Age-Related Macular Degeneration (ARMD)

Definition & Epidemiology

Pathogenesis

Dry AMD (left): drusen deposits, RPE atrophy, photoreceptor damage. Wet AMD (right): choroidal neovascularization, subretinal hemorrhage, intraretinal fluid.

Two Major Forms

Dry (Nonexudative / Atrophic) ARMD

• More common (~85–90%); usually precedes wet form
• Characterized by drusen — abnormal lipoprotein deposits within the RPE basement membrane (Bruch membrane), and geographic atrophy of the RPE
• Drusen types:
  • Hard drusen: small, well-defined (less significant)
  • Soft drusen: >60 μm, hypopigmented spots — higher risk of progression
• Lipofuscin accumulates in stressed RPE cells
• Symptoms: gradual, painless central vision loss; may be asymptomatic for years

Dry AMD with macular drusen (fine scattered deposits)

Wet (Neovascular / Exudative) ARMD

• Less common but causes the most profound vision loss
• Frail choroidal neovascular channels (CNV) breach Bruch membrane → grow into subretinal space beneath the RPE → leak fluid, blood, lipids
• Subretinal hemorrhage → acute, often permanent central visual acuity loss
• Both eyes typically affected to similar degree

Wet (exudative) AMD: subretinal hemorrhage and exudates

Key point: Dry and wet AMD are not simply sequential — they can coexist and each develops through distinct pathways. However, dry AMD can convert to wet AMD, especially with soft drusen + RPE clumping.

Types of CNV Lesions (Wet ARMD)

Symptoms

• Dry: Gradual central vision loss, Amsler grid changes; peripheral vision preserved
• Wet: Acute/subacute central/paracentral scotoma, metamorphopsia (distorted vision), photopsias; sudden vision loss with hemorrhage

Patients with advanced disease can walk down a street (peripheral retinal function intact) but cannot recognize facial features (macular function lost).

Investigations / Workup

1. Amsler grid / preferential hyperacuity perimetry (PHP): Detects central scotoma or metamorphopsia; key for monitoring conversion to wet form
2. Fundus biomicroscopy (60/90 D or fundus contact lens): Assess drusen type, geographic atrophy, signs of CNV
3. Fluorescein angiography (IVFA): Confirms CNV size, type, location; classic vs. occult lesions
4. OCT (optical coherence tomography): Primary modality for follow-up; assesses retinal thickness, SRF, ME, RPE detachment, CNV extent
5. OCTA: Non-invasive alternative to IVFA; useful if FA contraindicated (pregnancy, fluorescein allergy)
6. ICGA (Indocyanine green angiography): Better delineates occult CNV borders, RAP, and IPCV lesions

Management

Dry ARMD

• No curative treatment currently available
• AREDS2 formula supplements (Vitamins C & E + lutein + zeaxanthin + zinc + copper): Shown to retard progression from moderate → advanced AMD
  • ⚠️ β-carotene NOT recommended in smokers (increased lung cancer risk)
• Lifestyle modifications: Smoking cessation (most important modifiable risk factor), control of BP, blood sugar, and lipids
• Monitoring: Regular Amsler grid home testing; urgently seek evaluation if new metamorphopsia develops
• Complement inhibitors (e.g., pegcetacoplan): Emerging therapy targeting geographic atrophy progression

Wet ARMD — Anti-VEGF Therapy (Mainstay)

• Dosing regimens: PRN (treat and observe), treat-and-extend (TAE), or fixed interval — individualized based on disease activity
• Risk with wet AMD in one eye: 10–12% per year risk of CNV in the fellow eye

Additional Treatments

• Photodynamic therapy (PDT) with verteporfin: IV photosensitizing dye + cold laser; FDA-approved; given q3 months PRN; now mainly used in IPCV
• Vitrectomy: For massive subretinal hemorrhage in advanced cases
• Low vision aids: Special glasses, video-based magnification — help maintain independence

Key Differentials

Summary

• Dry: AREDS2 supplements + lifestyle modification + monitoring
• Wet: Prompt intravitreal anti-VEGF therapy — time-sensitive; delays lead to irreversible photoreceptor loss

Vitreous Substitutes

Classification

1. Gases

Air

• Duration of tamponade: 3–7 days
• Absorbed fastest; used for straightforward cases or short-term tamponade (e.g., after macular hole surgery)
• Non-expansile

Sulfur Hexafluoride (SF₆)

• Duration: 10–14 days
• Expansile — expands to ~2× original volume as it equilibrates with body gases; must be used at appropriate concentrations to avoid overfill
• Also used in anterior segment:
  • Non-expansile concentration after endothelial keratoplasty (DSAEK/DMEK) — helps graft adherence; patient lies face-up 3–5 days
  • Treats Descemet's membrane detachments post-cataract surgery

Perfluoropropane (C₃F₈)

• Duration: 55–65 days — longest-lasting gas
• Most expansile (~4× volume); highest risk of IOP elevation if over-concentrated
• Preferred for complex cases requiring prolonged tamponade (e.g., giant retinal tears, inferior breaks)

Key Points for Gases

• Patient posturing is mandatory to position the gas bubble over the retinal break
• ⚠️ Flying contraindicated while gas is in the eye — cabin pressure changes cause dangerous expansion → acute angle-closure glaucoma
• ⚠️ Nitrous oxide (N₂O) anaesthesia contraindicated — N₂O diffuses into gas bubble causing massive expansion
• Complications: elevated IOP, corneal edema, cataract (feathering of posterior subcapsular lens — usually transient), subretinal gas migration, pupillary block

2. Perfluorocarbon Liquids (PFCL)

• Examples: Perfluoro-n-octane, perfluorodecalin
• Specific gravity: 1.76–1.94 — much denser than vitreous and water; sink to the bottom of the eye
• Therefore tamponade the inferior retina (opposite to gases)
• Intraoperative use only — used to:
  • Flatten and stabilize the detached retina during surgery
  • Unroll giant retinal tears
  • Float and displace subretinal blood anteriorly
  • Stabilize the retina during membrane peeling in PVR
• After achieving retinal reattachment intraoperatively, PFCL is replaced by gas or silicone oil before wound closure
• Long-term retention is toxic to the retina — cannot be left in permanently

3. Silicone Oil (SO)

Properties

• Lighter than water (floats) → tamponades superior retina
• Clear, transparent — allows good visual acuity and fundus visualization
• Permanent/semi-permanent — remains until surgically removed
• Does not require strict posturing (unlike gas)

Indications

• Complex retinal detachments with PVR (grade C or worse)
• Giant retinal tears
• Trauma cases
• Retinal detachments with poor visual potential requiring longer tamponade
• Patients who cannot comply with face-down posturing
• CMV retinitis–related detachments (success rate ~75% with vitrectomy + SO + endolaser)
• Where air travel is required post-operatively (SO is not affected by altitude)

Viscosity Comparison

SO-PFA Combinations (Heavy Silicone Oil)

• Silicone oil combined with partially fluorinated alkanes (e.g., RMN-3, Oxane HD)
• Specific gravity close to 1 — sits at bottom → tamponades inferior retina
• Useful for inferior retinal breaks and PVR where conventional SO cannot reach
• FDA-approved for clinical use

Complications of Silicone Oil

Silicone Oil Removal

• Generally removed after 3–6 months once retinal reattachment is stable
• Early removal reduces risk of emulsification-related complications (glaucoma, cataract)
• Some eyes require permanent tamponade (one-eyed patients, poor surgical access)

Comparison Summary

Clinical Use: Tamponade Selection Guide

Uncomplicated posterior break (macular hole) → Air or SF₆
Superior breaks → SF₆ or C₃F₈ (gas)
Inferior breaks → Heavy SO (SO-PFA) or PFCL intraop then inferior gas
Complex PVR / cannot posture / needs to fly → Silicone oil
Giant retinal tear → PFCL intraop → C₃F₈ or SO
CMV retinitis detachment → SO + endolaser

Coats Disease

Definition

Epidemiology

• Age: Predominantly presents in the first decade of life (early childhood); may present at any age
• Sex: ~75% male
• Laterality: ~95% unilateral
• Inheritance: Not obviously inherited; idiopathic — but a genetic predisposition may exist. At least some patients have a somatic mutation in the NDP gene (the same gene mutated in Norrie disease)
• Leber miliary aneurysms: Previously considered a separate entity; now regarded as a milder, later-presenting form of the same disease with a better visual prognosis
• Younger children tend to have a more aggressive clinical course

Pathogenesis

Clinical Features

Symptoms

• Leukocoria (white pupillary reflex) — most common presenting feature
• Unilateral visual loss
• Strabismus (often first noticed by parents)
• Pain (with secondary glaucoma)

Fig. 13.57A: Leukocoria in Coats disease — note the yellow-orange reflex in the left eye vs normal right eye

Fundus Signs

• Retinal telangiectasia and fusiform focal aneurysmal arteriolar dilatations — often initially in the inferior and temporal quadrants between the equator and ora serrata

Fig. 13.57B: Retinal telangiectasia and aneurysmal dilatations (arrow)

• Intra- and subretinal exudates — characteristically affecting areas remote from the vascular abnormalities (lipid migrates to the macula = circinate exudation)
• Progression to extensive exudative retinal detachment

Advanced Coats disease: exudative retinal detachment with subretinal lipoproteinaceous material

Complications (End-Stage Disease)

• Rubeosis iridis (iris neovascularization)
• Neovascular glaucoma
• Uveitis
• Cataract
• Phthisis bulbi (end-stage atrophy of the globe)

Investigations

Fluorescein Angiography (FA)

• Early (venous) phase: Hyperfluorescence of telangiectasis and aneurysmal dilatations
• Late phase: Extensive hyperfluorescence from leakage and staining

OCT

• Useful for macular assessment in cooperative older children
• Demonstrates intraretinal and subretinal fluid

Ultrasound (B-scan)

• Shows exudative retinal detachment without mass (helps exclude retinoblastoma)
• No calcification (contrast with retinoblastoma)

CT/MRI (Imaging)

• CT: Increased attenuation along the subretinal space or filling the entire vitreous cavity
• MRI: Increased T1 and T2 signal due to lipoproteinaceous material
• No contrast enhancement (distinguishes from retinoblastoma, which enhances)

Differential Diagnosis

Key clinical rule: Any child with leukocoria or suspected Coats disease must have retinoblastoma excluded — this is a potentially life-threatening diagnosis.

Staging (Shields Classification)

Management

Observation

• Mild, non-vision-threatening disease
• Comfortable blind eye with total retinal detachment where no useful vision is recoverable

Laser Photocoagulation (Preferred)

• Ablation of telangiectatic/leaking vessels
• Indicated when progressive exudation is documented
• Multiple repeated treatments over extended time are commonly required
• Still preferred over cryotherapy when accessible

Anti-VEGF Therapy

• Limited studies but initial results promising — both as monotherapy and adjunct to laser
• Long-term safety in childhood not yet established

Intravitreal Triamcinolone (2–4 mg)

• Used with good effect in eyes with total exudative retinal detachment
• Reduces exudation and promotes retinal reattachment

Cryotherapy

• Double freeze-thaw method
• Used in eyes with extensive exudation or subtotal retinal detachment
• ⚠️ May cause marked inflammatory reaction with increased leakage — laser preferred if possible

Vitreoretinal Surgery

• For eyes with significant tractional preretinal fibrosis or total exudative detachment
• Poor visual prognosis but retinal reattachment may prevent neovascular glaucoma

Enucleation

• Reserved for painful eyes with neovascular glaucoma where no visual potential remains

Prognosis

• Highly variable — depends on severity at presentation and age
• Younger children → more aggressive course
• Vision is frequently severely compromised in advanced cases, particularly when the macula is involved with exudate at first presentation
• Treatment can stabilize the disease but rarely restores significantly reduced vision