Hereditary macular dystrophies

1. HEREDITARY MACULAR
DYSTROPHIES
Dr Shruti Laddha

2. • Historically, the term “macular dystrophy” has been used to refer to a group of
heritable disorders that cause ophthalmoscopically visible abnormalities in the
portion of the retina bounded by the temporal vascular arcades.
• inherited in a Mendelian fashion
• the associated pathology is limited to the eye
• lesions are biomicroscopically visible in the macula when symptoms first occur
(and in some cases, before symptoms occur)

3. An anatomical basis for classification is used commonly
1. Nerve fiber layer: X-linked juvenile retinoschisis.
2. Photoreceptors and RPE: Cone-rod dystrophy, Stargardt’s disease, Inverse retinitis
pigmentosa (RP), Progressive atrophic macular dystrophy.
3. RPE: Best’s disease, fundus flavimaculatus, dominant drusen, pattern
dystrophy, etc.
4. Bruch’s membrane: Sorsby’s pseudoinflammatory dystrophy, angioid streaks,
myopic macular degeneration.
5. Choroid: Central areolar choroidal dystrophy

4. X-LINKED JUVENILE
RETINOSCHISIS
• This X- linked recessive condition is relatively rare. The disease is caused by
mutations in the retinoschisis gene (RS1) which is located on the distal arm of the
X chromosome.
• The protein retinoschisin is expressed only in the retina, in the inner and outer retinal
layers.
• Misfolding of the protein, failure to insert into the endoplasmic reticulum
membrane and abnormalities involving the disulfide linked subunit assembly have
been found to be abnormalities causing retinoschisis

5. PATHOPHISIOL
OGY• In contrast to senile retinoschisis, the split occurs in the nerve fiber layer.
• The pathology is one of structural defect in Müller cells.
• Typically the peripheral retinoschisis is seen in inferotemporal quadrant .
• More common is the manifestation of macular schisis that is seen in almost all cases
and in roughly 50 percent of cases may be the only manifestation.
• Macular schisis can be differentiated from cystoid macular edema by absence of
leakage on fluorescein angiography and by the demonstration of the split in the nerve
fiber layer on OCT.

6. Clinical features
• Present in the first decade itself, although reading vision maybe maintained even up to
4th to 5th decade of life.
• May present as leucocoria
• Macular RPE atrophy occurs leading to gross loss of central vision.
• Field defects are absolute.
• The diagnosis is usually straight forward on binocular indirect ophthalmoscopy. It
differs from retinal detachment in being bilateral usually, with taut dome like
elevation without undulations

7. • absolute field defects corresponding to the area of schisis
• propensity for causing burns in the outer layer if test laser burns are applied
Left fundus picture demonstrating the large
peripheral retinoschisis with almost total absence
of the inner layer. traction caused by the posterior
edge of the inner layer on the intact posterior
retina. Afew laser marks are also seen beyond
the schisis area
Left eye fundus photograph
with typical foveal
retinoschisis

8. FFA-Foveoschisis
• AV phase-no leakage
• Late phase-no abnormality

9. • Electroretinography is also diagnostic with
the typical wave form being ‘negative’. The ‘b’
wave amplitudes are reduced while ‘a’ wave
amplitudes are maintained at a near normal
level and b/a ratio is <1.0 in the standard
combined maximal response.

10. • Treatment-
• Surgery is recommended for vitreous hemorrhage and retinal detachments
• Retinal detachment cannot be ruled out or when it does not clear in a short
period, pars plana vitrectomy can clear the hemorrhage.
• Retinal detachments due to breaks in the outer layer in the periphery can be
corrected by scleral buckling.

11. STARGARDT’S DISEASE
• Autosomal recessive
• Prevalence of 1 in 10,000.
• The disease is associated with accumulation of fluorescent lipofuscin pigments in cells of
the RPE, specifically A2E (bis-retinoid pyridinium salt) is the major component of
lipofuscin that is accumulated in the RPE cells
• The use of the term Stargardt’s disease should be ideally restricted to atrophic macular
dystrophy associated with flecks.
• Mild reduction in abca4 activity in Stargardt disease is associated with some bisretinoid
formation on the inner leaflet of the photoreceptor outer-segment disc membranes

12. GENETICS
The gene involved in this disease is the ABCR gene located on chromosome 1
codes for a transporter protein located in the rims of rod and cone outer segments.
removal of ‘all-trans-retinaldehyde’(bisretinoin) from the outer segment disks.(Bisretnoin is
useful for rhodopsin regeneration)
Bisretinoin sensitizes the photoreceptors to light induced damage (apoptosis) leading to slow
visual loss.
• ABCA4 mutations are now known to also cause cone dystrophy, cone–rod dystrophy, and
retinitis pigmentosa.

13. • Patient’s position within this disease spectrum is determined largely by the total
amount of residual ABCA4 function.
• Stargardt is known to be the least severe form whereas retinitis pigmentosa is
known to be most severe form

15. SYMPTOMS
• The usual age of presentation is between 6 and 20 years.
• Visual acuity can drop up to 6/60.
• Although the disease tends to be symmetrical, there may be asymmetry .
SIGNS
• Initial stages may show no fundus findings leading to wrong labeling as functional
blindness.
• Later stages Loss of foveal reflex followed by RPE defects in the center of macula occur
later.

16. • Perifoveal flecks also start appearing. Fully developed fundus lesion is characterized
by appearance of oval area of atrophy of RPE in the macula, typically described as
“beaten bronze” appearance
• More flecks appear beyond the macula but do not extend into the periphery.
• In some individuals with severe ABCA4 genotypes, the flecks are small and white
and are admixed with small patches of subretinal fibrosis that resemble confetti
• The disc and blood vessels remain normal throughout the process

17. There are extensive piscifom flecks throughout the
posterior pole and a small circular area of retinal
pigment epithelium atrophy centered on the fovea.
There are numerous very small crystalline deposits
overlying this atrophy
Compound heterozygous mutations in ABCA4 causing the
fundus flavimaculatus variant of stargardt disease. The
visual acuity in this eye is 6/6. There are extensive
Flecks throughout the posterior pole and a small fibrotic
nodule just inferior to the fovea.

18. Fundus photograph with compound heterozygous
mutations in ABCA4 causing Stargardt disease. The
photoreceptors and retinal pigment epithelium (RPE) of
the fovea are relatively spared in this patient and the
visual acuity remains 6/24 despite extensive injury to the
RPE throughout the remainder of the posterior pole.
There are numerous superficial confetti-like flecks that
seem to represent tiny foci of subretinal fibrosis.
Fluorescein angiography of this eye reveals the relative
preservation of the foveal and peripapillary retina and RPE.
The confetti-like flecks are intensely hyperfluorescent.
A B

19. At 27 years of age-
Fundus photograph with compound
heterozygous mutations in ABCA4
causing Stargardt disease. The visual
acuity is 6/60. The small patch of
geographic atrophy has a shiny base
that glistens in this photograph. A few
small flecks can also be seen ringing
the atrophy
At 30 yrs of age
Modest enlargement of the
central atrophy and an increase in
the number of peripheral flecks
but the acuity remains 6/60
At age 42,
The area of central atrophy has
continued to enlarge but the acuity
has fallen to only FC5MT . Some
clumps of dark pigment have
developed within the atrophic
lesion. The peripapillary retina is
noticeably spared.

20. • OCT-have shown expected reduction in macular function and reduction in foveal
thickness. Choroidal neovascularization is a very rarely reported complication.
• SD-OCT reveals selective loss of foveal photoreceptors

21. FFA
• RPE alterations at the fovea
• A V phase- stippled
hyperfluorescence in foveal
region due to transmission
defects. Silent choroid.
• No choroidal fluorescence is
seen even in the
midperiphery of the fundus
• Late phase - Fading of the
hyperfluorescence in the
foveal region ( window
defect). Silent choroid .

22. • ERG-The photopic and scotopic ERG is generally normal, although in advanced stages slight
reduction in amplitudes of ERG are noted.
• EOG- tends to be subnormal.

23. MANAGEME
NT
• Currently, there is no treatment for the disease.
• Experimental studies in knock out mice have shown beneficial effects of isotretinoin.
• The drug inhibits 11-cis-retinol dehydrogenase and hence reduces the
accumulation of A2E.
• However human studies are awaited. Low vision aids can be useful.

24. FUNDUS
FLAVIMACULATUS
• This is considered as a part of the spectrum of disease including Stargardt’s disease.
• SYMPTOMS- drop in visual acuity.
• SIGNS- not involving the fovea. The flecks are ill defined and can have variable shapes,
crescentric, fish tail shaped, linear and circular.
• Confluence of the flecks can result in a reticula appearance.
• The flecks never appear beyond the equator.

25. • FFA- shows window defects due to RPE atrophy in the involved areas,
although early lesions may have no actual RPE atrophy and so may not show
transmission defects
• ERG- ERG is normal in most cases.
• EOG shows reduced Arden’s ratio.

26. BEST
DISEASE
• Best macular dystrophy (BMD), or Best disease, is an autosomal dominant
condition caused by mutations in the BEST1 gene formerly known as VMD2
• The first family with this dystrophy was described by Friedrich Best in 1905.
• Other designations for this disease have since been used, including vitelline
dystrophy, vitelliruptive degeneration, and vitelliform dystrophy.
• It is one of the most common Mendelian macular dystrophies, occurring in
about 1 in 10,000 individuals.

27. GENITI
CS• The causative gene is VMD2 (on choromosome11q13) encoding bestrophin. The
protein has been localized to the RPE.
• Abnormal chloride conductance might be the initiator of the disease process.
• HISTOPATHOLOGIC - findings include increased RPE lipofuscin, loss of photoreceptors
(often seen over relatively intact RPE layer), sub-RPE drusenoid material and
accumulation of cells and material in the subretinal space.

28. • VA is often 6/6 or better in eyes with undisturbed vitelliform lesions, which is surprising
considering the substantial physical separation of the photoreceptor outer segments and
the RPE that exists for decades in some individuals.
• This suggests that the fluid within vitelliform lesions has an ionic composition relatively
similar to that of the normal interphotoreceptor matrix and quite distinct from the
composition of the subretinal fluid associated with rhegmatogenous retinal detachments.
• Some vitelliform lesions gradually flatten over time with persistence of good acuity, while
others develop nodular sub-RPE scars or RPE atrophy which are associated with poorer
visual acuities that are somewhat proportional to the size of the scar.

29. SIGNS
• Previtelliform stage. This is evident as a small, round
yellowish dot at the site of foveola.
• Vitelliform stage can lead to appearance of cyst with
fluid level or sometimes clear space in center with
the material situated all round. Sub- retinal
neovascularization (CNVM) is complication
• Pseudohypopyon may occur when part of the lesion
regresses often at puberty.
• Vitelliruptive: the lesion breaks up and visual acuity
drops
• Atrophic stage can be represented by area of RPE
atrophy or sometimes disciform scar if complicated by
CNVM

30. STAGES
Five stages:
(1) Previtelliform stage (normal macula or subtle RPE changes),
(2) Vitelliform stage (well- defined “egg yolk” lesion),
(3) Pseudohypopyon stage (the yellow material settles inferiorly),
(4) Vitelliruptive stage (a scrambled egg lesion with partial resorption of the
material)
(5) Atrophic stage (macular atrophy)

31. SD OCT characteritics
Previtelliform stage:
• A thickened middle highly reflective layer (HRL) between the RPE/ Bruch’s
complex and the EZ .
• The corresponding ONL starts to thin out at the fovea so the overall retinal
thickness is maintained.

32. Vitelliform stage
( 1 ) a dome-shaped accumulation of hyper-reflective material between the RPE layer and the
photoreceptor layer.
( 2 ) The ONL is thinned over the contour of the elevation,
( 3 ) the middle highly reflective layer (HRL) was seen to be elevated at the margins of the dome with
thickening and fragmentation above the dome elevation but intact and thickened along the rest of the
retina.

33. Pseudohypopyon stage
( 1 ) a localised neurosensory retinal detachment
( 2 ) clumps of hyper-reflective subretinal material seen at the base of this detachment.
( 3 ) The ONL was thinned with focal regions of heterogenous reflectivity
( 4 ) a pigment epithelial detachment

34. Vitelliruptive stage
( 1 ) irregular middle HRL with interspersed with focal
areas of EZ disruption
( 2) thinning of the ONL above the lesion.
Two types of hyper-reflective mounds at the level of the
RPE/Bruch’s complex were observed.
( 3 ) The first type of mound was associated with
shadowing of underlying choroidal structures.
( 4 ) a hyper-reflective spot of partially resorbed
vitelliform material.
( 5 ) The second type of RPE mound that was associated
with the overlying collapse of the outer retinal layers,
hyper-reflectivity of the underlying choroid
( 6 ) disruption of the EZ and middle HRL over the
area of the lesion

35. Atrophic stage
• Overall thinning of neurosensory layers
• Loss of photoreceptors
• Complete loss of EZ and middle HRL
• Thinning of overlying ONL

37. FFA - Depends on the stage of the disease.
• In the vitelliform stage, the early phases of angiogram shows some blocked choroidal
fluorescence in the region of the lesion. In the later phase of the angiogram, the
vitelliform lesion may appear nonfluorescent or may appear to fluoresce slightly.
• In the subsequent stages when the yellow material disrupts, the angiogram shows
areas of hyperfluorescence within the lesion and late staining.
• In the atrophic stage, the large choroidal vessels may be visualized within the atrophic
lesion.
• Angiography in Best’s disease permits the detection of choroidal neovascularization.

38. • Pseudohypopyon, subretinal scar
• AV phase-transmitted hyperflurocence within the lesion, scar shows intense
hyperfluroscence
• Late phase- scar shows hyperfluroscence

39. • Vitelliform lesion, greyish
membrane, subretinal and
intraretinal bleed
• Early AV phase- lacy
hyperfluroscence of CNV, blocked
hypofluroscence due to
haemorrhage
• Late AV phase-leakage
hyperfluroscence, blocked
hyperfluroscnec
• Late phase-intense
hyperflurosence

40. • RPE alteration with subretinal
deposits at macula
• Early phase-hyperfluroscence
• Late AV phase – increase in
hyperfluroscence
• Late phase-fading of
hyperfluroscence

41. • The subretinal material is strongly autofluorescent..
• EOG- Typically EOG is affected early in the stage of the disease. The light-dark ratio is
usually below 1.5.
• ERG is completely normal.

42. TREATME
NT
• Treatment for BEST1 disease consists primarily of recognizing choroidal
neovascularization and hastening its regression with anti-VEGF therapy.
• Even in the absence of CNV, subretinal hemorrhage can occur in patients with
Best disease following relatively modest head or eye trauma.
• As a result, usually patients are cautioned against playing sports in which
frequent blows to the head are to be expected. Protective eyewear is
recommended for all sports.

43. PATTERN
DYSTROPHY
• originally described with black pigmentation in the macular area at the level of RPE.
• Subsequent reports included yellow, gold and gray subretinal deposits as well.
• PD encompasses a broad spectrum of clinical appearances such as
o butterfly-shaped pigment dystrophy ,
o adult-onset vitelliform pattern dystrophy,
o peculiar foveomacular dystrophy,
o Sjögren’s reticular dystrophy of the RPE
o fundus pulverulentus.

44. GENETICS
• PRPH2 gene – most common
• autosomal dominant .
• Peripherin and RDS gene mutations have been identified in these families.
• peripherin that plays a critical role in establishing and maintaining the morphology of
photoreceptor outer-segment discs
• The same point mutation can cause vitelliform lesions in one patient, peculiar foveo-
macular dystrophy in another, and butterfly-shaped pigment dystrophy in others.

45. SYMPTOMS
• Vision is usually not affected to a great degree.
• Cases with significant vision loss in the 6th decade of life.
• The disease is very slowly progressive
• Experience macular photostress in their daily life; that is, their central acuity will be slow
to recover following exposure to bright light
SIGNS
• Reticular (Sjögren): a network of pigmented lines at the posterior pole.
• Fundus pulverulentus is extremely rare. Macular pigment mottling develops.

46. • Butterfly-shaped: foveal yellow and melanin pigmentation, commonly in a spoke-like or
butterfly wing-like conformation drusen- or Stargardt-like flecks may be associated with
any pattern dystrophy .
The pigmentation can be yellow, white, or black and accumulate in an unusual
configuration of three to five “arms” or “wings” that resemble the wings of a butterfly
• FAshows central and radiating hypofluorescence with surrounding hyperfluorescence

47. butterfly pattern dystrophy-
The visual acuity in this eye is 6/6.
Although the flecks in the periphery are somewhat
reminiscent of Stargardt disease, their globular
nature is more consistent with PRPH2-associated
disease.
area of geographic atrophy in the fovea of the left eye
surrounded by pigmentary alterations.
Though the appearance of the macula looks similar to
Stargardt disease, there were peripapillary pigment changes
in contrast to the peripapillary sparing often seen in
Stargardt disease.

48. adult vitelliform pattern dystrophy. Although this
lesion is very similar to those caused by BEST1
mutations, its slightly polygonal shape is more
consistent with PRPH2-associated disease
The fundus findings are very similar to the
fundus flavimaculatus phenotype of ABCA4-
associated Stargardt disease. However, the dark
pigment within the flecks adjacent to the fovea is
more characteristic of PRPH2-associated disease.

49. Sjögren’s Reticular Dystrophy of the RPE
• Clearly defined network of black-pigmented lines at the level of the RPE that
resemble a fishnet with knots or chicken wire.
The visual acuity in this eye is 6/6.
The “knots in the fishnet” described by Sjögren are particularly
evident in this patient

50. Central Areolar
Choroidal
Atrophy
• This disease has a characteristic fundus picture
with punched out area of chorioretinal atrophy
in the macular area.
• Barring large choroidal vessels, all other layers
are atrophic in the affected area in the late
stages.
• In the early stages, non-specific granular
pigmentation can be seen that can be confused
with other conditions such as Stargardt’s
disease.
• Central areolar choroidal dystrophy.
(A) Early; (B) intermediate; (C) end-stage

51. • The disease affects vision in the 4th to 5th decade and progressively deteriorates to
the level of 6/60 vision.
• central scotomas corresponding to the macular lesions.
• The earliest change is a fine, mottled depigmentation in the macula of both eyes that
appears between the second and fourth decades and gradually evolves into symmetric,
sharply outlined, bull’s-eye oval or round areas of geographic atrophy of the RPE.
• Within the area of RPE atrophy, the reddish-orange color of the large choroidal vessels
is replaced by a yellow–white color, sometimes called “choroidal sclerosis” in older
literature.
• Multifocal ERG can show reduced amplitude in the affected areas before obvious
clinical atrophic changes are visible.

52. (A) central areolar form of pattern dystrophy.
(B) SDOCT reveals a remarkable preservation
of photoreceptors and retinal pigment epithelium on the
superior edge of the fovea

53. • Fluorescein angiography reveals the patterns more clearly.
• ERG is normal while EOG can be variable.
TREATMENT
• Geographic atrophy
• CNVM-anti VEGF
• wearing dark glasses and a hat when outside can allow them to adapt more readily
when coming inside from bright light

54. Sorsby’ Dystrophy
• This condition was first described in five British families.
• Autosomal dominant
• characterized by macular hemorrhages that usually begin early in the fifth decade of life
and pigmentary changes in both macula
• GENETICS- mutations in the tissue inhibitor of metalloproteinase-3 (TIMP- 3) have been
identified as a possible cause of the disease.-thickening of Bruch’s membrane
• SYMPTOMS-The disease presents as reduced central vision along with night blindness.

55. • SIGNS-Choroidal neovascular membrane (CNVM)
formation and subretinal bleeding followed by
disciform scar formation takes place, sometimes
extending to the periphery as well.
• Early-ophthalmoscopically visible yellow-grey material
is present at the level of Bruch’s membrane.
• In some parts of the fundus this material can take the
form of drusen , while in other areas the material
coalesces into a fairly uniform yellowish-gray sheet that
becomes more prominent with increasing age
• Sorsby macular dystrophy.
(A) Confluent flecks nasal to the disc; (B) exudative
maculopathy; (C) scarring in end-stage disease

56. TREATMENT
• Argon laser therapy and PDT are not effective in treating CNV
• possibly due to the thickening of Bruch’s membrane.
• However, intravenous bevacizumab has been used in one patient and resulted in CNV
regression and improvement in VA.

57. AUTOSOMAL DOMINANT RADIAL DRUSEN (DOYNE HONEYCOMB
RETINAL DYSTROPHY, MALATTIA LEVENTINESE, HUTCHINSON-
TAY CHOROIDITIS)
• GENETICS-Autosomal Dominant
• EFEMP1 gene mutations have been associated with this disorder. The gene
encodes the EGF-containing fibulin like extracellular matrix protein-1.
• ‘Malaatia levantinese’ is a term used to describe a variant of dominant
drusen first seen in a family in Levantine valley in Switzerland.
• The drusen are oriented more radially in this condition

58. SIGNS- The drusen in this condition are small (25– 75 microns). More of them are
detected on fluorescein angiography rather than on ophthalmoscopy.
• Described as ‘stars in the sky’ or ‘milky way’, they
are seen in clusters in the posterior pole .
• The drusen are present as nodular thickening of the
basement membrane of the RPE
SYMPTOMS-
Vision can be affected due to CNVM, and geographic atrophy
• large drusen abutting the optic disc are characteristic
of this disease as are the delicate radially oriented
drusen that are visible along the temporal edge of the
macular lesion. A few of the medium-to-large drusen
in the central lesion have fused into a honeycomb
configuration

59. There is a dense honeycomb of large drusen occupying
most of the posterior pole, with dark pigment and RPE
atrophy near the center of the macula
The visual acuity in this eye is 6/6. Reticular
pigment changes outline the large central drusen. Fine
radial drusen along the temporal and inferior aspects of
the macular lesion are nearly invisible.

60. NORTH CAROLINA MACULAR DYSTROPHY
r
• North Carolina macular dystrophy’ as the
term indicates was originally described
in a family in North Carolina but has
been now identified all over the world
and in various ethnic groups.
• autosomal dominant
• The fundus findings tend to be bilateral
and quite symmetric.
• The most characteristic lesion is a circular
coloboma centered on fixation with a
shiny concave base surrounded by a thick,
white fibrotic rim

61. The characteristic fundus findings include a staphylomatous lesion centered in the
macula, with a shiny concave base and a thick white fibrotic rim. The disc, vessels, and
periphery are all completely normal

62. • Large lesions are large at birth and do not progress from smaller ones.
• This complete lack of progression is one of the most reliable diagnostic features
of the disease, and accounts to some degree for the amazingly good VA in some
patients with very large lesions.
• That is, because the lesions are present well before maturation of the visual
system, patients learn to fixate on the edges of the lesions and develop their
visual pathways accordingly.

63. • Mahajan et al.recently described seven members
of a three generation family with autosomal
dominant inheritance of a new dystrophy limited
to the macula and characterized by round, flat
pigmented spots with or without surrounding
hypopigmentation
• OCT :cysts in multiple retinal layers, and
neovascularization.
SPOTTED CYSTIC DYSTROPHY

64. • O/E: Amblyopia and strabismus were frequently present in affected individuals.
Visual acuity ranged from 6/6 to 6/60
• The pathophysiology and genetic mutation responsible for this condition have not
been identified.
• TREATMENT: When active macular neovascularization occurs in affected
individuals, it has been responsive to either focal laser or a single injection of
bevacizumab.

65. DOMINANT CYSTOID MACULAR DYSTROPHY
• described by Deutman in 1976
• autosomal dominant
• chromosome 7
• characterized by EARLY leaking perimacular capillaries, whitish punctate deposits in
the vitreous,
• In the LATE stages of the disease, an atrophic central “beaten-bronze” macula was
common.

66. • hyperopia
• normal ERG,
• a subnormal EOG
• Hogewind and coworkers evaluated intramuscular injections of a somatostatin analog
(octreotide acetate) in four patients with DCMD and seven of the eight eyes showed
improvement on FFA, with stabilization of visual acuity.
Fluorescein angiogram of the right eye of a patient
With dominant cystoid macular edema showing
leakage from perifoveal capillaries.

67. FENESTRATED SHEEN MACULAR DYSTROPHY (FSMD)
• Several families have been described with an autosomal dominant macular
disorder , occurring as early as the first decade of life and seen as late as the fifth
decade
• The chromosomal location of the disease- causing gene is currently unknown.
• FUNDUS FINDING:central macular sheen with small red
fenestrations
Some middle-aged family members
develop a bull’s- eye pattern of stippled
hypopigmentation in the central macula

68. • Mild functional abnormalities roughly correlate with more advanced age but
patients with the red fenestrations have 6/6 visual acuity.
• Normal or mildly abnormal ERG findings have been reported

69. GLOMERULONEPHRITIS TYPE II AND DRUSEN
• Glomerulonephritis (MPGN) type II (also known as dense-deposit disease)
develop subretinal deposits with the clinical appearance of basal laminar
drusen
• no progression and no vision loss . visual acuity tends to be preserved
unless CNV, exudative drusen,
or serous detachment complicate

70. • An abnormal EOG with a relatively normal ERG can be seen in some patients,
suggesting a more global retinal dysfunction than the visible drusen would
suggest.
• Histopathologic studies of the Bruch’s membrane deposits found in MPGN II
demonstrate that they are morphologically and compositionally similar to the
drusen found in AMD.
• Abnormal urinalysis with this phenotype in young adults should prompt a
referral for work- up of kidney disease.