Hereditary Retinal Dystrophies

HRD: Intro & Genetics - Pixel Perfect Genes

• Hereditary Retinal Dystrophies (HRDs): Genetically diverse group of disorders causing progressive retinal degeneration & vision loss.
• Classification:
  • Photoreceptor dystrophies (e.g., Retinitis Pigmentosa)
  • Macular dystrophies (e.g., Stargardt disease)
  • Vitreoretinopathies (e.g., Stickler syndrome)
• Inheritance Patterns: Autosomal Dominant (AD), Autosomal Recessive (AR), X-Linked (XL).
  • AR is most common overall for many HRDs.

⭐ Most HRDs are bilateral and symmetrical, though severity and onset can vary.

• Genetic testing is crucial for diagnosis, prognosis, and genetic counseling. Many genes implicated (e.g., ABCA4, RHO, RPGR).

Retinitis Pigmentosa - Dark Night's Fright

• Rod-cone dystrophy; rods primarily affected, progressive degeneration.
• Inheritance: Autosomal Dominant (AD), Autosomal Recessive (AR), X-linked (XLRP - most severe).
• Symptoms:
  • Nyctalopia (night blindness) - earliest symptom. 📌 "Dark Night's Fright".
  • Gradual peripheral visual field loss (tunnel vision).
• Key Signs (Classic Triad):
  • Mid-peripheral bony spicule pigmentation.
  • Arteriolar attenuation.
  • Waxy pallor of optic disc.
• Other Findings:
  • Visual fields: Ring scotoma.
  • ERG: ↓↓ scotopic (rod) response early; later ↓ photopic (cone).
• Associations: Usher syndrome (RP + deafness), Laurence-Moon-Biedl syndrome.

⭐ Electroretinogram (ERG) is crucial for diagnosis, often showing extinguished or severely reduced rod and cone responses.

Cone & Cone-Rod Dystrophies - Daylight's Demise

• Cone Dystrophies (CD):
  • Primarily cone photoreceptor loss.
  • Symptoms: ↓VA, severe photophobia, poor color vision (hemeralopia).
  • Signs: Bull's eye maculopathy, temporal optic disc pallor.
  • ERG: Photopic response severely ↓ or absent; scotopic normal.
• Cone-Rod Dystrophies (CRD):
  • Cones affected earlier and/or more severely than rods.
  • Symptoms: Initial CD symptoms, later nyctalopia & peripheral field loss.
  • Signs: Maculopathy, peripheral pigmentary changes, optic atrophy, arteriolar attenuation.
  • ERG: Both photopic & scotopic responses ↓ (photopic more significantly).
• Inheritance: Typically AD, AR, or X-linked.

⭐ Progressive loss of central vision, photophobia, and defective color vision are key indicators, with photopic ERG significantly reduced or absent in cone dystrophies.

Macular Dystrophies (Stargardt, Best) - Central Vision Crisis

Stargardt Disease (Fundus Flavimaculatus)

• Most common juvenile macular dystrophy; Autosomal Recessive (AR, ABCA4 gene).
• Onset: 1st-2nd decade; ↓ central vision, photophobia.
• Signs: Bilateral yellow "pisciform" (fish-tail) flecks, "beaten-bronze" macula (late).
• FFA: Dark/silent choroid (lipofuscin). ERG normal early.

Best Disease (Vitelliform Dystrophy)

• Autosomal Dominant (AD, BEST1 gene); onset 3-15 years.
• Characteristic "egg-yolk" macular lesion (lipofuscin).
• ERG: Normal. EOG: Markedly abnormal (Arden ratio < 1.5). 📌 Best has bad EOG. ⭐ > In Best disease, EOG is markedly abnormal (Arden ratio < 1.5) even with normal vision and fundus, while ERG remains normal.

Stages of Best Disease:

Choroidal Dystrophies - Support System Failure

• Degeneration of retinal support: RPE, choriocapillaris, choroid.
• Choroideremia: X-linked (CHM). Night blindness, progressive field loss. Widespread atrophy.
• Gyrate Atrophy: AR (OAT). ↑ Ornithine. Scalloped peripheral atrophy.
  • Rx: Vit B6, low arginine diet.
• CACD: AD (PRPH2). Central RPE/choriocapillaris atrophy.
• Bietti Crystalline Dystrophy: AR (CYP4V2). Retinal/corneal crystals.

⭐ Gyrate atrophy: OAT gene defect causes ↑ ornithine; treatable with Vit B6 & arginine restriction.

High‑Yield Points - ⚡ Biggest Takeaways

• Retinitis Pigmentosa (RP): Most common; night blindness, peripheral vision loss, bone spicule pigmentation.
• Stargardt disease: Most common juvenile macular dystrophy; ↓ central vision, "beaten-bronze" macula, pisciform flecks.
• Best disease: "Egg-yolk" macular lesion; subnormal EOG, normal ERG.
• Cone dystrophies: Photophobia, color vision defects, ↓ visual acuity; bull's eye maculopathy.
• Leber Congenital Amaurosis (LCA): Severe; blindness at/near birth, nystagmus, oculodigital sign.
• Usher syndrome: RP combined with sensorineural hearing loss.