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ORIGINAL ARTICLE
Year : 2013  |  Volume : 106  |  Issue : 3  |  Page : 163-167

Macular functional and anatomical ring maps in patients with best vitelliform macular dystrophy


Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission13-Jan-2013
Date of Acceptance14-Apr-2013
Date of Web Publication28-Feb-2014

Correspondence Address:
Dalia Sabry
Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2090-0686.127376

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  Abstract 

Purpose
This study aimed at assessing the macular anatomical and functional changes in patients having different stages of best vitelliform macular dystrophy (BVMD).
Design
This is a retrospective noncomparative case series.
Materials and methods
The study included patients in different stages of BVMD. All patients had a solitary lesion involving the fovea. They underwent complete ophthalmic evaluation, fluorescein angiography (FA), optical coherence tomography (OCT), and multifocal electroretinography (mfERG). The results were compared with those of an age-matched and sex-matched control group.
Results
This study included 14 eyes from 10 patients belonging to seven families. The mean log MAR BCVA was 0.5 ± 0.1 with significant reduction compared with the control group (P = 0.05). Both FA and OCT scans showed changes confined to the lesion only. OCT showed a significant increase in thickness in the foveal and perifoveal rings (P = 0.0003 and 0.05, respectively). Multifocal ERG showed significant changes between the study and control groups in the three rings (P = 0.0001 for both amplitude and implicit time for ring 1; P = 0.05 for the other two rings).
Conclusion
In different stages of BVMD with solitary lesions involving the fovea, the integrated FA and OCT findings were very helpful in the diagnosis; however, their changes were confined to the lesions only. Multifocal ERG revealed reduction of the cone function all over the macula, which was most evident centrally.

Keywords: Fluorescein angiography, multifocal electroretinogram, optical coherence tomography, vitelliform macular dystrophy


How to cite this article:
Sabry D, Enam K. Macular functional and anatomical ring maps in patients with best vitelliform macular dystrophy. J Egypt Ophthalmol Soc 2013;106:163-7

How to cite this URL:
Sabry D, Enam K. Macular functional and anatomical ring maps in patients with best vitelliform macular dystrophy. J Egypt Ophthalmol Soc [serial online] 2013 [cited 2019 Aug 19];106:163-7. Available from: http://www.jeos.eg.net/text.asp?2013/106/3/163/127376


  Introduction Top


Best vitelliform macular dystrophy (BVMD) was first described by Friedrich Best in 1905 with a complete description of the various stages of the disease in eight related individuals. It is a slowly progressive macular dystrophy with onset generally during childhood and sometimes in later teenage years [1],[2],[3]. BVMD is an autosomal dominant disease but with variable expressivity. The gene involved in BVMD is called BEST1 and encodes for a protein named bestrophin-1, which is localized to the basolateral plasma membrane of the retinal pigment epithelium (RPE) and appears to exhibit properties of Ca 2+ -activated Cl - channels [3],[4],[5],[6],[7],[8],[9],[10]. BVMD evolves gradually through five to six stages, described on the basis of a fundus examination. These stages can be classified into previtelliform, vitelliform, pseudohypopyon, vitelliruptive, atrophy, and fibrosis. Most cases have a solitary lesion in the macula; others have multifocal vitelliform lesions, which are mostly confined to the posterior pole [2],[3],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16]. Abnormal findings on an electro-oculogram (EOG) with a reduced or nondetectable light-to-peak to dark-to-trough ratio (≤1.55), combined with a normal full-field electroretinogram (ERG) and a blockage effect by vitelliform material on fluorescein angiography (FA) and autofluorescence from the vitelliform lesions, are helpful for diagnosis [17],[18],[19]. Optical coherence tomography (OCT) studies found that the yellow vitelliform accumulates in the subretinal space and on the outer retinal surface; a detailed appearance of various stages on OCT was also described [20],[21],[22],[23]. Multifocal electroretinogram (mfERG) allows studying the cone function in local retinal areas [24],[25],[26],[27].


  Aim of the work Top


This study aimed at assessing the macular anatomical and functional changes in patients having different stages of BVMD. Only patients with a solitary lesion involving the fovea were included to evaluate the effect of the disease on the rest of the macula.


  Materials and methods Top


This retrospective noncomparative case series included patients in different stages of BVMD. Patients were recruited from the imaging unit of Mansoura Ophthalmic Center from March 2008 to June 2012. Patients with a solitary BVMD involving the fovea and in different stages of the disease - namely, vitelliform, pseudohypopyon, vitelliruptive (scrambled egg), atrophy, and fibrosis - were selected. Patients with the following were excluded from the study: multifocal BVMD, BVMD with a secondary subretinal neovascular membrane, pervious ocular surgery, or patients with systemic or local disease that could affect the vascular blood supply to the macula. The nature of the procedures was explained to the participants in detail and written informed consent was given by all participants before being included in the study. Each patient underwent a complete ophthalmic evaluation including BCVA measurements using Snellen test charts, which were then converted into log MAR (logarithm of minimum angle of resolution), anterior segment examination, intraocular pressure measurement, and stereoscopic fundus examination. The following investigations were also performed: FA, OCT, and mf ERG.

Fluorescein angiography

FA was performed with a Topcon TRC 50 IX fundus camera (Topcon, Tokyo, Japan). The pupils were dilated using tropicamide 0.5% and phenylepherine 2.5%. Color and red free photos were taken. Then, 5 ml of 10% sodium fluorescein solution was injected through the anticubital vein and the barrier and exciter filters were activated. Early, mid, and late frames were taken of the macula. In addition, the midperiphery was imaged to exclude any abnormality.

Optical coherence tomography

OCT examination was performed with Topcon 3D OCT-1000 mark II (Topcon). The macular 3D mode was used. It scans a cube of 6.0 × 6.0 mm length and a resolution of 512 × 128 with the fixation on the macula. The printout includes a cross-sectional scan that shows the morphological changes. It also includes the foveal central thickness and a thickness map, which is a circle with a diameter of 6 mm centered on the foveola. The map divides the macula into nine ETDRS regions. Scans with image quality of at least 55 were used for analysis. Low-quality scans were reacquired.

Multifocal electroretinography (mfERG) was performed using RETIsacn21 multifocal ERG, version 07/01 (Roland Consult, Stasche and Finger, Brandenburg, Germany). The stimulus consisted of 61 hexagons; hexagon number 31 was used for fixation and was placed centrally. The instrument used in the study gives the opportunity to use many forms of targets such as spot, cross, rings, and lines. In this study, lines were used. There are two. Each extends diagonally from one angle of the screen to the opposite angle, crossing at the center of the screen. The advantage of this fixation target is the large size, which is helpful for patients with poor vision to maintain fixation during examination. Each hexagon is stimulated by alternating white and black stimuli on a gray background. The m-sequence, which is controlled by 58-binary pseudorandom sequences derived from a family of sequences called Kasami sequences, was 1024 elements/reversal. A high-stimulus luminance of 120 cd/m² was used, which was displayed on a CRT color monitor 20″ size. Eye to screen distance was nearly 310 mm; the field of view was 27°; stimulation consisted of eight cycles, and each cycle lasted for 38.0 s, with a total test time of about 5 min. Alternation between black and white stimulation was done at a frame frequency of 60 Hz/s. The distortion factor for hexagons was 4.0, starting at the central hexagon (Number 31). The recording procedure was repeated if the percentage of artifacts was more than 10%.

The pupils of the patient were dilated using tropicamide 0.5% and phenylepherine 2.5%. Eyes were optically corrected for near vision. Signals were picked up through electrodes placed in specific regions of the patient's head. The electrodes used were active HK-loop electrodes, reference, and ground silver EEG electrodes. The first electrode was attached to the lower lid with its thread (loop) touching the globe just below the cornea; the other electrodes were attached to the patient's head (forehead and temple) after cleaning the skin and placing conductive plast (TEN20). The location of the mERG stimuli and anatomical areas roughly corresponded as follows: ring 1 to the fovea, ring 2 to the parafovea, and ring 3 to the perifovea.

Colocalization of abnormalities on mfERG was performed objectively using the superimposing option in mfERG in which the resulting mfERG figure with the stimulus pattern is overlaid on the central fundus. The posterior segment was into three rings.

Comparison of areas of OCT and mfERG responses

The macula was divided into three regions, with the central one corresponding to the fovea, the inner ring to the perifovea, and the outer ring to the parafovea. In the OCT examination we used a semiquantitative method for easy comparison and hence the macula was divided into these three rings. Summation of four perifoveal ETDRS regions divided by four yielded the average perifoveal thickness. Similarly, the parafoveal thickness was calculated.

A control group (14 eyes from age-matched and sex-matched controls) was subjected to OCT and mfERG examinations.

Statistical analysis

Data were statistically analyzed using Excel program on Office 2003 software and statistical package of social science, version 16 (SPSS Inc., Chicago, Illinois, USA) on Windows 2003. For variables described as mean and SDs we used the Student t-test, and for variables described as percentages we used the χ2 -test. The paired sample t-test was used to compare one group at two time points, and the general linear model analysis of variance test was used to compare one group at different time points. P values less than or equal to 0.05 were considered statistically significant with a power of 95%.


  Results Top


This study included 14 eyes from 10 patients belonging to seven families. The mean age of the patients was 16.3 ± 1.6 years. Thirty percent of the patients were female and 70% were male. Mean log MAR BCVA was 0.5 ± 0.1 with significant reduction compared with the control group (P = 0.05). The mean spherical equivalent of the studied population was -0.3 ± 0.5. There was no statistically significant difference between the studied group and the control group with regard to age, sex, and spherical equivalent distribution (P = 0.5, 0.04, and 0.03, respectively).

The stages of BVMD included in this study and their FA and OCT cross-sectional features

Four eyes were in the vitelliform stage, in which FA showed blockage of the background choroidal fluorescence, whereas OCT showed accumulation of hyper-reflective material adhering to the outer retina corresponding to yellowish material. In addition, there were four eyes with pseudohypopyon and four eyes in vitelliruptive stage. FA showed hyperfluorescence within the lesion except when there was blocking by thick areas of yellowish material. These hyperfluorescent areas appeared early in the angiogram as window defects, followed by a subtle accumulation of fluorescence in the later phases of the angiogram, suggesting that there must have been some leakage of fluorescein. In contrast, the OCT showed elevation of the macula because of the cavity being filled with subretinal fluid. It also shows the residue of the lipofuscin materials appearing as accumulated material on the outer retina in the central macula and thicker ones at the edges of the retina elevation. The remaining two eyes were in the atrophic stage; the FA showed hyperfluorescence corresponding to the atrophic patch that appeared early in the angiogram and progressively increased suggesting staining, whereas the OCT showed a hyper-reflective subretinal patch that, in one eye, had a small horizontal space within it. In all eyes FA and OCT showed a normal appearance outside the involved areas ([Figure 1] shows the FA, OCT, and mfERG of one case in the vitelliform stage).
Figure 1:

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As regards the macular thickness, the OCT showed a significant change in thickness in the foveal and perifoveal rings. The foveal ring showed a marked increase in thickness (P = 0.0003), whereas in the perifoveal ring the increase in thickness was less evident (P = 0.05) [Figure 2].
Figure 2:

Click here to view


Multifocal ERG results showed significant changes between the study and control groups. P1 amplitudes showed a significant reduction, whereas P1 implicit time showed a significant increase in the three rings (P = 0.0001 for both amplitude and implicit time for ring 1; P = 0.05 for the other two rings; [Figure 3] and [Figure 4]).
Figure 3:

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Figure 4:

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  Discussion Top


BVMD is an autosomal dominant disease but with variable expressivity. The gene involved in BVMD is called BEST1 and encodes for the protein named bestrophin-1, which is localized to the basolateral plasma membrane of the RPE and appears to exhibit properties of Ca 2+ -activated Cl channels [3],[4],[5],[6],[7],[8],[9],[10]. As EOG reflects the RPE function, this explains its abnormal findings detected in patients with BVMD. Several previous studies have reported the abnormal EOG function [17],[18],[19]. Because of the close anatomical and functional relations between the RPE and photoreceptors, abnormality of the macular function is anticipated and accordingly abnormal ERG findings. However, several previous studies have reported that full-field ERG is usually normal in patients with BVMD, which was explained by the fact that its abnormality requires more widespread retinal lesions [27],[28]. In contrast, it was reported that a variable degree of central function loss can be detected with mfERG [24],[28]. This is because the mfERG (in contrast to the ERG) allows detailed evaluation of the macular function. Our results are consistent with these previous studies and highlight the subsequent affection of the cone function in BVMD. In this study, ring 1 corresponding to the fovea showed a marked reduction in P1 amplitude and increase in implicit time (P = 0.0001). These mfERG responses were anticipated as all eyes included in the study had their fovea involved with the vitelliform materials. However, the mfERG changes were not limited to the fovea only and instead extended to rings 2 and 3 in which similar but less significant changes were detected (P for both amplitude and implicit time was 0.05). Although the EOG has been regarded as the main diagnostic tool in BVMD, the use of mfERG should be reconsidered especially when EOG is not available.

Several previous studies highlighted the importance of both FA [17],[18],[19] and OCT [20],[21],[22],[23] in the diagnosis of BVMD. We found that the integration of both could be the reason behind several of the abnormalities seen, especially in the stages following the typical vitelliform lesions, such as the presence of submacular cavities filled with fluid, the residual lipofuscin materials, and the yellow deposits on the outer retinal surface. Both FA and OCT changes were limited to the clinically visible abnormalities. In this study OCT showed a significant increase in macular thickness in the foveal and perifoveal rings (P = 0.0003 and 0.05, respectively). The increase in thickness can be explained by the deposited lipofuscin material in the vitelliform stage, the subretinal cavity with fluid accumulation in the pseudohypopyon and vitelliruptive stages, and also by the scar found in the atrophic stage. These changes were very evident in the foveal ring; however, they also extended to the perifoveal one as the primary lesion is usually [1-2] discs in diameter and the subsequent changes with fluid accumulation usually extends to the surrounding areas, especially inferiorly.


  Conclusion Top


In this study, integrated FA and OCT findings contributed substantially to the diagnosis in patients with different stages of BVMD with solitary lesions involving the fovea; however, their changes were confined to the lesions only. Multifocal ERG revealed reduction of the cone function all over the macula, which was most evident centrally.


  Acknowledgements Top


Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.Mohler CW, Fine SL. Long-term evaluation of patients with Best′s vitelliform dystrophy. Ophthalmology 1981; 88:688-692.  Back to cited text no. 1
[PUBMED]    
2.Leu J, Schrage NF, Degenring RF. Choroidal neovascularisation secondary to Best′s disease in a 13-year-old boy treated by intravitreal bevacizumab. Graefe′s Arch Clin Exp Ophthalmol 2007; 245:1723-1725.  Back to cited text no. 2
    
3.Hartzell HC, Qu Z, Yu K, Xiao Q, Chien LT. Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. Physiol Rev 2008; 88:639-672.  Back to cited text no. 3
    
4.Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC. Genetic linkage of vitelliform macular degeneration (Best′s disease) to chromosome 11q13. Nat Genet 1992; 1:246-250.  Back to cited text no. 4
    
5.Zhang K, Nguyen TH, Crandall A, Donoso LA. Genetic and molecular studies of macular dystrophies: recent developments. Surv Ophthalmol 1995; 40:51-61.  Back to cited text no. 5
    
6.Stohr H, Marquardt A, Rivera A, Cooper PR, Nowak NJ, Shows TB, et al. A gene map of the Best′s vitelliform macular dystrophy region in chromosome 11q12-q13.1. Genome Res 1998; 8:48-56.  Back to cited text no. 6
    
7.Marquardt A, Stohr H, Passmore LA, Kramer F, Rivera A, Weber BH. Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best′s disease). Hum Mol Genet 1998; 7:1517-1525.  Back to cited text no. 7
    
8.Krämer F, White K, Pauleikhoff D, Gehrig A, Passmore L, Rivera A, et al. 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; 8:286-292.  Back to cited text no. 8
    
9.Apushkin MA, Fishman GA, Taylor CM, Stone EM Novel de novo mutation in a patient with Best macular dystrophy. Arch Ophthalmol 2006; 124:887-889.  Back to cited text no. 9
    
10.Atchaneeyasakul LO, Jinda W, Sakolsatayadorn N, Trinavarat A, Ruangvoravate N, Thanasombatskul N, et al. Mutation analysis of the VMD2 gene in Thai families with best macular dystrophy. Ophthalmic Genet 2008; 29:139-144.  Back to cited text no. 10
    
11.Fishman GA, Baca W, Alexander KR, Derlacki DJ, Glenn AM, Viana M Visual acuity in patients with best vitelliform macular dystrophy. Ophthalmology 1993; 100:1665-1670.  Back to cited text no. 11
    
12.Mullins RF, Oh KT, Heffron E, Hageman GS, Stone EM. Late development of vitelliform lesions and flecks in a patient with best disease: clinicopathologic correlation. Arch Ophthalmol 2005; 123:1588-1594.  Back to cited text no. 12
    
13.Meunier I, Senechal A, Dhaenens CM, Arndt C, Peuch B, Defoort- Dhellemmes S, et al. Systematic screening of BEST1 and PRPH2 in juvenile and adult vitelliform macular dystrophies: a rationale for molecular analysis. Ophthalmology 2011; 118:1130-1136.  Back to cited text no. 13
    
14.Zhuk SA, Edwards AO. Peripherin/RDS and VMD2 mutations in macular dystrophies with adult-onset vitelliform lesion. Mol Vis 2006; 12:811-815.  Back to cited text no. 14
    
15.Yu K, Cui Y, Hartzell HC. The bestrophin mutation A243V, linked to adult-onset vitelliform macular dystrophy, impairs its chloride channel function. Invest Ophthalmol Vis Sci 2006; 47:4956-4961.  Back to cited text no. 15
    
16.Yu K, Qu Z, Cui Y, Hartzell HC. Chloride channel activity of bestrophin mutants associated with mild or late-onset macular degeneration. Invest Ophthalmol Vis Sci 2007; 48:4694-4705.  Back to cited text no. 16
    
17.Pinckers A, Cuypers MH, Aandekerk AL. The EOG in Best′s disease and dominant cystoid macular dystrophy (DCMD). Ophthalmic Genet 1996; 17:103-108.  Back to cited text no. 17
    
18.Renner AB, Tillack H, Kraus H, Kohl S, Wissinger B, Mohr N, et al. Morphology and functional characteristics in adult vitelliform macular dystrophy. Retina 2004; 24:929-939.  Back to cited text no. 18
    
19.Testa F, Rossi S, Passerini I, Sodi A, Di Iorio V, Interlandi E, et al. A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene. Br J Ophthalmol 2008; 92:1467-1470.  Back to cited text no. 19
    
20.Pianta MJ, Aleman TS, Cideciyan AV, Sunness JS, Li Y, Campochiaro BA, et al. In vivo micropathology of Best macular dystrophy with optical coherence tomography. Exp Eye Res 2003; 76:203-211  Back to cited text no. 20
    
21.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 Ophtalmol 2003; 289:53-61.  Back to cited text no. 21
    
22.Querques G, Regenbogen M, Quijano C, Delphin N, Soubrane G, Souied EH. High-definition optical coherence tomography features in vitelliform macular dystrophy. Am J Ophthalmol 2008; 146:501-507.  Back to cited text no. 22
    
23.Kay CN, Abramoff MD, Mullins RF, Kay CN, Abramoff MD, Mullins RF, et al. Three-dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with best vitelliform macular dystrophy. Arch Ophthalmol 2012; 130:357-364.  Back to cited text no. 23
    
24.Scholl HP, Schuster AM, Vonthein R, Zrenner E. Mapping of retinal function in Best macular dystrophy using multifocal electroretinography. Vision Res 2002; 42:1053-1061.  Back to cited text no. 24
    
25.Rudolph G, Kalpadakis P. Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best′s disease. Ophthalmologica 2003; 217:154-159.  Back to cited text no. 25
    
26.Glybina IV, Frank RN. Localization of multifocal electroretinogram abnormalities to the lesion site: findings in a family with Best disease. Arch Ophthalmol 2006; 124:1593-1600.  Back to cited text no. 26
    
27.Palmowski AM, Allgayer R, Heinemann-Vernaleken B, Scherer V, Ruprecht KW. Detection of retinal dysfunction in vitelliform macular dystrophy using the multifocal ERG (MF-ERG). Doc Ophthalmol 2003; 106: 145-152.  Back to cited text no. 27
    
28.Eksandh L, Bakall B, Bauer B. Best′s vitelliform macular dystrophy caused by anew mutation (Val189Ala) in the VMD2 gene. Ophthalmic Genet 2001; 22:107-115.  Back to cited text no. 28
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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