2. • Misnomer- as it does not primarily affect choroid
• Genetic mutations affect the RPE can lead to atrophic changes of both the RPE
and choriocapillaris.
• Common feature of these disorders is degenerative changes of the RPE in the
early stages that progress to involve the choriocapillaris, photoreceptor cell layer,
and in later stages, the larger choroidal vessels
3.
4. Central Areolar Choroidal Dystrophy
• Nettleship
• Mostly AD
• Pheripherin /RDS gene
• Loss of RPE and choroidal tissue
• SYMPTOMS
• diminished central vision
• Generally seen in second decade
5. • SIGNS
solitary, central macular lesion with well-defined margins, and circular or ovoid
in shape Although they may increase in size and become irregular in shape,
they do not involve the peripapillary region or extend beyond the vascular
arcades
6. • early stage - mottling of the RPE in the macula. At this stage, the underlying
choroid may appear ophthalmoscopically normal.
• With the subsequent loss of RPE and choriocapillaris, the underlying choroidal
vessels are more readily visualized.
• With continued loss of RPE and choriocapillaris, the larger choroidal vessels may
undergo degeneration.
• In advanced stages of disease, the sclera is visible as a consequence of choroidal
atrophy.
7. • FFA-early stages of the disease shows hyperfluorescence (window defect)
• ERG -normal
8. Peripapillary Choroidal Dystrophy
• Usually AR
• Also called as peripapillary chorioretinal
degeneration , atrophia areata and peripapillary
chorioretinal degeneration
• Loss of RPE and choroidal tissue
• Begins in the region surrounding the optic disc
and slowly enlarges, in finger-like projections,
nasally, temporally, and into the macula,
eventually occupying the entire posterior pole
9. • Fundi of a 24-year-old woman with helicoidal peripapillary
chorioretinal degeneration
10. D/d
• Peripapillary pigment epithelial dystrophy - there are well-defined areas of RPE
loss, with direct visualization of the underlying choroidal vasculature. FFA- intact
choriocapillaris that differentiates it from those with choriocapillaris loss.
• Serpiginous choroiditis in peripapillary region and then extends into the retina in
pseudopod-like extensions, sometimes involving the macula.
11. Diffuse Choroidal Dystrophy
• Advanced stage of diffuse choroidal
dystrophy shows diffuse retinal pigment
epithelium and choroidal atrophy.
• Both the posterior pole and the retinal
periphery are involved to varying degrees
Advanced stage of diffuse choroidal dystrophy
shows diffuse retinal pigment epithelium and
choroidal atrophy. Both the posterior pole and
the retinal periphery are involved to varying
degrees
12. • Retinal pigment mottling and hypopigmentation.
( The disease may initially show a predilection for the posterior pole of the retina
before progressing to a more diffuse phenotype.)
Diffuse atrophy of both the RPE and choriocapillaris while the larger choroid
vessels appear sclerotic as yellowish-white bands.
• Both the posterior pole and the periphery are involved to varying degrees. Even
with diffuse involvement in the more advanced stages, the retinal vessels usually
remain normal
13. Right fundus (A) and fluorescein angiogram (B) of a 65-year-old woman with diffuse
choriocapillaris atrophy, widespread thinning of retinal pigment epithelium and
loss of choriocapillaris.
14. • Visual fields - concentric peripheral constriction
• ERG - subnormal or undetectable.
• EOG- abnormal in early disease
• FFA shows a loss of the choriocapillaris and visualization of the larger choroidal
vessels beneath atrophic-appearing RPE.
A few scattered areas show a patchy choroidal flush pattern indicative of some
remnants of the choriocapillaris
15. Progressive Bifocal Chorioretinal Atrophy
• Douglas
• AD
• Two foci of chorioretinal atrophy: one a congenital macular lesion and the other that starts
nasal to the disc in the first or second decade of life.
• Both these lesions increase in size until, in the advanced stages, there is only a residual
vertical band of normal retina and choroid confluent with the optic nerve.
• Usually associated with myopia, nystagmus and higher incidence of retinal detachments
16.
17. GYRATE ATROPHY OF THE CHOROID
AND RETINA
• AKA Diffuse total choroidal vascular atrophy
• Slowly progressive
• AR
• Discrete areas of chorioretinal atrophy in midperipheral retina
• Sharply demarcated from more posterior retina
• Hyperornithinemia (10 times above normal)- due to deficiency of OAT(vitamin B6
dependent enzyme)
18. • Develop nyctalopia (2ND TO 3RD DECADE)
• Earliest appearance may be restriction of peripheral field.
• VA is preserved until late
• Fundus shows atrophy of RPE and choriocapillaris during early and
intermediate stage with sharply demarcated scalloped areas of atrophy and a
tendency for pigment clumping at margin.
19. • Atrophy usually starts in midperipheral and
peripheral areas.
• Ultimately involves the entire fundus
including peripapillary areas with
relative sparing of macula.
• Optic disc and retinal arterioles are normal until late
• PVD and epiretinal membrane with
CME have been observed
• myopia, posterior sutural and subcapsular cataract are seen.
20. • Chromosome 10 –OAT gene-missense mutation
• mechanism of pathology for the ocular lesions in gyrate atrophy is unknown, but
the three major theories are that, secondary to the OAT deficiency:
• (1) intracellular proline in the retina may be deficient;
• (2) creatine phosphate stores in the retina and choroid may be deficient, leading
to cell dysfunction and cell death; and/or
• (3) elevated levels of ornithine may be toxic to the retinal pigment epithelium
21.
22. DIAGNOSIS
• H/O night blindness
• Scalloped areas of atrophy of RPE and choroid
• ERG subnormal (rod affected more severly)
• EOG – normal in early stages
• ERG & EOG maintained in vit. B6 responsive patients
• FA shows RPE transmission defects in areas of chorioretinal atrophy
• High ornithine levels in urine, liver, kidney, aqueous humor and CSF
23. TREATMENT:
• Restricted to a rigid schedule of a low protein diet, near total elimination of
arginine...with supplementation of essential amino acids.
• High doses of vit B6---(less than 5%) show partial vitamin B6 responsiveness
• Maintain ornithine level below 5.29-6.61 mg/dl
24. CHOROIDEREMIA
• X linked recessive
• Progressive
• Bilateral
• Marked loss of vision at night and progressive loss of peripheral visual fields.
PATHOGENESIS-
• primarily by degeneration of RPE cells, choroid or both with photoreceptors
degenerating secondarily.
• Primary defect in rods
25. Choroideremia gene CHM- long arm of chromosome X .Xq 21(encodes REP-1 rab
escort protein)
Mutations Stop Codon
Absence Of Gene Product Rep-1 Progressive Chorioretinal Degeneration
26. • Progressiveimpairmentof night vision.
• Usuallybeginsinthe1stdecadeof life
• Somemay havemidperipheral visual field loss.
• Posterior subcapsularchangescanbeseen.
• Initial fundus changesbegins in midperipheralretina inform of patchesof
pigment mottlingand hypopigmentation.
27. Subsequently, nummular areas of patchy RPE and choroidal atrophy develop
Intermediate stage of disease- atrophy of RPE and choriocapillaris becomes
more diffuse(intermediate and large choroidal vessels are preserved)
28. As the disease progresses these vessels also become atrophic
exposing the underlying sclera
29. • Macula - preserved until late.
• Only in more advanced stages -retinal arterioles become
attenuated
• optic disc - not as pale or waxy pale as occurs in RP
• VA remains favourable until the 7th decade of life.(VA may
be decreased because of degenerative maculopathy or
PSC)
•
30. • Fundus picture diagnostic in intermediate and late stages
• Good central VA and slowly progressive visual field changes.
• Both ERG & EOG are abnormal (carriers-usually normal EOG)
• SD-OCT can show cystic macular lesion and peripapillary nerve fibre layer defect.
• FA is not useful in diagnosis(define the extent of choriocapillaris atrophy and
degenerative changes of RPE)
• Clinical diagnosis of CHM in majority of male patients can be confirmed by
immunoblot analysis with RPE-1 antibody(female carriers cannot be identified)
DIAGANOSIS
31.
32. • At present no treatment
• Cystic macular changes can be diminished or resolve by
topical 2% dorzolamide leading to decreased macular
thickness.
TREATMENT
33. CLINICAL PHENOTYPES RESEMBLING HEREDITARY
CHOROIDAL DISEASES
X-linked retinitis pigmentosa (XLRP)
• Abnormalities of the RPE and photoreceptors
• Night blindness, restricted visual field
• AD ,AR , X linked
• Later stages of particularly choroideremia, when the loss of choroid and retina is
significant, the fundus appearance may be confused with end-stage X linked RP;
however, the degree and appearance of pigment migration into the retina that typifies
RP are not characteristically seen in individuals with choroideremia
34. Color fundus photograph from the right eye of a patient with an advanced stage
of X-linked retinitis pigmentosa shows extensive atrophy of retinal pigment
epithelium and choroid in the posterior pole
and midperipheral retina with scattered pigment clumps. The retinal vessels are
attenuated
35. Kearns–Sayre Syndrome (KSS)
• Mitochondrial disease
• Detected before 20 years of age
• pigmentary retinopathy
progressive external
ophthalmoplegia, as well as
ptosis.
Diffuse hypopigmentary changes
In the posterior pole and midperipheral retina.
36. • Patients may have at least one of the following:
Cardiac conduction block,
Cerebellar ataxia,
CSF protein concentration greater than 100 mg/dl.
• Muscle biopsy - ragged red fibers by light microscopy
• Subnormal cone and rod a- and b-wave amplitudes
37. Bietti Crystalline Dystrophy
• AR
• CYP4V2 gene
• Present within third decade of life
• Visual impairment and glistening crystalline-like changes in the posterior pole of
the retina
• 1/3 rd patients-crystals in the superficial stromal layer of the paralimbal region of
the cornea.
• May be a systemic abnormality of lipid metabolism
• Cholesterol or cholesterol esters can also be found in fibroblasts as well as
circulating lymphocytes
38.
39. • Extensive degenerative changes of the RPE, choriocapillaris, and photoreceptors
are seen
• ERG amplitude reduction often parallels the degree of fundus pigmentary
changes.
40. Thioridazine (Mellaril) Retinal Toxicity
• Nightblindness, central and paracentral scotoma
• Extensive degenerative changes of the RPE, choriocapillaris,and photoreceptors
are seen
• Geographic, scalloped regions of hypopigmentation and loss of choriocapillaris
vessels
• ERG - various degrees of diminished photopic and scotopic a- and b-wave
responses that parallel in severity the clinically evident fundus changes.
41. Geographic, scalloped regions of hypopigmentation and loss of the retinal pigment
epithelium and choroid that are similar to the fundus changes observed in patients with
choroideremia and gyrate atrophy of the choroid and retina
42. Stargardt Disease
• “Beaten bronze” appearance of the macula, with small pisciform yellow–white flecks
scattered within the posterior pole and, to a lesser extent, in the midperipheral retina.
• FFA - silent choroid
• Advanced stages of stargardt disease may appear as extensive atrophy of the RPE and
choroid in the posterior pole and anterior to the vascular arcades .
• ERG is often normal to modestly subnormal in the early to middle course of disease
• It is often more notably abnormal by the advanced stage of disease
43. Extensive atrophy of RPE and choroid in the posterior pole and anterior to the vascular arcades
phenotypically similar to the changes observed in diffuse choroidal dystrophy.
RPE and the choroid in the peripapillary area are relatively spared .
44. Pattern Macular Dystrophy
• AD
• Accumulation of lipofuscin within RPE cells with subsequent cell degeneration
and secondary choriocapillaris loss
• In late stages, occasionally produce diffusely atrophic changes of the RPE and
choroid that resembles chorideremia or localized RPE and choroidal atrophy
resembling central areolar choroidal dystrophy.
45. CONCLUSION
• Periodic ophthalmic examination
• Ultraviolet and short-wavelength (blue)-blocking sunglasses
• Genetic counselling
• Gene therapy
• Introduction of recombinant adenovirus containing the full-length REP-1 CHM coding region
• Topical dorzolamide 2 % for CME in choroideremia
