Adult-onset foveomacular vitelliform dystrophy: a study by optical coherence tomography

Adult-onset Foveomacular Vitelliform Dystrophy: A Study by Optical Coherence Tomography NATHANAEL BENHAMOU, MD, ERIC H. SOUIED, MD, PHD, RICKY ZOLF, MD, FLORENCE COSCAS, MD, GABRIEL COSCAS, MD, AND GISE`LE SOUBRANE, MD, PHD

● PURPOSE:

To evaluate the morphology of adult-onset foveomacular vitelliform dystrophy (AFVD) using optical coherence tomography (OCT) and to correlate the OCT findings with those of biomicroscopy and fluorescein angiography (FA). ● DESIGN: Prospective observational case series. ● METHODS: A complete ophthalmologic examination, including visual acuity, fundus biomicroscopy, FA, and OCT was performed in 21 eyes of 14 consecutive patients with AFVD. ● RESULTS: Mean age at presentation was 64 years (range, 39 to 84 years), and best-corrected visual acuity ranged from 20/25 to 20/400 (median 20/50). Sixteen of 21 eyes (11 patients) exhibited late staining of lesions on FA. In these 16 eyes, OCT revealed that AFVD material consists of a hyperreflective structure located between the photoreceptor and the retinal pigment epithelium layers. The retinal pigment epithelium layer was linear and was not elevated, unlike what is observed in retinal pigment epithelium detachment. Five other eyes (ⴛ4 patients) without late staining in FA showed, by OCT, a hyperreflective area at the level of the retinal pigment epithelium band, with no material visible between the photoreceptor and retinal pigment epithelium layers. In all 21 eyes, the retina overlying the hyperreflective structure was raised by the pseudovitelliform material and was markedly thinned. ● CONCLUSIONS: Optical coherence tomography is a noninvasive useful tool that provides new information on the morphology of AFVD. It demonstrates, better than biomicroscopy, the location of the yellowish material under the sensory retina but above the retinal pigment epithelium, corresponding angiographically to the late staining. The foveal thinning found by OCT in all cases Accepted for publication Sept 18, 2002. From the Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil, Universite´ Paris 12, Paris, France. Inquiries to Eric H. Souied, MD, Department of Ophthalmology, Centre Hospitalier Intercommunal de Creteil, 40 Av de Verdun, 94000 Creteil, France; fax: (⫹33) 1-45175227; e-mail: [email protected]

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probably explains the progressive visual loss and possible evolution toward a full-thickness macular hole. (Am J Ophthalmol 2003;135:362–367. © 2003 by Elsevier Science Inc. All rights reserved.)

S

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trophy (AFVD) was first described by Gass1 in 1974, it has been analyzed and clinically defined by many authors.2–11 Biomicroscopically, it is characterized by a subretinal deposit of yellowish material that is oval or round, elevated, localized in the macular area, and often centered by a pigmented spot. Adult onset foveomacular vitelliform differs from vitelliform dystrophy (Best disease) by many characteristics: late onset (40 to 70 years of age), moderate symptoms, normal or subnormal electro-oculogram, and an indeterminate genetic inheritance. While some authors suggest an autosomal dominant inheritance,1,4,10,12,13 others emphasize that many cases are sporadic, with no evidence of a familial inheritance pattern.6,11,14 Until now, the exact location of material in AFVD has not been elucidated either by biomicroscopy or by histological descriptions.1,15–17 Optical coherence tomography (OCT) is a noninvasive technique based on low interferometry that provides optical crosssectional images of the retina and morphologic information close to that obtained from histologic sections. The purpose of this study was to assess the new information on AFVD provided by OCT and to compare it with the clinical, angiographic, and histologic data.

DESIGN THIS STUDY WAS CONSECUTIVE PROSPECTIVE OBSERVA-

tional cases series.

METHODS TWENTY-ONE EYES FROM 14 CONSECUTIVE PATIENTS (6

women and 8 men; Table 1) who presented to our

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TABLE 1. Characteristics of 14 Patients (21 Eyes) With Adult-onset Foveomacular Vitelliform Dystrophy Patient

1 2 3 4 5 6 7 8 9 10 11 12

13 14

Eye

Age/Gender

BCVA

Late Stage FA

OCT Findings

OS OD OD OD OD OD

68, M

20/63 20/63 20/100 20/100 20/25 20/40

OD OS OD OS OS OD OS

66, F

Staining of the lesion Staining of the lesion Staining of the lesion Staining of the lesion Staining of the lesion Persistent hypofluorescence Staining of the lesion Staining of the lesion Staining of the lesion Staining of the lesion Staining of the lesion Staining of the lesion Persistent hypofluorescence Staining of the lesion Staining of the lesion Staining of the lesion Persistent hypofluorescence Staining of the lesion Staining of the lesion Persistent hypofluorescence Persistent hypofluorescence

Hyperreflective area Hyperreflective area Hyperreflective area Hyperreflective area Hyperreflective area Focal thickening of the RPE, no identifiable material Hyperreflective area Hyperreflective area Hyperreflective area Hyperreflective area Hyperreflective area Hyperreflective area Focal thickening of the RPE, no identifiable material Hyperreflective area Hyperreflective area Hyperreflective area Focal thickening of the RPE, no identifiable material Hyperreflective area Hyperreflective area Focal thickening of the RPE, no identifiable material Focal thickening of the RPE, no identifiable material

54, M 70, M 67, M 61, M

84, M 77, M 66, F 43, M

OD OS OD OS

75, F

OD OS OD

56, F

OS

75, F

39, F

20/25 20/25 20/200 20/400 20/63 20/50 20/32 20/63 20/40 20/50 20/50 20/50 20/63 20/63 20/50

BCVA ⫽ best-corrected visual acuity; F ⫽ female; FA ⫽ fluorescein angiography; M ⫽ male; OCT ⫽ optical coherence tomography; OD ⫽ right eye; OS ⫽ left eye; RPE ⫽ retinal pigment epithelium.

department with adult-onset foveomacular vitelliform dystrophy were examined using fluorescein angiography (FA) and OCT. Mean age at presentation was 64 years (range, 39 to 84 years). Three of the 28 eyes originally examined had an atrophic scar after photocoagulation for choroidal neovascularization, 3 eyes had lesions smaller than 500 ␮m, and 1 fellow eye did not have AVDM (unilateral lesion), so that 21 eyes were finally included. Patients presenting with lesions less than 500 ␮m, or with associated diseases (myopia ⱖ6 diopters, angioid streaks, diffuse retinal epitheliopathy, or confluent drusen), or eyes complicated with choroidal neovascularization were excluded from this study. All patients underwent a complete ophthalmologic examination, including assessment of best-corrected visual acuity and fundus biomicroscopy using a contact lens (Centralis Direct of Volk Optical, Mentor, Ohio, USA). FA (Canon 60 fundus camera, Tokyo, Japan) was also performed. For each stage of the angiogram, the pattern and location of hyper and hypofluorescence were noted. Optical coherence tomography examination was performed with commercially available equipment (Humphrey Zeiss, San Leandro, California, USA) derived from VOL. 135, NO. 3

the prototype described by Hee and coworkers.18 Crosssectional tomographic images integrate 100 axial measurements in 1 second while scanning the probe beam across the retina. The lateral resolution varied from 30 ␮m for the 3-mm scans to 70 ␮m for the 7-mm scans. For each patient, multiple vertical and horizontal scans of 3 and 6 mm, centered on the fovea, were performed. For each scan, the shape and reflectivity of the material, its location, the reflectivity, and appearance of the retinal pigment epithelium and retinal changes were specified. When the reflectivity of the material and retinal pigment epithelium were too close to be differentiated, OCT examination was performed using lower intensity energy (350 – 400 ␮W, ie, half of the maximum).

RESULTS THE COMMON PRESENTING COMPLAINT WAS A GRADUAL

decrease in visual acuity and sometimes metamorphopsia. Best-corrected visual acuity ranged from 20/25 to 20/400 (median, 20/50) and was better than 20/40 in six eyes,

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FIGURE 1. (Upper panel) Optical coherence tomography of the right eye of a 68-year-old man, visual acuity: 20/63. (Top left) Color photograph showing the round yellowish foveal lesion of adult onset foveomacular dystrophy. (Top middle) Red-free photograph showing the whitish foveal lesion. (Top right) Late frame of fluorescein angiogram showing staining of the pseudovitelliform lesion. (Bottom left) Three-millimeter horizontal scan: the pseudovitelliform lesion is shown as a hyperreflective structure close to the retinal pigment epithelium reflectivity, lying on the retinal pigment epithelium (arrows). (Bottom right) Three-millimeter vertical scan: the deposit of material raises the hyporeflective photoreceptor layer, thus leading to the disappearance of the foveal depression (arrows). The retinal pigment epithelium layer (arrowheads) located under the material looks less reflective than usual, probably due to attenuation of the signal by the material. FIGURE 2. (Lower panel) Comparison between optical coherence tomography (OCT) in adult-onset foveomacular dystrophy (left) and in drusenoid retinal pigment epithelium detachment (right). (Top left) Red-free photograph showing the whitish pseudovitelliform lesion of the right eye of an 84-year-old man, best-corrected visual acuity: 20/200. (Bottom left) Optical coherence tomography: the pseudovitelliform material is located between the retinal pigment epithelium layer (arrows) and the photoreceptor layer. Although slightly less reflective than usual, the retinal pigment epithelium layer is still easily identifiable and linear (arrows). (Top right) Red-free photograph of a drusenoid retinal pigment epithelium detachment in the right eye of a 64-year-old woman, best-corrected visual acuity: 20/80. (Bottom right) Optical coherence tomography: the retinal pigment epithelium layer is clearly raised by the drusen, and there is no separation between the retinal pigment epithelium and the photoreceptor layer. Owing to the high concentration of melanin, the retinal pigment epithelium is responsible for the attenuated reflectivity of the drusenoid material.

between 20/63 and 20/40 in 11, and less than 20/63 in four (Table 1). All lesions but one were centered on the fovea. The size of the lesions ranged from 500 ␮m to one disk 364

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diameter. Adult-onset foveomacular vitelliform dystrophy was associated with drusen in four eyes: hard and soft drusen in three cases and basal laminar drusen in one. OF

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On biomicroscopy, with direct illumination, pseudovitelliform lesions appeared round and yellowish, with fairly regular borders and slightly elevated (Figures 1–3). On the red-free photographs, AFVD lesions were round and whitish (Figures 1– 4). In the early stages, FA disclosed, in all cases, early hypofluorescence, corresponding to the area of whitish material seen in the red-free photographs. In 16 eyes (11 patients), the late stages showed a central staining of variable intensity but without leakage (Figures 1–3). However, in the remaining five eyes (four patients), the hypofluorescence persisted until the late stage with no staining (Figure 4). In the 16 eyes presenting with late staining on FA, the yellowish material appeared as a highly reflective area located between the hyporeflective photoreceptor layer and the hyperreflective retinal pigment epithelium layer (Figures 1–3). In most cases, the retinal pigment epithelium layer was more reflective than the material (Figures 1, 2). However, in some cases, the reflectivity of the retinal pigment epithelium and the material was very close and thus could not be distinguished by OCT. In the latter cases, OCT examination was performed again using lower intensity energy (300– 400 ␮W), thus reducing reflectivity of the two structures and allowing their differentiation (Figure 3). In all eyes, the macular retina was raised by the material and had markedly thinned. In 20 eyes, the material was subfoveal and led to the disappearance of the foveal depression (Figures 1– 4). In the five eyes without late staining on FA, the lesions appeared as a focal thickening of the retinal pigment epithelium, and OCT showed no identifiable overlying material (Figure 4). In all 21 eyes, The retinal pigment epithelium band was linear and continuous without retinal pigment epithelium detachment. In all 21 eyes, no edema, retinal cysts, retinal thickening, or serous detachment were found on OCT examination.

DISCUSSION OPTICAL COHERENCE TOMOGRAPHY HAS BEEN SHOWN TO

provide useful information about intraretinal structures in various macular diseases.19 –21 The aim of this study was to analyze the morphology of AFVD using OCT and to compare the findings with those of biomicroscopy and FA. The exact location of the deposit of material in AFVD, whether below, above, or inside the retinal pigment epithelium, has indeed not yet been determined, either by clinical examination or histologic study. In previous reports, subjective analysis of color or monochromatic stereoscopic photographs led to the conclusion that the material was subretinal,1,7 sometimes at the level of14 or under the retinal pigment epithelium.22 In a recent case report documented by OCT, AFVD material was described of as a focal detachment of the retinal pigment epithelium.23 In this study, OCT provided new information on the location of the material and showed the pseudovitelVOL. 135, NO. 3

liform material as a hyperreflective structure located above the retinal pigment epithelium that raises the neurosensory retina. As the principle of OCT is based upon differences between reflectivity of structures, which are imaged by a false color scale,18 two adjacent structures can be distinguished from each other if their reflectivity is different. Thus, the lower reflectivity of the material observed in AFVD makes it distinguishable from the retinal pigment epithelium band, even if this difference is sometimes minimal. In such cases, OCT performed using low-intensity energy was able to distinguish between the two structures. Our study clearly shows the difference between retinal pigment epithelium detachment and AFVD (Figure 2). It is well known that in retinal pigment epithelium detachment the hyperreflective layer corresponding to the retinal pigment epithelium is clearly elevated and is not separated from the photoreceptor layer.24 Here, in AFVD, the retinal pigment epithelium layer was linear and was not elevated. On the other hand, the photoreceptor layer was separated from the retinal pigment epithelium by the hyperreflective material. In addition, in drusenoid retinal pigment epithelium detachment, the signal of the drusenoid material located under the retinal pigment epithelium is markedly weakened (hyporeflective signal; Figure 2, bottom right) as opposed to the hyperreflective signal of the pseudovitelliform material (Figure 2, bottom left). This feature is probably due to the high melanin concentration of the retinal pigment epithelium layer, which is known to be responsible for attenuating the signal from deeper tissues.25 In some cases, the retinal pigment epithelium band located under the material looked slightly thinner than the retinal pigment epithelium band in the normal adjacent retina but remained identifiable in all cases. This was probably due to the attenuation of the retinal pigment epithelium signal by the dense pseudovitelliform material. Two groups of eyes were distinguished in this study. One group consisted of 16 eyes, which on FA exhibited a central late staining of the lesion. The finding of moderate late staining of the lesion in FA correlated with the presence on OCT of a high reflectivity area corresponding to the subretinal deposit of material. Comparison of FA and OCT data therefore indicated that the late staining observed on FA is due to the presence of this material. These features are consistent with the clinicopathologic observations of Sarks and colleagues (unpublished data, Macula Society, XXIVth annual meeting, 2001) who demonstrated that the pseudovitelliform material consists of a collection of subretinal debris, associated with an intact retinal pigment epithelium and a thinned inner retina. Here, in the second group of five eyes, there was no late staining on FA but only the persistence of central hypofluorescence. No subretinal material was visible on OCT scans (Figure 4). The OCT findings of the second group are close to the histologic findings for AFVD in the literature1,15–17 in which AFVD is described as crown-shaped retinal pigment epithelium atrophy, with a central pigmented spot and

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FIGURE 3. (Upper panel) Optical coherence tomography (OCT) of the left eye of a 77-year-old man, visual acuity: 20/63. The pseudovitelliform lesion looks round and yellowish on the color photograph (top left), whitish on the red-free photograph (top middle), and stained in the late frame of the fluorescein angiogram (top right). (Bottom left) Horizontal scan. The material has almost the same reflectivity as the retinal pigment epithelium layer and is therefore barely distinguishable from it by OCT. Note that the neurosensory retina above the material is thinned (arrowheads). (Bottom right) Same OCT scan, but performed using a low-intensity signal. The retinal pigment epithelium layer is now more reflective than the material and therefore distinguishable from it. FIGURE 4. (Lower panel) Optical coherence tomography (OCT) of the right eye of a 75-year-old woman, best-corrected visual acuity: 20/50. (Top left) Red-free photograph showing the small whitish foveal lesion. (Top right) Late frame of the fluorescein angiogram showing the persistence of central hypofluorescence without staining, associated with a ring of hyperfluorescence due to retinal pigment epithelium atrophy. (Bottom) Horizontal scan showing the hyperreflective lesion, which is not distinguishable from the retinal pigment epithelium layer, and leads to the masking of the OCT signal in the deep choroidal layers. The neurosensory retina above the lesion has thinned.

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associated with photoreceptor degeneration. In these studies, there was no mention of the subretinal material observed here on OCT in the first group of 16 eyes. However, the histologic studies concerned AFVD lesions in very late stages, in which the material has already disappeared. It has indeed been shown that, with time, the material progresses slowly toward fragmentation and then disappears. This disappearance is followed by the occurrence of atrophic retinal pigment epithelium lesions and the appearance of pigmented spots.9,14 It might explain why OCT showed no subretinal material in these five eyes. We therefore suggest that the different stages of AFVD explain the major differences between the morphology of these two groups observed by OCT in this study. Neither serous retinal detachment nor cystoid macular edema were found in any of the 21 eyes in this series. As opposed to this, OCT disclosed that the foveal retina had clearly thinned and was raised by the material in all cases. This feature probably explains the progressive decrease in vision observed in most patients. The persistent separation of the photoreceptor from the retinal pigment epithelium, due to the presence of the material, could be responsible for the usual evolution to central retinal atrophy.9,14 A full-thickness macular hole has also been reported as a possible evolution of AFVD26 and Best disease.27–29 In this disease, it has already been suggested that progressive foveal atrophy might play a role,29 and the marked foveal thinning observed here on OCT in AFVD is in keeping with this theory. Progressive foveal atrophy in AFVD might explain the mechanism of evolution toward a macular hole rather than tangential vitreous traction, as shown in idiopathic macular hole.19 In conclusion, OCT is a useful noninvasive tool that provides new information on the morphology of AFVD. It demonstrates, better than biomicroscopy, the location of the yellowish deposit of material under the sensory retina but above the retinal pigment epithelium corresponding angiographically to the late staining. In the late stage of the disease, the characteristics of AFVD shown by OCT are very close to those reported in histologic descriptions. The foveal thinning found here by OCT in all cases probably explains the progressive visual loss and the possible evolution toward a full-thickness macular hole.

7. 8. 9. 10. 11. 12. 13. 14. 15.

16. 17.

18. 19.

20. 21. 22. 23. 24.

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