Subfoveal choroidal thickness in multiple evanescent white dot syndrome

Authors


Dr Takaaki Hayashi, Department of Ophthalmology, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi Minato-ku, Tokyo, 105-8461, JAPAN, E-mail: taka@jikei.ac.jp

Abstract

Background:  Multiple evanescent white dot syndrome (MEWDS) is an inflammation of the choriocapillaris, which typically presents with unilateral vision loss and is characterised by the presence of multiple yellow-white spots in the posterior pole to the midperipheral fundus. This study was conduced to evaluate subfoveal choroidal thickness between the acute and convalescent phases in two patients with MEWDS.

Methods:  Two young female Japanese patients underwent a comprehensive ophthalmic examination, including slitlamp biomicroscopy, funduscopy and both fluorescein and indocyanine green angiographies. The subfoveal choroidal and central retinal thicknesses were measured using Cirrus high-definition spectral-domain optical coherence tomography.

Results:  The two patients were diagnosed with unilateral MEWDS based on characteristic funduscopic and angiographic findings. The disrupted foveal inner segment–outer segment boundary line in the acute phase was restored in the convalescent phase in both patients. In the affected eye of Patient 1, the subfoveal choroidal thickness (337 µm) noted in the acute phase decreased to 249 µm at 133 days after the initial visit (convalescent phase). Similarly, the acute phase thickness (440 µm) in Patient 2 decreased to 358 µm at 133 days after the initial visit. The thickness in the asymptomatic opposite eye also decreased during the convalescent phase in both patients. In the acute phase, thickness in the affected eyes was greater than that in the opposite eyes in both patients. In contrast, central retinal thickness remained unchanged in both eyes during follow up in both patients.

Conclusion:  This is the first report to describe the relationship between subfoveal choroidal thickness and MEWDS. We found that the choroid was thicker in the acute phase than the convalescent phase in both the affected and opposite eyes of both patients, suggesting that an inflammatory reaction might occur in the choroidal stroma in addition to the choriocapillaris and might be bilateral rather than unilateral.

Multiple evanescent white dot syndrome (MEWDS), first described in 1984 by Jampol and colleagues1 and Sieving and colleagues,2 is a typically unilateral retinopathy with sudden onset of vision loss that occurs predominantly in young females. Ophthalmoscopic examination in patients with MEWDS reveals multiple faint, yellow-white spots in the posterior pole to the midperipheral fundus. The disease is self-limiting with almost all patients regaining good visual acuity within several weeks. Fluorescein angiography (FA) shows hyperfluorescence of the yellow-white spots, whereas late-phase indocyanine green angiography (ICGA) reveals more hypofluorescent spots than what is seen with fluorescein angiography.3,4 Although the pathogenesis of MEWDS remains unknown, electroretinography and electrooculography have revealed dysfunction of the photoreceptors and retinal pigment epithelium.5–7

Recent spectral-domain optical coherence tomographic (SD-OCT) studies have noted disruptions in the photoreceptor inner segment/outer segment junction (IS/OS) in patients with acute phase MEWDS, but no pathological changes in the retinal pigment epithelium or choroid.8,9 Here, we investigate changes in subfoveal choroidal thickness between acute and convalescent phases in two patients with MEWDS.

METHODS

This study was conducted under a retrospective design in two patients diagnosed with MEWDS. They had undergone a comprehensive ophthalmic examination, including assessment of visual acuity (VA), slitlamp biomicroscopy, dilated funduscopy and fluorescein angiography (VISUCAM NM/FA; Carl Zeiss Meditec AG, Dublin, CA, USA). We also performed indocyanine green angiography using a scanning laser ophthalmoscope Model 101 (Rodenstock Instruments, Munich, Germany) in one of the two patients.

Cross-sectional retinal images were evaluated using SD-OCT (Cirrus HD-OCT, Carl Zeiss Meditec AG) in both patients. The SD-OCT was taken horizontally through the centre of the fovea (6.0 mm line) using programs with either five-line raster or HD five-line raster. Using the Cirrus linear measurement tool, two independent observers manually measured subfoveal choroidal thickness from the posterior edge of the retinal pigment epithelium to the choroid/sclera junction at the position of the foveal depression, in accordance with a previously published method.10 The average of the obtained measurements was determined as the subfoveal choroidal thickness. Similarly, the central retinal thickness (at the position of the foveal depression) was manually measured at this time to compare changes in both retinal and choroidal thickness during follow-up periods.

RESULTS

Patient 1

A 21-year-old female Japanese patient with no previous history of ocular disease presented to our hospital with sudden loss of visual acuity in the right eye. On initial examination, VA was 0.2 (with -11.00 DS) in the right eye and 1.2 (with -9.00 DS) in the left eye. No inflammatory cells were observed in the anterior segment or vitreous of either eye. Fundus examination revealed foveal granularity and scattered yellow-white spots in the posterior pole in the right eye (Figure 1A). Early phase fluorescein angiography in the right eye showed small hyperfluorescent lesions that were determined to be retinal spots (Figure 1B). Late-phase ICGA of the right eye revealed numerous hypofluorescent spots throughout the posterior pole (Figure 1C). In contrast, no significant findings were noted in the left eye on funduscopy, fluorescein angiography or indocyanine green angiography. SD-OCT of the right eye revealed a disrupted external limiting membrane (ELM) and IS/OS lines in the foveal region (Figure 2A). There was no evidence of systemic inflammation (normal erythrocyte sedimentation rate and C-reactive protein levels). No therapy was administered.

Figure 1.

Fundus images of the right eye of Patient 1 (A–D) and the left eye of Patient 2 (E–G). Fundus photograph showing foveal granularity and scattered yellow-white spots in the posterior pole (A). Early phase fluorescein angiographic image showing small hyperfluorescent retinal spots (B). Late-phase indocyanine green angiographic image showing numerous hypofluorescent spots throughout the posterior pole (C). Fundus photograph showing that the foveal granularity and yellow-white spots had disappeared at five weeks after the initial visit (D). Fundus photograph showing foveal granularity and faint, scattered, yellow-white spots in the posterior pole (E). Early phase fluorescein angiographic image showing small hyperfluorescent retinal spots (F). Fundus photograph showing that the foveal granularity and yellow-white spots had disappeared one month after the initial visit (G).

Figure 2.

Horizontal scan images (6.0 mm) of spectral-domain optical coherence tomography (SD-OCT) of the right eye of Patient 1 (A and C) and the left eye of Patient 2 (B and D). The SD-OCT images reveal a disrupted external limiting membrane (ELM) and photoreceptor inner segment/outer segment junction (IS/OS) lines in the foveal region (A) and a disrupted IS/OS line in the foveal region (B) in the acute phase. The asterisks indicate dilated choroidal stromal vessels (A and B). The SD-OCT images show restoration of the ELM line and IS/OS lines at the final visit (345 days after the initial visit) (C) and restoration of the IS/OS line at the final visit (133 days after the initial visit) (D) in the convalescent phase. The arrowheads indicate the choroid/sclera junction (A–D). The double-headed arrows indicate subfoveal choroidal thickness (A and B). The subfoveal choroidal thickness markedly decreased from 337 µm (A) to 249 µm (C) in Patient 1 and from 440 µm (B) to 358 µm (D) in Patient 2.

Five weeks after the initial visit, VA had recovered to 1.0, all evidence of foveal granularity and yellow-white spots had disappeared (Figure 1D) and the ELM and IS/OS lines had been restored without therapy. At the final visit (345 days after the initial visit), VA was 1.2 and ELM and IS/OS lines in the right eye were preserved (Figure 2C).

Patient 2

A 16-year-old female Japanese patient with a history of familial hypercholesterolaemia and simvastatin treatment was referred to our hospital three days after complaining of blurred vision in the right eye. She reported flu-like symptoms seven days before the initial visit. On initial examination, VA was 1.2 (-3.00 DS) in the right eye and 0.8 (-3.00 DS) in the left eye. No significant findings were observed in the anterior segment or vitreous of either eye. Funduscopy revealed foveal granularity and faint, scattered, yellow-white spots in the posterior pole in the left eye (Figure 1E). While early phase fluorescein angiography in the left eye showed small hyperfluorescent retinal spots (Figure 1F), the right eye appeared normal on funduscopy or fluorescein angiography. SD-OCT in the left eye revealed a disrupted IS/OS line in the foveal region (Figure 2B). There was no evidence of systemic inflammation and no therapy was administered.

Subjective visual improvement was reported within several days from the onset of the symptom. VA recovered to 1.2 six days after the initial visit, and after one month the foveal granularity and yellow-white spots had disappeared entirely (Figure 1G) and the IS/OS line was restored. At the final visit (133 days after the initial visit), VA was 1.5 and the IS/OS line in the left eye was found to be preserved (Figure 2D). The simvastatin treatment has been continued during the follow-up period.

Assessment of subfoveal choroidal and central retinal thickness

In Patient 1, while the subfoveal choroidal thickness at the initial visit (acute phase) was 337 µm in the affected right eye (Figures 2A and 3A), this thickness markedly decreased to 249 µm at 133 days after the initial visit (convalescent phase) and measured 243 µm on the final visit (345 days after the initial visit) (Figure 3A). The subfoveal choroidal thickness in the opposite left eye also decreased over the course of follow up, from 277 µm to 241 µm (Figure 3A).

Figure 3.

Changes in subfoveal choroidal thickness (A and B) and central retinal thickness (C and D) during the follow-up period for Patients 1 (A and C) and 2 (B and D). In Patient 1, the subfoveal choroidal thickness at the initial visit (day zero, acute phase) in the right eye was 337 µm (A), markedly decreased to 249 µm (day 133, convalescent phase) and was 243 µm at the final visit (Day 345) (A). The thickness in the left eye (asymptomatic opposite eye) also decreased from 277 µm (day zero) to 241 µm (day 345) (A). Similarly, in Patient 2, the subfoveal choroidal thickness at the initial visit (day zero, acute phase) in the left eye was 440 µm (B) and markedly decreased to 358 µm at the final visit (day 133, convalescent phase) (B). The thickness in the right eye (asymptomatic opposite eye) also decreased from 382 µm (day zero) to 331 µm (day 133) (B). No changes were noted in central retinal thickness for either eye of Patients 1 (C) or 2 (D) during the follow-up period.

Similarly, in Patient 2, the subfoveal choroidal thickness at the initial visit (acute phase) was 440 µm in the affected left eye (Figures 2B and 3B) but markedly decreased to 358 µm at the final visit (133 days after the initial visit, convalescent phase) (Figures 2D and 3B). The subfoveal choroidal thickness in the opposite eye (RE) also decreased, from 382 µm to 331 µm (Figure 3B).

In both patients, the choroidal stromal vessels in the acute phase (Figures 2A and 2B) were more dilated than in the convalescent phase (Figures 2C and 2D); however, no change was noted in the central retinal thickness of either eye of either patient (Figures 3C and 3D for Patients 1 and 2, respectively) during the follow-up periods.

DISCUSSION

Here, we report new SD-OCT findings in two patients with MEWDS. The subfoveal choroidal thickness in patients during the acute phase was considerably thicker than in the convalescent phase, not only in the affected eye but also in the asymptomatic opposite eye. In addition, thickness during the acute phase was thicker in the affected eye than in the opposite eye in both patients.

Although the aetiology of MEWDS is not well understood, fluorescein angiographic and electrophysiological studies have suggested that this inflammatory disease affects the retinal pigment epithelium and outer retina. Subsequently, several reports have suggested that the numerous hypofluorescent spots noted on ICGA are likely to be due to hypoperfusion of the choriocapillaris, making the disease primary inflammation of the choriocapillaris.11,12 Schaal and colleagues13 reported a single case of simultaneous appearance of MEWDS and multifocal choroiditis, suggesting a possible common causal entity.

In contrast to indocyanine green angiographic findings, recent SD-OCT studies have noted no abnormalities in the retinal pigment epithelial layer or choroid in MEWDS patients,8,9 although choroidal thickness has not been compared between the acute and convalescent phases. SD-OCT findings for affected eyes in the present study revealed a marked decrease in subfoveal choroidal thickness from the acute phase without therapy in both patients after four or more months (Figures 2 and 3). A recent study described electroretinographic and SD-OCT findings in seven patients with MEWDS,7 noting that the choroidal thickness and the choroidal stromal vessels in the convalescent phase (four months after the initial visit) appeared to be reduced over values in the acute phase in at least one (Patient 1 in Figure 27) of the seven patients, although the authors did not explicitly mention choroidal thickness.7 The SD-OCT findings in our two patients showed greater dilation in the choroidal stromal vessels during the acute phase (Figures 2A and 2B) compared with the convalescent phase (Figures 2C and 2D), suggesting that choroidal thickening might be due to dilation of the choroidal stromal vessels. These present and previous findings suggest that in addition to a disrupted IS/OS line, choroidal thickening might be a feature of the acute phase of MEWDS (Figures 2A and 2B).7–9

Marked increases in choroidal thickness can be observed in patients with Vogt–Koyanagi–Harada (VKH) disease14 or central serous chorioretinopathy (CSC).15,16 VKH disease is a bilateral granulomatous uveitis, in which the target of the inflammatory reaction is located within the choroidal stroma, making the disease primary stromal choroiditis.17 While the increased choroidal thickness in VKH disease might be related to inflammatory infiltration or increased exudation,14 the thickening in central serous chorioretinopathy, which is characterised by an idiopathic and mostly unilateral serous retinal detachment in the posterior pole,18 has been confirmed to be due to choroidal vascular hyperpermeability.15,16 While typically seen in patients with VKH or CSC, no leakage or hyperpermeability of choroidal stromal vessels is noted with indocyanine green angiography in the acute phase of MEWDS;12,19 however, several studies4,20 of MEWDS patients have reported focal segmental staining of choroidal vessels and discrete nodular hyperfluorescent areas in the inner choroid with ICGA. Taken together, these findings suggest that an inflammatory reaction might also occur at the level of the choroidal stroma in addition to the choriocapillaris.

In most patients with MEWDS, recovery of visual function occurs within several weeks.19 Interestingly, Patient 2, who had simvastatin treatment, reported a more rapid improvement in both symptoms and visual acuity. Simvastatin belongs to the class of cholesterol-lowering statins. It has been proposed that statins have anti-inflammatory effects that are not directly related to their cholesterol-lowering activity.21,22 Although anti-inflammatory effects of statins have not been demonstrated in inflammatory choroidal disease, the rapid visual improvement in Patient 2 might be associated with simvastatin treatment.

Explaining why choroidal thickening was observed even in the asymptomatic opposite eyes in the present study is difficult (Figures 3A and 3B). A recent study7 observed that five of seven patients with unilateral MEWDS manifested visual field abnormalities in both eyes, not just the affected eyes, during the acute phase, suggesting that visual dysfunction is bilateral in most patients. Given these present and previous findings, the inflammatory reaction in MEWDS might occur bilaterally more often than unilaterally, even though the condition is believed to be unilateral in most patients.

In conclusion, this is the first report to describe the relationship between subfoveal choroidal thickness and MEWDS. We noted the previously unreported finding that choroid thickness was greater in the acute phase than in the convalescent phase in both eyes, not just the affected eyes, suggesting that an inflammatory reaction might occur in the choroidal stroma in addition to the choriocapillaris. Because our findings were derived from only two patients, further study is needed to determine the presence of choroidal thickening in other patients with MEWDS.

GRANTS AND FINANCIAL SUPPORT

This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant-in-Aid for Scientific Research) (TH), The Jikei University Research Fund (TH) and the Vehicle Racing Commemorative Foundation (TH and HT).

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