Multiple Evanescent White Dot Syndrome Associated with Coronavirus Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) causes ocular manifestations in approximately 11% of patients. Most patients typically develop ocular symptoms within 30 days of the onset of the first COVID-19 symptoms. The most common ocular manifestation is conjunctivitis, which affects nearly 89% of patients with eye problems. Other much less common anterior segment abnormalities caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are scleritis, episcleritis, and acute anterior uveitis. Posterior segment abnormalities caused by SARS-CoV-2 are mainly vascular, such as hemorrhages, cotton wool spots, dilated veins, and vasculitis. Herein, we report a rare manifestation of COVID-19 and multiple evanescent white dot syndrome (MEWDS) of the retina. In April 2021, a 40-year-old female patient was admitted to the Eye Clinic of Clinical Center of Montenegro (Podgorica, Montenegro). The patient's main complaint was sudden vision impairment, which occurred 14 days after a positive polymerase chain reaction (PCR) test result for SARS-CoV-2 infection. A complete eye examination was performed, followed by fundoscopy, optical coherence tomography (OCT), and fluorescein angiography (FA) tests. The results showed retinal changes associated with MEWDS. The patient underwent additional examinations to rule out common causes of multifocal retinitis, all of which were unremarkable. Therefore, it was concluded that retinitis was a complication of COVID-19. Given its non-invasive nature, fundus examination should be used as a standard screening method for retinal changes in patients with COVID-19.

A case of APMPPE-like panuveitis presenting with extensive outer retinal layer impairment following COVID-19 vaccination (preprint)

Background Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of newly onset uveitis after vaccination have been reported. We report a case of bilateral acute posterior multifocal placoid pigment epitheliopathy-like (AMPPE-like) panuveitis after COVID-19 vaccination in which the patient’s pathological condition was evaluated using multimodal imaging. Case presentation A 31-year-old woman experienced bilateral hyperemia and blurred vision starting 6 days after her second inoculation of the COVID-19 vaccination. At her first visit, her visual acuity was decreased bilaterally, and severe bilateral anterior chamber inflammation and bilateral scattering of cream-white placoid lesions on the fundus were detected. Optical coherence tomography (OCT) showed serous retinal detachment (SRD) and choroidal thickening in both eyes (OU). Fluorescein angiography (FA) revealed hypofluorescence in the early phase and hyperfluorescence in the late phase corresponding to the placoid legions. Indocyanine green angiography (ICGA) showed sharply marginated hypofluorescent dots of various sizes throughout the mid-venous and late phases OU. The patient was diagnosed with APMPPE and was observed without any medications. Three days later, her SRD disappeared spontaneously. However, her anterior chamber inflammation continued, and oral prednisolone (PSL) was given to her. Seven days after the patient’s first visit, the hyperfluorescent lesions on FA and hypofluorescent dots on ICGA partially improved; however, the patient’s best corrected visual acuity (BCVA) dropped to 0.7 OD and 0.6 OS, and the impairment of the outer retinal layer was broadly detected as hyperautofluorescent lesions on fundus autofluorescence (FAF) examination and as irregularity in or disappearance of the ellipsoid and interdigitation zones on OCT, which were quite atypical for the findings of APMPPE. Steroid pulse therapy was performed. Five days later, the hyperfluorescence on FAF had disappeared, and the outer retinal layer improved on OCT. Moreover, the patient’s BCVA recovered to 1.0 OU. Twelve months after the end of treatment, the patient did not show any recurrences. Conclusions We observed a case of APMPPE-like panuveitis after COVID-19 vaccination featuring some atypical findings for APMPPE. COVID-19 vaccination may induce not only known uveitis but also atypical uveitis, and appropriate treatment is required for each case.

Bilateral Optic Nerve Head Drusen Complicated by Choroidal Neovascularization Misdiagnosed as Papilledema and Neuroretinitis.

We report a case of bilateral optic nerve head drusen complicated by choroidal neovascularization (CNV) in the left eye at presentation. The presence of optic disc and macular edema in addition to exudation led to the misdiagnosis of neuroretinitis at an outside medical center. Swept-source optical coherence tomography (SS-OCT) and SSOCT angiography were critical in establishing the diagnosis and follow-up in a noninvasive manner. Secondary CNV associated with optic nerve head drusen responded well to intravitreal injections of anti-vascular endothelial growth factor in the left eye. Asymptomatic nonexudative CNV that developed in the right eye during follow-up regressed spontaneously without treatment. [Ophthalmic Surg Lasers Imaging Retina 2022;53:518-521.].

Post-COVID-19 syndrome: retinal microcirculation as a potential marker for chronic fatigue (preprint)

Post-COVID-19 syndrome (PCS) summarizes persisting sequelae after infection with the severe-acute-respiratory-syndrome-Coronavirus-2 (SARS-CoV-2). PCS can affect patients of all covid-19 disease severities. As previous studies revealed impaired blood flow as a provoking factor for triggering PCS, it was the aim of the present study to investigate a potential association of self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT-Angiography (OCT-A) and quantified by the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic Fatigue (CF) was assessed with the variables Bell score, age and gender. The VD in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed considering the repetitions (12 times). Taking in account of such repetitions a mixed model was performed to detect possible differences in the least square means between different groups of analysis. An age effect on VD was observed between patients and controls (p<0.0001). Gender analysis yielded that women with PCS showed lower VD levels in SVP compared to male patients (p=0.0015). The PCS patients showed significantly lower VD of ICP as compared to the controls (p=0.0001, [CI: 0.32; 1]). Moreover, considering PCS patients, the mixed model reveals a significant difference between chronic fatigue (CF) and without CF in VD of SVP (p=0.0033, [CI: -4.5; -0.92]). The model included age, gender and the variable Bell score, representing a subjective marker for CF. Consequently, the retinal microcirculation might be an objective biomarker in subjective-reported chronic fatigue of patients with PCS.

Herpes simplex virus retinitis following ChAdOx1 nCoV- 19 (Covishield) vaccination for SARS CoV 2: A case report.

PURPOSE: To report a case of herpes simplex virus retinitis following ChadOx1 nCoV-19 (covishield) vaccination. CASE REPORT: A 29 year old immunocompetent male presented with unilateral disc edema with adjacent retinitis two days after receiving the first dose of ChAdOx1 nCoV-19 vaccination. Extensive investigations to rule out infective etiology were negative except for polymerase chain reaction (PCR) of the vitreous specimen which was positive for the herpes simplex virus. A diagnosis of herpes simplex (HSV) retinitis post covid vaccination was made. The patient responded well to oral antivirals and steroids. CONCLUSION: HSV retinitis is a rare complication following the COVID-19 vaccination.

A case of neuro retinitis in association with COVID-19.

A 36-year-old female presented with blurring of vision in one eye for 10 days after 1 month of an episode of COVID-19 infection. Her fundus showed disc edema with blurring of margins along with exudation around the fovea. Her C-reactive protein levels were raised. She responded well to oral steroids. A likely association with COVID-19 infection and its associated immune response was suspected.

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids (preprint)

Several studies have pointed to retinal involvement in COVID 19 disease, yet many questions remain regarding the ability of SARS CoV 2 to infect and replicate in retinal cells and its effects on the retina. Here we have used human stem cell derived retinal organoids to study retinal infection by the SARS CoV 2 virus. Indeed, SARS CoV 2 can infect and replicate in retinal organoids, as it is shown to infect different retinal lineages, such as retinal ganglion cells and photoreceptors. SARS CoV 2 infection of retinal organoids also induces the expression of several inflammatory genes, such as interleukin 33, a gene associated with acute COVID 19 disease and retinal degeneration. Finally, we show that the use of antibodies to block the ACE2 receptor significantly reduces SARS CoV 2 infection of retinal organoids, indicating that SARS CoV 2 infects retinal cells in an ACE2 dependent manner. These results suggest a retinal involvement in COVID 19 and emphasize the need to monitor retinal pathologies as potential sequelae of long COVID.

[Ocular manifestations of viral diseases]. / Atteintes ophtalmologiques des infections virales.

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.

Acute Bilateral Neuroretinitis and Panuveitis in A Patient with Coronavirus Disease 2019: A Case Report.

Purpose: Herein, we report a case of bilateral neuroretinitis and panuveitis in a patient recovered from coronavirus disease 2019 (COVID-19).Case presentation: A 37-year-old male patient with a history of recovered COVID-19, which was confirmed with nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), about one-month ago was referred with one-week history of bilateral severe vision loss. Visual acuity was counting fingers, and bilateral retinitis and panuveitis were revealed in ocular examination. The result of the vitreous sample using RT-PCR was positive for SARS-CoV-2 and negative for Herpesviridae viruses and mycobacterium tuberculosis. The patient was successfully treated with corticosteroid.Conclusion: We report a case of bilateral neuroretinitis and panuveitisin a recovered COVID-19 patient and positive RT-PCR of the vitreous sample. It is suggested to apply intraocular sampling and evaluation for COVID-19 in patients with the new-onset of uveitis and/or retinitis during the pandemic.

Post COVID-19 opportunistic candida retinitis: A case report.

A 42-year-old male patient presented with profound impairment of vision in both eyes, just as he was recovering from COVID-19. A known diabetic and hypertensive, he suffered from COVID-19 pneumonia further complicated by ARDS, septicaemia and acute kidney injury. His vision on presentation was finger counting close to face bilaterally with multiple, yellowish lesions at the posterior pole. Based on the clinical findings and previous blood culture report, it was diagnosed as candida retinitis and treated with oral and intravitreal anti-fungals. The lesions were regressing at follow-up. This is a post COVID-19 presumed candida retinitis case report.

Emergency treatment of ophthalmologic diseases during the first phase of SARS-CoV2 pandemic in a tertiary referral center in Germany – the COVID-DETOUR questionnaire study (preprint)

Background: During the first wave of the COVID-19 pandemic, the need of treatment of urgent ophthalmological diseases and the possible risk of a SARS-CoV-2 infection had to be weighed against each other. In this questionnaire study, we aimed to analyze potential barriers and patients’ health beliefs during and after the lockdown early 2020 in a tertiary referral center in Kiel, Germany. Methods: Patients admitted for the treatment of urgent ophthalmic diseases between March 1 st , 2020, and June 3 rd , 2020, were asked to participate in a questionnaire study. After informed consent was obtained, patients were interviewed using a standardized questionnaire which addressed aspects of their medical history, their health beliefs concerning the COVID-19 pandemic and barriers on their way to the treatment center. The study group was subdivided into two subgroups, depending on the occurrence of their symptoms, before and after the lockdown was ended on April 20 th , 2020. Results: Ninety-three patients were included, 43 in subgroup A (before April 20 th ) and 50 in subgroup B (April 20 th or later). Retinal disorders were most common (approximately 60%), with retinal detachments being the most singular reason for admission. Only 8 patients (8.6%) experienced a delay between their decision to visit a doctor until the actual examination. Every fourth patient was afraid of a COVID-19 infection, and expected a higher likelihood for an infection at the hospital. Patients with comorbidities tended to be more likely to be afraid of an infection (correlation coefficient 0.183, p=0.0785) and were significantly more likely to be concerned about problems with organizing follow-up care (corr. coefficient 0.222, p=0.0328). Higher age was negatively correlated with fear of infection (corr. coefficient -0.218, p-value 0.034). Conclusion: In this questionnaire study, only a minority of patients indicated a delay in treatment, regardless of whether symptoms occurred before or after the lockdown before April 20 th . While patients with comorbidities were more concerned about infection and problems during follow-up care, patients of higher age – who have a higher mortality – were less afraid. Protection of high-risk groups should be prioritized during the SARS-CoV-2 pandemic.Trial registration:The study was registered as DRKS00021630 at the DRKS (Deutsches Register Klinischer Studien) before the conduction of the study on May 5 th , 2020.

Vascular Damage May Mimic Retinitis and Optic Neuritis in COVID-19.

Ophthalmologic nvolvement in SARS-CoV-infected patients is variegated. One of the ophthalmologic pathologies is optic neuritis. Optic neuritis in SARS-CoV-infected patients may precede the classical pulmonary manifestations of COVID-19 and can be unilateral or bilateral. Optic neuritis has been repeatedly reported in COVID-19 patients and may occur with or without affection of other cranial nerves. Since cerebro-spinal fluid parameters can be abnormal in COVID-19 associated optic neuritis, these patients require a spinal tap. Before diagnosing SARS-CoV-2 associated optic neuritis various differentials need to be excluded. Since SARS-CoV-2 causes endothelial damage complicated by thrombus formation and thromboembolism, ophthalmologic vascular complication due to an infection with SARS-CoV-2 such as anterior ischemic optic neuropathy (AION), central retinal artery occlusion (CRAO), and retinal vein occlusion need to be excluded. CRAO may result from arterial hypertension, myocarditis, heart failure, Takotsubo syndrome, atrial fibrillation, or atrial flutter, frequent cardiac complications of COVID-19. Since CRAO can be accompanied by ischemic stroke, patients with SARS-CoV-2 associated optic neuritis need to undergo a cerebral MRI.

COVID-2019 Associated with Acquired Monocular Blindness.

OBJECTIVE: We documented an older female with Coronavirus(CoV) Disease 2019 (COVID-19) and concomitant acquired monocular blindness. We examined this phenomenon in order to understand COVID-19 better. METHODS: We observed an older female with COVID-19 and concomitant acquired monocular blindness. The following indicators were monitored during the course of the disease: ocular examinations, flash visual evoked potential examination, a blood test for COVID-19 IgM antibodies, as well as nasopharyngeal swab and tear sample tests for COVID-19 nucleic acid. RESULTS: The patient's visual acuity for the left eye was NLP and the intraocular pressure was 51 mmHg. Keratic precipitates similar to mutton-fat were spread over the corneal endothelium of the left eye. The funduscopic examination of the patient's left eye revealed severe retinal arterial ischemia, and the color of the retina was off-white. Compared to the right eye, the flash visual evoked potential examination revealed a moderate decrease in P2 wave amplitude for the left eye. A blood test was positive for COVID-19 IgM antibodies, and a nasopharyngeal swab test taken for COVID-19 nucleic acid was positive on May 4, 2020. A sample of the patient's tears was taken, and the nucleic acid test for COVID-19 was still positive two weeks later. CONCLUSIONS: Our study was the first to find that acute viral retinitis could occur in patients with COVID-19 and severe blindness could be associated with SARS-CoV-2 infection. Therefore, physicians should consider the possibility of coronavirus infection in patients with an abnormal fundus or suddenly vision loss.

COVID-19: More than a Respiratory Virus, An Optical Coherence Tomography Study (preprint)

Purpose: The purpose of this study is to investigate anatomic and morphologic features of inner and outer retinal layers in patients recovered from COVID-19 with Spectral Domain Optical Coherence Tomography (SD-OCT), whwther correlate with any symptoms during disease process.Methods: 32 patients recovered from COVID-19; age and gender matched 36 healthy controls were included in this cross-sectional study. Ganglion cell-inner plexiform layer, macular and periapiller retinal nerve fiber layer (RNFL), inner nuclear layer (INL), outer nuclear layer (ONL), outer plexiform layer (OPL) and the outer retinal hyperreflective bands including external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) were examined with SD-OCT. The differences of each retinal layers thickness among subgroup analysis of ocular pain and headache were also compared. Results: Macular RNFL of inner and outer nasal and outer inferior quadrants were thinner in COVID-19 patients compared to healthy control group. (p=0.046, p=0.014 and p=0.016, respectively). Thinning in outer superior quadrant of GCIPL and INL quadrants were detected in patients with headache (p=0.026 and p=0.01). Superonasal and inferotemporal sectors of pRNFL were thinner in patients with ocular pain compared to patients without ocular pain (p=0.024 an p=0.015). Integrity of EZ, ELM and IZ were evaluated as continious line and protected on each OCT scans. Conclusion: The study demostrated convincing evidence that SARS-CoV-2 can affect the inner and outer retinal layers, with subclinical localized alterations particularly in patients with headache and ocular pain symptoms during COVID-19 period.  

Collateral damage: the impact of the COVID-19 pandemic on the care of a patient with tuberculous neuroretinitis in Lagos, Nigeria.

Tuberculous neuroretinis, a relatively rare manifestation of extra-pulmonary tuberculosis, is characterized by optic disc edema, peripapillary and macula swelling, with hard exudates forming a partial or complete 'macular star' While the disease may present a diagnostic challenge for Ophthalmologists, prognosis is usually good, with proper management. The Coronavirus Disease 2019 (COVID-19) pandemic has presented a healthcare delivery dilemma in many parts of the world, with poor accessibility to, and under-utilization of, important healthcare services by non-COVID-19-related cases. Herein is a report of a case of tuberculous neuroretinitis in Lagos, Nigeria, whose care was negatively impacted by the ongoing pandemic through the combined factors of the interruption of clinical services during the lockdown, patient avoidance of healthcare facilities and the absence of robust telehealth services. These all culminated in the delayed institution of therapy which may be responsible for the poor visual outcome of no-light-perception.

Suppressing STAT3 activity protects the endothelial barrier from VEGF-mediated vascular permeability (preprint)

ABSTRACT Vascular permeability triggered by inflammation or ischemia promotes edema, exacerbates disease progression, and impairs tissue recovery. Vascular endothelial growth factor (VEGF) is a potent inducer of vascular permeability. VEGF plays an integral role in regulating vascular barrier function physiologically and in pathologies, such as cancer, ischemic stroke, cardiovascular disease, retinal conditions, and COVID-19-associated pulmonary edema and sepsis, which often leads to acute lung injury, including acute respiratory distress syndrome. However, after initially stimulating permeability, VEGF subsequently mediates angiogenesis to repair damaged tissue. Consequently, understanding temporal molecular regulation of VEGF-induced vascular permeability will facilitate developing therapeutics that achieve the delicate balance of inhibiting vascular permeability while preserving tissue repair. Here, we demonstrate that VEGF signals through signal transducer and activator of transcription 3 (STAT3) to promote vascular permeability. Specifically, we show that genetic STAT3 ablation reduces vascular permeability in STAT3-deficient endothelium of mice and VEGF-inducible zebrafish crossed with CRISPR/Cas9 generated genomic STAT3 knockout zebrafish. Importantly, STAT3 deficiency does not impair vascular development and function in vivo. We identify intercellular adhesion molecule 1 (ICAM-1) as a STAT3-dependent transcriptional regulator and show VEGF-dependent STAT3 activation is regulated by JAK2. Pyrimethamine, an FDA-approved anti-microbial agent that inhibits STAT3-dependent transcription, substantially reduces VEGF-induced vascular permeability in zebrafish, mouse, and human endothelium. Indeed, pharmacologically targeting STAT3 increases vascular barrier integrity using two additional compounds, atovaquone and C188-9. Collectively, our findings suggest that the VEGF, VEGFR-2, JAK2, and STAT3 signaling cascade regulates vascular barrier integrity, and inhibition of STAT3-dependent activity reduces VEGF-induced vascular permeability in vertebrate models. Key Points Genetic STAT3 deficiency in VEGF-inducible zebrafish and mice reveals that VEGF signals through STAT3 to promote vascular permeability Pyrimethamine, a clinically available agent that inhibits STAT3 activity, reduces VEGF-induced vascular permeability in preclinical models

Varicella Zoster Virus Induced Acute Retinal Necrosis Following Acute Meningoencephalitis in a Patient with Presumed COVID-19 (preprint)

Background: To report the coincidence of acute retinal necrosis syndrome (ARN) following acute meningoencephalitis and presumed coronavirus disease 2019 (COVID-19) in an immunocompetent patient. Case presentation: A 58-year old female presented to our emergency department complaining of sudden unilateral visual loss following a recent hospitalization for a viral meningoencephalitis. Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, polymerase chain reaction (PCR) of the aqueous humor, reverse transcriptase polymerase chain reaction (RT-PCR) of the nasopharyngeal swab specimen, chest computed tomography (CT), and fundus photography were performed for the patient. Ophthalmic examination revealed severe ocular inflammation and yellowish patches of necrotizing retinitis in the right eye compatible with the diagnosis of ARN. The result of PCR on the aqueous humor was positive for VZV. The patient received one intravitreal ganciclovir injection and 10 days intravenous ganciclovir followed by oral acyclovir. The patient underwent COVID-19 screening tests; chest CT-scan showed the features highly suggestive for COVID-19 while the RT-PCR was negative two times. Two months later, BCVA reached 20/70 in the right eye. The anterior chamber reaction and KPs resolved and the vitreous haziness significantly decreased Conclusion: A case of VZV induced ARN following acute meningoencephalitis was observed in association with presumed COVID-19. This could be an incidental finding in the pandemic era of COVID-19; however, it could also suggest that COVID-19 might trigger ARN in cases having latent herpes family viruses.