This document discusses hereditary retinal dystrophies. It begins by introducing retinal dystrophies and classifying them based on inheritance pattern and the pathological process affected. Several specific dystrophies are then discussed in more detail, including retinitis pigmentosa, Stargardt disease, and Best vitelliform macular dystrophy. For each, the document outlines clinical features, inheritance patterns, investigations, treatment approaches, and complications. Overall, the document provides an overview of hereditary retinal dystrophies with a focus on several common genetic subtypes.

1. Hereditary Retinal Dystrophy
Dr. Md. Ashfakur Rahaman (Rayhan)
DO Student
Ophthalmology Dept.
RpMCH

2. Introduction
• Group of disorders
• Commonly exert their major effect on
Retinal pigment epithelium
Photoreceptor complex
Choriocapillaris

3. Classification
By inheritance pattern:
A.Generalized
B. Central/Macular
Focus of the pathological process (e.g. photoreceptors,
RPE or choroid)
by whether they are stationary (non-progressive) or
progressive

4. Generalized Photoreceptor
Dystrophy:
1) Retinitis Pigmentosa
2) Atypical Retinal Pigmentosa
3) Leber Congenital Amaurosis
4) Cone Dystrophy
5) Bietti crystalline corneo-
retinal dystrophy
6) Familial Benign Fleck Retina
7) Congenital Stationary Night
Blindness
Macular Dystrophy:
1) Stargardt’s Dystrophy
2) Best Vitelliform Macular
Dystrophy
3) Familial Dominant Drusens
4) Sorbsy Pseudo-inflammatory
macular Dystrophy
5) North Carolina Macular
Dystrophy
6) Butterfly Macular Dystrophy
7) Concentric annular macular
Dystrophy

5. Retinitis pigmentosa
Introduction
• Most common hereditary fundus dystrophy.
• Clinically and genetically diverse group of inherited diffuse
retinal degenerative disease.
• Predominantly affecting the rod photoreceptors, with later
degeneration of cones (rod-cone dystrophy).

6. Inheritance
 Sporadic disorder: Isolated without family history due to mutation
of multiple gene including rhodopsin gene.
 Inherited disorder:
Autosomal recessive –. most common(25%), intermediate severe.
Autosomal dominant – next common(25%), least severe.
X-linked – least common(10%), most severe.

7. Epidemiology
Prevalence: approximately 1 : 5000.
Age: appears in childhood and progresses slowly.
Sex: males are more commonly affected than females.
Laterality: Almost invariably bilateral.
Leading cause of blindness certification in the working
age population (age 16–64 years) in the UK.

8. Pathogenesis
• Degeneration of rods and cones.
• Migration of pigments into the retina.
• Degenerated ganglion cells and their axons are
replaced by neuroglial tissue.
• Attenuation of the blood vessels.
• Atrophy of the optic disc.

9. Clinical features
The classic triad of findings comprises
bone-spicule retinal pigmentation
arteriolar attenuation and
‘waxy’ disc pallor.

10. Symptoms
• Night blindness.
• Dark adaptation difficulties.
• Tubular vision.
• Reduced central vision tends to be a late feature.

11. Signs
• Visual acuity (VA) may be normal.
• Bilateral mid-peripheral intraretinal perivascular ‘bone-
spicule’ pigmentary changes.
• RPE atrophy associated with arteriolar narrowing.
• Tessellated fundus appearance develops due to
unmasking of large choroidal vessels.

12. • Peripheral pigmentation may become severe, with marked
arteriolar narrowing and disc pallor.
• The macula may show atrophy, epiretinal membrane
(ERM) formation and cystoid macular oedema (CMO).
• Myopia is common.
• Optic disc drusen occur more frequently in patients with
RP.

13. Investigation
• Full-field ERG is a sensitive diagnostic test. In early
disease it shows reduced scotopic rod and combined
response.
• EOG is subnormal, with absence of the light rise.
• Perimetry initially demonstrates small mid-peripheral
scotomata.

14. • Optical coherence tomography (OCT) will identify
CMO.
• Genetic analysis may identify the particular mutation
responsible in an individual patient.

15. Treatment
• Regular follow-up (e.g. annual) is essential to detect
treatable vision-threatening complications.
• No specific treatment is yet commercially available, but
modalities such as gene therapy and retinal prostheses show
promise for the future.
• Cataract surgery is generally beneficial.
• Low-vision aid provision, rehabilitation.

16. • Sunglasses, ‘nanometer-controlled’ to block wavelengths up
to about 550 nm.
• High-dose vitamin A supplementation (e.g. palmitate 15 000
units per day) probably has a marginal benefit.
• Potentially (even mildly) retinotoxic medications should be
avoided or used with caution.

17. Complications
 Posterior subcapsular cataract.
 Open-angle glaucoma (3%).
 Keratoconus.
 Posterior vitreous detachment.
 Occasionally seen intermediate uveitis.
 Exudative retinal detachment.

18. Atypical retinitis pigmentosa
Atypical RP associated with a systemic disorder
(syndromic RP)
Usher syndrome
• Type I (75%): profound congenital sensorineural deafness and
severe RP.
• Type III (2%): progressive hearing loss, vestibular dysfunction
and relatively late-onset pigmentary retinopathy.
Kearns–Sayre syndrome
• Characterized by chronic progressive external
ophthalmoplegia with ptosis associated with other systemic
problems.

19. Bassen–Kornzweig syndrome
• Fat and fat-soluble vitamin absorption is dysfunctional.
• There is a failure to thrive in infancy, with the
development of severe spinocerebellar ataxia.
• The fundus exhibits scattered white dots followed by
RP-like changes developing towards the end of the first
decade.

20. Refsum disease
• Phytanic acid accumulates throughout the body, with
substantial and varied skin, neurological and visceral
features.
• Retinal changes may be similar to RP or take on a salt
and pepper appearance.
• Ocular features such as cataract and optic atrophy.

21. Atypical retinitis pigmentosa
Retinitis pigmentosa sine pigmento
• Characterized by an absence or paucity of pigment
accumulation, which may subsequently appear with time.
• Functional manifestations are similar to typical RP.

22. Atypical retinitis pigmentosa
Retinitis punctata albescens
• Characterized by scattered whitish-yellow spots, most
numerous at the equator, usually sparing the macula, and
associated with arteriolar attenuation.
• Nyctalopia and progressive field loss occur.

23. Atypical retinitis pigmentosa
Sector retinitis pigmentosa
• Sector (sectoral) RP is AD.
• Characterized by involvement of inferior quadrants only.
• Progression is slow, and many cases are apparently
stationary.
• Unilateral RP can also occur.

24. Atypical retinitis pigmentosa
Leber congenital amaurosis
• Severe rod-cone dystrophy that is the commonest genetically
defined cause of visual impairment in children.
• Systemic associations include mental handicap, deafness,
epilepsy, central nervous system and renal anomalies, skeletal
malformations and endocrine dysfunction.

25. Presentation
• Blindness at birth or early infancy.
• Roving eye movements or nystagmus, and photoaversion.
Signs
• Absent or diminished pupillary light reflexes.
• The fundi may be normal in early life apart from mild arteriolar
narrowing.
• Initially mild peripheral pigmentary retinopathy, salt and pepper
changes, and less frequently yellow flecks.
• Severe macular pigmentation or coloboma like atrophy.

26. Atypical retinitis pigmentosa
Pigmented paravenous chorioretinal atrophy
• Predominantly AD, usually asymptomatic and non-progressive.
• Paravenous bone-spicule pigmentation is seen, together with
sharply outlined zones of chorioretinal atrophy that follow the
course of the major retinal veins.

27. Stargardt disease/fundus
flavimaculatus
Introduction
• Characterized by the accumulation of lipofuscin
within the RPE.
• Three types are recognized:
- STGD1 (AR): most common, and is usually caused by
mutation in the gene ABCA4.
- STGD3 (AD).
- STGD4 (AD): uncommon, and are related to different
genes.

28. Clinical features
Symptoms
• Gradual impairment of central vision.
• Reduced colour vision.
• Impairment of dark adaptation.
Signs
• Macula may initially be normal or show non-specific mottling
• Later progressing to an oval ‘snail slime’ or ‘beaten-bronze’
appearance and subsequently to geographic atrophy that may
tend to a bull’s-eye configuration.
• Small proportion develop choroidal neovascularization (CNV).

29. Stargardt disease: (A) Non-specific macular mottling; (B) ‘snail
slime’ maculopathy surrounded by flecks; (C) ‘beaten-bronze’
paramacular appearance;

30. Investigation
• OCT: demonstrate flecks and atrophy.
• FAF: shows a characteristic appearance with hyperautofluorescent
flecks and macular hypoautofluorescence.
• ERG: Photopic is normal to subnormal, scotopic may be normal.
• EOG: subnormal, especially in advanced cases.

31. (A) Central visual field loss; (B) OCT showing RPE and outer retinal atrophy sparing the
fovea; (C) FAF showing macular hypoautofluorescence and surrounding flecks. The black
areas in the macula represent RPE atrophy; (D) FA showing hyperfluorescent spots and a
‘dark choroid’

32. Treatment
• Protection from excessive high energy light exposure.
• Vitamin A supplementation is avoided as it may accelerate
lipofuscin accumulation.
• Gene therapy and stem cell trials have been initiated and
show promising results.

33. Best vitelliform macular dystrophy
Introduction
• Early- or juvenile-onset vitelliform macular
dystrophy
• second most common macular dystrophy, after
Stargardt disease.
• Due to allelic variation in the bestrophin (BEST1)
gene on chromosome 11q13.
• Inheritance is AD with variable penetrance and
expressivity.

34. Diagnosis
Signs
There is gradual evolution through the following stages:
○ Pre-vitelliform is characterized by a subnormal EOG
in an asymptomatic infant or child with a normal
fundus.
○ Vitelliform develops in infancy or early childhood and
does not usually impair vision.
-Asymmetrical

35. A round, sharply delineated (‘sunny side up egg yolk’) macular lesion
between half a disc and two disc diameters in size develops within the RPE

36. • Pseudohypopyon may occur when part of the lesion
regresses, often at puberty.
• Vitelliruptive:The lesion breaks up and visual acuity
drops.
• Atrophic in which all pigment has disappeared
leaving an atrophic area of RPE

37. B.Pseudohypopyon C.Vitelliruptive

38. Investigation
• FAF: the yellowish material is intensely
hyperautofluorescent. In the later atrophic stages
hypoautofluorescent areas supervene
• FA shows corresponding hypofluorescence due to
masking
• OCT shows material beneath, above and within the
RPE
• EOG is severely subnormal during all stages and is
also abnormal in carriers with clinically normal fundi

39. D.FA shows corresponding hypofluorescence E.OCT showing subretinal hyporeflective
component

40. Treatment
• There is no medical & Surgical management
available
• Treatment of Complications