Retinal Vascular Occlusion after COVID-19 Vaccination : More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study

Background: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). Methods: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June–31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case– control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. Results: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case–control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60–1.45, p = 0.75) in connection with a vaccination within a 4-week window. Conclusions: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk

The Rise of Retinal Organoids for Vision Research

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field's improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

This review highlights the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age-related macular degeneration, and rare retinal dystrophies. We first discuss the mechanisms how loss of retinal homeostasis evokes an unbalanced retinal immune reaction involving responses of local microglia and recruited macrophages, activity of the alternative complement system, and inflammasome assembly in the retinal pigment epithelium. Presenting these key mechanisms as complementary targets, we specifically emphasize the concept of immunomodulation as potential treatment strategy to prevent or delay vision loss. Promising molecules are ligands for phagocyte receptors, specific inhibitors of complement activation products, and inflammasome inhibitors. We comprehensively summarize the scientific evidence for this strategy from preclinical animal models, human ocular tissue analyses, and clinical trials evolving in the last few years

Silicone oil tamponade for persistent macular holes

Background!#!A variety of treatment strategies have been proposed for macular holes that persist or recur after surgery, and the debate about the best re-treatment approach is ongoing. To allow for a comparison with alternative surgical therapies, we assessed the anatomical and functional outcome of a temporary tamponade with conventional silicone oil in persistent or recurrent full-thickness macular holes.!##!Methods!#!We retrospectively investigated consecutive patients with full-thickness macular holes that persisted or recurred following vitrectomy with internal limiting membrane peeling and gas tamponade. All patients received re-treatment by temporary tamponade of silicone oil and were allowed free postoperative positioning. Anatomical closure rate was assessed by optical coherence tomography, and change of best-corrected visual acuity (BCVA) was analyzed.!##!Results!#!A total of 33 eyes of 33 consecutive patients were included. Macular hole closure following silicone oil tamponade was achieved in 30 of 33 eyes (90.9%). Median BCVA improved from 1.00 logMAR (interquartile range, 0.60-1.00) to 0.65 logMAR (0.49-1.00; p = 0.010) after silicone oil removal. In patients with macular hole closure, 61.3% exhibited functional improvement with median BCVA changing from 1.00 logMAR (0.70-1.00) to 0.60 logMAR (0.49-1.00; p = 0.0005). Mean minimal linear diameter of macular holes before primary surgery was 391.0 µm (±137.8; range 133-630), and 48.5% of macular holes were >400 µm in diameter.!##!Conclusions!#!Treatment of persistent or recurrent full-thickness macular holes by temporary conventional silicone oil tamponade without postoperative positioning results in a high closure rate and a significant mean improvement of visual acuity

Retina, Vitreous Humor, Ocular Fundus Prenatal Retinopathy

Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness. This proliferative retinal vascular disease affects only prematurely born infants. Major risk factors include low gestational age and prolonged postnatal oxygen supplementation. ROP screening allows for timely identification of treatment-requiring infants and thus significantly reduces the risk of severe visual impairment and blindness from ROP. Current treatment options comprise retinal laser coagulation and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We provide a review of scientific data and current treatment recommendations, with special attention to the updated German guideline on ROP screening, the statement of the German ophthalmological societies on anti-VEGF therapy of ROP, and the new third edition of the International Classification of Retinopathy of Prematurity (ICROP3)

Screening for retinopathy of prematurity-the most important changes in the new German guidelines 2020

Background Due to improvements in neonatal care of premature infants and the development of novel treatment options for retinopathy of prematurity (ROP), the requirements for screening for ROP have changed since publication of the last version of the German ROP screening guideline in 2008. Based on results of recent studies, the guideline has been extensively revised in 2020 and published in an updated version. Objective This article summarizes the most important changes in the new guideline. Results The age limit for screening inclusion was lowered to a gestational age of below 31 weeks for infants without additional risk factors. The minimum duration of oxygen supplementation necessitating screening inclusion in preterm infants was increased to more than 5 days. Treatment for ROP in zone II can now be given at any stage 3 with plus disease, regardless of the number of clock hours affected. Criteria for the frequency and duration have been defined for follow-up examinations after anti-vascular endothelial growth factor (VEGF) treatment. The binding document for these and other new recommendations is the guideline itself. Conclusion The guideline recommendations enable a reliable identification of infants at risk for ROP for screening inclusion and a timely detection of advanced disease stages for treatment initiation, thus preventing blindness from ROP

Retinopathy of Prematurity Update on Classification, Screening, and Therapy

Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness. This proliferative retinal vascular disease affects only prematurely born infants. Major risk factors include low gestational age and prolonged postnatal oxygen supplementation. ROP screening allows for timely identification of treatment-requiring infants and thus significantly reduces the risk of severe visual impairment and blindness from ROP. Current treatment options comprise retinal laser coagulation and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We provide a review of scientific data and current treatment recommendations, with special attention to the updated German guideline on ROP screening, the statement of the German ophthalmological societies on anti-VEGF therapy of ROP, and the new third edition of the International Classification of Retinopathy of Prematurity (ICROP3)

Oxalobacter formigenes treatment combined with intensive dialysis lowers plasma oxalate and halts disease progression in a patient with severe infantile oxalosis

Background!#!Infantile oxalosis, the most devastating form of primary hyperoxaluria type 1 (PH1), often leads to end-stage renal disease (ESRD) during the first weeks to months of life.!##!Case-diagnosis!#!Here, we report the outcome of the therapeutic use of Oxalobacter formigenes (Oxabact OC5; OxThera AB, Stockholm, Sweden) in a female infant with PH1 who exhibited severely elevated plasma oxalate (Pox) levels, pronounced nephrocalcinosis, anuretic end-stage renal disease, and retinal oxalate deposits. Following the diagnosis of PH1 at an age of 8 weeks, a combined regimen of daily peritoneal dialysis, daily pyridoxine treatment and hemodialysis (3 times a week) was unable to reduce the pronounced hyperoxalemia. After the addition of Oxalobacter formigenes therapy to the otherwise unchanged treatment regimen, Pox levels first stabilized and subsequently declined from 130 μmol/L to around 80 μmol/L. Nephrocalcinosis and retinal deposits stabilized. Oxalobacter formigenes treatment was well-tolerated and no related adverse events were observed. The patient showed nearly age-appropriate growth and development and received successful combined liver-kidney transplantation at the age of two years.!##!Conclusions!#!Treatment with O. formigenes combined with intensive dialysis led to reduction of Pox, stabilization of systemic oxalosis, and improvement in the clinical disease course. O. formigenes treatment may be an option for reduction of oxalosis in infantile patients with insufficient response to conservative treatments until combined liver-kidney transplantation can be performed