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

Dalia Sabry; Kamal Enam

doi:10.4103/2090-0686.127376

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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

Dalia Sabry, Kamal Enam
Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission	13-Jan-2013
Date of Acceptance	14-Apr-2013
Date of Web Publication	28-Feb-2014

Correspondence Address:
Dalia Sabry
Department of Ophthalmology, Faculty of Medicine, Mansoura University, Mansoura
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/2090-0686.127376

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 2023 Jan 31];106:163-7. Available from: http://www.jeos.eg.net/text.asp?2013/106/3/163/127376

Introduction

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

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

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

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:

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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

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

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

Conflicts of interest

There are no conflicts of interest.

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