO: Patients lie face down to bring the heavy oil to the inferior retina.

Contraindications to Gas Tamponade

• Inability to maintain required positioning
• Contralateral poor vision (risk of temporary visual loss from the gas)
• Anticipated need for general anesthesia soon (N₂O risk)
• Air travel within the gas resorption period (expansion at altitude)

The "Ideal" Vitreous Substitute

• Optically clear, non-toxic, biocompatible
• Stable over the long term without emulsification
• Correct density and viscosity to maintain retinal tamponade
• Self-resorbing with no surgical removal needed
• Able to serve as a drug delivery vehicle

SOURCES

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (Table 74-14, Vitreous Substitutes section)
• Shettigar MP et al. (2024). Vitreous substitutes and tamponades - A review. Indian Journal of Ophthalmology [PMID: 39078953]
• Siwik P et al. (2025). Retinal displacement following vitrectomy for RRD. J Clin Med [PMID: 39797332]
• Mondelo-Garcia C et al. (2021). Current Situation and Challenges in Vitreous Substitutes. Macromol Biosci [PMID: 33987966]

Impression Cytology - Short Note

Definition and Introduction

Relevant Anatomy

• The anterior surface of the globe (bulbar conjunctiva)
• The posterior surface of the eyelids (palpebral conjunctiva)

• Arise from the basal layer of the epithelium
• Are most concentrated in the inferonasal quadrant
• Are responsible for the mucin layer of the tear film
• Are destroyed by chronic inflammation and severe dry eye
• Are a marker of conjunctival health - their density reflects ocular surface status

Technique

1. Patient Preparation

• Topical anesthesia is applied (e.g., proparacaine 0.5%), though the procedure can be done without it
• The ocular surface is dried carefully - excessive tears or medications are wiped away to maximize cell yield
• Patient looks in the direction opposite to the area being sampled

2. Filter Paper Preparation

• Standard filter: Cellulose acetate filter paper (Millipore, pore size 0.025-0.45 µm), cut into strips approximately 5 × 10 mm
• Newer alternatives: pure nitrocellulose membranes (better for immunocytochemistry)
• The filter is applied with firm, even pressure to the area of interest for 2-5 seconds
• Generally 2-3 layers of cells are removed per application
• Deeper layers can be sampled by repeat application at the same site

3. Sites of Sampling

• Bulbar conjunctiva (nasal and temporal quadrants most common)
• Tarsal conjunctiva
• Limbal area
• Corneal surface (when conjunctivalization is suspected)

4. Staining Methods

Grading Systems

Nelson's Classification (for squamous metaplasia)

Grade 2 or higher = Abnormal (pathological squamous metaplasia)

Tseng's Classification

• Presence/absence and density of goblet cells
• Nuclear morphology and nucleus-to-cytoplasm (N:C) ratio
• Metachromatic changes in cytoplasmic color
• Emergence of keratinization

Indications

1. Dry Eye Disorders

• Keratoconjunctivitis sicca (KCS) / Sjögren's syndrome - assess goblet cell loss and squamous metaplasia
• Vitamin A deficiency - one of the earliest and most sensitive markers; xerophthalmia staging
• Superior limbic keratoconjunctivitis (SLK)

2. Cicatricial / Inflammatory Conditions

• Cicatricial ocular pemphigoid (MMP) - staging fibrosis and metaplasia
• Stevens-Johnson syndrome / Toxic epidermal necrolysis
• Trachoma
• Vernal keratoconjunctivitis (VKC) - eosinophils and goblet cell changes
• Atopic keratoconjunctivitis
• Graft-versus-host disease (GVHD) affecting the ocular surface

3. Limbal Stem Cell Deficiency (LSCD)

• Diagnosis of conjunctivalization of the cornea
• Monitoring after limbal stem cell transplantation
• Chemical/thermal burns
• Aniridia

4. Neoplastic / Pre-neoplastic Conditions

• Ocular Surface Squamous Neoplasia (OSSN) - dysplasia, CIN, SCC
  • Sensitivity: ~80% accuracy for predicting histological diagnosis
  • 77% predictability for moderate dysplasia
• Conjunctival melanoma / primary acquired melanosis (PAM)
• Differentiating benign vs. malignant lesions

5. Infections

• Acanthamoeba keratitis - IC has a yield as high as 94.6%, higher than corneal scraping in some reports
• Viral conjunctivitis (inclusion bodies)
• Chlamydial conjunctivitis
• Fungal keratitis

6. Systemic Disease Monitoring

• Mucopolysaccharidoses
• Epidermolysis bullosa
• Ichthyosis
• Psoriasis affecting the ocular surface

7. Treatment Monitoring

• Assessing response to topical cyclosporine, vitamin A drops, or anti-inflammatory therapy
• Post-limbal stem cell transplantation
• Documenting sequential changes over time (serial IC)

Advantages

• Non-invasive / minimally invasive - no surgical excision required
• Easy to perform in the outpatient clinic
• Minimal patient discomfort
• Can be repeated serially to monitor disease progression or treatment response
• Allows multiple types of analysis (histology, immunocytochemistry, molecular)
• Does not disturb the deeper epithelial layers
• No need for local injection or surgical setup

Limitations

• Only the superficial 2-3 epithelial layers are sampled - subepithelial pathology is not accessible
• Sampling variability - cell yield can vary considerably with technique
• Drying of the ocular surface is essential but technically challenging
• False negatives can occur in patchy lesions
• Cannot replace histopathological biopsy for definitive diagnosis of malignancy
• Immunocytochemistry on cellulose acetate is technically difficult (background staining, antigen destruction with xylene)
• Requires an experienced cytopathologist for interpretation

Summary

• Singh R et al. (2005). Impression cytology of the ocular surface. Br J Ophthalmol [PMID: 15834085] - foundational review, 344 citations
• EyeWiki: Impression Cytology - American Academy of Ophthalmology
• Laver NMV (2021). Ocular cytology: Diagnostic features and ongoing practices. Cancer Cytopathology [PMID: 33136340]

Choroidal Effusion (Choroidal Detachment) - Short Note

Definition

Types

Etiology

Serous Choroidal Effusion

• Wound leak or filtering bleb over-filtration (after trabeculectomy / glaucoma drainage surgery)
• Perforation of the sclera from a superior rectus bridle suture
• After retinal detachment repair (scleral buckling or vitrectomy)
• After laser photocoagulation or cryotherapy
• Cyclodialysis cleft (traumatic or surgical)
• Post-cataract surgery

• Ruptured globe
• Blunt ocular trauma

• Posterior uveitis
• Posterior scleritis
• Sympathetic ophthalmia

• Sulfonamide drugs: acetazolamide, topiramate (ciliary body edema causing anterior rotation and angle closure)

• Nanophthalmos / uveal effusion syndrome
• Carotid-cavernous fistula
• Primary or metastatic choroidal tumor
• Hypotony from any cause
• Chronic rhegmatogenous retinal detachment

Hemorrhagic Choroidal Detachment

• Intraoperative (expulsive hemorrhage): Rupture of short posterior ciliary arteries during anterior displacement of ocular contents - the most feared intraoperative complication
• Postoperative
• Spontaneous (especially in patients on anticoagulants)
• Perforation of a corneal ulcer

Clinical Features

Fundus Appearance

Choroidal detachment - characteristic smooth, orange-brown bullous peripheral elevation (Wills Eye Manual)

• Four lobes typically present, separated by the vortex veins
• Temporal and nasal bullae tend to be most prominent
• Elevations are convex, smooth, and relatively immobile (unlike RD which undulates with eye movement)
• The ora serrata can be seen without scleral depression (elevations extend beyond the ora serrata anteriorly)
• Elevations do not extend to the posterior pole - limited by the vortex veins entering their scleral canals
• "Kissing choroidals" - when two large lobules of detached choroid appose each other in the central vitreous cavity, obscuring the view of the fundus

Symptoms

• Decreased vision (if extends posteriorly or involves the macula)
• Visual field defect (peripheral shadow) if extensive
• No photopsia or floaters (no vitreoretinal traction)
• Often asymptomatic if peripheral

• Moderate to severe pain
• Red eye
• Sudden marked visual loss

Slit Lamp / Anterior Segment

Differential Diagnosis

Investigations (Workup)

1. History - Recent ocular surgery, trauma, medication use (topiramate, acetazolamide), systemic disease
2. Slit lamp examination - Anterior chamber depth, Seidel test (to rule out wound leak / filtering bleb leak)
3. Gonioscopy - Look for cyclodialysis cleft
4. Dilated fundus examination - Extent and location of choroidal elevation; assess for concomitant RD; examine the contralateral eye
5. B-scan ultrasonography - Most useful investigation:
   • Distinguishes serous (optically empty, low reflectivity) from hemorrhagic (echogenic)
   • Determines if hemorrhage is mobile (fresh) or coagulated (organized, solid)
   • Shows characteristic V-shaped or dome-shaped elevation
   • Rules out intraocular tumor
6. Transillumination of globe - Serous transilluminates; hemorrhagic does not

Management

General Treatment (Both Types)

1. Cycloplegic - Atropine 1% three times daily (deepens anterior chamber, reduces ciliary spasm, prevents posterior synechiae)
2. Topical corticosteroids - Prednisolone acetate 1% four to six times per day (reduces inflammation)
3. Oral corticosteroids - Consider in inflammatory cases

Surgical Drainage - Indications

1. Flat anterior chamber - especially with inflammation (risk of peripheral anterior synechiae, PAS)
2. Lens-corneal touch (Grade III flat chamber) - surgical emergency; prompt correction needed to prevent corneal decompensation and lens opacification
3. "Kissing" choroidals with:
   • Intractable pain, or
   • IOP elevation
   • (Note: kissing choroidals alone can be tolerated if no pain or IOP rise)
4. Progressive shallowing of anterior chamber unresponsive to medical treatment

Specific Treatment - Directed at Underlying Cause

Uveal Effusion Syndrome (Special Entity)

• Affects middle-aged hypermetropic men predominantly
• Often bilateral
• Associated with nanophthalmos (abnormally small eye) or abnormal scleral thickness/composition
• Pathogenesis: impaired fluid drainage from choroid via sclera or vortex veins
• Fundus: ciliochoroidal detachment + exudative RD; on resolution, characteristic "leopard spot" RPE mottling due to protein-rich SRF
• Treatment: Full-thickness sclerectomy, particularly in nanophthalmos

Summary

• The Wills Eye Manual, 8th ed. - §11.27 Choroidal Effusion/Detachment
• Kanski's Clinical Ophthalmology, 10th ed. - Choroidal Detachment & Uveal Effusion Syndrome

Metabolic Diseases Involving Ocular Structures

Introduction

I. DISORDERS OF CARBOHYDRATE METABOLISM

1. Diabetes Mellitus

• "Snowflake" or "metabolic" cataract in type 1 DM - bilateral, rapid subcapsular opacification from sorbitol accumulation
• Nuclear sclerosis accelerated in type 2 DM
• Mechanism: Aldose reductase converts glucose → sorbitol → osmotic damage to lens fibers

• New vessels on iris (rubeosis) from VEGF secretion in ischemic retina
• Progress to neovascular glaucoma with angle closure

• Reduced corneal sensitivity (peripheral neuropathy)
• Persistent epithelial defects (diabetic keratopathy)
• Susceptibility to recurrent erosions

• Acute hyperglycemia → lens swelling → myopia (from increased refractive index)
• Glucose-induced osmotic shifts in lens

• Ischemic mononeuropathy affects CN III, IV, VI
• Pupil-sparing CN III palsy is characteristic (ischemia spares outer pupillomotor fibers)

• Non-arteritic anterior ischemic optic neuropathy (NAION) - more common in diabetics

2. Galactosemia

• Cataract - the hallmark; may be the sole manifestation in galactokinase deficiency
• Characteristic "oil-droplet" opacity - seen with retroillumination, a central nuclear opacity resembling an oil droplet in water
• In classic galactosemia: associated with mental retardation, cirrhosis, sepsis
• May be reversible with early dietary galactose restriction (neonatal screening is key)
• Mechanism: galactose → galactitol accumulation in lens → osmotic damage

II. DISORDERS OF AMINO ACID METABOLISM

3. Homocystinuria

• Ectopia lentis (lens subluxation) - most characteristic; typically bilateral, inferior and medial subluxation (downward and inward) - contrast with Marfan's where subluxation is superior and temporal
• Lens dislocation can be complete, causing acute angle-closure glaucoma
• Myopia (due to axial elongation and lens changes)
• Retinal detachment (secondary to lens dislocation)
• Optic atrophy (from vascular occlusions)
• Thromboembolic tendency → central retinal artery/vein occlusion

4. Alkaptonuria (Ochronosis)

• Scleral ochronosis - brownish-black pigmentation of the sclera, most prominent in the horizontal palpebral fissure (anterior to the insertions of the lateral and medial rectus muscles) - pathognomonic
• Conjunctival pigmentation
• Corneal involvement (rare)

5. Tyrosinemia (Type II - Richner-Hanhart Syndrome)

• Dendritic corneal ulcers (may be mistaken for herpetic keratitis)
• Corneal crystals
• Photophobia and lacrimation
• Associated with palmoplantar keratoderma and intellectual disability

III. DISORDERS OF LIPID / SPHINGOLIPID METABOLISM (STORAGE DISEASES)

6. Tay-Sachs Disease (GM₂ Gangliosidosis)

• Cherry-red spot at the macula - the single most important sign
• Pathogenesis: ganglioside accumulation in all ganglion cells of the retina → retina appears white/opaque; however, the foveola has no ganglion cells → underlying choroidal circulation shows through as a red spot against the white surrounding retina
• Progressive optic atrophy and blindness
• Also seen in: GM₁ gangliosidosis, Niemann-Pick disease, Sandhoff disease, metachromatic leukodystrophy (rarely), Farber disease, sialidosis

7. Niemann-Pick Disease

• Cherry-red spot (Types A and B)
• Ocular motor apraxia (inability to initiate voluntary saccades) - Types C and D
• Impairment of vertical gaze (Type C - supranuclear vertical gaze palsy)
• Macular degeneration

8. Gaucher Disease

• Pinguecula-like conjunctival changes (wedge-shaped yellow-brown triangular deposits near limbus)
• Ocular motility defects - jerky eye movements, limited abduction (late infantile form)
• Macular degeneration (occasionally)

9. Fabry Disease (X-Linked Lysosomal Storage Disorder)

• Cornea verticillata (vortex keratopathy) - bilateral whorl-like subepithelial opacities radiating from a central point, visible on slit-lamp; does not affect vision but is virtually pathognomonic
• Spoke-wheel lens opacities - anterior and posterior subcapsular cataracts in a spoke-wheel pattern
• Dilated tortuous conjunctival and retinal vessels ("Fabry vessels")
• Retinal vascular occlusions

Note: Cornea verticillata is also caused by amiodarone, chloroquine, indomethacin - drug-induced keratopathy (important differential)

10. Mucopolysaccharidoses (MPS)

IV. DISORDERS OF COPPER METABOLISM

11. Wilson's Disease (Hepatolenticular Degeneration)

• Golden-to-greenish-brown ring in the peripheral cornea (Descemet's membrane)
• Copper deposits in Descemet's membrane; fluid streaming favors accumulation near the limbus
• Starts at the superior and inferior poles (12 and 6 o'clock), then progresses circumferentially
• Best seen with slit-lamp examination; may not be visible to the naked eye in early stages
• Present in virtually 100% of patients with neurological Wilson's disease
• May disappear with successful chelation therapy (penicillamine, trientine)

• A disc-shaped, greenish-brown posterior subcapsular cataract with petal-like projections resembling a sunflower
• Due to copper deposition in the lens
• Rare but specific for Wilson's disease
• Does not impair vision significantly
• Also resolves with copper chelation

V. DISORDERS OF PURINE METABOLISM

12. Gout (Hyperuricemia)

• Episcleritis and scleritis - urate deposits in episcleral/scleral tissue causing inflammation
• Band keratopathy - calcium deposits (secondary to chronic uveitis from gout)
• Urate crystals in conjunctiva and cornea - rare direct deposits
• Acute anterior uveitis - urate crystal-induced inflammation
• Corneal urate crystalline keratopathy - rare, subepithelial yellow-white deposits

VI. ENDOCRINE METABOLIC DISORDERS

13. Thyroid Eye Disease (Graves' Ophthalmopathy / TED)

• Lid retraction - most common sign; Dalrymple's sign (upper lid retraction - sclera visible above limbus)
• Lid lag - von Graefe's sign (upper lid lags behind globe on downgaze)
• Stellwag's sign (infrequent blinking)
• Joffroy's sign (absent forehead wrinkling on upgaze)

• Usually bilateral but often asymmetric
• Hertel exophthalmometry measures the degree

• Restrictive myopathy from muscle fibrosis
• Order of frequency: Inferior rectus > Medial rectus > Superior rectus > Lateral rectus (mnemonic: I'M SLow or I'M a Slow Learner)
• Inferior rectus restriction → limitation of upgaze (most common motility complaint)
• Diplopia on extremes of gaze

• From compression of optic nerve at orbital apex by enlarged extraocular muscles
• Presents with decreased vision, color vision defect, RAPD
• Most serious complication of TED

• Exposure keratopathy from incomplete lid closure (lagophthalmos)
• Conjunctival chemosis and injection
• Superior limbic keratoconjunctivitis (SLK)

14. Hypothyroidism

• Periorbital puffiness/myxedema (mucopolysaccharide infiltration of dermis)
• Loss of outer third of eyebrows (Hertoghe's sign)
• Dry eye
• Delayed relaxation of extraocular movements

VII. DISORDERS OF CALCIUM METABOLISM

15. Hypercalcemia (Hyperparathyroidism, Sarcoidosis, Vitamin D toxicity)

• Band keratopathy - calcium (calcium hydroxyapatite) deposits in Bowman's layer, initially at the 3 and 9 o'clock positions (within the palpebral aperture), eventually forming a band across the cornea with characteristic "Swiss cheese" holes (from corneal nerve perforations)
• Conjunctival calcium deposits ("conjunctival calcification")
• Calcium deposits in eyelid skin (metastatic calcification)

VIII. LIPID DISORDERS

16. Hyperlipidemias

• Arcus senilis (Corneal arcus) - bilateral white-grey lipid (cholesterol ester) arc/ring in the peripheral stroma with a clear zone between it and the limbus; normal in elderly but arcus in patients < 45 years suggests hyperlipidemia (Type II)
• Xanthelasma - yellowish cholesterol deposits in the nasal eyelid skin (particularly type IIa and III hyperlipoproteinemia)
• Xanthomas of eyelids - also represent lipid deposits
• Lipemia retinalis - triglycerides > 2000 mg/dL → creamy-white retinal vessels ("salmon-colored" arteries and veins) from chylomicrons; typically in type I or V hyperlipoproteinemia

IX. DISORDERS OF AMINO ACID TRANSPORT

17. Cystinosis

• Corneal cystine crystals - polychromatic, needle-shaped crystals distributed throughout the full-thickness corneal stroma; visible on slit-lamp; cause photophobia, blepharospasm, and eventually corneal erosions
• The most characteristic ocular sign; corneal crystals develop in the first year of life
• Retinal pigment epithelial changes ("salt-and-pepper" retinopathy)
• Photophobia is often the presenting complaint
• Treatment: Topical cysteamine drops dissolve corneal crystals

18. Marfan Syndrome (Fibrillin-1 Defect / Connective Tissue - Associated)

• Ectopia lentis - bilateral, typically superior and temporal subluxation of the lens (zonular dehiscence); in ~60% of patients
• Iridodonesis (trembling of the iris with eye movement - loss of zonular support)
• High myopia (axial elongation)
• Flat cornea (decreased keratometry)
• Increased risk of rhegmatogenous retinal detachment
• Megalocornea, glaucoma

Comparison of ectopia lentis:

• Marfan syndrome: superotemporal subluxation
• Homocystinuria: inferonasal subluxation
• Weill-Marchesani: microspherophakia, anteroinferior subluxation

X. LYSOSOMAL ENZYME DEFICIENCY

19. Metachromatic Leukodystrophy (MLD)

• Optic atrophy and blindness (progressive)
• Brown-colored macula (granular pigmentation)
• Nystagmus
• Absent foveal reflex

SUMMARY TABLE: Key Ocular Signs in Metabolic Diseases

• Kanski's Clinical Ophthalmology, 10th ed. - Thyroid Eye Disease, Ectopia Lentis, Uveal conditions
• The Wills Eye Manual, 8th ed. - Cataract Etiology, Metabolic Cataracts
• Adams & Victor's Principles of Neurology, 12th ed. - Ophthalmic Signs in Metabolic/Storage Diseases
• Harrison's Principles of Internal Medicine, 22nd ed. - Wilson's Disease, Graves' Ophthalmopathy
• Goldman-Cecil Medicine - Wilson's Disease
• Sleisenger & Fordtran's GI and Liver Disease - Kayser-Fleischer ring