Metabolic Disorders

Diabetes Mellitus - Sugar-Coated Sight Stealers

Pathophysiology: Chronic hyperglycemia → sorbitol pathway, Advanced Glycation End-products (AGEs) → microvascular damage, osmotic stress.

Diabetic Retinopathy (DR)

• Non-Proliferative DR (NPDR):
  • Microaneurysms (earliest sign)
  • Dot & blot hemorrhages, hard exudates
  • Cotton Wool Spots (CWS), Intraretinal Microvascular Abnormalities (IRMA)
  • Severe NPDR: 📌 4:2:1 rule (hemorrhages/microaneurysms in 4 quadrants, venous beading in 2 quadrants, IRMA in 1 quadrant)
• Proliferative DR (PDR):
  • Neovascularization: NVD (disc), NVE (elsewhere)
  • Vitreous hemorrhage, tractional retinal detachment (TRD)
• Diabetic Macular Edema (DME)/Clinically Significant Macular Edema (CSME): Major cause of visual loss in diabetics.

Other Ocular Manifestations

• Cataract: True diabetic "snowflake" cataract (acute, young Type 1 DM); earlier onset & progression of senile cataract.
• Refractive changes: Transient hyperopic or myopic shifts.
• Cranial nerve palsies: III (often pupil-sparing), IV, VI.
• Rubeosis iridis, neovascular glaucoma.

⭐ Diabetic retinopathy is the leading cause of new blindness in adults aged 20-74 years.

Wilson, Galactosemia, Cystinosis - Copper, Crystals, Cataracts

• Wilson's Disease (ATP7B gene)

  • Kayser-Fleischer (K-F) ring: Copper in Descemet's membrane (superiorly first).
  • Sunflower cataract (anterior/posterior subcapsular).
  • 📌 Mnemonic: Copper Is HEavy MEtal (K-F ring, Hepatitis, Extrapyramidal, MEmory).

  ⭐ The Kayser-Fleischer ring in Wilson's disease is a golden-brown copper deposit in Descemet's membrane, best seen with gonioscopy.

• Galactosemia (GALT/GALK/GALE deficiency)

  • Oil-drop cataract: Reversible, due to galactitol accumulation. Onset often within first few days/weeks of life.
  • Nuclear and cortical changes.

• Cystinosis (CTNS gene)

  • Corneal crystals: Iridescent, needle-shaped cystine crystals in stroma.
  • Photophobia, retinopathy.
  • Nephropathic form most common.

Fabry, MPS, Homocystinuria - Storage & Structural Snafus

• Fabry's Disease (GLA gene, α-galactosidase A deficiency)
  • Cornea verticillata (whorl-like) 📌 Fabry's Whorls
  • Posterior spoke-like cataract
  • Vascular tortuosity (conjunctival/retinal)
• Mucopolysaccharidoses (MPS) (GAG accumulation)
  • Corneal clouding (e.g., Hurler, Scheie)
  • Retinal degeneration/pigmentary retinopathy (e.g., Hunter)
  • Optic atrophy, glaucoma
• Homocystinuria (CBS gene defect)
  • Ectopia lentis: inferonasal, bilateral

    ⭐ Inferonasal lens subluxation is characteristic of homocystinuria, contrasting with the superotemporal subluxation seen in Marfan syndrome.

  • Marfanoid habitus, ↑ thromboembolism risk
  • Glaucoma, optic atrophy
  • 📌 LENS: Lens subluxation (down & in), INtellectual disability, N aracnodactyly, Stroke.

Hyperlipidemia, Albinism, Gout - Lipid, Light & Purine Alerts

• Hyperlipoproteinemias:
  • Lipemia retinalis: Creamy retinal vessels (triglycerides > 2500 mg/dL).
  • Corneal arcus (senilis/juvenilis): Peripheral corneal lipid deposit.
  • Xanthelasma: Yellowish eyelid plaques.
• Albinism: (TYR gene for OCA1)
  • Types: Oculocutaneous (OCA) & Ocular (OA).
  • Key signs: Foveal hypoplasia, nystagmus, iris transillumination, photophobia, ↓ visual acuity, abnormal optic nerve fiber decussation.

  ⭐ Foveal hypoplasia is the primary determinant of poor visual acuity in individuals with albinism.

• Gout/Hyperuricemia:
  • Urate crystal deposition: Cornea, conjunctiva, sclera.
  • Ocular signs: Band keratopathy, uveitis, scleritis.
  • Eyelid tophi.

A collage displaying lipemia retinalis, corneal arcus, xanthelasma, ocular signs of albinism like iris transillumination, and gouty tophi or band keratopathy.

High‑Yield Points - ⚡ Biggest Takeaways

• Diabetes Mellitus: Key risks are diabetic retinopathy (NPDR/PDR) and macular edema.
• Wilson's Disease: Presents with Kayser-Fleischer ring (corneal copper) and sunflower cataract.
• Galactosemia: Characterized by oil-droplet cataracts in infants, often reversible.
• Fabry Disease: Look for cornea verticillata (whorled keratopathy) and posterior spoke cataracts.
• Homocystinuria: Causes inferonasal lens subluxation (ectopia lentis).
• Thyroid Eye Disease: Features proptosis, diplopia, lid retraction, and optic neuropathy.
• Mucopolysaccharidoses: Often show progressive corneal clouding and retinal degeneration.