Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

Fundus Autofluorescence and Photoreceptor Bleaching in Multiple Evanescent White Dot Syndrome

Anthony Joseph, MD; Ehsan Rahimy, MD; K. Bailey Freund, MD; John A. Sorenson, MD; David Sarraf, MD

Abstract

The authors present three cases of multiple evanescent white dot syndrome (MEWDS) with characteristic fundus autofluorescence (FAF) findings, including one patient without any visible white dots on funduscopic examination and another with many more hyperautofluorescent lesions than seen ophthalmoscopically. Additionally, the findings support an alternative mechanism for the hyperautofluorescent lesions in MEWDS, whereby photoreceptor loss causes unmasking of normal underlying retinal pigment epithelium autofluorescence. This hypothesis is demonstrated in two cases by optical coherence tomography showing clear ellipsoid zone attenuation with registration to hyperautofluorescent lesions. It is further supported in two cases by photoreceptor bleaching in successive FAF images captured in the same session leading to diminished autofluorescence intensity of the characteristic dots.

[Ophthalmic Surg Lasers Imaging Retina. 2013;44:588–592.]

From Jules Stein Eye Institute, UCLA, Los Angeles, California (AJ, ER, DS); Vitreous Retina Macula Consultants of New York, New York (KBF, JAS); Department of Ophthalmology, New York University School of Medicine, New York, New York (KBF, JAS); and Greater Los Angeles VA Healthcare Center, Los Angeles, California (DS).

Supported by the Macula Foundation, New York, NY.

The authors have no relevant financial or proprietary interest in the materials presented herein.

Address correspondence to David Sarraf, MD, Retinal Disorders and Ophthalmic Genetics Division, Jules Stein Eye Institute, UCLA, 100 Stein Plaza, Los Angeles, CA 90095; 310-794-9921; fax: 310-206-7826; email: dsarraf@ucla.edu.

Received: April 04, 2013
Accepted: September 20, 2013

Abstract

The authors present three cases of multiple evanescent white dot syndrome (MEWDS) with characteristic fundus autofluorescence (FAF) findings, including one patient without any visible white dots on funduscopic examination and another with many more hyperautofluorescent lesions than seen ophthalmoscopically. Additionally, the findings support an alternative mechanism for the hyperautofluorescent lesions in MEWDS, whereby photoreceptor loss causes unmasking of normal underlying retinal pigment epithelium autofluorescence. This hypothesis is demonstrated in two cases by optical coherence tomography showing clear ellipsoid zone attenuation with registration to hyperautofluorescent lesions. It is further supported in two cases by photoreceptor bleaching in successive FAF images captured in the same session leading to diminished autofluorescence intensity of the characteristic dots.

[Ophthalmic Surg Lasers Imaging Retina. 2013;44:588–592.]

From Jules Stein Eye Institute, UCLA, Los Angeles, California (AJ, ER, DS); Vitreous Retina Macula Consultants of New York, New York (KBF, JAS); Department of Ophthalmology, New York University School of Medicine, New York, New York (KBF, JAS); and Greater Los Angeles VA Healthcare Center, Los Angeles, California (DS).

Supported by the Macula Foundation, New York, NY.

The authors have no relevant financial or proprietary interest in the materials presented herein.

Address correspondence to David Sarraf, MD, Retinal Disorders and Ophthalmic Genetics Division, Jules Stein Eye Institute, UCLA, 100 Stein Plaza, Los Angeles, CA 90095; 310-794-9921; fax: 310-206-7826; email: dsarraf@ucla.edu.

Received: April 04, 2013
Accepted: September 20, 2013

Introduction

Recent reports have documented a variety of fundus autofluorescent (FAF) findings associated with multiple evanescent white dot syndrome or MEWDS, most commonly hyperautofluorescent lesions in the posterior pole corresponding with the white lesions typically seen on clinical examination.1–4 We present three cases of MEWDS with these characteristic FAF findings, including one patient without any visible white dots. Additionally, we use spectral-domain optical coherence tomography (SD-OCT) to demonstrate photoreceptor loss as the probable mechanism of the hyperautofluorescent lesions in MEWDS and discuss the phenomenon of photoreceptor bleaching to offer new insight into the etiology of FAF findings in this and potentially other related conditions.

Case Reports

Case 1

A 29-year-old woman presented with a 1-week history of paracentral scotoma in the left eye. She had received the influenza vaccine approximately 3 weeks prior to presentation. She denied any other relevant medical or ocular history.

Best corrected visual acuity was 20/20 in the right eye and 20/40 in the left eye. Anterior segment examination findings were within normal limits. Funduscopic examination of the left eye demonstrated subtle granularity of the fovea but was otherwise unremarkable, with no obvious white dots (Figure 1A, page 589). FAF imaging revealed multiple discrete hyperautofluorescent spots involving the posterior pole and midperiphery in a peripapillary distribution (Figure 1B–C, page 589). Fluorescein angiography (FA) demonstrated speckled hyperfluorescent dots during the late phase corresponding to these same lesions detected by FAF (Figure 1D, page 589). Indo-cyanine green angiography (ICGA) showed multiple smaller, round hypofluorescent spots in the posterior pole that did not consistently correlate to FA and FAF lesions (Figure 1E, page 589). Finally, SD-OCT through the fovea revealed central attenuation of the ellipsoid zone corresponding to the region of granularity seen clinically in the left eye (Figure 1F, page 589). Findings from examination and imaging studies of the right eye were within normal limits.

Case 1. (A) Baseline color montage of the left eye showing granularity of the fovea but no visible white dots. (B) Optos 200 Tx (Dun-fermline, United Kingdom) widefield green light (532 nm) fundus autofluorescence (FAF) demonstrating multiple discrete hyperautofluorescent dots in and around the posterior pole. (C) Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) 30° blue light (488 nm) FAF with similar findings. (D) Fluorescein angiogram showing speckled hyperfluorescent dots during the late phase. (E) ICG angiography showing multiple hypofluorescent spots in the posterior and midperipheral fundus. (F) SD-OCT through the fovea showing attenuation of the ellipsoid zone beneath the papillomacular bundle and fovea.

Figure 1.

Case 1. (A) Baseline color montage of the left eye showing granularity of the fovea but no visible white dots. (B) Optos 200 Tx (Dun-fermline, United Kingdom) widefield green light (532 nm) fundus autofluorescence (FAF) demonstrating multiple discrete hyperautofluorescent dots in and around the posterior pole. (C) Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) 30° blue light (488 nm) FAF with similar findings. (D) Fluorescein angiogram showing speckled hyperfluorescent dots during the late phase. (E) ICG angiography showing multiple hypofluorescent spots in the posterior and midperipheral fundus. (F) SD-OCT through the fovea showing attenuation of the ellipsoid zone beneath the papillomacular bundle and fovea.

At 2-week follow-up, the patient’s subjective complaints had largely resolved, with corresponding improvement of visual acuity to 20/25 in the left eye. Funduscopic examination showed resolving foveal granularity and still no discrete white dots. Repeat FAF showed diminished hyperautofluorescent dots while SD-OCT showed restoration of the ellipsoid zone at the fovea. Five weeks later, the hyperautofluorescent dots had completely resolved.

Case 2

A 22-year-old woman presented with a 1-week history of “white patches” in the central vision of her left eye. She denied any other relevant medical or ocular history.

Best corrected visual acuity was 20/20 in the right eye and 20/25 in the left eye. There was no afferent pupillary defect, and anterior segment examination was unremarkable. Funduscopic examination of the left eye demonstrated occasional cells in the anterior vitreous, scattered gray-white lesions in the outer retina, and foveal granularity (Figure 2A, page 590). FAF imaging revealed multiple hyperautofluorescent dots surrounding the posterior pole in much greater number than those lesions seen clinically or with color photographs (Figure 2B, page 590). FA demonstrated speckled hyperfluorescent dots during the late phase corresponding to the spots seen clinically and with FAF (Figure 2C, page 590). ICGA showed multiple hypofluorescent spots in the posterior and midperipheral fundus (Figure 2D, page 590). Notably, SD-OCT line images registered to the hyperfluorescent dots demonstrated associated attenuation of the ellipsoid zone with no evidence of hypertrophy to the retinal pigment epithelium (RPE) band (Figure 2E, page 590).

Case 2. (A) Initial color photograph of the left eye showing granularity of the fovea with white dots in the posterior pole. (B) Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) 55° blue light (488 nm) fundus autofluorescence (FAF) with multiple discrete hyperautofluorescent dots. Note that there are many more dots with autofluorescence (dashed circle) than with color fundus photography (solid circle). (C) Fluorescein angiography showing speckled hyperfluorescent dots during the late phase. (D) ICG angiography demonstrating multiple hypofluorescent spots in the posterior and midperipheral fundus. (E) SD-OCT with registration through the temporal dots (2B black arrowhead and 2E white arrowhead) showing associated attenuation of the ellipsoid zone.

Figure 2.

Case 2. (A) Initial color photograph of the left eye showing granularity of the fovea with white dots in the posterior pole. (B) Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) 55° blue light (488 nm) fundus autofluorescence (FAF) with multiple discrete hyperautofluorescent dots. Note that there are many more dots with autofluorescence (dashed circle) than with color fundus photography (solid circle). (C) Fluorescein angiography showing speckled hyperfluorescent dots during the late phase. (D) ICG angiography demonstrating multiple hypofluorescent spots in the posterior and midperipheral fundus. (E) SD-OCT with registration through the temporal dots (2B black arrowhead and 2E white arrowhead) showing associated attenuation of the ellipsoid zone.

Two weeks later, the patient noted partial resolution of her subjective symptoms, with improvement in visual acuity to 20/15 in the left eye. Funduscopic examination showed decreased foveal granularity and resolution of the white dots.

Case 3

A 30-year-old woman presented with 4 days of decreased vision in her right eye. She reported having similar symptoms in the same eye several years prior to presentation that resolved over several weeks. She denied any other relevant medical or ocular history.

On presentation, visual acuity was 20/80 in the right eye and 20/20 in the left eye. Funduscopic examination of the right eye showed scattered gray-white lesions of the outer retina (Figure 3A) with corresponding hyperfluorescent dots on FA (Figure 3B) and hyperautofluorescent spots on FAF (Figure 3C). SD-OCT showed attenuation of the ellipsoid zone with no obvious change in the RPE band in the right eye, both centrally and in areas corresponding precisely to the hyperautofluorescent lesions in the temporal macula (Figure 3E). Examination and ancillary imaging findings were entirely normal in the left eye. At 1-month follow up, visual acuity in the right eye had returned to 20/20, with resolution of the lesions on examination and FAF (Figure 3D) and associated restoration of the ellipsoid zone by SD-OCT (Figure 3F).

Case 3. (A) Ultra-widefield color photograph of the right eye showing white dots in and around the posterior pole. (B) Ultra-widefield fluorescein angiogram showing corresponding speckled hyperfluorescent dots during the late phase. (C) Topcon TRC-50DX (Tokyo, Japan) 50° fundus autofluorescence (FAF) (excitation range 535–585 nm; barrier filter range 605–715 nm) at presentation showing corresponding hyperautofluorescent lesions. (D) Topcon TRC-50DX 50° FAF on follow-up showing resolution of the previously hyperautoflurescent lesions. (E) SD-OCT showing attenuation of ellipsoid zone corresponding to FAF lesions (black arrowhead in C and white arrowhead in E). (F) Follow-up SD-OCT showing restoration of ellipsoid zone.

Figure 3.

Case 3. (A) Ultra-widefield color photograph of the right eye showing white dots in and around the posterior pole. (B) Ultra-widefield fluorescein angiogram showing corresponding speckled hyperfluorescent dots during the late phase. (C) Topcon TRC-50DX (Tokyo, Japan) 50° fundus autofluorescence (FAF) (excitation range 535–585 nm; barrier filter range 605–715 nm) at presentation showing corresponding hyperautofluorescent lesions. (D) Topcon TRC-50DX 50° FAF on follow-up showing resolution of the previously hyperautoflurescent lesions. (E) SD-OCT showing attenuation of ellipsoid zone corresponding to FAF lesions (black arrowhead in C and white arrowhead in E). (F) Follow-up SD-OCT showing restoration of ellipsoid zone.

Autofluorescence and Bleaching

A notable finding observed in cases 1 and 2 was reduced autofluorescence of the white spots in the second of two images captured in the same session. In case 1, a 30° field was captured first (Figure 4A, page 592), followed immediately by capture of a 55° field (Figure 4B, page 592), both using the Heidelberg Spectralis BluePeak HRA (Heidelberg Engineering, Heidelberg, Germany). The second image showed decreased intensity of the hyperautofluorescent spots as well as generalized bleaching of the fundus in the 30° field of the first image capture. In case 2, a 55° field was captured first (Figure 4C, page 592) followed by a 30° field, both using the HRA system (Figure 4D, page 592), with the second image showing a markedly diminished signal of the previously hyperautofluorescent lesions. In both cases, the first and second images were captured using identical parameters, including the same detector gain. The interpretation and implications of this phenomenon are discussed below.

Autofluorescence and bleaching. (A) Case 1: Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) blue light (488 nm) 30° fundus autofluorescence (FAF) showing hyperautofluorescent dots. (B) Case 1: repeat 55° HRA blue light FAF shows attenuated intensity of the hyperautofluorescent dots at same detector gain. (C) Case 2: 55° HRA blue light FAF with hyperautofluorescent lesions. (D) Case 2: repeat 30° HRA blue light FAF shows markedly diminished signal of prior hyperautofluorescent lesions at same detector gain (white and dashed circles show corresponding areas of the retina). Note that this phenomenon in each case may be attributed to bleaching of the photoreceptors with a subsequent increase in the background autofluorescence due to unmasking of the overall RPE autofluorescence.

Figure 4.

Autofluorescence and bleaching. (A) Case 1: Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany) blue light (488 nm) 30° fundus autofluorescence (FAF) showing hyperautofluorescent dots. (B) Case 1: repeat 55° HRA blue light FAF shows attenuated intensity of the hyperautofluorescent dots at same detector gain. (C) Case 2: 55° HRA blue light FAF with hyperautofluorescent lesions. (D) Case 2: repeat 30° HRA blue light FAF shows markedly diminished signal of prior hyperautofluorescent lesions at same detector gain (white and dashed circles show corresponding areas of the retina). Note that this phenomenon in each case may be attributed to bleaching of the photoreceptors with a subsequent increase in the background autofluorescence due to unmasking of the overall RPE autofluorescence.

Discussion

First described in 1984, MEWDS was initially considered a clinical diagnosis reinforced with FA and visual field findings.6 As understanding of the condition progressed and new imaging modalities became available, OCT demonstrated photoreceptor abnormalities as the likely etiology of visual symptoms.7

While multimodal imaging in our cases reliably confirmed the characteristic findings of MEWDS,8 FAF notably provided a quick and noninvasive means to establish the diagnosis. With FAF, we observed multiple hyperautofluorescent dots surrounding the posterior pole that correlated to the white dots when present clinically. Even in the absence of white dots on funduscopic examination or color photographs in case 1, FAF showed characteristic hyperautofluorescent lesions, helping to confirm the diagnosis of MEWDS. Similarly, case 2 demonstrated a greater number of lesions with FAF than seen on clinical examination or with color photographs, again suggesting that FAF may be the most sensitive and practical ancillary imaging test to detect the white dots of MEWDS. A recent report by Boretsky et al4 reported similar findings in a patient with a few white lesions on examination but multiple lesions observed with FAF. In our cases, it is unclear whether white dots were never present or rather had faded prior to presentation, but in either situation FAF would appear to provide an essential diagnostic tool.

The basis of these FAF findings has been a topic of recent interest. Given that the FAF signal depends on both the amount of fluorophores in the RPE and the attenuation of the autofluorescence by RPE melanin and photoreceptor and macular pigments, disturbances affecting these layers could presumably alter the FAF signal. It has been previously suggested that increased FAF signal observed in inflammatory diseases may be a result of RPE cellular alterations, specifically activation of prooxidative pathways leading to an increase in size and number of fluorophores in these cells. Accordingly, prior studies attributed the hyperautofluorescent lesions in MEWDS to accumulation of lipofuscin granules, either from hypertrophy and hyperplasia of the RPE with increased production of lipofuscin1,2,5 or impaired function of the RPE with impaired clearance of lipofuscin.3

Our findings support an alternative mechanism in which photoreceptor loss causes unmasking of normal underlying RPE autofluorescence. This hypothesis is supported by the SD-OCT findings from cases 2 and 3, demonstrating clear ellipsoid zone attenuation with registration to the hyperautofluorescent lesions (Figures 2E and 3E, pages 590 and 591, respectively), and is further reinforced by the photoreceptor bleaching effect observed with successive FAF images captured in the same session. The phenomenon of photoreceptor bleaching by the short-wavelength blue excitation light has been described previously9 and is nicely illustrated in cases 1 and 2 (Figure 4, page 592). In each instance, an initial FAF image was obtained in one field of view and immediately followed by repeat FAF capture in an overlapping field, using the same parameters including detector gain in both images. With the second capture, we noted an overall increase in the background FAF signal and a relatively diminished intensity of the previously hyperautofluorescent dots. This finding is presumably due to bleaching of photoreceptors in the initial field of capture by the blue excitation light, thereby unmasking underlying RPE autofluorescence. The relative increase in background autofluorescence causes the previously prominent hyperautofluorescent MEWDS lesions to appear less autofluorescent.

In summary, this series supports an expanding role for FAF as an adjunct or first-line diagnostic tool in patients suspected of having MEWDS or similar inflammatory chorioretinopathies. FAF provides a faster, cheaper, and less invasive alternative to FA and ICGA, both of which are relatively contraindicated in pregnancy, a concern given the higher incidence of MEWDS in young women. Additionally, we illustrate a probable mechanism for the presence of hyperautofluorescent lesions on FAF: photoreceptor outer segment loss with unmasking of underlying RPE auto-fluorescence as exhibited by SD-OCT examination of the hyperautofluorescent lesions and supported by the retinal bleaching effects of the blue excitation light.

References

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10.3928/23258160-20131105-08

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