White Dot Syndrome in Patients with Prior Ocular Toxoplasmosis

Multiple evanescent white dot syndrome (MEWDS) was first described in 1984 by Jampol et al. [1] It is characterized by unilateral diminished vision and enlargement of the blind spot and has a predilection for young, healthy, myopic females. Retinal findings include macular granularity, multifocal, small white lesions concentrated in the paramacular, peripapillary, and midperipheral fundus, as well as posterior vitreous cells [2]. Recent studies have shown that MEWDS affects predominantly the outer retina, centered at the ellipsoid zone (EZ) and interdigitation zone (IZ), with some changes extending into the outer nuclear layer (ONL) [2]. The pathogenesis of MEWDS is unknown, although an immunemediated process in genetically predisposed individuals has been postulated. Toxoplasmosis is the leading cause of infectious posterior uveitis in the world, accounting for 80% of cases in some regions [3]. Although toxoplasmosis chorioretinitis usually has a self-limited course, it can lead to irreversible visual loss, particularly when the macula and op-tic nerve are involved. In 2011, Vance et al. reported a unilateral white dot syndrome occurring in a healthy 27-year-old woman 1 month after documented resolution of recurrent toxoplasmosis chorioretinitis involving the same eye [4]. Herein, we report 2 similar patients with retinal findings resembling MEWDS in eyes with evidence of prior ocular toxoplasmosis.


Introduction
Multiple evanescent white dot syndrome (MEWDS) was first described in 1984 by Jampol et al. [1] It is characterized by unilateral diminished vision and enlargement of the blind spot and has a predilection for young, healthy, myopic females. Retinal findings include macular granularity, multifocal, small white lesions concentrated in the paramacular, peripapillary, and midperipheral fundus, as well as posterior vitreous cells [2]. Recent studies have shown that MEWDS affects predominantly the outer retina, centered at the ellipsoid zone (EZ) and interdigitation zone (IZ), with some changes extending into the outer nuclear layer (ONL) [2]. The pathogenesis of MEWDS is unknown, although an immunemediated process in genetically predisposed individuals has been postulated. Toxoplasmosis is the leading cause of infectious posterior uveitis in the world, accounting for 80% of cases in some regions [3]. Although toxoplasmosis chorioretinitis usually has a self-limited course, it can lead to irreversible visual loss, particularly when the macula and op-tic nerve are involved. In 2011, Vance et al. reported a unilateral white dot syndrome occurring in a healthy 27-year-old woman 1 month after documented resolution of recurrent toxoplasmosis chorioretinitis involving the same eye [4].
Herein, we report 2 similar patients with retinal findings resembling MEWDS in eyes with evidence of prior ocular toxoplasmosis.

Case Report-1
A 25-year-old healthy woman complained of floaters and photopsia in her right eye (OD) for 2 days. As a child, she was diagnosed with ocular toxoplasmosis in both eyes (OU) and had received treatment for several recurrences of active chorioretinitis OD. Visual acuity in her left eye (OS) had always been poor. On examination, best-corrected visual acuity (BCVA) was 20/30 OD and counting fingers at 3 meters OS. Anterior segment examination was normal OU with no cell or flare detected. Intraocular pressures were 14 mmHg OU. Ophthalmoscopy OD showed inactive peripheral chorioretinal scars and a small deep white lesion with ill-defined margins located superotemporal to the fovea ( Figure   1). Ophthalmoscopy OS revealed inactive chorioretinal scars in the macula and peripheral retina ( Figure 1). No vitreous cells were noted OU. Given concern regarding a possible recurrence of toxoplasmosis chorioretinitis OD, the patient was start-ed on a 6-week course of BID oral sulfamethoxazole/trimethoprim (800mg/160mg). Five days later, she returned complaining of worsening of vision OD. BCVA was 20/50 OD.      there was an initial concern regarding early reactivation of ocular toxoplasmosis [4]. Similar to this prior case, both of our patients were treated with oral anti-toxoplasma therapy. Our first patient was also treated with oral corticosteroids. A diagnosis of punctate outer toxoplasmosis (PORT) was considered, since multifocal graywhite lesions at the level of the deep retina and retinal pigment epithelium have been described with this entity.
However, the 2 cases herein reported presented with findings that were more widespread than the lesions described with PORT. Minimal retinal pigment epithelium involvement and the absence of persistent retinal pigment epithelium changes or new scars following resolution were also inconsistent with PORT.
Furthermore, while the initial descriptions of PORT occurred prior to the availability of high-resolution OCT, a recent study has shown that both inner and outer retinal involvement occur, as well as punctate preretinal hyperreflective lesions [5], which were not present in our cases. We admit that treatment could have altered the course of our patients' disease. Previous studies have shown that MEWDS can present after the primary occurrence or recurrence of choroidal neovascularization [6]. Whether choroidal  [7] or systemic viral infection [8], thus an immune-mediated process in genetically predisposed individuals is strongly suggested.
It is possible that toxoplasmosis may trigger a white dot syndrome by means of a local immune-mediated process induced by the parasite. One interesting aspect of both cases was the predilection for the white dots to occur near the old chorioretinal scars. This pattern was particularly evident on FAF of Case n.2.
In the acute phase of MEWDS, FAF demonstrates: (1) multiple, small (< 50 µm) auto-hypofluorescent areas in the posterior pole and (2) areas of increased autofluorescence corresponding to white dots seen on ophthalmoscopy [9]. In the case n.2, we noted multiple hypo-autofluorescent dots around the chorioretinal scars, the optic disc head and near the inferotemporal vascular arcade.

Summary Statement
The authors report 2 cases of retinal findings resembling MEWDS occurring in eyes with evidence of prior ocular toxoplasmosis. Further study is needed to determine if this rare, but previously reported white dot syndrome, is causally related to the presence of prior ocular toxoplasmosis or merely a coincidental occurrence.