The lecture lists a systematic exam progressing from simple bedside tests to specialist investigations. ^[1]

Definition: Clouding of the crystalline lens. ^[1]

The crystalline lens is a transparent, biconvex structure behind the iris that focuses light onto the retina. Any loss of transparency = cataract.

Types of cataract: ^[1]

Three types based on anatomy: Nuclear sclerotic, Cortical, Posterior subcapsular. ^[1]

Multifactorial: Compaction and stiffening of central lens material; chemical and structural changes in lens protein leading to loss of transparency; pigmentation of lens protein → yellow → brown. ^[1]

From first principles: The lens grows throughout life by adding new fibre cells peripherally. Old central fibres get compressed (nuclear sclerosis). Crystallin proteins in the lens aggregate and become insoluble over time due to oxidative damage, UV exposure, and loss of protective mechanisms (glutathione depletion). Large protein aggregates scatter light instead of transmitting it → opacity. Pigment accumulates in the nucleus (yellow → brown → black in hypermature cataracts).

Gradual painless blurring of vision, glare, refractive changes, loss of contrast. ^[1]

• Painless — this is key. Pain suggests another process such as acute angle closure, uveitis, keratitis or lens-induced inflammation rather than an uncomplicated cataract.
• Glare — scattered light from opacities, especially bothersome at night driving.
• Refractive changes — nuclear sclerosis → index myopia (patient needs stronger minus lenses).
• Loss of contrast — colours look washed out; difficulty distinguishing similar shades.

Decreased best corrected visual acuity; refraction changes (e.g. index myopia); decrease in red reflex; slit lamp examination shows lens opacification. ^[1]

The red reflex test (using a direct ophthalmoscope at arm's length) is the most useful bedside test. A normal red reflex means light passes through transparent media. A cataract appears as a dark shadow against the orange reflex.

Inflammation (uveitis), lens subluxation or dislocation, secondary glaucoma (phacomorphic/phacolytic). ^[1]

This is important because it explains why we don't just leave cataracts alone indefinitely:

Cataract extraction and intraocular lens (IOL) implantation. ^[1]

The decision to operate is based on how the cataract affects the person's visual function and quality of life, after discussing benefits, risks and preferences - not on a fixed visual-acuity cut-off. ^[10]

Surgical options: ^[1]

IOL placement options: ^[1]

A form of optic neuropathy, characterized by visual field loss, usually associated with raised intraocular pressure. ^[1]

Key concept: Glaucoma is fundamentally an optic neuropathy — it's about damage to the optic nerve, not just high pressure. The IOP is the most important modifiable risk factor, but some patients have glaucoma with normal IOP (normal-tension glaucoma), and some have high IOP without glaucoma (ocular hypertension). ^[4]

Acute vs Chronic; Open angle vs Closed angle; Primary vs Secondary; High IOP vs Normal/Low IOP. ^[1]

Common types in practice:

• POAG (Primary Open Angle Glaucoma) — most common worldwide; insidious; the prototypical chronic glaucoma
• CACG (Chronic Angle Closure Glaucoma) — common in East Asians; short axial length, shallow anterior chamber
• NTG (Normal Tension Glaucoma) — IOP within normal range but still progressive optic neuropathy
• AACG — covered in Acute Visual Loss lecture (GC 121) but mentioned in classification here

From first principles ^[4]:

1. Production: Ciliary body (pars plicata) secretes aqueous humour into the posterior chamber
2. Flow: Aqueous flows through the pupil into the anterior chamber
3. Drainage:
   • Conventional (90%): Trabecular meshwork → Schlemm's canal → episcleral veins
   • Uveoscleral (10%): Across ciliary body into suprachoroidal space

Glaucoma occurs when drainage is impaired (most cases) or rarely when production is increased → IOP rises → mechanical compression + ischaemia of optic nerve head → progressive axon loss → visual field defects → blindness if untreated.

The slide states: "Usually silent until late stages. Visual field constriction. Dull eye pain." ^[1]

Current-safety correction: chronic open-angle glaucoma and chronic angle closure are typically painless and asymptomatic until advanced. Do not use dull pain as a positive feature of chronic glaucoma. Eye pain, redness, haloes, headache, nausea or vomiting should prompt assessment for acute/intermittent angle closure or another painful eye disorder. ^[11]

This is the most dangerous feature of chronic glaucoma — patients don't notice peripheral visual field loss until it's severe because:

• The brain "fills in" missing peripheral vision
• Central VA is preserved until very late
• The disease is bilateral (no comparison eye to notice difference)

This is why case-finding and regular comprehensive eye assessment matter, particularly when risk is increased by age, family history, ancestry, raised IOP, myopia or a narrow anterior chamber. Risk assessment and testing are more useful than relying on symptoms.

Increased IOP ( > 21 mmHg) but may be normal in some types; angle closure on gonioscopy for closed-angle glaucoma; increased vertical cup/disc ratio (thinning of neurosensory rim); disc pallor; notching, bayoneting of blood vessels, splinter haemorrhages. ^[1]

Disc morphology, IOP measurement, visual field assessment (Humphrey 24-2 or 30-2), OCT retinal nerve fibre analyser. ^[1]

Current case-finding guidance uses the combination of standard automated perimetry, stereoscopic optic-nerve/fundus assessment (plus OCT or an optic-nerve image when available), Goldmann-type applanation tonometry, and anterior-chamber angle assessment. It specifically advises against referral decisions based only on non-contact tonometry. ^[11]

Medications: Alpha agonists, Beta blockers (contraindicated in asthma/COAD), Carbonic anhydrase inhibitors, Prostaglandin analogues, Oral: Diamox (acetazolamide), IV: acetazolamide or mannitol. ^[1]

Treatment aims for an individualised target IOP low enough to reduce progression, with adherence and structural/field change reviewed over time. In NICE guidance, 360° SLT is offered first-line for newly diagnosed non-advanced chronic open-angle glaucoma; a prostaglandin analogue is used when SLT is declined, unsuitable, unavailable or insufficient. Local pathways differ. Oral/IV acetazolamide and hyperosmotic agents are short-term tools for marked or acute IOP elevation - they are not routine maintenance treatment for stable chronic glaucoma. ^[11]

Laser and Surgical treatments: ^[1]

Mechanism matters: laser trabeculoplasty treats an accessible open trabecular meshwork. Primary angle-closure disease instead needs angle-directed specialist management (often laser peripheral iridotomy and/or lens extraction, with additional IOP-lowering treatment as required).

Progressive degenerative disease of photoreceptors and retinal pigment epithelium (RPE) characterized by extracellular deposits under the retina/RPE that can evolve to atrophy of the retina, RPE and choroidal neovascularization. Causes blurring of vision or distortion (metamorphopsia) in the center of the visual field. ^[1]

Why it matters:

Leading cause of blindness in older populations. Increasing in prevalence (population aging). Increasing health resource utilization. High societal cost burden. ^[1]

Non-exudative vs exudative (dry vs wet). ^[1]

Visual loss occurs in: Late dry AMD (Geographic Atrophy) and Wet AMD (Choroidal Neovascularization). ^[1]

Important: Early and intermediate dry AMD may be asymptomatic. Not all dry AMD progresses to wet AMD, but wet AMD can develop from any stage of dry AMD.

AREDS Classification: ^[1]

Drusen size thresholds to memorise: < 63μm (small), 63–124μm (intermediate), ≥125μm (large).

Age ( > 50), genetics (complement factor H gene variation), race (Caucasians → more GA; Asians → more polypoidal choroidal vasculopathy), smoking, ?excessive UV exposure, ?obesity/high cholesterol. ^[1]

Polypoidal choroidal vasculopathy (PCV) is specifically mentioned as more common in Asians — this is a subtype of wet AMD with branching vascular networks ending in polypoidal lesions; may respond better to PDT ± anti-VEGF.

Aging → cumulative oxidative injury → buildup of uncleared cellular debris (drusen) between RPE and Bruch's membrane → persistent complement cascade activation and inflammation → thickened Bruch's membrane with decreased permeability → impaired nutrient/waste exchange → degeneration of outer retina, RPE changes, thinning of choriocapillaris → geographic atrophy (dry). Upregulation of pro-inflammatory cytokines and VEGF → angiogenesis (CNV) and increased vascular permeability → wet AMD. ^[1]

Step-by-step from first principles:

1. RPE cells sit between photoreceptors and the choroid. They recycle photoreceptor outer segments daily — an enormous metabolic burden.
2. Over decades, incompletely digested lipofuscin and other waste products accumulate.
3. Some waste is deposited between the RPE and Bruch's membrane → drusen.
4. Drusen activate the complement cascade (especially alternative pathway; CFH normally inhibits this).
5. Chronic inflammation thickens Bruch's membrane → blocks diffusion of oxygen and nutrients from the choriocapillaris to the RPE/photoreceptors.
6. Dry AMD pathway: Starvation and inflammation → RPE and photoreceptor death → geographic atrophy.
7. Wet AMD pathway: Hypoxia upregulates VEGF → sprouting of new vessels from choroid through breaks in Bruch's membrane → these vessels are leaky and fragile → subretinal fluid, haemorrhage, lipid exudation → rapid central vision loss.

May not have any in early and intermediate stages. Late stages: decreased central visual acuity, distorted central vision (metamorphopsia, micropsia, scotoma). Exudative AMD may have acute/subacute loss of vision. ^[1]

Amsler grid — the lecture's three panels show the comparison explicitly: a normal square grid, a central missing/grey patch (scotoma), and bent or wavy lines (metamorphopsia). Test at the usual near-reading distance with reading correction, one eye at a time, while fixating the central dot. A new defect is a symptom trigger for prompt macular assessment; a normal grid does not exclude AMD. Suspected active wet AMD needs urgent referral, normally within 1 working day in the NICE pathway. ^[12]

Non-exudative: Drusen (hard, soft), RPE changes/atrophy, geographic atrophy. Exudative: Retinal thickening, intraretinal/subretinal fluid/haemorrhage, RPE detachment, retinal fluid/exudate, subretinal fibrosis. ^[1]

OCT, Fundus Fluorescein Angiography (FFA), Indocyanine Angiography (ICG). ^[1]

Microvascular end-organ (retina) damage as a result of diabetes mellitus. Disease ranges from non-proliferative DR to proliferative DR. May be associated with diabetic macular oedema. ^[1]

Hyperglycaemia → oxidative damage to pericytes → damage to capillary walls → microaneurysms → rupture → retinal haemorrhages. Activated leukocytes → vascular occlusion → nerve fibre infarction → cotton wool spots. Inflammation → increased capillary leakage → retinal oedema, exudates, haemorrhage. Upregulated VEGF → angiogenesis → new vessels → proliferative DR. New vessels are fragile → vitreous haemorrhage. Fibrous scaffold contraction → tractional retinal detachment. ^[1]

Detailed pathogenesis from first principles:

1. Chronic hyperglycaemia activates multiple biochemical pathways:

   • Polyol pathway → sorbitol accumulation → osmotic damage
   • Advanced glycation end-products (AGEs) → endothelial dysfunction
   • Protein kinase C activation → vascular permeability
   • Hexosamine pathway → oxidative stress

2. Pericyte loss: Pericytes wrap around capillaries and maintain structural integrity. They are selectively vulnerable to hyperglycaemia. Their loss weakens capillary walls.

3. Microaneurysms form at weak points → the earliest clinical sign of DR.

4. Capillary leakage → retinal oedema + lipid exudation (hard exudates = lipid deposits).

5. Capillary occlusion → retinal ischaemia → nerve fibre layer infarcts = cotton wool spots (fluffy white patches).

6. VEGF upregulation from ischaemic retina → drives angiogenesis → neovascularization (new, abnormal, fragile vessels) = proliferative DR.

7. Vitreous haemorrhage from fragile new vessels → sudden vision loss.

8. Fibrovascular proliferation → contraction → tractional retinal detachment → severe vision loss.

Duration of DM, diabetic control, comorbidities (HT, renal impairment, smoking). ^[1]

Symptoms: Central blurring of vision, metamorphopsia. ^[1]

Clinically Significant Macular Oedema (CSME) - the legacy ETDRS clinical definition shown on the slide: ^[1]

Any ONE of these = CSME. Retain this definition for exams and slit-lamp clinical description, but contemporary OCT-guided management also distinguishes centre-involving from non-centre-involving DMO and considers visual acuity and central retinal thickness. Treatment choice is therefore not simply "CSME = laser". ^[16]

Usually none in early stages! Later stages: gradual blurring of vision; may have sudden deterioration (e.g. vitreous haemorrhage or retinal detachment). ^[1]

OCT, +/- FFA. ^[1]

• OCT — quantifies macular thickness; detects intraretinal/subretinal fluid; monitors treatment response
• FFA — identifies areas of capillary non-perfusion, microaneurysm leakage, neovascularization

Treatment by stage: ^[1]

Current management nuance: PRP is usually first treatment when PDR is diagnosed; anti-VEGF is used when PDR remains active after complete PRP or temporarily when haemorrhage/cataract prevents PRP, with careful follow-up because missed injections can permit recurrence. For DMO, non-centre-involving CSME is generally treated with macular laser. Centre-involving DMO with good vision may be observed or treated with macular laser, whereas centre-involving DMO causing visual impairment commonly receives anti-VEGF; steroid implants are selected alternatives when response is suboptimal or non-corticosteroid treatment is unsuitable. ^[16]

Why PRP works: By destroying peripheral (ischaemic) retina with laser, you reduce the total retinal oxygen demand. This decreases VEGF production and causes regression of neovascularization. The trade-off is some peripheral visual field loss and reduced night vision.

Why anti-VEGF for DMO: VEGF drives vascular permeability → macular oedema. Blocking VEGF reduces fluid leakage and can improve vision. It is a principal treatment for centre-involving DMO with visual impairment, not an automatic first treatment for every OCT-detected centre-involving case. ^[16]

The 2025 MCQ Q11 directly tests DR knowledge ^[7]:

• A 50-year-old diabetic with dot-blot haemorrhages and microaneurysms in all 4 quadrants, hard exudates at the macula/fovea, no new vessels or cotton wool spots.
• Answer: Diabetic macular oedema — because the hard exudates at the fovea with likely retinal thickening meet CSME criteria. There are no new vessels (not PDR), no vitreous haemorrhage, no tractional RD, and no NVG.

The 2023 MCQ Q15 tests RAPD in sudden unilateral visual loss in a diabetic with stroke history ^[8]. A marked RAPD localises asymmetric dysfunction to the retina or optic nerve; an isolated media opacity such as cataract or uncomplicated vitreous haemorrhage should not be accepted as a complete explanation without looking for severe retinal ischaemia, detachment or optic neuropathy.