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NR 4-6/2008
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Exudative
age-related macular degeneration
or Best vitelliform macular dystrophy? – a case report
Wysiękowe AMD czy żółtkowata
dystrofia dołkowo-plamkowa
dorosłych Besta – opis przypadku
Agnieszka Kubicka-Trząska, Agnieszka
Filemonowicz-Skoczek, Izabella Karska-Basta,
Bożena Romanowska-Dixon
Department of Ophthalmology, Clinic of Ophthalmology and Ocular
Oncology,
Medical College, Jagiellonian University, Kraków, Poland
Head: Ass. Prof. Bożena Romanowska-Dixon, MD, PhD |
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| Summary: |
Purpose: To report
a case of Best vitelliform macular dystrophy referred to
the Department of Ophthalmology in Krakow with a
diagnosis of exudative age-related macular degeneration
(AMD).
Materials and methods: 70-years old man was
diagnosed in our clinic because of a two years history
of slow, progressive visual acuity worsening in both
eyes with the presence of metamorphopsia. The basic
ophthalmic examination was performed with additional
diagnostic methods including: colour vision test (Panel
D-15), Amsler grid test, contrast sensitivity test (Pelli-Robson
chart), fluorescein angiography (FA), indocyanine green
angiography (ICGA), electroretinogram (ERG),
electrooculogram (EOG) and optical coherence tomography
(OCT).
Results: Visual acuity in the right eye was: 0.16
and in the left: 0.25. Amsler grid test revealed the
presence of bilateral mild metamorphopsia with the
relative central scotoma. Pelli-Robson test showed
decreased contrast sensitivity perception in both eyes;
PO>LO. On fundoscopy in macula of both eyes the
symmetrical round, elevated lesions of 1.5 dd with the
meniscus of subretinal creamy-yellow masses were present.
The early frames of FA showed the presence of round
lesions with distinct borders, unchanged in size and
shape throught the examination, hypofluorescent in the
lower and hyperfluorescent in the upper half of the
lesions. Late frames of FA revealed the irregular
hyperfluorescence also in lower aspects of the lesions.
ICGA showed: round hypofluorescent lesions with
isofluorescence in the upper part of the lesions. ERG –
revealed no pathology, EOG – showed decreased light
response and depressed Arden ratio in both eyes. OCT
demonstrated hiperreflectivity of the retinal pigment
epithelium with elevation of retina and deletion of the
foveolar depression in both eyes.
Conclusions: Based on the results of performed
tests the diagnosis of the Best vitelliform macular
dystrophy was established. In some cases various
pathologies involving the macula may mimic the exudative
AMD. The basic ophthalmic examination supported by
additional diagnostic methods allow to establish the
definitive diagnosis in most cases of macular disorders. |
| Słowa kluczowe: |
wysiękowe zwyrodnienie
plamki żółtej związane z wiekiem (AMD), żółtkowata
dystrofia dołkowo-plamkowa dorosłych Besta, angiografia
fluoresceinowa, angiografia indocyjaninowa, ERG, EOG,
OCT. |
| Key words: |
exudative-age related
macular degeneration, Best vitelliform macular dystrophy,
fluorescein angiography, indocyanine green angiography,
ERG, EOG, OCT. |
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Best disease, also known as Best
vitelliform macular dystrophy, is an autosomal dominant form of
progressive macular dystrophy first described by Frederich Best
in 1905. This disease occurring primarily in European Caucasians
is characterized by an accumulation of lipofuscin-like material
in the macula that results in an “egg-yolk-like appearance
(1,2). Best disease is caused by mutations in the VMD2 gene that
encodes a chloride channel in the basolateral membrane of the
retinal pigment epithelium (RPE), resulting in lipofuscin
deposits in the RPE layer (3,4). The defective chloride channels
result also in an abnormal electrooculogram (EOG); depressed
Arden ratio, which can be used to diagnose patients without
classic macular lesions, as well as identifying patients that
are unlikely to have the disease (1,2). Individuals with Best
disease generally show a gradual loss of central vision,
although the frequency with which an affected person may show
symptoms and the severity of those symptoms are highly variable
(5).
There are two forms of vitelliform macular dystrophy with
similar features. The early-onset form usually appears in
childhood. However, the onset of symptoms and the severity of
vision loss vary widely. The adult-onset form begins later,
usually in middle age, and tends to cause relatively mild vision
loss (2,6). The aim of the study is to report a case of Best
vitelliform macular dystrophy referred to the Department of
Ophthalmology in Krakow with a presumptive diagnosis of
exudative age-related macular degeneration (AMD).
A case report
A 70-years old man was admitted to our clinic with a two years
history of slow, progressive visual acuity worsening in both
eyes with the presence of bilateral metamorphopsia. The basic
ophthalmic examination was performed with additional diagnostic
methods including: colour vision test (Panel D-15), Amsler grid
test, contrast sensitivity test (Pelli-Robson chart),
fluorescein angiography (FA), indocyanine green angiography (ICGA),
electroretinogram (ERG), electrooculogram (EOG) and optical
coherence tomography (OCT).
The patient was complaining of blurred and distorted vision
affecting near and far vision. The colour vision in both eyes
was affected in blue-yellow axis, more in the right eye compared
with the left. The symptoms affected activities of his daily
life. No ocular disorders run in patient’s family. Best
corrected visual acuity of the right eye was: 0.16 and 0.25 in
the left eye. Amsler grid test revealed the presence of
bilateral mild metamorphopsia with the relative central scotoma
in both eyes. Pelli-Robson contrast sensitivity test showed
decreased contrast sensitivity perception in both eyes; in the
right eye it was worse as compared to the left. Intraocular
pressure in both eyes was normal; right eye – 14 mmHg, left eye
– 16 mmHg. Anterior segment examination revealed the presence of
senile arcus in the periphery of the cornea and early stages of
cortical cataract in both eyes. On fundoscopy in macula of both
eyes the symmetrical round, elevated lesions (cysts) of 1.5 disc
diameter (dd) with the meniscus of subretinal creamy-yellow
masses were present (Fig. 1a, 1b). The early frames of FA showed
the presence of round lesions with distinct borders, unchanged
in size and shape throught the examination, hypofluorescent in
the lower and hyperfluorescent in the upper half of the lesions
(Fig. 2a, 2b). Late frames of FA revealed the irregular
hyperfluorescence also in lower aspects of the lesions (Fig. 3a,
3b). ICGA showed round hypofluorescent lesions with
isofluorescence in the upper part of the lesions (Fig 4a, 4b and
Fig. 5a, 5b). ERG revealed normal scotopic and photopic a and b
waves. EOG showed decreased light response and depressed Arden
ratio in both eyes which was: 0.97 in the right eye and 0.92 in
the left eye. OCT demonstrated in both macular regions
hyperreflectivity of the retinal pigment epithelium with
elevation of retina and deletion of the foveolar depression
(Fig. 6a, 6b).
Discussion
Clinical expression of Best vitelliform dystrophy vary from one
individual to another, thus in some cases it may cause problems
in differential diagnosis. Onset of the disease may occur in
childhood or decades later. Within 5 identifiable stages,
examination of the eye discloses a distinct progression (2,6).
At first and second stages, there may be little or no effect on
sight. At the second stage (usually between 10-25 years of age),
typical yellow spots, sometimes accompanied by material leaking
into a space by the retina, can be observed; a pathology called
“egg-yolk” lesion. When part of this lesion becomes absorbed a
pseudohypopyon (aqueous-lipid fluid level) is identified as
stage three. Even at this stage there may be little affect on
vision. At the fourth stage, when the “egg-yolk” breaks up, in a
process referred to as “scrambled-egg”, sight will be affected.
The fifth and final stage is when the condition causes the most
severe sight loss due to choroidal neovascularization (CNV) and
RPE atrophy. In typical Best disease the EOG is usually abnormal
even in asymptomatic patients. However there are some data about
the normal EOG in patients suffering from this disease and also
in adult onset of Best disease the EOG is normal (5). Other
tests such as FA, ICGA and OCT might add information for the
correct diagnosis (7-10). In our patient based on the results of
EOG we diagnosed the Best vitelliform dystrophy and the results
of FA, ICGA and OCT were consistent with the third stage of this
disease. Differential diagnosis of Best vitelliform dystrophy
includes: pattern macular dystrophies, Stargardt disease, fundus
flavimaculatus, central serous retinopathy, pigment epithelial
detachment (PED), North Carolina macular dystrophy, age-related
macular degeneration (6). Best disease is genetically passed
through families by the autosomal dominant pattern of
inheritance.
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Many affected people,
however, have no history of the disorder in their family and the
disease develops as a result of a new mutation in an affected
person. Without a family history, only 25% of patients will have
a mutation (3). In our patient we did not perform the genetic
tests because they are not available on a routine way. Currently,
there is no treatment for Best disease but scientific research,
both traditional and genetic, may provide useful treatments for
the future. In cases complicated with subfoveal CNV photodynamic
therapy with verteporfirin may be a useful method of treatment
(11).
Prognosis for this disease is mixed. Some carriers will never
phenotypically express the disorder. Some individuals will never
have progression beyond the earliest stages of the disease and
will maintain better than 20/40 vision in both eyes. In general,
most affected people will maintain reading vision in at least 1
eye throughout life. Almost 90% of patients retained 20/40 or
better visual acuity, and only 4% of them had 20/200 or worse
visual acuity in the better eye (12). The deterioration of
vision usually is very slow and is not significant in most
individuals until after age of 40 years.
In some cases the diagnosis of various pathologies involving the
macula may be difficult. The basic ophthalmic examination
supported by additional diagnostic methods allow to establish
the definitive diagnosis in most cases of macular disorders.
Praca została przedstawiona w postaci plakatu na XXVIII
Sympozjonie Retinologicznym w Poznaniu w dniach
12-14.04.2007 r.
References:
1. Apushkin MA, Fishman GA, Taylor CM, Stone EM: Novel de novo
mutation in a patient with Best macular dystrophy. Arch
Ophthalmol 2006, 124(6), 887-889.
2. Kański JJ, Milewski SA: Choroby plamki. Wyd. I polskie pod
red. K. Pecold. Górnicki Wydawnictwo Medyczne, Wrocław 2003,
195-197.
3. Schatz P, Klar J, Andreasson S, Ponjavic V, Dahl N: Variant
phenotype of Best vitelliform macular dystrophy associated with
compound heterozygous mutations in VMD2. Ophthalmic Genet 2006,
27(2), 51-56.
4. Kramer F, White K, Pauleikhoff D, Gehrig A, Passmore L,
Rivera A, Rudolph G, Kellner U, Andrassi M, Lorenz B,
Rohrschneider K, Blankenagel A, Jurklies B, Schilling H, Schutt
F, Holz FG, Weber BH: Mutations in the VMD2 gene are associated
with juvenile-onset vitelliform macular dystrophy (Best disease)
and adult vitelliform macular dystrophy but not age-related
macular degeneration. Eur J Hum Genet 2000, 8(4), 286-292.
5. Wabbels B, Preising MN, Kretschmann U, Demmler A, Lorenz B:
Genotype-phenotype correlation and longitudinal course in ten
families with Best vitelliform macular dystrophy. Graefes Arch
Clin Exp Ophthalmol 2006, 244(11), 1453-1466.
6. Brecher R, Bird AC: Adult vitelliform macular dystrophy. Eye
1990, 4, 210-215.
7. Hayami M, Decock C, Brabant P, Van Kerckhoven W, Lafaut BA,
De Laey JJ: Optical coherence tomography of adult-onset
vitelliform dystrophy. Bull Soc Belge Ophthalmol 2003, 289,
53-61.
8. Sanfilippo P, Troutbeck R, Vandeleur K, Lenton L: Optical
coherence tomography of adult-onset fovemacular vitelliform
dystrophy. Clin Experiment Ophthalmol. 2004, 32(1), 114-118.
9. Pierro L, Tremolade G, Introini U, Calori G, Brancato R:
Optical coherence tomography findings in adult-onset
foveomacular vitelliform dystrophy. Am J Ophthalmol 2002,
134(5), 675-680.
10. Lanzetta P, Virgili G, Menchini U: Indocyanine green
angiography in vitelliform macular lesions. Ophthalmologica
1996, 210(4), 189-194.
11. Andrade RE, Farah ME, Costa RA: Photodynamic therapy with
verteporfin for subfoveal choroidal neovascularization in Best
disease. Am J Ophthalmol 2003, 136(6), 1179-1181.
12. Fishman GA, Baca W, Alexander KR, Derlacki DJ, Glenn AM,
Viana M: Visual acuity in patients with Best vitelliform macular
dystrophy. Ophthalmology 1993, 100(11), 1665-1670.
Praca włynęła do redakcji 20.12.2007 r. (1008)
Zakwalifikowano do druku 26.03.2008 r.
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Fig. 1a. Fundus of the right
eye.
Ryc. 1a. Dno oka prawego.
Fig. 1b. Fundus of the left
eye.
Ryc. 1b. Dno oka lewego.
Fig. 2a. Early phase of the
FA of the right eye.
Ryc. 2a. AF – wczesna faza oka prawego.
Fig. 2b. Early phase of the
FA of the left eye.
Ryc. 2b. AF – wczesna faza oka lewego.
Fig. 3a. Late phase of the
FA of the right eye.
Ryc. 3a. AF – późna faza oka prawego.
Fig. 3b. Late phase of the
FA of the left eye.
Ryc. 3b. AF – późna faza oka lewego.
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Fig. 4a. Early phase of the
ICGA of the right eye.
Ryc. 4a. ICA – wczesna faza oka prawego.
Fig. 4b. Early phase of the
ICGA of the left eye.
Ryc. 4b. ICA – wczesna faza oka lewego.
Fig. 5a. Late phase of the
ICGA of the right eye.
Ryc. 5a. ICA – późna faza oka prawego.
Fig. 5b. Late phase of the
ICGA of the left eye.
Ryc. 5b. ICA – późna faza oka lewego.
Fig. 6a. OCT of the right
eye.
Ryc. 6a. OCT – oko prawe.
Fig. 6b. OCT of the left eye.
Ryc. 6b. OCT – oko lewe.
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