central areolar choroidal dystrophy with associated ... · areolar choroidal dystrophy, and is...
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ournal of Optometry (2013) 6, 114---122
www.journalofoptometry.org
ASE REPORT
entral areolar choroidal dystrophy with associatedominant drusen
ulie Rodman ∗, Greg Black, Albert Woods
ova Southeastern University College of Optometry, Davie, FL, United States
eceived 10 May 2012; accepted 25 June 2012vailable online 23 October 2012
KEYWORDSRetina;Choroid;Electrodiagnostics;Dystrophy
AbstractIntroduction: Central areolar choroidal dystrophy (CACD) is a rare, inherited disease that canlead to profound visual disturbance. It is characterized by atrophic changes, particularly in themacula. Specific genotypic mutations are responsible for the autosomal dominant form of thisdisease. However, there is a distinct retinal dystrophy that combines central areolar choroidaldystrophy with autosomal dominantly inherited drusen. It has been proposed that patients witha specific mutation in the peripherin/RDS gene may manifest a combined presentation.Case report: Here we describe a case of a patient who reported with significantly decreasedbest-corrected visual acuity of fifteen years of duration in the right eye more than the left.Dilated fundus examination found macular changes that were consistent with central areolarchoroidal dystrophy. In addition, there was evidence of surrounding congenital drusen through-out the arcades of both eyes. Electrodiagnostics, optical coherence tomography, and fundusfluorescein angiography were used to confirm the diagnosis of CACD.Conclusion: Central areolar choroidal dystrophy normally presents without drusen. However, inpatients manifesting a specific mutation, central areolar choridal dystrophy may present in con-junction with drusen. It appears that the Arg142Trp mutation is one of the factors predisposingto drusen formation.© 2012 Spanish General Council of Optometry. Published by Elsevier España, S.L. All rightsreserved.
PALABRAS CLAVERetina;
Distrofia coroidea areolar central asociada a drusas dominantes
Coroideo;Electrodiagnóstico;Distrofia
ResumenIntroducción: La distrofia coroidea areolar central (DCAC) es una enfermedad rara y hered-itaria, que puede originar una gran alteración visual. Se caracteriza por cambios atróficos,particularmente en la mácula. Las mutaciones genotípicas específicas son responsables de laforma dominante autosómica de esta enfermedad. Sin embargo existe una distrofia retiniana
∗ Corresponding author at: Nova Southeastern University College of Optometry, 3200 S. University Drive, Davie, FL 33328, United States.E-mail address: [email protected] (J. Rodman).
888-4296/$ – see front matter © 2012 Spanish General Council of Optometry. Published by Elsevier España, S.L. All rights reserved.ttp://dx.doi.org/10.1016/j.optom.2012.09.003
Central areolar choroidal dystrophy with associated dominant drusen 115
diferente, que combina la distrofia coroidea areolar central con las drusas autosómicas domi-nantes hereditarias. Según se ha propuesto, los pacientes con una mutación específica del genperiferina-RDS pueden manifestar una presentación combinada.Informe de un caso: Describimos aquí el caso de un paciente que se presentó con una disminu-ción considerable de la agudeza visual mejor corregida, desde hacía quince anos, más acusadaen el ojo derecho que en el izquierdo. El examen del fondo de ojo bajo dilatación mostró unoscambios maculares en consistencia con una distrofia coroidea areolar central. Además, existíaevidencia de drusas congénitas circundantes en las arcadas de ambos ojos. Se utilizaron elec-trodiagnóstico, tomografía de coherencia óptica y angiografía fluoresceínica del fondo de ojopara confirmar el diagnóstico de DCAC.Conclusión: La distrofia coroidea areolar central se presenta normalmente sin drusas. Sinembargo, en pacientes que manifiestan una mutación específica, la distrofia coroidea areo-lar central puede presentarse acompanada de drusas. Parece que la mutación Arg142Trp es unode los factores que influyen en la formación de drusas.© 2012 Spanish General Council of Optometry. Publicado por Elsevier España, S.L. Todos losderechos reservados.
diawc1rsaegdpunremarkable in OU. Optical coherence tomography wasperformed in office. On OCT examination in OD, the atrophicmacular area correlated with a total absence of the outer
Background
Central areolar choroidal dystrophy (CACD) is a hereditaryretinal disorder that primarily affects the macula. In theearly stages, there is subtle, mottled depigmentation inthe posterior pole. Ultimately, the depigmentation enlargesinto in a well-circumscribed round or oval area of atrophyof the retinal pigment epithelium (RPE) and choriocapil-laris in the center of the macula.1,2 Patients usually becomesymptomatic in the 3rd to 4th decade when a fine, hardlydetectable, mottling of the RPE leads to the developmentof absolute central visual scotomas. Later, between the 4thand 7th decade of life, progressive macular atrophy leadsto a dramatic decline in central visual acuity and severevisual disability.3,4 CACD may be autosomal dominant orrecessive; however, autosomal-recessive cases are rare.1
Although CACD has a genetic basis, sporadic cases have beenreported.5
Autosomal-dominant CACD is heterogeneous, but muta-tions in the peripherin/RDS (peripherin-2 or PRPH2) geneseem to be the most common cause.1,6 Seven differentmutations in the peripherin/RDS have been described inautosomal-dominant CACD.1,5 The p.Arg142Trp mutationin the peripherin/retinal degeneration slow (RDS) gene hasbeen implicated in both autosomal-dominant CACD anddominant drusen.2,7 However, no flecks or drusen are typ-ically seen in CACD.7,8 Therefore, the expression of thisparticular mutation is not common.
Case report
A 47-year-old black female presented with a chief com-plaint of decreased vision in her right eye (OD) for the past15 years. Her ocular history included a prior episode ofanterior uveitis in the OD which resolved with conventional
treatment. Medical history was remarkable for hyperten-sion and type 2 non-insulin dependent diabetes of 17 yearsduration. Her systemic medications included glyburide, met-formin, and lisinopril. Her family history was remarkable forFa
iabetes, hypertension, and glaucoma in her mother. Exam-nation revealed best corrected visual acuity of OD 20/200nd OS 20/25. Pupillary reactions were normal and thereas no restriction of gaze. Visual fields were full to fingerounting. The intraocular pressures were 20 mmHg in OD and7 mmHg in OS. Slit lamp evaluation exhibited nuclear scle-osis and cortical cataracts in OU with a posterior subcap-ular cataract in OS. Fundus examination was significant for
well-circumscribed area of choroidal and retinal pigmentpithelial atrophy involving the macula in OD, and overalleographic atrophic changes in OS (Figs. 1 and 2). Drusenoideposits surrounded both maculae. The optic nerves wereink with distinct margins and the peripheral fundus was
igure 1 (Top) Fundus photo OD with well-delineated,trophic macular lesion with surrounding drusenoid deposits.
116
Figure 2 (Top) Fundus photo OS with drusenoid deposits sur-r
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ounding a mottled, irregular macula.
etinal layers with shadowing into the choroid. (Fig. 3A)n addition, the OCT revealed ‘‘lumpiness’’ at the level of
he retinal pigment epithelium, consistent with the heavyrusenoid deposition. (Fig. 3B) Based on clinical appearancend OCT, a tentative diagnosis of CACD was made and thefls
igure 3 (A) On OCT examination in OD, the atrophic macular arith shadowing into the choroid. (B) OCT revealing bumpiness at thrusenoid deposits seen throughout the posterior pole.
J. Rodman et al.
atient was sent for further evaluation including fluoresceinngiography and electrodiagnostic evaluation.
Both a flash electroretinogram (fERG) and multifocallectroretinogram (mfERG) were performed. (Figs. 4---6) TheERG findings showed normal rod responses along with a mildeduction in the photopic response amplitude and minimalelay, with the right eye affected to a greater degree. Thesendings are consistent with the most common fERG patternnormal responses overall with slightly impaired photopicesponses) seen in patients with central areolar choroidalystrophy.2,9 The mfERG findings further mapped the ampli-ude reduction across 50◦ of the posterior pole. The resultsndicated a loss of central cone population, consistent withatient’s loss of vision in both eyes, and with the fovealrea response significantly more depressed in the right eye.t is worth noting that the retinal dysfunction noted wither mfERG is not limited to the demarcated central atrophicetinal areas, but expands beyond centrifugally. This findingas been reported in the literature in patients with cen-ral areolar choroidal dystrophy, and is thought to reflect aore diffuse retinal involvement relative to the clinically
vident morphological changes.10,11 The mfERG is able toetect abnormalities localized in the macula, and is there-ore a very useful instrument in the diagnosis of macularystrophies such as CACD.11 It is also useful to help mappingreas of visual loss in patients unable to perform reliable
Fluorescein angiography revealed small areas of hyper-uorescence corresponding to the RPE atrophy in the earlytages. In the later frames, there is loss of choriocapillaris
ea correlated with a total absence of the outer retinal layerse level of the retinal pigment epithelium consistent with the
Central areolar choroidal dystrophy with associated dominant drusen 117
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Figure 4 fERG shows normal scotopic responses OU (dark-adapted waveforms above), reduced photopic response amplitudes andminimal delay OU (light-adapted waveforms above), with right eye 30 Hz flicker responses slightly reduced compared to left eye.These findings are consistent with the most common fERG pattern seen in patients with central areolar choroidal dystrophy.
118 J. Rodman et al.
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Figure 5 OD mfERG findings show marked 1st order response amplitude reduction across the central retina with a normal to tracedelay in implicit time. Note the marked central response amplitude depression in the foveal zone, however the retinal dysfunctionnoted in the mfERG is not limited to the demarcated central atrophic area as can be seen in the retinal photo (Figs. 1 and 2).This finding of retinal response depression on mfERG testing extending beyond the borders of the ophthalmoscopic lesions hasbeen reported in patients with CACD, and is thought to reflect a more diffuse retinal involvement relative to the clinically evidentmorphological changes.
Central areolar choroidal dystrophy with associated dominant drusen 119
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Figure 6 OS mfERG findings showing marked 1st order response amplitude reduction across the central retina with a normal
implicit time. While significantly attenuated, there is still the presethis eye.nce of a foveal response peak consistent with the better VA in
120 J. Rodman et al.
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Figure 7 The early frames of the angiogram indicate hyperfluorescence of the lesions corresponding to RPE atrophy. The laterf hy.
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n the area of RPE atrophy. The hard drusen can be dis-inguished as small, well-defined, hyperfluorescent lesionsFig. 7).
Several clinical entities resemble the fundoscopicppearance described and the differential diagnosesncluded central areolar choroidal dystrophy, cone dystro-hy, macular degeneration, and Stargardt’s Disease. In ouratient, the diagnosis of central areolar choroidal dystro-hy was made by clinical evaluation, ancillary testing andy exclusion.
iscussion
entral Areolar Choroidal Dystrophy was initially called Cen-ral Senile Areolar Choroidal Atrophy by Nettleship in 1884.12
n 1939, Sorsby renamed the condition Choroidal Angio-clerosis. The current name of CACD was designated afterhe inheritance pattern was deemed primarily dominant.
ince CACD is predominantly an autosomal dominant disor-er with complete or almost complete penetrance, almostll people carrying the peripherin/RDS (Arg142Trp) mutationan be considered potential CACD patients.5,7fr
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The hard drusen can be seen as tiny, hyperreflective lesions.
Central areolar choroidal dystrophy is a heterogeneousrogressive macular dystrophy that primarily affects thehoriocapillaris. Clinically, it presents as a regional, geo-raphic area of atrophy involving the choroid and RPE. Fineymmetric mottling of the RPE in the macula can resem-le that of a bulls-eye.13 Patients are initially asymptomaticith normal visual acuity. Between the 3rd and 4th decades,
he area may begin to mirror that of a macular coloboma.14
ver time, retinal blood vessels begin to course over theesion and sclera becomes visible. Visual acuity may dropo the 20/50 level at this stage.13 As the patient gets older5---6th decade), the lesion may begin to spread more periph-rally leading to further visual disturbance.
Four clinical stages of the disease have been described.5
tage 1 is characterized by subtle focal parafoveal pigmen-ary RPE changes that can be observed ophthalmoscopically.tage 2 would appear as an oval-to-round, mildly atrophic,ypopigmented area. Stage 3 is characterized by one orore patches of well-demarcated RPE atrophy outside the
ovea. In stage 4, the atrophic area involves the fovea whichesults in a profound decrease in vision.
The retinal findings seen in CACD vary and range frominimal RPE changes without drusen to CACD associated
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with dominant drusen. Literature on similar clinical pre-sentations is limited. Klevering et al.7 report on an entitycalled Zermatt macular dystrophy which affects patientsin their late teens and twenties and presents with drusen-like deposits and central pigmentary changes. Focal atrophicdefects with eventual geographic atrophy and severe visualloss results in these patients. Interestingly, this maculardystrophy is linked to a mutation in the Arg172Trp muta-tion of the RDS/peripherin gene which is located alongsidethe Arg142Trp mutation in the large intradiscal loop D2 ofthe RDS/peripherin protein.7,15 It is possible that drusenand CACD are variable expressions of the same disease, asthese are allelic disorders of the RDS/peripherin gene.4,7
Mutations in the peripherin/RDS gene have also been linkedto retinitis pigmentosa, progressive macular degeneration,cone-rod dystrophy, and pattern dystrophy.7,16
Differential diagnosis
Because of the type of fundus changes seen in CACD, dif-ferential diagnosis can be quite challenging. Several ofthe macular dystrophies can present with symmetric RPEmottling, bull’s eye maculopathy, and central geographicatrophy mimicking those changes seen in early CACD. Conedystrophy presents with a bull’s eye appearance in themacula appearing as a central reddish circular area (pig-ment clumping), which is surrounded by depigmented areas.It can be autosomal dominant or recessive and usuallypresents in the first to second decade with moderate tosevere vision loss. Fluorescein angiography will show win-dow defects late if there is chorioretinal atrophy or breaks.Electrodiagnostic testing typically demonstrates a moder-ate reduction and delay of the b-wave on fERG testing and anormal EOG. CACD will have a normal to slightly subnor-mal fERG and EOG. Additionally, with mfERG testing theimplicit time in CACD is normal (as in our patient) or mini-mally delayed, this is in contrast to a more moderate delay incone dystrophy patients. The differential diagnosis can alsobe established by looking for the presence of large choroidalvessels that characterize CACD and are rarely encounteredin cone dystrophy.4,7
Late stage CACD shares similar clinical characteristicswith atrophic age-related macular degeneration (AMD), suchas geographic atrophy and drusen.17,18 Several features mayaid in distinguishing between the two. In the early stagesof CACD, subtle parafoveal pigmentary RPE changes with orwithout the presence of an oval, mildly atrophic hypopig-mented area in the center of the fovea can be seen. In AMD,there is usually hard/soft drusen concentrated in the mac-ula, or hyperpigmentation. The geographic atrophy of AMDusually arises from these drusen or hyperpigmentation.18,19
In all but the initial stage of CACD, a speckled fundus auto-fluorescence (FAF) pattern that is sharply demarcated fromthe surrounding retina, regularly oval shaped and confinedto the central macula is observed. Although speckled FAFpatters have been described in AMD, the alterations wereless regularly shaped, less well demarcated, and often
extended beyond the macula.20,21 Drusen associated withCACD show intense fundus autofluorescence, whereas thosedrusen seen in AMD do not.7,18,22 In the speckled FAF areas inCACD, OCT will show a corresponding disorganization of theDtL
usen 121
hotoreceptors and a loss of photoreceptor outer segments,een as a disruption of the inner-outer photoreceptorunction and thinning of the Outer Nuclear Layer.23 OCT ofMD may also exhibit sub-RPE deposits, whereas these arextremely rare in CACD. The atrophic zones in geographictrophy were are highly irregular and show residual materialn Bruch’s membrane. In contrast, in CACD the atrophicreas are smooth and homogeneous. The higher occurrencef sub-RPE deposits and irregular structure of retinal layersithin the atrophic lesion in AMD patients indicates differ-nt pathogenic mechanisms for CACD and AMD. Choroidaleovascularization is also rare in CACD due to the absence of
functional choriocapillaris or choroidal vascular system.22
esides the circumscribed atrophic lesions that characterizehe late stages in both disorders, drusen-like deposits haveeen described in a limited number of patients with CACD.
The prevalence of end-stage AMD has been estimated at% in people aged over 65 years, and climbs to 11% in thosever 85 years old. Therefore, young patients with atrophicesions should be suspected of having entities other thanMD until proven otherwise.24
Two angiographic patterns of wet AMD have beenescribed, classic and occult choroidal neovascular mem-rane (CNV). Classic CNV shows up in the early phase as
bright, well delineated area of hyperfluorescence whichncreases in intensity and size through the mid and laterames. This is due to progressive leakage of the dye thatbscures the boundaries of the CNV. With occult CNV, theuorescein pattern varies from speckled hyperfluorescence
nitially with persistence of leakage in later frames to lateeakage of dye at the level of the RPE in the late phasesf the angiogram (not corresponding to the area of theNV).25
Stargardt’s disease or fundus flavimaculatus can presentith an array of fundus changes including a beaten-bronzeppearance to the macula and yellow, fish-tail shaped flecksn the retina. The fERG is usually normal in these patients,hile the mfERG usually reveals markedly reduced focal
oveal and central retinal responses, even in the presencef normal acuity.26 The dominance pattern is the same asACD. In Stargardt’s/fundus-flavimaculatus, the macula isottled; whereby with CACD, the macula is excavated and
trophic. Additionally, the fish-tail flecks seen outside theacula in Stargardt’s are not seen in CACD. Early on, the
wo entities are difficult to differentiate. However, in Star-ardt’s fundus fluorescein angiography will exhibit continualacular hyperfluorescence and mid-peripheral involvementith a silent choroid.25
Central areolar dystrophy (CAD) of the RPE must also beifferentiated from CACD. CAD of the RPE almost exclusivelyffects white females.22 Visual acuity begins to be compro-ised in the late 5th to early 6th decade of life. Fundusndings are similar, however CAD of the RPE is usually uni-
ateral and the atrophic changes affect the RPE and thehoroid.18,25
anagement
ue to the hereditary nature of CACD, it is crucial to educatehe patient and refer the patient for genetic counseling.ow vision rehabilitation can be especially useful in affected
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atients. Visual acuity prognosis is poor; however, periph-ral vision is preserved so mobility can be fairly maintained.ven though management options are scarce, proper diag-osis is essential in order for these patients to be properlyounseled.
onflicts of interest
he authors have no conflicts of interest to declare.
eferences
1. Boon CJ, Klevering J, Cremers FPM, et al. Central areolarchoroidal dystrophy. Ophthalmology. 2009;116:771---781.
2. Hoyng CB, Deutman AF. The development of central areo-lar choroidal dystrophy. Graefes Arch Clin Exp Ophthalmol.1996;234:87---93.
3. Lotery AJ, Ennis KT, Silvestri G, et al. Localisation of a gene forcentral areolar choroidal dystrophy to chromosome 17p. HumMol Genet. 1996;5:705---708.
4. Ouechtati F, Tahar OB, Mhenni A, et al. Central areolarchoroidal dystrophy associated with inherited drusen in amultigeneration Tunisian family: exclusion of the PRPH2 geneand the 17p13 locus. J Hum Genet. 2009;54:589---594.
5. Zhang K, Garabaldi DC, Carr RE, et al. Hereditary choroidal dis-ease. In: Ryan, SJ, editor. Retina. 3rd ed. St Louis: Mosby, 2001:462---463.
6. Gamundi MJ, Hernan I, Muntanyola M, et al. High prevalenceof mutations in peripherin/RDS in autosomal dominant mac-ular dystrophies in a Spanish population. Mol Vis. 2007;13:1031---1037.
7. Klevering BJ, van Driel M, van Hogerwou A, et al. Central are-olar choroidal dystrophy associated with dominantly inheriteddrusen. Br J Ophthalmol. 2002;86:91---96.
8. Gass JMD. Steroscopic Atlas of Macular Diseases. St Louis: CVMosby; 1987. p. 262.
9. Keithahn MAZ, Huang M, Keltner JL, Small KW, Morse LS. Thevariable expressivity of a family with central areolar pigmentepithelial dystrophy. Ophthalmology. 1996;103:406---415.
10. Nagasaka K n, Horiguchi M, Shimada Y, Yuzawa M. Multifocal
electroretinograms in cases of central areolar choroidal dys-trophy. Invest Ophthalmol Vis Sci. 2003;44:1673---1679.11. Hartley KL, Blodi BA, VerHoeve JN. Use of the multifocalelectoretinogram in the evaluation of a patient with central
J. Rodman et al.
areolar choroidal dystrophy. Am J Ophthalmol. 2002;133:852---855.
12. Ponjavic V, Andreasson S, Ehinger B. Full-field electroretino-grams in patients with central areolar choroidal dystrophy. ActaOphthalmol Scand. 1994;72:537---544.
13. Rothman RJ. Photoreceptor dysfunction in central areolarchoroidal dystrophy. Ann Ophthalmol. 1994;26:25---30.
14. Chopdar A. A variant of central areolar choroidal dystrophy.Ophthalmic Paediatr Genet. 1993;1:151---164.
15. Piguet B, Haimovici R, Bird AC. Dominantly inherited drusenrepresent more than one disorder: a historical review. Eye.1995;9:34---41.
16. Kohl S, Christ AM, Apfelstedt SE, et al. RDS/peripherin genemutations are frequent causes of central retinal dystrophies. JMed Genet. 1997;34:620---626.
17. Keilhauer CN, Meigen T, Weber BH. Clinical findings in a multi-generation family with autosomal dominant central areolarchoroidal dystrophy associated with an Arg195Leu mutationin the peirpherin/RDS gene. Arch Ophthalmol. 2006;124:1020---1027.
18. Boon CJF, Klevering BJ, Hoyng CB, et al. Basal laminar drusencaused by compound heterozygous variants in the CFH gene.Am J Hum Genet. 2008;82:516---523.
19. De Jong PT. Age-related macular degeneration. N Engl J Med.2006;355:1474---1485.
20. Holz FG, Bindewald-Wittich A, Fleckenstein M, et al.Progression of geographic atrophy and impact of fundus auto-fluorescence patterns in age related macular degeneration. AmJ Ophthalmol. 2007;143:463---472.
21. Bindewald A, Bird AC, Dandekar SS, et al. Classification offundus autofluorescence patters in early age-related maculardisease. Invest Ophthalmol Vis Sci. 2005;46:3309---3314.
22. Alexander LJ, ed. Primary Care of the Posterior Segment.Philadephia: Appleton and Lange; 1994.
23. Smailhodzic D, Fleckenstein M, Theelen T, et al. Central areo-lar choroidal dystrophy and age-related macular degeneration:differentiating characteristics in multimodal imaging. InvestOphthalmol Vis Sci. 2011;52:8908---8918.
24. Vingerling JR, Klaver CC, Hofman A, et al. Epidemiology of age-related maculopathy. Epidemiol Rev. 1995;17:347---360.
25. Cavender J, Ai E. Hereditary macular dystrophies. Duane’s Clin-ical Ophthalmology, vol. 3. Philadelphia: JB Lippincott; 1990
[chapter 9, pp. 1---29].26. Vollmer LA, Shechtman DL, Woods AD, Pizzimenti JJ. Use ofmultifocal ERG and OCT for diagnosing Stargardt’s disease. ClinExp Optom. 2011;94:309---313.