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

BACKGROUND: Vaccination against the worldwide pandemic coronavirus disease 2019 (COVID-19) is underway; however, some cases of new 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) recovered only 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.

Management of autoimmune retinopathy treated with intravitreal dexamethasone implant.

PURPOSE: The purpose of this study is to evaluate clinical outcomes of autoimmune retinopathy (AIR) in the patients treated with intravitreal dexamethasone implant (IDI). METHOD: Twenty-one eyes of 11 AIR patients treated with at least 1 injection of IDI were retrospectively reviewed. Clinical outcomes before and after treatment, including best corrected visual acuity (BCVA), optic coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ff-ERG), and visual field (VF) at last visit within 6 and/or 12 months, were recorded. RESULTS: Among all the patients, 3 had cancer-associated retinopathy (CAR) and 8 had non-paraneoplastic-AIR (npAIR) with mean followed up of 8.52 ± 3.03 months (range 4-12 months). All patients achieved improved or stable BCVA within 6 and/or 12 months after the treatment. Cystoid macular edema (CME) in 2 eyes and significant retinal inflammation in 4 eyes were markedly resolved after single injection. Central retinal thickness (CFT) in all eyes without CME, ellipsoid zone (EZ) on OCT in 71.4% of eyes, ERG response in 55% of eyes, and VF in 50% of eyes were stable or improved within 6 months after treatment. At last visit within 12 months, both BCVA and CFT remained stable in the eyes treated with either single or repeated IDI; however, progression of EZ loss and damage of ERG response occurred in some patients with single IDI. CONCLUSION: Clinical outcomes, including BCVA and parameters of OCT, ERG, and VF, were stable or improved after IDI in a majority of AIR patients. Local treatment of AIR with IDI was a good option to initiate the management or an alternative for the patients' refractory to the systemic therapy but with limited side effect.

Tomographic Findings in the Retina of Unvaccinated Patients with COVID Pneumonia: Prospective Longitudinal Study.

There is no definitive evidence on the extent of SARS-CoV-2's effect on the retina. This study aims to determine if the natural history of SARS-CoV-2 infection affects tomographic findings in the retina of patients with COVID-19 pneumonia. This is a prospective cohort study of patients hospitalized with COVID-19 pneumonia. The patients underwent ophthalmological explorations and optical coherence tomography during the acute phase of the infection and at a follow-up 12 weeks later. The primary outcomes were the central retinal thickness and central choroidal thickness, which were compared longitudinally and with non-COVID-19 historical controls. No statistically relevant differences were observed in the longitudinal analysis of the thickness of the central retina (p = 0.056), central choroid (p = 0.99), retinal nerve fiber layer (p = 0.21), or ganglion cell layer (p = 0.32). Patients with acute COVID-19 pneumonia showed significantly greater central retinal thickness than non-COVID controls (p = 0.006). In conclusion, tomographic measures of the retina and choroid are not influenced by the phase of COVID-19 infection and remain stable during 12 weeks. The central retinal thickness may increase in the acute phase of COVID-19 pneumonia, but more epidemiological studies using optical coherence tomography in the early stages of the disease are needed.

Different Cases, Different Manifestations of Post-COVID-19 Retinal Artery Occlusion: A Case Series.

Coronavirus disease 2019 (COVID-19) is a procoagulant disease that increases the risk of clinically evident thrombotic complications. Herein we present 3 cases with different retinal artery occlusions that emerged soon after the diagnosis of COVID-19. The first patient had central retinal artery occlusion (CRAO) that resulted in visual loss in one eye. The second patient had inflammatory peripheral retinal artery occlusion, vasculitis, and uveitis which did not affect vision. The third patient presented with CRAO following the progression from orbital cellulitis to orbital apex syndrome. Interestingly, CRAO progressed to internal carotid artery occlusion in this case within days and resulted in monocular visual loss. Variations in the underlying pathophysiology and the characteristics of individual immune responses in patients with COVID-19 may be factors that determine differences in clinical manifestations. This article aims to describe different presentations of COVID-19-related retinal artery occlusions and discuss possible pathophysiological aspects.

Long-term follow-up of acute retinal necrosis with retinal detachment secondary to herpes simplex virus type 2 with a successful visual outcome.

A man in his early 20s presented with acute loss of vision in his only eye, the left eye (OS), and was on oral steroids. He had lost vision in his right eye during his childhood and the cause was unknown. There was no history of trauma. Best-corrected visual acuity (BCVA) in OS was 20/100 and in the right eye was hand movements. OS showed non-granulomatous keratic precipitates on the cornea, anterior chamber flare 1+ and cell 1+, early cataract, vitreous haze and cells 2+ with nasal retinal detachment and superior full thickness retinitis. He underwent pars plana vitrectomy with intravitreal ganciclovir and barrage laser away from the necrotic retina. PCR for herpes simplex virus 2 was positive from the aqueous and vitreous sample. He was started on oral valacyclovir 1 g three times a day and continued on tapering dose of oral steroids. BCVA in OS at 6-month follow-up was 20/25.

Evaluation of the retina with optical coherence tomography angiography (OCTA) in patients with coronavirus (COVID-19) infection.

PURPOSE: The goal of this study is to compare the optical coherence tomography angiography (OCTA) findings in Coronavirus (COVID-19) positive adult and pediatric patients with those of healthy volunteers with the same demographic characteristics. METHODS: The right eye of 157 adults infected with covid, 168 healthy adult volunteers, 40 children (6-18 years of age) infected with covid, and 44 healthy children (6-18 years of age) were included in this prospective study. All participants underwent ophthalmological examination and OCTA. The OCTA findings were evaluated. RESULTS: Deep nasal density (DND), deep inferior density (DID), and deep parafoveal density (DPD) were significantly lower in the pediatric covid-affected group (PCAG) than in the pediatric healthy control group (PHCG) (P=0.034, P=0.029, P=0.022 respectively). On the other hand, radial peripapillary capillary vessel density (RPCVD) intra-disc measurements were significantly higher in the PCAG compared to the PHCG (P=0.025). There was no significant difference between the OCTA measurements of the adult covid-affected group (ACAG) and the adult healthy control group (AHCG). CONCLUSION: In our study, significant differences were found in OCTA measurements between the covid group and the healthy control group in children. Retinal microvascular changes may occur in patients with covid infection, and these patients might be followed for long-term retinal changes.

Evaluation of vascular and perfusional changes in the retina and choroid of children with multisystem inflammatory syndrome.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is hyperinflammation following coronavirus disease 2019 (COVID-19), which affects many organs. The retina and choroid are affected by COVID-19 through microangiopathy and thrombosis but the literature on MISC-C is limited. METHODS: Thirty children (60 eyes) with MIS-C (the study group, or SG) and 32 age-and gender-matched healthy children (64 eyes) (the control group, or CG) were included in the prospective case-control study. Complete ophthalmological examinations, measurements of the vessel densities of the retinal layers, and flow area of the outer retina and choriocapillaris in both groups were conducted with optical coherence tomography angiography (OCT-A). RESULTS: The mean age of the SG was 11.9 ± 3.9 and that of the CG was 12.5 ± 4.6 years (p = 0.197). In this study we found that the vessel density of the deep layer of the inner retina was decreased significantly and was reduced in the outer retina of flow area in the SG in comparison with the CG (p < 0.05, for all). However, there was no significant difference between the groups regarding other measurements. CONCLUSIONS: In MIS-C patients, vessel densities in the deep layer of the inner retina and in the flow area of the outer retina decreased significantly. This OCTA-A finding suggests that MIS-C is related to endothelial thrombotic condition problems in small branches of the retinal artery. The results of this study support the idea that there is a need for screening of MIS-C patients for the presence of these microangiopathic and perfusional complications.

Evaluation of the Long-Term Clinical Results of 3 Patients Implanted with the Argus II Retinal Prosthesis.

This study presents the long-term clinical results of Argus II retinal prosthesis implantation in eyes with light perception and projection in 3 patients with end-stage retinitis pigmentosa. No conjunctival erosion, hypotony, or implant displacement was observed during postoperative follow-up. The electrical threshold values were lower in the macular region and higher close to the tack fixation region and peripherally. Optical coherence tomography scans showed fibrosis and retinoschisis formation at the retina-implant interface in two cases. This was attributed to mechanical and electrical effects on the tissue due to the active daily use of the system and the electrodes' proximity to the retina. The patients were able to integrate the system into their daily lives and perform activities that they could not do before. Studies on retinal prostheses for the rehabilitation of hereditary retinal diseases are ongoing, so both social and clinical observations and experiences related to the implant are valuable.

Retinal microvascular changes in patients recovered from COVID-19 compared to healthy controls: A meta-analysis.

PURPOSE: To investigate changes in retinal microcirculation in patients recovered from COVID-19 infection compared to healthy controls, using optical coherence tomography-angiography. METHODS: Meta-analysis of eligible studies comparing retinal microcirculation between patients recovered from COVID-19 infection and healthy controls up to 7th of September 2022 was performed, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. The following search algorithm was used: (COVID-19 OR coronavirus) AND (retina OR optical coherence tomography OR optical coherence tomography angiography OR vessel density OR foveal avascular zone). Standardized Mean Difference (SMD) with 95% confidence interval (CI) was calculated to compare continuous variables. Revman 5.3 was used for the analysis. RESULTS: 12 studies were included in our analysis. Foveal avascular zone (FAZ) area was larger in patients recovered from COVID-19 infection compared to healthy controls, while there was no statistically significant difference in FAZ perimeter between the two groups. The foveal, parafoveal and whole image vessel density in the superficial capillary plexus showed no significant difference between the two groups. The foveal, parafoveal and whole image vessel density in the deep capillary plexus was statistically lower in patients recovered from COVID-19 compared to healthy controls. CONCLUSION: FAZ area was enlarged and foveal, parafoveal and whole image vessel density in deep capillary plexus were reduced in patients recovered from COVID-19 infection compared to healthy controls, suggesting that COVID-19 infection may induce long-term retinal microvascular changes in patients recovered from the virus infection.

Retinal tissue and microvasculature loss in COVID-19 infection.

This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p < 0.05). Retinal tissue and microvascular loss may be a biomarker of COVID-19 severity. Further monitoring of the retina in COVID-19-recovered patients may help further understand the COVID-19 sequela.

OCTA evaluation of posterior ocular blood flow in patients after COVID-19 infection without pneumonia.

INTRODUCTION: We aimed to demonstrate the changes in optic nerve and retinal microvascular structures with Optical Coherence Tomography Angiography (OCTA) in patients who had COVID-19 infection. METHODS: Prospective study. Retina, choroid and optic nerve head microvascular flow and vascular densities of both groups were measured by OCTA. RESULTS: OCTA measurements of 122 right eyes of a total of 122 patients, including 72 patients in the COVID-19 group and 50 patients in the control group, were included in the study. The Deep Capillary Plexus (DCP) Flow Area (FA) in the COVID-19 group was 1.42±0.23 mm2, in the control group was 1.50±0.15 mm2, Choriocapillary Plexus FA was 1.89±0.04 mm2 in the COVID-19 group, was 1.91±0.05 mm2 in the control group, and a statistically significant difference was found between the two groups (respectively; P=0.03; P=0.02). DCP Whole Vascular density (VD) values were 56.76±4.16% in the COVID-19 group, 58.28±3.88% in the control group; difference between the values was statistically significant (P=0.04). There was no statistically significant difference between the two groups in terms of optic nerve head flow areas and other parameters examined according to quadrants. CONCLUSIONS: Results show that the retinal microcirculation in subjects with mild disease is affected. Even if the disease is mild, patients may need to be followed up for retinal changes that may develop in the future.

Nanoparticles-mediated CRISPR-Cas9 gene therapy in inherited retinal diseases: applications, challenges, and emerging opportunities.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Detection of SARS-CoV-2 genomic and subgenomic RNA in retina and optic nerve of patients with COVID-19.

PURPOSE: Presence of SARS-CoV-2 RNA in human retinal biopsies (RBs) was previously reported by us. In this consecutive study, we analysed RB and optic nerve biopsies (ONBs) in deceased patients with confirmed COVID-19 assessing viral RNA load, possible virus replication and infectivity. PATIENTS AND METHODS: In this case series, 14 eyes of 14 deceased patients with COVID-19 were enucleated during autopsy. RB and ONB were subjected to molecular detection of viral RNA, virus cultivation and immunohistochemistry. SARS-CoV-2 RNA loads were compared with RNA loads in the respective throat swabs, vitreous humour and blood samples. RESULTS: SARS-CoV-2 RNA was detected in 7/14 RBs and in 10/13 ONBs. While virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, subgenomic RNA (sgRNA) was detectable (40% RB; 60% ONB). CONCLUSION: SARS-CoV-2 RNA is detectable in RB and ONB of patients with COVID-19. Presence of sgRNA could point to a SARS-CoV-2 infection of neuronal tissue, but as virus isolation failed and immunohistochemistry of SARS-CoV-2 spike protein was negative, an active infection seems unlikely.

Evaluation of acute effects of pulmonary involvement and hypoxia on retina and choroid in coronavirus disease 2019: An optic coherence tomography study.

PURPOSE: We investigated the acute subclinical choroidal and retinal changes caused by Coronavirus Disease 2019 (COVID-19) in patients with and without pulmonary involvement, using spectral domain optic coherence tomography. METHODS: This prospective case-control study included COVID-19 patients: 50 with pulmonary involvement and 118 with non-pulmonary involvement. All patients were examined 1 month after recovering from COVID-19. The changes were followed using optic coherence tomography parameters such as choroidal and macular thickness and retinal nerve fibre layer and ganglion cell complex measurements. RESULTS: All choroidal thicknesses in the pulmonary involvement group were lower than in the non-pulmonary involvement group and the subfoveal choroidal thickness differed significantly (p=0.036). Although there were no significant differences between the central and average macular thicknesses in the two groups, they were slightly thicker in the pulmonary involvement group (p=0.152 and p=0.180, respectively). A significant decrease was detected in the pulmonary involvement group in all ganglion cell complex segments, except for the outer nasal inferior segment (p<0.05). In addition, a thinning tendency was observed in all retinal nerve fibre layer quadrants in the pulmonary involvement group compared to the non-pulmonary involvement group. CONCLUSION: In COVID-19 patients with pulmonary involvement, subclinical choroidal and retinal changes may occur due to hypoxia and ischemia in the acute period. These patients may be predisposed to ischemic retinal and optic nerve diseases in the future. Therefore, COVID-19 patients with pulmonary involvement should be followed for ophthalmological diseases.

Central retinal artery occlusion with cilioretinal artery sparing secondary to COVID-19: Additional ocular complication.

We describe a 68-year-old female patient with unilateral central retinal artery occlusion (CRAO) with cilioretinal artery sparing post-coronavirus disease 2019 (COVID-19) infection. The patient presented with acute vision loss in the left eye 11 days after discharge from a severe COVID-19 infection, with altered D-dimer, C-reactive protein, and fibrinogen levels. The best-corrected visual acuity (BCVA) in the left eye was 20/400; fundoscopic examination revealed diffuse pallor retina with a patent arterial branch from the optic disk to the fovea, confirmed by fluorescein angiography. CRAO with a cilioretinal artery sparing post-COVID-19 may be considered an additional ocular manifestation of the post-acute COVID-19 syndrome spectrum.

Retinal Findings in Hospitalized COVID-19 Patients, Is Routine Ophthalmological Examination Required after Discharge? Prospective Case-Control Study.

OBJECTIVES: To investigate retinal findings by comparing patients hospitalized for COVID-19 with the control group. METHODS: In this prospective study, 188 eyes of 94 recovered COVID-19 patients and 108 eyes of 54 healthy participants as a control group were evaluated. Patients were divided into three groups, those with mild, moderate, and severe COVID-19. Refractometry, tonometry, optical biometry, optical coherence tomography (OCT) measurements, and complete ophthalmological examinations were performed on healthy volunteers and COVID-19 patients on average 2 weeks after discharge. Pulse O2 and vital parameters were also assessed. Primary outcomes were evaluated, such as retinal findings, and secondary outcomes as retinal thickness, choroidal thickness (CT), retinal nerve fiber layer thickness, and ganglion cell layer thickness. RESULTS: There was no difference between the groups in terms of demographic data, ocular biometry, and intraocular pressure (p > 0.05). Pulse O2 was lower in the study group (p < 0.001). Retinal findings were detected in 68 (36.1%) of 188 eyes in the study group and 28 (25.9%) of 108 eyes in the control group (p = 0.07). The two most common retinal findings were hypertensive retinopathy and retinal pigment epithelium alterations and/or drusen in both groups. In OCT measurements, significant thinning was observed in nasal macular thickness and superior 2 mm CT in the study group compared to the control group (p < 0.05). In patients divided into subgroups according to disease severity, no significant difference was found between the groups in any OCT parameter (p > 0.05). CONCLUSION: It has been observed that COVID-19 infection does not cause a specific and sensitive finding in the ocular tissues, especially the retina, and does not produce a reproducible measurement result. Recommending routine eye exam after COVID-19 does not seem cost-effective.

The effect of COVID-19 on referral patterns for clinical electrophysiological testing.

PURPOSE: To provide an overview of the effect that the COVID-19 pandemic has had on visual electrophysiology referral patterns and the subsequent effect this may have on patients. METHODS: All electrodiagnostic tests performed at Kensington Vision and Research Centre, Toronto Canada, in a 3-month period prior to the COVID-19 pandemic (1 September 2019 to 30 November 2019) were compared to a 3-month period after the start of the COVID-19 pandemic (1 September 2021 to 30 November 2021). RESULTS: A total of 502 patients had electrodiagnostic testing carried out in the designated time periods: 292 in the time period prior to the COVID-19 pandemic and 210 patients after. There was a significant change in the reason for referral in patients pre-COVID compared to post-COVID (p = 0.004). There was a 43% reduction in referrals for drug monitoring, 25% reduction for hereditary pathology and a 27% increase in acquired pathology after the start of the COVID-19 pandemic compared to before. CONCLUSIONS: There was a substantial decrease in the total number of patients referred after the start of the COVID-19 pandemic compared to pre-COVID with inherited retinal pathology and drug monitoring patients being 2 populations most affected by the disruption to healthcare services.