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.

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.

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.

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.

Presumed Müller Cell Activation in Multiple Evanescent White Dot Syndrome.

Purpose: The purpose of this study was to investigate the foveal changes occurring in multiple evanescent white dot syndrome (MEWDS) using multimodal imaging techniques with a specific focus on hyper-reflective dots (HRDs). Methods: This was a retro-prospective observational study including 35 eyes with active MEWDS. Structural and en face optical coherence tomography (OCT) was performed, with follow-up visits at 2 weeks, 6 weeks, and 2 months from baseline. HRD percentage area (HRD % area) was calculated in a 600 µm fovea centered circle on en face OCT, after background subtraction and image binarization. HRD % area was compared with 23 fellow control eyes. Longitudinal changes in the HRD % areas were assessed using repeated-measure statistics. Results: HRDs were observed as scattered hyper-reflective spots on the vitreoretinal interface on en face OCT images, colocalizing with HRDs or vertical hyper-reflective lines on structural OCT images. The baseline evaluation showed a significantly higher HRD % area in MEWDS eyes compared to fellow eyes (0.10 ± 0.03 vs. 0.08 ± 0.04, P = 0.01). The HRD % area correlated positively with LogMAR visual acuity and inversely with the duration of symptoms. Longitudinal analysis revealed a significant reduction in the HRD % area over time. There was no significant interaction between the rate of HRD disappearance and clinical or demographic factors at baseline. Conclusions: As HRD potentially represents the end-feet projections of activated Müller cells on the retinal surface, this study supports the involvement of Müller cells in the pathogenesis of the disease. The findings highlight the potential of en face OCT imaging for monitoring the progression of MEWDS.

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

PURPOSE: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

A Case of Acute Zonal Occult Outer Retinopathy in which Oct en Face Imaging Was Useful for Diagnosis and Follow-up.

A 23-year-old woman presented with a 1-month history of visual abnormalities in her right eye. A visual field test revealed temporal abnormalities in the right eye. Optical coherence tomography revealed an indistinct ellipsoid zone (EZ) on the B-scan image and hyporeflective areas in the EZ layer on the en face image in the right eye. We diagnosed the patient with acute zonal occult outer retinopathy. Visual field tests and B-scan images improved to almost normal at 6 months, but hyporeflective areas remained on the en face images. Thus, en face images may be more sensitive at detecting abnormalities in the outer retina than other modalities.

Latest advances in white spot syndromes: New findings and interpretations.

White spot syndromes (WSS) pose challenges in the field of ophthalmology, particularly in terms of accurate diagnosis and effective management. However, recent advancements in multimodal imaging (MMI) have significantly contributed to our understanding of WSS, allowing for improved characterization of these inflammatory chorioretinopathies. By employing various imaging modalities, including fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, optical coherence tomography (OCT), ultra-widefield imaging, and OCT angiography, researchers and clinicians have gained valuable insights into the underlying pathophysiological changes and clinical progression of WSS. Furthermore, MMI has unveiled novel and atypical variants within the spectrum of WSS, expanding our knowledge in this field. Notably, the identification of secondary forms of WSS occurring concurrently with unrelated chorioretinal disorders has suggested a potential autoimmune mechanism underlying these conditions. The introduction of MMI has also facilitated a more comprehensive evaluation of previously ill-defined entities, such as acute zonal occult outer retinopathy, leading to improved diagnostic criteria and enhanced recognition of distinct features. This review paper provides a comprehensive overview of the latest advances and interpretations in WSS. By integrating MMI into the diagnosis and management of these conditions, this review aims to enhance patient outcomes and provide valuable insights into the complexities surrounding WSS.

A Case of Concurrent Acute Macular Neuroretinopathy and Paracentral Acute Middle Maculopathy Following Pfizer-BioNTech COVID-19 Vaccination.

We present a 65-year-old woman who developed sudden and severe vision loss in her left eye one day after the administration of the second dose of COVID vaccine. The best corrected visual acuity in this eye was 1/10. Diffuse paracentral acute middle maculopathy was detected on spectral domain optical coherence tomography (OCT). OCT angiography images revealed concurrent vascular flow defects consistent with acute macular neuroretinopathy in the deep retinal capillary plexus and choriocapillaris layers. At the end of the six-month follow-up, there was no improvement in visual acuity, and atrophy and thinning developed in all layers of the retina.

[Acute posterior multifocal placoid pigment epitheliopathy, serpiginous choroiditis and related diseases]. / Épithéliopathie en plaque, choroïdite serpigineuse et leurs formes frontières.

Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE) and serpiginous choroiditis are two diseases classified as "white spot syndromes." Both are inflammatory/autoimmune diseases with suspected primary involvement of the choriocapillaris. The former usually has an excellent prognosis, while the latter can rapidly induce legal blindness. Whereas these diseases are well defined and well known, other entities (such as persistent placoid maculopathy or ampiginous choroiditis) with features of both APMPPE and serpiginous choroiditis have been described more recently. This review aims to describe demographic characteristics and multimodal imaging features to help differentiate between these four diseases.

Multiple Evanescent White Dot Syndrome Following Adenovirus Vector-Based COVID-19 Vaccine (Covishield).

PURPOSE: To report a case of multiple evanescent white dot syndrome (MEWDS) following adenovirus vector-based Coronavirus disease 2019 (COVID-19) vaccine, Covishield and to present a summary of previously reported cases of MEWDS following COVID-19 vaccines. METHODS: Retrospective case report and review of literature. RESULTS: A 22-year-old Indian female presented with blurred vision, scotomata, and photopsias in her left eye, a day after administration of second dose of Covishield vaccine. Her clinical findings and imaging features confirmed the diagnosis of MEWDS. Her symptoms resolved spontaneously after 2 weeks. CONCLUSION: This is the first reported case of MEWDS following an adenovirus vector-based COVID-19 vaccine. Comparison with previously reported cases of MEWDS following COVID-19 vaccination showed that patients are generally healthy, young to middle-aged women, who develop symptoms after a median time of one week and recover spontaneously over a median period of 4 weeks.

Topographic patterns of retinal lesions in multiple evanescent white dot syndrome.

PURPOSE: To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations. METHODS: Clinical evaluation and multimodal retinal imaging in 27 subjects with MEWDS (29 discrete episodes of MEWDS). Ophthalmic assessment included best-corrected visual acuity testing and multimodal retinal imaging with OCT, blue-light autofluorescence, fluorescein and indocyanine green angiography, fundus photography, and widefield pseudocolor and autofluorescence fundus imaging. RESULTS: The topographic distribution of MEWDS lesions was centered on or around the optic disc (n = 17, 59%), centered on the macula (n = 7, 24%), sectoral (n = 2, 7%), or was indeterminate (n = 3, 10%). The MEWDS episodes either occurred in the absence ('primary MEWDS'; n = 14, 48%) or presence of concurrent chorioretinal pathology ('secondary MEWDS'; n = 15, 52%). In patients with the latter, MEWDS lesions were often centered around a coexisting chorioretinal lesion. The majority of patients in both groups experienced resolution of their symptoms and retinal changes on multimodal imaging by 3 months. CONCLUSIONS: Distinct distributions of MEWDS lesions were identified. MEWDS may occur in tandem with other chorioretinal pathology, which may impact the topography of MEWDS lesions.