Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations.

Purpose: The purpose of this study was to investigate structure-function correlations in multiple evanescent white dot syndrome (MEWDS) using microperimetry (MP) and spectral-domain optical coherence tomography (SD-OCT). Methods: Single-center prospective observational study including 14 eyes from 13 patients with MEWDS monitored over a median of 49.5 days (interquartile range = 29-92 days). Investigations focused on best-corrected visual acuity (BCVA), foveal granularity, and the Photoreceptor Reflectivity Ratio (PRR) as a measure of photoreceptor integrity. MP assessed average retinal threshold sensitivity (RTS) and bivariate contour ellipse area (BCEA) for fixation stability. A linear mixed model was used to test associations and interactions among RTS, time, and clinical variables. A hierarchical linear mixed model was used to analyze structure-function relationships, addressing both individual and location-specific variations. Results: Overall, 2340 MP locations were tested. PRR revealed a transient decrease within 30 days post-presentation, indicative of early photoreceptor disruption, followed by a progressive increase, signaling recovery. Significantly lower foveal sensitivity (RTS = 14.8 ± 7.4 vs. 22.5 ± 4.4 decibel [dB], P = 0.04) and increased fixation spread (63% BCEA = 1.26 ± 0.97 vs. 0.48 ± 0.35 deg2, P = 0.06) were noted in eyes with foveal granularity compared to those without. A significant increase in RTS was demonstrated over time (0.066 dB/day, P < 0.001), with a central-to-peripheral gradient of improvement. The interaction between follow-up time and baseline BCVA (P < 0.001) indicated more rapid improvement in eyes with worse initial vision. There was a robust, nonlinear association between PRR and RTS across all tested locations (P < 0.001), becoming asymptotic for sensitivity losses exceeding 20 dB. Conclusions: Photoreceptor reflectivity accurately aligned with visual function in MEWDS on longitudinal examinations. The central-to-peripheral gradient of improvement may suggest specific vulnerabilities underlying the area around the disc.

The characteristics of white dot syndromes following COVID-19 Vaccines: a systematic review.

PURPOSE: To review all studies reporting the onset of white dot syndromes following COVID-19 vaccines. METHODS: Our protocol was registered prospectively on PROSPERO [registration number: CRD42023426012]. We searched five different databases including PubMed, Scopus, Web of Science, Google Scholar, and Science Direct up to May 2023. All the studies that reported the occurrence of white dot syndrome following COVID-19 vaccines were included. All statistical tests were conducted with a 95% confidence interval and a 5% error margin. A p value of less than 0.05 was considered statistically significant. The methodological quality of included studies was performed using the IHE Quality Appraisal Checklist for Case Series studies and JBI Critical Appraisal Checklist for Case Reports. RESULTS: Fifty studies involving seventy-one subjects were included. Multiple evanescent white dot syndrome (MEWDS) was the most common disease (n = 25, 35.2% %), followed by acute macular neuroretinopathy (AMN) (n = 22, 31.0%) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 4, 5.6%). They were mostly unilateral (n = 50, 70.4%). The presenting symptoms were blurred vision (n = 26, 36.6%), paracentral scotoma (n = 19, 26.8%), visual field disturbance, and photopsia (n = 7, 9.9%). The mean duration for follow-up was 10.15 ± 14.04 weeks. Nineteen subjects (29.69%) received steroids with improvement reported in 68.4%. Eleven subjects (17.19%) were managed by observation only with reported full recovery and improvement. CONCLUSION: White dot syndromes are very rare entities. Our findings highlight a possible association between COVID-19 vaccines and the occurrence of white dot syndromes. However, larger studies with good quality should be implemented to confirm these findings.

Atypical multiple evanescent white dot syndrome presenting with peripheral retinal lesions.

Multiple evanescent white dot syndrome (MEWDS) is a rare inflammatory eye condition. We report an atypical case of MEWDS in a man in his 30s who presented with blurred vision (visual acuity 6/9), floaters and photopsia in his left eye. Funduscopy examination showed mild peripheral nasal vascular sheathing with subtle grey-white dots highlighted on fundus autofluorescence. As far as the authors are aware, this is the first case presentation whereby areas affected by MEWDS started in the peripheral retina and migrated centrally. Fluorescein angiography showed hyperfluorescent areas in wreath-like patterns nasally. Optical coherence tomography showed disruption of the ellipsoid zone and hyperreflective projections into the outer nuclear layer. The size of the involved area increased over 3 weeks and subsequently resolved over 4 months. Simultaneously, the patient's symptoms also resolved, without treatment. This case highlights the importance of multimodal imaging, especially ultrawidefield imaging in diagnosing MEWDS.

A COVID-19 perspective of multiple evanescent white dot syndrome (MEWDS).

Multiple evanescent white dot syndrome (MEWDS) is a rare form of posterior uveitis characterized by involvement in the posterior pole and mid-periphery. A viral etiology that provokes an immune-mediated response has been hypothesized to be the inciting factor of the pathology. Recently, there has been an increase in the literature regarding new-onset uveitis and reactivation of previously diagnosed cases of uveitis following COVID-19 vaccinations. The COVID-19 vaccination has been speculated to trigger an immunomodulatory shift in recipients, resulting in an autoimmune event. MEWDS following COVID-19 vaccination was reported in 31 patients. It was most commonly observed following the first dose, affecting 15 patients, and least commonly after the booster dose, in only one patient. MEWDS-like disease following anti-SARS-CoV-2 vaccinations was reported the most in 16 cases after the Pfizer-BioNTech vaccination (BNT162b2 mRNA). Most of these cases had Primary MEWDS without any previous history of a similar event in the past.

Punctate inner choroidopathy: A review of the current diagnostic and therapeutic approaches.

Punctate inner choroidopathy (PIC) is an uncommon idiopathic inflammatory condition characterized by multifocal chorioretinopathy that primarily affects young adults, with a predilection for myopic females. Clinically, it manifests as small, yellowish-white lesions in the inner choroid and outer retina, often associated with inflammatory changes. Accurate diagnosis remains a challenge due to its resemblance to other posterior uveitic entities, necessitating an astute clinical eye and advanced imaging techniques for differentiation. Multimodal imaging plays a crucial role by offering valuable insights, as it enables the visualization of various abnormalities related to uveitis. The pathogenesis of PIC is still a subject of debate, with a complex interplay of genetic, immunological, and environmental factors proposed. Managing PIC presents multiple challenges for clinicians. Firstly, variable disease severity within and among patients requires diverse treatments, from observation to aggressive immunosuppression and/or anti-VEGF therapy. Secondly, treatment must distinguish between primary causes of vision loss. New or worsening PIC lesions suggest active inflammation, while new neovascular membranes may indicate secondary neovascular processes. Thirdly, deciding on maintenance therapy is complex, balancing PIC prognosis variability against immunosuppression risks. Some patients have long periods of inactivity and remission, while others face sudden, vision-threatening episodes during quiescent phases. Through a systematic review of the literature, this paper sheds light on the current understanding of PIC, its challenges, and the prospects for future research. By synthesizing existing knowledge, it aims to aid clinicians in accurate diagnosis and guide treatment decisions for improved visual outcomes in individuals affected by PIC.

Unilateral acute posterior multifocal placoid pigment epitheliopathy (APMPPE) with delayed contralateral eye involvement.

BACKGROUND: Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare presumed inflammatory chorioretinopathy characterized by creamy, yellow-white placoid lesions at the level of the retinal pigment epithelium (RPE). Unilateral cases often have fellow eye involvement within days to a few weeks. This report details a rare case of delayed contralateral APMPPE, in which unilateral lesion resolution was followed by contralateral eye involvement 31 months later. CASE PRESENTATION: A 38-year-old woman presented with three days of blurry vision and photopsias in the right eye (OD). She endorsed a viral GI illness one month prior. Visual acuity was 20/25 -2 OD and 20/20 -1 in the left eye (OS). Examination revealed creamy, yellow-white placoid lesions in the posterior pole. Fluorescein angiography (FA) was notable for early hypofluorescence and late hyperfluorescence of the lesions, consistent with APMPPE. MRI and MRA brain were negative for cerebral vasculitis. She was treated with oral prednisone with complete resolution of her symptoms, vision, and lesion regression. She then presented 31 months later, with blurry vision OS and similar new creamy, yellow-white placoid lesions in the posterior pole OS. She endorsed receiving an influenza vaccine one month prior. FA again was notable for early hypofluorescence. She was diagnosed with APMPPE, this time involving the left eye, and was once again started on oral steroids with complete resolution. She denied any neurologic symptoms. CONCLUSIONS: APMPPE is an inflammatory vasculitis of the choroid, leading to hypoperfusion and ischemic injury of the RPE with subsequent lesion formation. APMPPE may be preceded by a viral prodrome or vaccination, both of which were seen in this case. Choroidal inflammation seen in APMPPE is therefore thought to stem from immune-mediated processes. Unilateral cases often have fellow eye involvement within days to a few weeks. Single eye involvement with delayed contralateral presentation, as seen in our patient, is rare. This case demonstrates that lesion resolution in one eye can be followed by contralateral eye involvement up to 31 months later, highlighting the importance of routine ophthalmic monitoring for patients with unilateral APMPPE.

The characteristics of acute macular neuroretinopathy following COVID-19 infection.

BACKGROUND: In this study, we report a case series of acute macular neuroretinopathy (AMN) associated with COVID-19 infection. METHODS: This retrospective observational study was conducted at Beijing Tongren Hospital. We reviewed patients who were diagnosed with AMN within one month of testing positive for COVID-19 using real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A total of 11 AMN patients (20 eyes) were included in the study. The mean age was 33.8 ± 12.6 years. The average interval between a positive COVID-19 PCR test and the onset of ocular symptoms was 2.8 ± 2.5 days. The mean follow-up period for the patients was 12.5 ± 3.8 weeks. Imaging characteristics of AMN patients following COVID-19 infection included areas of low reflectivity on near-infrared reflectance (NIR) imaging, hyperreflective lesions at the level of the outer plexiform layer (OPL) and outer nuclear layer (ONL) and disruption of the ellipsoid zone (EZ) on spectral domain optical coherence tomography (SD-OCT) B-scans. Visual field examinations revealed parafoveal scotomas that closely corresponded to the clinical lesions. Optical coherence tomography angiography (OCT-A) demonstrated impaired perfusion in the deep retinal vascular plexus. Fluorescein angiography (FA), indocyanine green angiography (ICGA), and spontaneous fundus autofluorescence showed no significant abnormalities. During follow-up, partial improvement in retinal lesions was observed in NIR imaging and SD-OCT in some patients, but a proportion of patients still exhibited persistent retinal damage and no improvement in visual field scotomas. CONCLUSION: COVID-19-related AMN share similar clinical and imaging features with AMN due to other causes, as evidenced by the persistent presence of visual field scotomas over a longer duration. TRAIL REGISTRATION: https://www.chictr.org.cn/ ; identifier: ChiCTR2100044365.

The multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy lesion with multiple evanescent white dot syndrome-like features: a retrospective study.

BACKGROUND: Multiple evanescent white dot syndrome (MEWDS)-like features is a rare condition triggered by a macular disease or iatrogenic injury, exhibiting MEWDS changes in the fundus. This study aims to describe the multimodal imaging features and outcomes of multifocal choroiditis/punctate inner choroidopathy (MFC/PIC) lesions with MEWDS-like features. METHODS: Six cases were studied retrospectively. All cases were given regional and oral corticosteroids. RESULTS: All cases showed an isolated juxtafoveal yellowish-white MFC/PIC lesion with disruption of RPE-Bruch's membrane-choriocapillaris complex (RPE-BM-CC), subretinal hyperreflective materials and choroidal thickening on optical coherence tomography. Two weeks after presentation, the grayish-white dots disappeared spontaneously and the corticosteroids were given. After four weeks, the ellipsoid zone (EZ) around the lesion and hyper-autofluorescence resolved. After 13 weeks, five cases showed shrinkage of the juxtafoveal lesion and restoration of foveal EZ. After six months, the juxtafoveal lesion became pigmented. Only one case developed type 2 choroidal neovascularization. CONCLUSIONS: The clinical course of MEWDS-like manifestations is still evanescent in our cases. The yellowish-white juxtafoveal MFC/PIC lesions with disruption of RPE-BM-CC and choroidal thickening showed a well-controlled prognosis after corticosteroid treatment.

Acute posterior multifocal placoid pigment epitheliopathy: clinical presentation and risk of stroke and transient ischaemic attack.

BACKGROUND/AIMS: Acute posterior multifocal placoid pigment epitheliopathy is a rare but important disease that can be associated with life-threatening complications due to cerebral vasculitis. The primary objective was to determine the incidence of neurological complications and risk factors for stroke and transient ischaemic attack (TIA) associated with acute posterior multifocal placoid pigment epitheliopathy. Secondary objectives included the clinical presentation, visual outcomes and recurrence rates. METHODS: This was a multicentre retrospective case series including 111 eyes from 60 subjects presenting from January 2009 to June 2020. RESULTS: Median age at presentation was 29 years (IQR 24.7-35.1) and 36 subjects (60.0%) were male. 20 subjects (33.3%) reported a viral prodrome. Stroke and TIA were observed in seven subjects (11.7%). Older age was the only significant risk factor for stroke/TIA (p=0.042). Vision loss occurred in seven eyes, with four eyes (3.6%) having final visual acuity 6/15-6/60 and three eyes (2.7%) having visual acuity of 6/60 or worse. Recurrence occurred in 10 subjects (16.7%). CONCLUSIONS: The presence of headache cannot reliably predict those at risk of stroke/TIA. Individuals presenting with acute posterior multifocal pigment epitheliopathy should therefore undergo a clinical neurological review and work-up for cerebral vasculitis as deemed appropriate by the treating ophthalmologist and collaborating neurologist.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy: A Rare Presentation of Anklylosing Spondylitis or a Paradoxical Reaction to Secukinumab?

PURPOSE: To describe an atypical presentation of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) in a patient with ankylosing spondylitis (AS) receiving secukinumab. METHODS: Retrospective chart review. RESULTS: A 48-year-old female patient with AS receiving secukinumab complained of impaired vision in her left eye. Left eye examination revealed multiple yellow-white lesions at the posterior pole and central subfoveal fluid.The lesions regressed without scarring. The case was diagnosed with clinically APMPPE. CONCLUSION: In AS patients, posterior uveitis can manifest as APMPPE. It should be recorded as an entity to be considered in the differential diagnosis.

Bilateral Acute Macular Neuroretinopathy (AMN) after COVID-19 and its Clinical Course. / Bilaterale akute makuläre Neuroretinopathie (AMN) nach COVID-19 und Verlauf.

Acute macular neuroretinopathy (AMN) is a rare disease entity. It is mainly observed in young women with a history of influenza-like infection or who have been taking oral contraceptives for several years. Patients typically describe subjective visual deterioration and mono- or bilateral paracentral relative scotomas. In some cases, funduscopic ophthalmic examination may reveal subtle sharply demarcated flat lesions of reddish-brown or orange colour in the macular region. Diagnosis is usually made by near-infrared fundus imaging which shows hyporeflective areas, and SD-OCT imaging which manifests changes in the outer retinal layers. In the following, three patient cases with bilateral AMN are described which occurred in direct temporal relationship to a recent SARS-CoV-2 infection.

Choroidal neovascularization and MEWDS like reaction in a child: A rare case.

PURPOSE: To report a case of choroidal neovascularization (CNV) associated with Multiple Evanescent White Dot Syndrome (MEWDS) in a child. STUDY DESIGN: Case report. RESULTS: A 13-year-old child visited us with a month-long history of blurred vision in his right eye. His right fundus showed several subretinal white dots and an atrophic macular lesion corresponding to a CNV. Angiography and optical coherence tomography (OCT) were consistent with the diagnosis of MEWDS. The patient's condition poorly improved after an intravitreal injection of anti-vascular endothelial growth factor (anti VEGF) in his right eye. CONCLUSIONS: We reported the case of CNV associated with MEWDS like reaction. The hypothesis of a triggered-MEWDS was highly suspected but no cause was found, which is often the case in paediatric inflammatory eye disorders. Long-term follow-up is needed to judge the evolution.

MULTIPLE EVANESCENT WHITE DOT SYNDROME FROM A PATIENT'S PERSPECTIVE.

PURPOSE: Multiple evanescent white dot syndrome is a self-limiting inflammatory condition of the outer retina. Only little information is available how patients experience their symptoms. METHOD: We report a case of a 28-year-old male graphic designer with multiple evanescent white dot syndrome, who precisely illustrated the development and course of the characteristic symptoms while looking at the ceiling, at a face and on his phone. RESULT: At onset, the scotoma was sparking/shiny and appeared on the temporal field of view, consistent with an enlarged blind spot. Over the course of the disease, the scotoma decreased in intensity and moved superiorly and nasally until it completely faded. CONCLUSION: Illustrations from a patient's perspective over the course of the disease can be beneficial for physicians and other multiple evanescent white dot syndrome patients for a better understanding and monitoring of their disease.

RECONSTITUTION OF THE CHORIOCAPILLARIS IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

PURPOSE: The purpose of this study was to describe findings derived from extensions of optical coherence tomography, including volume rendering and frame-averaged optical coherence tomography angiography (OCT-A), in a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE). METHODS: This is a case report of a patient with APMPPE imaged during the acute and convalescent stages. RESULTS: A 20-year-old man presented with an acute change in vision. He had multiple yellow-white placoid lesions at the level of the retinal pigment epithelium in the macula and nasal to the optic nerve in both eyes. Within 2 weeks, his visual acuity worsened to 20/80 and 20/400 in the right and left eyes, respectively. Spectral domain OCT showed focal defects in the ellipsoid and retinal pigment epithelium layers. Volume-rendering OCT-A showed inflammatory cells in the outer nuclear layer above the APMPPE lesion. Frame-averaged OCT-A revealed significant loss of capillary flow signal within capillary segments of the choriocapillaris. Ten weeks after presentation, there was resolution of the placoid changes, discontinuance of the inflammatory infiltrate in the outer nuclear layer, and significant reconstitution of flow in the choriocapillaris. The visual acuity was 20/20 in both eyes. CONCLUSION: Novel volume-rendered and frame-averaged OCT-A images in a patient with APMPPE allowed detection of inflammatory cell infiltrate in the outer nuclear layer and reversible capillary segment nonperfusion of associated APMPPE lesions. The findings suggest short-term insults to choriocapillaris function may be reversible and can be tracked with modern imaging techniques.