Retinal dystrophy

Retinal Dystrophies
-Dr. Deepayan Sarkar

A) 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 Bening Fleck Retina
7) Congenital Stationary Night Blindness
B) Macular Dystrophies-
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
8) Familial ILM Dystrophy

Generalised Choroidal Dystrophy-
1) Choroideremia
2) Gyrate Atrophy
3) Progressive Bifocal Chorioretinal Atrophy
Vitreoretinopathies-
1) Juvenile X linked Retinoschisis
2) Stickler syndrome
3) Wagner Syndrome
4) Familial exudative vitreo-retinopathy
5) Enhanched S-cone syndrome and Goldmann-Favre syndrome
6) Snowflake vitreoretinal degeneration
7) Autosomal dominant neovascular inflammatory vitreo-retinopathy
8) Autosomal dominant vitreoretinochoroidopathy
9) Kneist Dysplasia

Retinitis Pigmentosa
• It is a pigmentary retinal dystrophy with clinically and genetically
diverse group of inherited diffuse retinal degenerative disease
predominantly affecting the rod photoreceptors, with later
degeneration of the cones.
• Most common hereditary retinal dystrophy.
• Incidence:
- World wide- 1: 5000
- Age- Appears in childhood, progresses slowly causing blindness in
advanced middle age.
- Race- Equal in all races.
- Sex- Males> Females 3:2
- Laterality- Invariably Bilateral disease.

Inheritance:
1) Sporadic- 60%- Most common
2) Inherited- 40%
a) Autosomal Dominant- 43% ;Best Prognosis
b) Autosomal Recessive- 20%
c) X-linked – uncommon 10%; Worst Prognosis
d)Uncertain family history 6-8%
e) Digenic mode in some family
Genetic Basis of Disease:
1) Rhodopsin Mutation (Chr 3q21)- Rhodopsin initiates the cascade of
phototransduction, at least 100 mutations in Rhodopsin gene can
RP.
2) RDS protein Mutation (Chr 6p12)- Peripherin or RDS protein is
in structural integrity of the photoreceptor. Generally associated with
Autosomal Dominant disease.
3) Abnormal p mRNA splicing- Mutation in PRPF8 gene, PRPF31 gene,
PRPF3 gene. It due to faulty mRNA splicing.
4) Others- Mutation in RP GTPase regulator, Mutation in ABCR gene.

Symptoms of RP-
1) Nyctalopia-
• Characteristic feature that appears before the appearance of fundus changes. Occurs due to
degeneration of the rods.
• Characteristic age of onset- 10.7 years for autosomal recessive and 23.4 years for autosomal
dominant disease.
• Masof & Finkestein classified RP as-
1) Type 1 RP- Childhood onset night blindness. Early loss of rod sensitivity compared to cone
sensitivity.
2) Type 2 RP- Adult onset night blindness. Combined loss of rod and cone sensitivity.
2) Dark Adaptation difficulties- Dark Adaptation difficulties are increased due to increased light
threshold to peripheral retina.
3) Visual field loss- Progressive loss of peripheral vision, ultimately leading to tunnel vision in
advanced disease.
4) Others- Photopsia, diminished contrast sensitivity.
Visual acuity remains normal till late stage disease.

Theories of Retinitis Pigmentosa:
1) Vascular theory-
a) Sclerosis of choroid and choriocapillaris.
b) Sclerosis of retinal vessels.
2) Pigmentary changes-
Changes in neuroepithelium and pigmentary
epithelium.
3) Abiotrophic- Early degeneration and loss of
function of cells.
4) Premature seniling and death of cells of
specified tissue.

Fundus Finding-
1) Bony spicules: It is due to migration of pigments in the retina from disintegration of RPE cells
with accumulation in the interstitial space surrounding retinal vessels.
The changes are found in the equatorial region first, and spread anteriorly and posteriorly.
Gradual increase in density of the pigment with progressing disease.
2) Gliotic Optic nerve gliosis head: It starts with a variable waxy disc pallor (which is due to a thick
pre-retinal membrane centered on the disc that extends over the retina in all the quadrants, the
retinal membrane appears to originate from fibrous astroglial cells in the optic nerve). In later
in leads to consecutive optic atrophy.
3) Vascular changes: There is gross arteriolar narrowing.
4) General retinal changes: Generalized granularity of the fundus. Pigment clumps or bone spicule
appearing pigment deposits. A generalized mottling or moth eaten pattern of the RPE.
5) Macular change: Loss of foveal reflex. 3 types of Maculopathy- Atrophic, Cellophane and CME.
6) Vitreous change: Fine dust like particles which progress into vitreous condensation and collapse
with progressing disease.

Associated Ocular features:
1) Myopia.
2) Keratoconus.
3) Open angle glaucoma.
4) Posterior subcapsular cataract.
5) Optic disc drusens.
6) Microphthalmus

Investigations:
1) ERG- Reduced scotopic rod and combined responses .Photopic
responses reduce with progression and eventually ERG becomes
extinguished. Rod B wave amplitudes are reduced in the earliest stage
the disease.
2) EOG- Subnormal, with absence of the light rise.
3) Visual fields- Perimetry initially demonstrates small mid-peripheral
scotomata that gradually coalesce and deteriorate to leave a tiny
of residual central vision.
4) OCT- OCT shows retinal thinning due to photoreceptor layer loss or
retinal thickening due to macular oedema.
5) Fundus Autofluorescence- Lack of signals on FAF (due to RPE atrophy).
Most patients demonstrates a perifoveal ring of increased
autofluorescence within the retina, which denotes border between
functional and dysfunctional retina.
6) Genetic analysis- To identify the particular mutations, to facilitate
genetic counseling and for research purpose.

Variants of RP-
1) Inverse RP or central RP- Pigments are seen more
centrally and equatorial and peripheral retina is spared.
2) Sectoral RP- Pigmentary changes confined to one
quadrant . Visual function remains good for many years.

3) RP with exudative vasculopathy- It is bilateral and consists of
vascular anomalies, serous RD and lipid deposition in the retinal
periphery.
4) Unilateral RP- Patients with unilateral pigmentary
degenerations.
5) RP sine pigmento- Presence of typical symptoms and
presence of signs except pigmentary deposition.

Treatment-
1) No definitive treatment is yet available.
2) Regular follow up to detect and treat , treatable vision threatening
complications (PSC, CME).
3) Smoking to be avoided, as it aggravates the disease.
4) Vit A supplementation- Vit A supplementation at 15,000 IU per day suggested
by Beron et al, based on the study conducted by them on 601 patients. The
study showed Vit A has marginal benefits and has risks of Vit A toxicity and
should be used with caution.
5) Valproate/Phenytoin- Is used as a retino-protective drug. The use of the drug is
not yet shown proven benefit.
6) CMO in RP responds to oral Acetazolamide.
7) Potential retinotoxic medications should be avoided or used with caution.
8) Cataract surgery for PSC is beneficial for vision.

9) Low vision aids- Optical aids – Distance vision
(Hand held telescope, Mounted Telescope). Near
vision (Prismatic /bifocal spectacle, Hand held
magnifiers, Illuminated magnifiers).
Non optical device (Glare reduction, Contrast
enhancement, Computer software, Accessory
devices like talking watches, writing guide, tactile
markers).
10) Retinal prosthesis/Implants- Another method to
address the loss of retinal cells seen in a range of
retinal degenerations has been to use an artificial
implant that would detect light, convert light energy
into an electrical signal, and then pass on that
electrical signal to other cells in the visual system
that would get the electoral signal to the brain
where it could be interpreted as vision. Artificial
implants like Bionic eye/Argus 2 implant proof
beneficial.

Atypical RP
”Atypical RP” has conventionally been used to group together heterogenous disorders
clinically having features in common with typical pigmentary retinal dystrophy.
• Atypical RP with systemic disorder [Syndromic association]-
1) Usher Syndrome-
• Autosomal Recessive.
• Accounts for about 5% of all cases of profound deafness in children and half of all the
cases of combined deafness and blindness.
• 3 major types- a) Type 1 (75%)-characterized by profound hearing loss in both ears at
birth (congenital deafness) and balance problems. In many cases, affected children do
not learn to walk until 18 months of age or later. Vision problems usually begins at
approximately the age of ten years to early teens, although some parents report onset
in children younger than 10.
b) Type 2 (23%)- characterized by moderate to severe hearing loss in
both ears at birth. In some cases, hearing loss may worsen over time. Onset of night
blindness occurs during the late teens or early twenties. Peripheral vision loss is ongoing,
but central vision is usually retained into adulthood. Visual problems associated with
Usher syndrome type 2 tend to progress more slowly than those associated with type 1.
c) Type 3 (2%)- Usher syndrome type 3 is characterized by later onset
hearing loss, variable balance (vestibular) dysfunction and RP that can present between
the second and fourth decade of life.

2) Kearn-Sayre syndrome-
• Mitochondrial inheritance.
• Characterized by chronic progressive external ophthalmoplegia with ptosis,
associated with other systemic problems.
• The fundus has a salt-pepper appearance most striking at the macula, with less
typical presentation of RP.
3) Basen-Kornweig syndrome-
• Autosomal recessive.
• There is dysfunction in absorption of fat and fat soluble vitamins(A,D,E,K).
• Charecterized by failure to thrive in infancy and development of severe spino-
cerebellar ataxia.
• Fundus finding- Scattered white dots followed by RP-like changes developing
towards the end of the first decade, associated with ptosis, ophthalmoplegia,
strabismus and nystagmus.
• Vit supplementation and low fat diet are implemented.

4) Refsum disease-
• Autosomal recessive.
• Consists of genetically and clinically distinct infantile and adult forms.
• Phytanic acid accumulates throughout the body with substantial and varied skin,
neurological and visceral features.
• Retinal changes may be similar to RP or salt-pepper appearance associated with cataract
and optic atrophy.
5) Bardet-Biedel syndrome-
• Genetically heterogenous.
• Associated polydactyl and mental handicap.
• Fundus picture- Bull’s eye maculopathy due to cone-rod dystrophy and less frequently
typical RP, RP sine pigmento, retinitis puncta albescens.

Retinitis Punctata Albescens
• Autosomal recessive or Autosomal Dominant inheritance,
compound heterozygous mutations in RLBP1 (15q26.1)
• Characterized by scattered whitish-yellow spots, most numerous
at the equator, usually sparing the macula and associated with
arteriolar attenuation. The spots are similar to spots in Fundus
albipunctatus. By the fifth and sixth decades there may be retinal
pigment atrophy in the midperiphery and this eventually
progresses to geographic atrophy of the macular RPE as the
visual field becomes more constricted. The fundus in older
individuals resembles that seen in retinitis pigmentosa with
retinal vascular attenuation, frank bone spicule pigmentation,
macular disease, and pallor of the optic nerves with significant
loss of vision. The ERG shows reduction in scotopic responses
and mild reductions in photopic amplitudes.
• Prognosis is poor. ERG reduced.
• Symptoms- Nyctalopia, Progressive visual field loss.
• Treatment- No definitive treatment. Low vision aids are useful.

Bietti Crystalline Corneo-retinal dystrophy
• Inheritance- Autosomal Recessive. CYP4VZ
• Deposition of crystals in the retina and superficial peripheral
cornea, it is associated with systemic lipid metabolism error.
• More common in East Asian population.
• Presentation- Young adults with slowly progressing visual loss.
• Signs-
1) Superficial peripheral corneal crystals.
2) Numerous fine yellow-white crystals scattered across the
fundus.
3) Diffuse atrophy of the choriocapillaris subsequently develops,
with decrease in size and number of crystals.
4) Gradual confluence and expansion of the atrophic areas into
periphery, leading to diffuse chorio-retinal atrophy in end stage
disease.

Investigation-
o Visual field shows constriction.
o OCT demonstrates the crystalline deposits and macular changes.
o ERG is subnormal.
o FA in moderate disease shows characteristic large hypofluorescent
corresponding to choriocapillaris loss, with intact overlying retinal vessels;
the patches become confluent over time.

Cone Dystrophy
• Cone dystrophies are actually cone-rod dystrophies with
cones being affected earlier and more severely than the rods.
• Inheritance- Sporadic (most common), Autosomal Dominant,
XLR.
• Presentation- In early adulthood, with impairment of central
vision rather than the nyctalopia of rod-cone dystrophy.
• Symptoms- Gradual bilateral impairment of central and color
vision.
• Signs- The macula may virtually be normal or show non-
specific central pigmentary changes or atrophy. Bull’s eye
maculopathy is classically found, but not universal.
Progressive RPE atrophy at the macula with eventual
geographic atrophy.

• Investigations-
1) FAF- Shows annular pattern concentric with the fovea.
2) ERG- Photopic responses are sub normal or non
recordable and flicker fusion frequency is reduced.
3) EOG- Normal or subnormal.
4) Color vision- Severe deuteron-tritan defect.
5) FA- Shows a round hyperfluorescent window defect with
hypo fluorescent center.
• Prognosis- Poor, with visual acuity of 6/60 or worse.
• Treatment- No specific treatment.
Lutein, Zeaxanthin and omega 3 fatty acids
have been prescribed in some cases have shown good
outcome.

Alport Syndrome
• Inheritance X-linked Recessive.
• Mutation in several gene that encode particular forms of
type 4 collagen, major basement membrane component.
• It is characterized by chronic renal failure and
sensorineural deafness.
• Fundus: Scattered yellowish punctate flecks in
perimacular area, larger peripheral flecks, some of which
may become confluent.
• ERG is normal and visual prognosis is excellent.
• Anterior lenticonus and posterior polymorphous corneal
dystrophy may be present.

Familial Bening Fleck Retina
• Rare Autosomal Recessive disorder.
• Asymptomatic.
• Incidental finding.
• Fundus- Yellow-white polymorphous lesion spare
the fovea and extend to the far-periphery.
• The flecks are made of lipofuschin, auto fluoresce.
• ERG is normal.
• Prognosis excellent.

Leber Congenital Amaurosis
• It is a severe rod-cone dystrophy that is commonest
genetically defined cause of visual impairment in children.
• Inheritance- AR. It is genetically heterogeneous, with at
least 14 gene loci identified.
• Systemic association- Mental handicap, Deafness,
Epilepsy, CNS anomaly, Renal anomaly, Skeletal
malformation and Endocrine dysfunction.
• Presentation- Blindness at birth or early infancy,
associated with roving eye movements or nystagmus and
photo aversion.
• Signs-
1. Absent or diminished pupillary light reflex.
2. The fundi may be normal in early life apart from mild
arteriolar narrowing.
3. Initially mild peripheral pigmentary retinopathy, salt-
pepper changes and less frequently yellow flecks.
4. Severe macular pigmentation or coloboma like atrophy.
5. Pigmentary retinopathy, optic atrophy and severe
arteriolar narrowing in later childhood.

6. Oculodigital syndrome- constant rubbing of the eyes may cause
orbital fat atrophy with enophthalmos and subsequent keratoconus
or keratoglobus.
7. Other associations include strabismus, hypermetropia and
cataract.
8. First sign noticed by parents is nystagmus.
• ERG is usually non-recordable even in early cases with normal-
appearing fundi.
• Prognosis- Poor.
• Treatment- No definite treatment.
Gene therapy is the only hope.

Congenital Stationary Night Blindness
• Congenital Stationary Night Blindness refers to a group of disorders
characterized by infantile-onset nyctalopia but non progressive retinal
dysfunction.
• With Normal fundus appearance-
Type 1 (complete)- The former is characterized by complete absence of
rod pathway function and essentially normal cone function clinically and
on ERG.
Type 2(incomplete)- Impairment of rods and cones.
Inheritance- AD form is usually associated with normal visual acuity,
AR, XLR patients have poor vision with nystagmus, often
significant myopia.

• With an Abnormal Fundus Appearance-
1) Oguchi disease-
Autosomal Recessive inheritance.
The fundus has an unusual golden-yellow color in the light
adapted state which becomes normal after prolonged dark
adaptation. (Mizuo or Mizuo- Nakamura phenomenon).
Rod function is absent after 30 minutes of dark adaptation but
recovers to a near normal level after a long period of dark
adaptation.

2) Fundus Albipunctatus-
• Inheritance-Recessive.
• Congenital stationary night blindness.
• There are multiple tiny white dots that are very regularly
spaced, involve the posterior pole, spare the fovea, and extend
into the mid-periphery.
• In contrast to Retinitis Punctata Albescens, the retinal blood
vessels, optic disc, peripheral fields and visual acuity remain
normal.
• Prognosis-Excellent.
• FA- Shows mottled hyperfluroscence, indicating
depigmentation of RPE.
• ERG- Reduced.

Stargardt’s disease
• Fundus Flavimaticus and Stargardt’s are the variant of the same
disease.
• Most common Macular dystrophy.
• Characterized by accumulation of Lipofuscin within the RPE.
• Types:
1) STGD1- Autosomal Recessive. Most common type. Mutation in
gene ABCA4.
2) STGD3- Autosomal Dominant.
3) STGD4- Autosomal Dominant.
• Presentation in Childhood/Adolescence.
• Prognosis for maculopathy is poor. Visual acuity is usually 6/12
to 6/60.
Patients with flecks in early stages have relatively good prognosis.
Symptoms- Gradual impairment of central vision that is out of
proportion to examination findings. Reduced color vision and
impairment of dark adaptation.

• Signs-
o The macula may initially be normal or show
non-specific mottling, progressing to oval snail
slime or ‘beaten-bronze appearance’ and
subsequently to geographic atrophy that may
tend to a bull’s eye configuration.
o There may be superadded choroidal
neovascularization.
o Numerous yellow-white round, oval or pisciform
fish-shaped) lesion at the level of the RPE; this
may be confined to the posterior pole or extend
to the mid-periphery.
o New lesions develop as older ones become ill
defined and atrophic.

Investigation
• OCT will demonstrate flecks and atrophy.
• FAF shows characteristic appearance with
hyperautofluorescent flecks and macular
hypoautofluorescence.
• Visual field shows central loss and micro perimetry
can accurately document progression.
• ERG: Photopic is normal to sub normal , scotopic may
be normal.
• EOG: Commonly subnormal, especially in advanced
cases.
• FA: The classic feature is a “dark choroid” due to
masking of the background choroidal fluorescence by
diffuse RPE abnormality. Macula shows mixed hyper
and hypo fluroscence. Fresh flecks show early
hypofluroscence.
• ICGA shows fresh hypofluroscent spots.

Treatment
• General measures as like in Retinitis Pigmentosa, protection from excessive
high energy light exposure may be particularly important.
• Vit A supplementation is avoided as it accelerates lipofuscin deposition.
• Gene therapy and stem cell trial show promising results.

Best Vitelliform Macular dystrophy
• It is the second most common macular dystrophy.
• Inheritance- AD, Allelic variation in BEST 1 gene.
• Prognosis- Good, until middle age, after which visual acuity
declines in one or both eyes due to CNV, scarring or
geographic atrophy.
• Signs-
1) Pre-vitelliform stage- Characterized by a subnormal EOG in
an asymptomatic infant or child with a normal fundus.
2) Vitelliform stage- It develops in infancy or early childhood
and does not impair vision. 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.
The size of the lesions and stage of development in the two
eyes may be asymmetrical and only one eye is involved initially.
3)Pseudohypopyon- Occur when part of the lesion regresses,
often at puberty.

4) Vitelliruptive- The lesion breaks up and visual acuity drops.
5) Atrophic in which all pigments has disappeared leaving an atrophic
area of RPE.
• Investigation-
1) FAF- The yellowish material is intensely hyperautofluorescent,
hypoautofluorescent areas supervene in the later atrophic stages.
2) OCT- OCT shows material beneath and within RPE.
3) FA – FA shows corresponding hypo fluorescence due to masking.
4) EOG- EOG is severely subnormal during all stages and is also
abnormal.

Adult Onset Vitelliform Macular Dystrophy
• AOVMD is classified with Juvenile onset vitelliform macular
dystrophy. AOVMD may be a form of pattern dystrophy of the
RPE.
• In contrast to Juvenile BEST disease, the foveal lesions are
typically smaller, present later and generally donot evolve in a
similar fashion.
• A minority of cases is caused by mutation in PRPH2 or BEST1
gene.
• Symptoms-
The condition is generally an incidental finding, presenting in the
middle age or old age. Though the vision is reduced by one or more
lines by presentation and mild deterioration occurs subsequently.
• Signs-
A round or oval slightly elevated yellowish subfoveal deposit,
generally smaller than lesions of BEST disease is seen in both the
eyes. There may be central pigmentation and numerous associated
drusens. The material may persist, absorb, breakup and disperse at
a late stage leaving atrophy of variable severity.

• Investigations-
o OCT shows hyper-reflective material associated with the RPE, similar
to BEST disease.
o FAF imaging shows hyperautofluroscence corresponding to the
deposited material, if atrophy supervenes, there is
hypoautofluroscence.
o FA shows central hypofluorescence surrounded by a small irregular
hyperfluorescent ring.

Multifocal Vitelliform lesion without Best disease
• Occasionally multifocal vitelliform lesions identical to
those in Best dystrophy, but distributed around the
macular vascular arcades and optic disc may become
manifest in adult life.
• EOG is normal.
• Family history negative.

North Carolina Macular Dystrophy
• It is a rare non-progressive condition.
• Inheritance- Autosomal Dominant.
• Grade 1- Charecterized by yellow-
white drusens like peripheral and
macular deposits that develop during
the first decade but may remain
asymptomatic throughout life.
• Grade 2- Charecterized by deep,
confluent macular deposits. The long
term visual prognosis is guarded
because some patients develop
neovascular maculopathy and sub
retinal scarring.
• Grade 3- Charecterized by coloboma
like atrophic macular lesions
associated with variable acuity.

Pattern Dystrophy
• Inheritance – Autosomal Dominant. Mutation in protein
Peripherin on Chr 6.
• Ocular Manifestations- Reticular pigmentation at the level of
the RPE. Yellow flecks and drusens are not found. The
pigments take a characteristic pattern such as butterfly
dystrophy. Demonstrates pigment deposits that radiate from
the fovea in the pattern of butterfly wings. Less commonly
yellowish deposits similar to Stargardt’s are seen.
• Pathology- Primary abnormality of the RPE in the macula.
• Treatment & Course- Initial symptom is slightly diminished
visual acuity or mild metamorphosia. Visual acuity is usually
good through the first five to six decades of life. The prognosis
for good visual acuity is excellent, except in patients who
develop geographic macular atrophy which mimics ARMD in
old age. Small risk of developing CNVM.

Familial Dominant Drusens
• Familial Dominant Drusens (Doyne
honeycomb choroiditis) represents a early
onset variant of ARMD.
Mutation in gene EFEMP1 is responsible.
• Asymptomatic yellow-white, elongated,
radially oriented drusen develop in the
second decade, that may involve the disc
margin and extend nasal to the disc.
• With age the drusens increasingly become
dense and acquire a honeycomb pattern.
• Visual symptoms may occur in 4th to 5th
decade due to RPE degeneration,
geographic atrophy or occasionally CNV.
• ERG is normal, EOG is subnormal.

Dominant Cystoid Macular Oedema
• Rare AD disease mapped to Chr 7q.
• The inner nuclear layer is primarily affected. Muller cells are
specific cellular constituents that are involved.
• Fundus picture- Reveals multilobulated cysts in the macula.
Macular disease of an atrophic appearance develops.
Peripheral pigmentary changes can be present.
• FA- Shows capillary leakage with petaloid dye accumulation in
the macula.
• ERG is normal, EOG is subnormal.
• Pathology- Macular cysts, disorganized and gliotic inner
nuclear membrane, abnormal deposition of basement
membrane in the perivascular space.
• Treatment & Course- Slowly progressive decreasing visual
acuity. Advanced cases have macula of atrophic appearance,
with window defects seen on fluorescein angiography. No
effective treatment exists.

Sorsby Pseudoinflammatory Dystrophy
• It is a macular dystrophy.
• Inheritance- Autosomal Dominant. Allelic variation of gene TIMP3,
Chr 22 is responsible.
• Early presentation may be in the third decade, usually presents in ;late
middle age. Presents with- Nyctalopia, when confluent yellow-white
drusens like deposits may be seen along the arcades, nasal to the disc
and in the mid-periphery. In later stages it leads to sudden visual loss
due to exudative maculopathy secondary to CNV and sub retinal
scarring. Peripheral chorioretinal atrophy is seen in the seventh
decade and results in loss of ambulatory vision.
• ERG is initially normal but my be subnormal in later diseases.
• Pathology- Lipid containing deposits between the Basement
membrane, RPE and inner collagenous layer of Bruch’s membrane.
• Treatment- Patients have severe loss of central vision from extensive
macular scarring and choroidal neovascular membranes. Low vision
aids are advised. Laser treatment has poor results.

Sjogren-Larsson syndrome
• Inheritance- Autosomal Recessive.
• It is a neurocutaneous disorder characterized by
congenital ichthyosis and neurological problem.
• Pathology- Defective enzyme Fatty Aldehyde
Dehydrogenase.
• Presentation- Photophobia, Poor vision, Glistening
yellow-white crystalline deposits develop at the
macula. Presents in first 2 years of life.
• Associated features- Pigmented retinopathy,
Cataract, Colobomatous microphthalmos.

Concentric Annular Macular dystrophy
• Prognosis- Good. Some may develop
progressive loss of acuity and nyctalopia.
• Presentation- Mild impairment of central
vision, Bull’s eye maculopathy is associated
with slight vascular attenuation but normal
disc.
• A paracentral ring scotoma is present on
visual field testing.
• FA shows annular RPE window defect.

Central Areolar Choroidal Dystrophy
• Inheritance- Autosomal Dominant. Chr 17p13.
• Pathology- Primary dystrophy of choroidal vessels or pigment
epithelium. There is an atrophic, fibrosed rea of loss of RPE,
Photoreceptor layer and underlying choriocapillaries.
• Ocular manifestations- Non-specific granular hyperpigmentation of the
fovea, which is indicative of pigment epithelial dystrophy. Gradually a
sharply demarcated area of RPE atrophy with underlying loss of chorio-
capillaries leave intermediate and large choirodal vessels visible. As the
disease progresses, the macular atrophic area expands.
• Fluoresceince Angiography- Shows background hyperfluorescence
from RPE atrophy.
• ERG & EOG are normal.
• Treatment & Course- Complain of central vision loss during third-
fourth decade of life. Atrophy and fibrosis is noted in the avascular
zone. No treatment at present.

Congenital Monochromatism (Achromatopsia)
• This a group of congenital disorders in which colors cannot be perceived and
visual acuity is reduced, particularly in brightly illuminated environment.
• Rod Monochromatism (Complete Achromatopsia)-
o Autosomal Recessive.
o Visual acuity is poor typically 6/60.
o Associated with congenital nystagmus and photophobia.
o Colour vision is totally absent, all colours appearing as shades of grey.
o Macula appears normal but may be hypoplastic.
o The photopic ERG is abnormal and scotopic may be subnormal.
• Blue cone Monochromatism (Incomplete Achromatopsia)-
o X linked Recessive.
o Slightly subnormal visual accuity at 6/6-6/9.
o Colour vision is completely absent.
o Nystagmus and photophobia are not typical features.
o Normal Macula.
o ERG is normal except for the absence of cone responses to red and white light.

Atrophic Areata
• It is a rare disease, reported only in Icelandic Families.
• Inheritance- AD, Chr 11p15.
• Ocular manifestations- It is bilateral, symmetrical maculopathy
and has an early onset. Marked choroidal atrophy radiates from
the optic disc, with two or more ring shaped extensions that
donot follow the major retinal vessels. The disorder is
associated with high myopic astigmatism.
• Color vision is usually normal.
• Treatment and Course- Chorio-retinal atrophy begins in
childhood and is progressive throughout life. Young patients
usually have good visual accuity, but gradual decline in central
vision as macular atrophy sets in.

Familial ILM Dystrophy
• Presents in middle age.
• Presentation- Reduced central vision.
• Fundus- Glistening inner retinal surface is evident at the
posterior pole.
• Prognosis is poor

Maternally Inherited Diabetes and Deafness
• MIDD constitutes 1% of Diabetes.
• Inheritance- Mitochondrial DNA.
• Develop progressive dystrophic macular changes
• Vision is not usually actually.
• Other ocular features- Pigmentary retinopathy and ptosis

Generalized Choroidal Dystrophies

Choroideremia
• Also known as Tapeto-choroidal dystrophy.
• Progressive diffuse degeneration of the choroid, RPE and
Photoreceptors.
• Inheritance is XLR with the locus on Xq21.2 (CHM gene).
Female carriers show mild, patchy peripheral RPE atrophy and
mottling
• Presentation is in the 2nd–3rd decades with nyctalopia,
followed some years later by loss of peripheral vision.
• Signs -
1) Mid-peripheral RPE abnormalities.
2) Atrophy of the RPE and choroid spreads peripherally and
centrally.
3) End-stage disease shows a few large choroidal vessels coursing
over the bare white sclera, vascular attenuation and optic atrophy.
In contrast to primary retinal dystrophies, the fovea is spared until
late
• ERG. Scotopic is non-recordable; photopic is severely
subnormal.
• FA shows filling of the retinal and large choroidal vessels but
not of the choriocapillaris. The intact fovea is hypofluorescent
and is surrounded by hyperfluorescence due to an extensive
window defect

Gyrate atrophy
• Inheritance is AR with the gene locus on 10q26.
• Presentation is in the 1st–2nd decades with myopia and
nyctalopia.
• Signs
1) Mid-peripheral depigmented spots associated with diffuse
pigmentary mottling may be seen in asymptomatic cases.
2) Sharply-demarcated circular or oval areas of chorioretinal
atrophy that may be associated with numerous glistening crystals
at the posterior pole
3) Coalescence of atrophic areas and gradual peripheral and
central spread
4) The fovea is spared until late
5) Extreme attenuation of retinal blood vessels.
6) Vitreous degeneration and early-onset cataracts are common.
• FA shows sharp demarcation between the choroidal atrophy
and normal filling of the choriocapillaris.
• ERG is subnormal is early disease and later becomes
extinguished.

6. Treatment. There are two clinically different subtypes of
gyrate atrophy based on response to pyridoxine (vitamin B6),
which may normalize plasma and urinary ornithine levels.
Patients who are responsive to vitamin B6 generally have a less
severe and more slowly progressive clinical course than those
who are not. Reduction in ornithine levels with an arginine-
restricted diet is also beneficial.
7. Prognosis is generally poor with blindness occurring in the
4th–6th decades from geographic atrophy, although vision
may fail earlier due to cataract, CMO or epiretinal membrane
formation.

Progressive Bifocal Chorioretinal Atrophy
• Inheritance- AD, with complete penetrance. Disease mapped
to MCDR1 on Chr 6.
• Ocular Manifestation- An initial focus of atrophic retina and
choroid is seen temporal to the disc. The focus enlarges in all
directions and temporal border typically has a serrated edge.
Although the atrophy extends to the equator, it doesnot cross
the vertical midline.
The end stage fundus appearance has the unusual image of two
separate foci of chorio-retinal atrophy, with intervening segment
of normal retina.
• Treatment & Course of Disease- It is present at birth and is
progressive. Visual acuity loss corresponds to its proximity to
fovea. No effective treatment.

Juvenile X-linked Retinoschisis
• Inheritance is X linked with the implicated gene
designated RS1 on Xp22.1-22.2
• Pathogenesis -Juvenile retinoschisis is characterized by
bilateral maculopathy, with associated peripheral
retinoschisis in 50% of patients. The basic defect is in
the Müller cells, causing splitting of the retinal nerve
fibre layer from the rest of the sensory retina.
• Presentation is between the ages of 5–10 years with
reading difficulties due to maculopathy. Less frequently
the disease presents in infancy with squint
• Fundus- Peripheral silver dendritic figures ,vascular
sheathing and pigmentary changes are common. Nasal
dragging of retinal vessels and retinal flecks may be seen.
• Prognosis is poor due to progressive maculopathy.
Visual acuity deteriorates during the first two decades
and may remain stable until the 5th–6th decades when
further deterioration occurs.
• OCT is useful for documenting progression of
maculopathy
• ERG is normal in eyes with isolated maculopathy. 9.
EOG is normal in eyes with isolated maculopathy but
subnormal in eyes with advanced peripheral lesions.
• FA of maculopathy may show mild window defects but

Stickler Syndrome
• Disorder of collagen connective tissue.
• Inheritance is AD. Stickler syndrome is the
commonest inherited cause of retinal detachment in
children.
• Classification:
1. STL1 is the most common mutations in the COL2A1
gene. These subjects have the classic ocular and systemic
features as originally described by Stickler.
2. STL2 is caused by mutations in the COL11A1 gene.
These subjects have congenital non-progressive high
myopia, sensorineural deafness, and other features of
Stickler syndrome type 1.
3. STL3 is due to mutations in the COL11A2 gene. These
subjects have the typical systemic features, but no ocular
manifestations.
• Systemic features:
Facial anomalies, Skeletal involvement, Sensorineural
deafness.

Presentation is in early childhood with high non-
progressive myopia.
• Signs
o In STL1 -optically empty vitreous, a retrolenticular
membrane and circumferential equatorial membranes
that extend a short way into the vitreous cavity
o In STL2 patients the vitreous has a fibrillary and
beaded appearance
o Radial lattice-like degeneration associated with RPE
hyperplasia, vascular sheathing and sclerosis
o Retinal detachment develops in approximately 50% in
the first decade of life, often as a result of multiple or
giant tears that may involve both eyes.
3. Associations
Presenile cataract, Ectopia lentis, Glaucoma

Wagner Syndrome
• Wagner syndrome (erosive vitreoretinopathy) shows similar
vitreous changes to Stickler syndrome but is not associated
with systemic abnormalities.
• Inheritance is AD with the gene locus on 5q12-q14.
• Presentation is in early life with pseudostrabismus due to
congenital temporal displacement of the fovea with a positive
angle kappa, and nyctalopia.
• Signs
- The vitreous is optically empty with complete absence of
normal scaffolding.
- Avascular greyish-white preretinal membranes extending from
the posterior pole to the periphery.
- Progressive chorioretinal atrophy.
• FA shows non-perfusion due to gross loss of the
choriocapillaris.
• ERG may initially be normal and then shows reduction of
scotopic b-wave amplitudes and diffuse cone-rod loss.
• Prognosis is poor.

Familial Exudative Vitreoretinopathy
Familial exudative vitreoretinopathy (Criswick–Schepens syndrome)
is a slowly-progressive condition characterized by failure of
vascularization of the temporal retinal periphery, similar to that seen
in retinopathy of prematurity, but not associated with low birth
weight and prematurity.
• Inheritance is AD and rarely XLR or AR,
• Presentation is in late childhood.
• Signs
- Vitreous degeneration and peripheral vitreoretinal attachments
associated with areas of ‘white without pressure’.
- Abrupt termination of peripheral retinal vessels in a scalloped
pattern at the temporal equator.
- Peripheral vascular tortuosity, telangiectasia and
neovascularization.
- Fibrovascular proliferation and vitreoretinal traction resulting in
ridge formation.
- Progressive peripheral fibrovascular proliferation.
-Vascular straightening and temporal ‘dragging’ of the macula and
disc.
• FA shows peripheral retinal non-perfusion and highlights
straightening of blood vessels
• Prognosis is poor

Enhanced S cone syndrome and Goldmann –Favre Syndrome
• Inheritance is AR. The gene implicated is NR2E3 at
15q23.
• Presentation is with nyctalopia in childhood.
• Signs
- Pigmentary changes along the vascular arcades or mid-
periphery that may be associated with round pigment
clumps in more advanced case.
- Cystoid maculopathy without fluorescein leakage, or
schisis.
- Vitreous degeneration and peripheral retinoschisis
• ERG- Non-recordable rod function.

Snowflake Vitreo-Retinal Degeneration
• Inheritance is AD
• Signs -
- Stage 1 shows extensive areas of ‘white-without-
pressure’ in patients under the age of 15 years.
-Stage 2 shows snowflake-like, yellow-white spots in areas
of ‘white with pressure’ in patients between 15 and 25
years.
- Stage 3 manifests vascular sheathing and pigmentation
posterior to the area of snowflake degeneration in
patients between 25 and 50 years.
-Stage 4 gross vascular attenuation, areas of chorioretinal
atrophy, and less prominent snowflakes in patients over
the age of 60 years. The macula and disc remain normal.
• ERG shows low scotopic b-wave amplitude.
• Prognosis is usually good

Kneist Dysplasia
• Pathogenesis. Defect in the type II
collagen gene, COL2A1, also involved in
Stickler syndrome type 1.
• Inheritance is AD.
• Ocular features include high myopia,
vitreous degeneration, retinal detachment
and ectopia lentis.

References
1) Kanski’s Clinical Ophthalmology 9th Edition.
2) Ophthalmology –Myron Yanoff. 4th Edition.
3) Ryan’s Retina 6th Edition.
4) AAO series. Retina and Vitreous. Section 12.
5) Albert and Jackoeib’s Principle and Practice of Ophthalmology. 3rd Edition. Retina
and Vitreous.
6) Valproic Acid for a Treatment of Retinitis Pigmentosa: Reasons for Optimism and
Caution –Levi Todd, Christopher Zerlika
7) The retinoprotective role of phenytoin. Silvia Bartollino et al
Published online 2018 Oct 16. doi: 10.2147/DDDT.S169621
PMCID: PMC6198895

Retinal dystrophy

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