April 2011, Issue 50

The Clinical Course of Adult "Vitelliform" Macular Lesions

Kevin K. Suk, MD Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine, Miami, FL	Avinash Pathengay, FRCS Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine, Miami, FL	Harry W. Flynn, Jr., MD Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine, Miami, FL

The clinical course and visual prognosis of “vitelliform” macular lesions is highly variable.  In Best disease, “vitelliform” macular lesions occur in childhood and may evolve into varying stages of atrophy, but it generally has a very good visual prognosis. Adult vitelliform macular dystrophy (AVMD), first described by Gass in 1974, is characterized by yellowish, focal macular lesions similar to those seen in Best disease, but without electroretinography (ERG) and electrooculography (EOG) abnormalities.^1,2  

“Vitelliform” macular lesions may be in seen in patients with cuticular drusen (CD). Once thought to be distinct from the drusen associated with age-related macular degeneration (AMD), histologic studies have found them to be identical.³ It is unclear, however, if AVMD with CD represents a distinct disease entity from AMD.

Vitelliform lesions represent the effects of retinal pigment epithelium (RPE) dysfunction with accumulation of degenerated photoreceptor outer segments in the subretinal space.⁴ Imaging modalities have helped further our understanding of “vitelliform” macular lesions. Spectral domain optical coherence tomography (SD-OCT) has demonstrated the location of the deposits in AVMD to be in the subretinal space between the junction of the photoreceptor inner and outer segments (IS/OS interface) and the RPE/choriocapillaris complex.⁵ On autofluorescence (AF), the subretinal accumulation is intensely hyperfluorescent, suggesting that the material is composed of retinoid fluorophores such as photoreceptor outer segment debris.⁶ We present two patients with “vitelliform” macular lesions with variable clinical outcomes as documented by photography, AF and OCT.

Case 1
A 62 year old Hispanic woman presented with CD in both eyes and a “vitelliform” macular lesion in the left eye. Visual acuity was 20/20 in the right eye and 20/30 in the left eye. The patient gradually developed a “vitelliform” macular lesion over the following 2 years in the right eye (Fig. 1B). As the yellowish material accumulated under the fovea, there was a corresponding increase in hyperfluorescence on AF as well as an increased dome shaped elevation of the neurosensory retina by the subfoveal deposits on OCT (Fig. 1B,C,D). Visual acuity remained 20/30 in the right eye. The “vitelliform” lesion size and density appeared to increase up to 2.5 years after the initial diagnosis, after which time it began to collapse (Fig. 1). There was a speckled loss of AF which eventually progressed to a central area of hypofluorescence. Six years after the initial presentation, SD-OCT showed severe RPE atrophy, and visual acuity decreased to 20/200 (Fig. 1E).

Figure 1

A. TOP. Fundus photograph of the right eye at initial presentation. Multiple cuticular drusen are concentrated near the fovea. BOTTOM. Horizontal and vertical scans through the fovea with TD-OCT. The characteristic “sawtooth” appearance of the cuticular drusen is seen.
B. TOP. 28 months later, a small yellowish subfoveal lesion is beginning to form. MIDDLE. Horizontal and vertical scans through the subretinal material with TD-OCT shows the accumulation of a hyper reflective material with areas of hyporeflectivity suggestive of subretinal fluid (SRF). BOTTOM. Autofluorescence shows mild hyperautofluorescence of the subfoveal lesion with a surrounding ring of hypoautofluorescence.  Visual acuity is 20/25.
C. TOP. 16 months later (44 months after the initial presentation) the subfoveal “vitelliform” lesion has increased in size and density. MIDDLE. TD-OCT shows a broad dome shaped elevation of the neurosensory retina by the subretinal material. BOTTOM. There is increased autofluorescence of the “vitelliform” lesion.  Visual acuity is maintained at 20/30.
D. TOP. 8 months later (52 months after initial presentation) the “vitelliform” lesion is larger. MIDDLE. SD-OCT shows a dome shaped elevation of the neurosensory retina and preservation of the IS/OS interface. BOTTOM. The “vitelliform” lesion is intensely autofluorescent. Visual acuity is 20/50.
E. TOP. 19 months later (71 months after initial presentation) the “vitelliform” lesion has collapsed, leaving behind an area of geographic atrophy. MIDDLE. SD-OCT shows resolution of the subretinal material. The IS/OS interface and ELM is disrupted and the RPE has focal areas of atrophy. BOTTOM. There is a corresponding loss of autofluorescence.  Visual acuity has diminished to 20/200.

Similarly, the “vitelliform” lesion in the left eye collapsed over two years after the initial diagnosis with gradual loss of AF (Fig. 2). Six years after the initial presentation, clinical examination and SD-OCT showed RPE and retinal atrophy with a corresponding area of central hypoautofluorescence (Fig. 2E). Visual acuity decreased to 20/200 in the left eye.

Figure 2

A. TOP. Fundus photograph of the left eye at initial presentation. A subfoveal “vitelliform” lesion is present along with cuticular drusen. BOTTOM. Horizontal and vertical scans with TD-OCT show elevation of the neurosensory retina by the hyper reflective subretinal material. A small amount of SRF can be seen in the superior aspect of the lesion.
B. TOP. 28 months later, there is spontaneous resolution of the “vitelliform” lesion. MIDDLE. The subretinal material has disappeared. There is mild RPE atrophy but the neurosensory retina appears to be preserved on TD-OCT. BOTTOM. On autofluorescence, the inferior two-thirds of the fovea, including the center of the fovea, is hyperautofluorescent. The rest of the fovea shows hypoautofluorescence. Visual acuity is 20/300.
C. TOP. 16 months later (44 months after the initial presentation), geographic atrophy has developed centrally. MIDDLE. TD-OCT shows retinal and RPE atrophy. BOTTOM. There is loss of autofluorescence centrally. The periphery of the hypoautofluorescent area has speckled autofluorescence. Visual acuity is 20/100.
D. TOP. 8 months later (52 months after initial presentation). There is a central area of geographic atrophy. MIDDLE. Disruption of the IS/OS interface and RPE atrophy is seen on SD-OCT. BOTTOM. The area of hypoautofluorescence is slightly larger. Visual acuity has decreased to 20/150.
E. TOP. 19 months later (71 months after initial presentation), there is advanced geographic atrophy with surrounding cuticular drusen. MIDDLE. Atrophy of the outer retina with disruption of the IS/OS interface and focal areas of RPE loss are seen on SD-OCT. BOTTOM. The central area of hypoautofluorescence is larger. There are a few areas of speckled hyperautofluorescence in the periphery of the lesion. Visual acuity has decreased to 20/200.

Case 2
An 85 year old white man with decreased vision in the right eye was noted to have bilateral “vitelliform” macular lesions with no other fundus abnormalities (Fig. 3A, 4A).  Visual acuity was 20/50 in the right eye and 20/25 in the left eye. The decreased vision was attributed to nuclear sclerotic cataracts and the patient underwent successful cataract surgery in both eyes with improvement of vision to 20/20 in both eyes.

Figure 4

A. TOP. Fundus photograph of the right eye at presentation, after removal of cataract.  A small subfoveal “vitelliform” lesion is present. MIDDLE. SD-OCT, horizontal scan through the lesion. An amorphous material is present above the RPE with a dome shaped elevation of the overlying neurosensory retina. The IS/OS interface and ELM are intact and appear to be draped over the subfoveal mass. BOTTOM. Autofluorescence shows a speckled pattern of moderate hyperautofluorescence.
B. TOP. 11 months later, the “vitelliform” lesion appears larger and is more prominently visible. BOTTOM. The subfoveal mass appears larger and the IS/OS interface and ELM are still intact. Visual acuity is 20/40.

Over two years of follow-up, the SD-OCT findings remained unchanged (Fig. 3,4). Hyperautofluorescence of the “vitelliform” lesions was noted on AF, although the right eye had a speckled pattern and was less intensely hyperautofluorescent (Fig. 3A, 4A). Visual acuity decreased to 20/40 in the right eye after 2 years of follow up but remained 20/20 in the left eye.

Figure 4

A. TOP. Fundus photograph of the left eye at initial presentation. A yellowish subretinal lesion is present just nasal to the foveal center. MIDDLE. SD-OCT, horizontal scan. A relatively homogeneous mass can be seen above the RPE and elevating the overlying neurosensory retina. The IS/OS interface and ERM are intact. BOTTOM. Autofluorescence shows bright hyperautofluorescence of the lesion just nasal to the fovea center. Visual acuity is 20/20.
B. TOP. 11 months later, the “vitelliform” lesion is unchanged. BOTTOM. The appearance of the lesion is unchanged on SD-OCT. Visual acuity remains 20/20.

Discussion
“Vitelliform” macular lesions can occur in a variety of diseases that affect the RPE. A broad differential diagnosis exists, ranging from non-neovascular AMD and CD to acute exudative polymorphous vitelliform maculopathy (AEPVM).^3,7 The underlying etiologies are not well established, although genetic3 and autoimmune7 causes have been suggested. Regardless of the pathogenesis, the “vitelliform” lesions appear to be secondary to a poorly functioning RPE. However, most patients with submacular “vitelliform” lesions have a favorable prognosis and are able to maintain good vision.^3,7

AVMD associated with CD was first described by Gass in 1985.8 The small, uniform, round subretinal lesions typical of CD demonstrate early fluorescence during fluorescein angiography (FA) with a “stars-in-the-sky” pattern, differing from the “typical drusen” of AMD which tend to fluoresce later in the FA.4 Imaging and genetic findings have suggested that AVMD with CD may be a distinct disease entity,^9,10 rather than a variant of AMD, and has been thought to have a better visual prognosis than AMD.⁸ A recent study, however, found worse visual outcomes than expected in eyes with AVMD.⁹ In our patient with “vitelliform” lesions in the macula and CD, visual acuity deteriorated over 3.5 years in the right eye after formation of the “vitelliform” lesion, and over 4.5 years in the left eye, with resulting bilateral geographic atrophy (GA). In the right eye, the “vitelliform” lesion developed at age 64 and grew larger over 3 years and the OCT showed the accumulation of a mostly hyper reflective material beneath the fovea. Visual acuity remained stable even with elevation of the neurosensory retina by the subfoveal material. Loss of visual acuity paralleled the disruption of the IS/OS interface and the external limiting membrane (ELM) on SD-OCT (Fig. 1E), a feature noted by others.³ Vision loss also seemed to correlate with the collapse of the “vitelliform” lesion and loss of hyperfluorescence on AF (Fig. 1E). Similarly, in the left eye, good visual acuity was maintained until the “vitelliform” lesion collapsed, leaving behind severe retinal and RPE atrophy (Fig. 2).

Our second patient had “vitelliform” lesions without any other retinal abnormalities. With over 2 years of follow-up, the patient maintained good visual acuity, which correlated with preservation of the IS-OS interface on SD-OCT as well as hyperautofluorescence of the “vitelliform” lesions (Fig. 3,4). 

The differing clinical course of “vitelliform” macular lesions may reflect differing underlying pathologic mechanisms.³ Visible changes on ophthalmoscopy do not correlate with vision until there is advanced geographic atrophy. Thus, OCT and AF findings may be helpful in following disease progression and evaluating visual prognosis.

We have presented two adult patients with submacular “vitelliform” lesions followed by OCT and AF, one with CD and the other with no other funduscopic abnormalities, with variable clinical presentations and outcomes.

REFERENCES

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9. Finger RP, Issa PC, Kellner U, Schmitz-Valckenberg S, Fleckenstein M, Scholl HP, Holz FG. Spectral domain optical coherence tomography in adult-onset vitelliform macular dystrophy with cuticular drusen. Retina. 2010 Oct;30(9):1455-64.
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Core grant: P30EY014801 Research to Prevent Blindness Unrestricted Award.
The authors have no conflicting relationship or proprietary interest in any aspect of this manuscript.