Genetic underpinnings explored: OPA1 deletion and complex phenotypes on chromosome 3q29.

BACKGROUND: Copy number variations (CNVs) have emerged as significant contributors to the elusive genetic causality of inherited eye diseases. In this study, we describe a case with optic atrophy and a brain aneurysm, in which a de novo CNV 3q29 deletion was identified. CASE PRESENTATION: A 40-year-old female patient was referred to our department after undergoing aneurysm transcatheter arterial embolization for a brain aneurysm. She had no history of systemic diseases, except for unsatisfactory best-corrected visual acuity (BCVA) since elementary school. Electrophysiological tests confirmed the findings in retinal images, indicating optic nerve atrophy. Chromosomal microarray analysis revealed a de novo deletion spanning 960 kb on chromosome 3q29, encompassing OPA1 and six neighboring genes. Unlike previously reported deletions in this region associated with optic atrophy, neuropsychiatric disorders, and obesity, this patient displayed a unique combination of optic atrophy and a brain aneurysm. However, there is no causal relationship between the brain aneurysm and the CNV. CONCLUSION: In conclusion, the optic atrophy is conclusively attributed to the OPA1 deletion, and the aneurysm could be a coincidental association. The report emphasizes the likelihood of underestimating OPA1 deletions due to sequencing technology limitations. Recognizing these constraints, healthcare professionals must acknowledge these limitations and consistently search for OPA1 variants/deletions in Autosomal Dominant Optic Atrophy (ADOA) patients with negative sequencing results. This strategic approach ensures a more comprehensive exploration of copy-number variations, ultimately enhancing diagnostic precision in the field of genetic disorders.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

Semiautomated design and soluble expression of a chimeric antigen TbpAB01 from Glaesserella parasuis.

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.

Efficient production and characterization of a newly identified trehalase for inhibiting the formation of bacterial biofilms.

Trehalase has attracted widespread attention in medicine, agriculture, food, and ethanol industry due to its ability to specifically degrade trehalose. Efficient expression of trehalase remains a challenge. In this study, a putative trehalase-encoding gene (Tre-zm) from Zunongwangia mangrovi was explored using gene-mining strategy and heterologously expressed in E. coli. Trehalase activity reached 3374 U·mL-1 after fermentation optimization. The scale-up fermentation in a 15 L fermenter was achieved with a trehalase production of 15,068 U·mL-1. The recombinant trehalase TreZM was purified and characterized. It displayed optimal activity at 35 °C and pH 8.5, with Mn2+, Sn2+, Na+, and Fe2+ promoting the activity. Notably, TreZM showed significant inhibition effect on biofilm forming of Staphylococcus epidermidis. The combination of TreZM with a low concentration of antibiotics could inhibit 70 % biofilm formation of Staphylococcus epidermidis and 28 % of Pseudomonas aeruginosa. Hence, this study provides a promising candidate for industrial production of trehalase and highlights its potential application to control harmful biofilms.

Longitudinal Changes in Choroidal Thickness in Children with a History of Prematurity: An 18-month Prospective Cohort Study.

PURPOSE: To evaluate choroidal changes over time in school-aged children with a history of prematurity. METHODS: A study of 416 eyes, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity (ROP), intravitreal bevacizumab (IVB)-treated ROP, and laser-treated ROP groups, respectively. The choroidal thickness was measured 4 times at 6-month intervals by optical coherence tomography. RESULTS: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µm, P = .04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µm/year, P = .03), whereas no difference was observed between IVB and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µm/year, P = .46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < .05). CONCLUSION: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between IVB and laser treatments. Axial elongation was associated with choroidal thinning in school-aged children.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Clinical Characteristics and Genetic Variants in Taiwanese Patients With PROM1-Related Inherited Retinal Disorders.

Purpose: This study investigated the clinical characteristics of patients with PROM1-related inherited retinal diseases (IRDs). Methods: Patients diagnosed with IRDs who had mutations in PROM1 were identified at Linkou Chang Gung Memorial Hospital and Kaohsiung Medical University Hospital in Taiwan. Information on clinical characteristics and best-corrected visual acuity was recorded. Color fundus (CF) images, fundus autofluorescence photography (FAF), spectral-domain optical coherence tomography (SD-OCT), and electroretinograms (ERGs) were analyzed to examine patient phenotypes. PROM1 variants were detected using whole exome sequencing and verified by Sanger sequencing. Results: Fourteen patients from nine families with PROM1-related IRDs were analyzed. Most patients exhibited chorioretinal atrophy in the macular area, with or without extramacular involvement on CF. Similarly, hypo-autofluorescence confined to the macular area, with or without extramacular involvement, was present for most patients on FAF. Furthermore, SD-OCT revealed outer retinal tubulations and focal or diffuse retinal thinning. ERGs showed variable findings, including maculopathy with normal ERG, subnormal cone response, and extinguished rod and cone responses. We detected five variants of the PROM1 gene, including c.139del, c.794del, c.1238T>A, c.2110C>T, and c.1117C>T. Conclusions: In this study, we evaluated 14 Taiwanese patients with five PROM1 variants. Additionally, incomplete penetrance of heterozygous PROM1 variants was observed. Furthermore, patients with autosomal dominant PROM1 variants had lesions in the macular area and the peripheral region of the retina. SD-OCT serves as a useful tool for early detection of PROM1-related IRDs, as it captures certain signs of such diseases.

The Value of Electroretinography in Identifying Candidate Genes for Inherited Retinal Dystrophies: A Diagnostic Guide.

Inherited retinal dystrophies (IRDs) are a group of heterogeneous diseases caused by genetic mutations that specifically affect the function of the rod, cone, or bipolar cells in the retina. Electroretinography (ERG) is a diagnostic tool that measures the electrical activity of the retina in response to light stimuli, and it can help to determine the function of these cells. A normal ERG response consists of two waves, the a-wave and the b-wave, which reflect the activity of the photoreceptor cells and the bipolar and Muller cells, respectively. Despite the growing availability of next-generation sequencing (NGS) technology, identifying the precise genetic mutation causing an IRD can be challenging and costly. However, certain types of IRDs present with unique ERG features that can help guide genetic testing. By combining these ERG findings with other clinical information, such as on family history and retinal imaging, physicians can effectively narrow down the list of candidate genes to be sequenced, thereby reducing the cost of genetic testing. This review article focuses on certain types of IRDs with unique ERG features. We will discuss the pathophysiology and clinical presentation of, and ERG findings on, these disorders, emphasizing the unique role ERG plays in their diagnosis and genetic testing.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

Purpose: This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Methods: Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. Results: A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. Conclusions: VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Spatiotemporal control of genome engineering in cone photoreceptors.

BACKGROUND: Cones are essential for color recognition, high resolution, and central vision; therefore cone death causes blindness. Understanding the pathophysiology of each cell type in the retina is key to developing therapies for retinal diseases. However, studying the biology of cone cells in the rod-dominant mammalian retina is particularly challenging. In this study, we used a bacterial artificial chromosome (BAC) recombineering method to knock in the "CreERT2" sequence into the Gnat2 and Arr3 genes, respectively and generated three novel inducible CreERT2 mice with different cone cell specificities. RESULTS: These models (Gnat2CreERT2, Arr3T2ACreERT2, and Arr3P2ACreERT2) express temporally controllable Cre recombinase that achieves conditional alleles in cone photoreceptors. Cre-LoxP recombination can be induced as early as postnatal day (PD) two upon tamoxifen injection at varying efficiencies, ranging from 10 to 15% in Gnat2CreERT2, 40% in Arr3T2ACreERT2, and 100% in Arr3P2ACreERT2. Notably, knocking in the P2A-CreERT2 cassette does not affect cone cell morphology and functionality. Most cone-phototransduction enzymes, including Opsins, CNGA3, etc. are not altered except for a reduction in the Arr3 transcript. CONCLUSIONS: The Arr3P2ACreERT2 mouse, an inducible cone-specific Cre driver, is a valuable line in studying cone cell biology, function, as well as its relationship with rod and other retinal cells. Moreover, the Cre activity can be induced by delivering tamoxifen intragastrically as early as PD2, which will be useful for studying retinal development or in rapid degenerative mouse models.

LONG-TERM CLINICAL OUTCOMES AND GENOTYPE-PHENOTYPE CORRELATION IN FAMILIAL EXUDATIVE VITREORETINOPATHY IN A TERTIARY REFERRAL CENTER.

BACKGROUND/PURPOSE: To evaluate clinical outcomes and assess genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR). METHODS: Clinical charts of 40 patients with FEVR were reviewed. FEVR was staged per Pendergast and Trese, and retinal dragging and folds further classified per Yaguchi et al. We performed whole-exome sequencing and compared clinical characteristics between genetic-positive and genetic-negative groups. RESULTS: The mean duration of follow-up was 5.4 years (range: 0.33, 15) for genetic-positive and 6.9 (range: 1, 20) for genetic-negative patients. The mean age at diagnosis was 5.6 years (0.25, 27) for genetic-positive and 6.0 (0, 32) for genetic-negative patients. Genetic-positive patients reported 100% full-term births and genetic-negative patients reported 45% full-term births ( P = 0.0012). There were more patients with retinal folds with all major vessels affected (Yaguchi's Group 4) in genetic-positive compared with genetic-negative patients (21.4% vs. 2.6%, P = 0.045). TSPAN12 was the most common (57.1%) genetic mutation in our population of which 50% exhibited asymmetric presentation. CONCLUSION: Patients who test positive for a typical FEVR gene mutation reported more term births and had more severe disease by Yaguchi's classification. TSPAN12 was the most common genetic mutation in our population and had highly asymmetrical disease.

Maternal mosaicism in SSBP1 causing optic atrophy with retinal degeneration: implications for genetic counseling.

BACKGROUND: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions. RESULTS: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband's unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before. CONCLUSIONS: In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1. Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.

Retrospective Analysis of Surgical Outcomes on Axial Length Elongation in Eyes with Posterior and Combined Persistent Fetal Vasculature.

This study aims to investigate the outcomes and risk factors associated with poor vision (vision less than counting fingers, 2.0 logMAR, Snellen vision 20/2000) in patients with posterior or combined persistent fetal vasculature (PFV), with or without surgery. We retrospectively reviewed the medical records of patients who were diagnosed with PFV from January 2008 to April 2021. We included 51 eyes of 44 patients who presented with PFV, of which 38 eyes underwent surgical correction (pars plicata/plana vitrectomy, with or without lensectomy, and intraocular lens implantation) at the median age of 6.0 months (range: 0.7 to 82.0). The mean follow-up was 68.8 months ± 38.0 months. The axial length change in the eyes undergoing surgery was significantly higher than the eyes without surgery (p = 0.025). Initial anterior chamber collapse and retinal detachment were associated with poor vision (p = 0.006 and p = 0.002, respectively). In addition, 37% of eyes with posterior or combined PFV had vision better than counting fingers. Surgery for eyes with PFV could result in better eye growth. Visual outcomes remained poor and were associated with the level of macular abnormality. Initial anterior chamber collapse and retinal detachment at presentation were the risk factors for poor visual outcomes. Vitrectomy for selected PFV eyes is valuable and associated with a better cosmetic outcome (better eye growth).

The Association of Intravitreal Injections of Different Anti-Vascular Endothelial Growth Factor with Systemic Outcomes in Diabetic Patients.

This retrospective cohort study aimed to assess the systemic effects of three commonly available anti-vascular endothelial growth factor intravitreal injections in patients with diabetes, using data taken from a multi-institutional database in Taiwan. Patient data were sourced from the multi-institutional Chang Gung Research Database. Participants were divided into groups based on treatment with bevacizumab, ranibizumab, or aflibercept. Baseline characteristics were matched among the groups by the inverse probability of treatment weighting. The incidence rate of outcome events was calculated as the number of events divided by 100 person-years of follow-up. The cumulative incidence function was used to estimate the incidence rate of the outcome events among groups. The incidence of ischemic stroke was higher in the ranibizumab group than the bevacizumab and aflibercept groups (1.65, 0.92, and 0.61 per 100 person-years, respectively). The incidence of major adverse lower-limb events was higher in the bevacizumab group (2.95), followed by ranibizumab (2.00) and aflibercept (0.74). Major bleeding was relatively higher in bevacizumab (12.1) compared to ranibizumab (4.3) and aflibercept (3.8). All-cause death was higher for both bevacizumab (3.26) and aflibercept (2.61) when compared to ranibizumab (0.55), and all-cause admission was found to be highest with bevacizumab (58.6), followed by aflibercept (30.2), and ranibizumab (27.6). The bevacizumab group demonstrated a greater decrease in glycated hemoglobin compared to the baseline level (-0.33%). However, a few differences in the clinical condition between the groups were still observed after matching. In conclusion, this study suggests that different anti-vascular endothelial growth factor agents may be associated with various and differing systemic adverse events. The differences might also be attributed to differences in patient characteristics and clinical status.

Maternal Mosaicism in SSBP1 Causing Optic Atrophy with Retinal Degeneration: Implications for Genetic Counseling.

Background: Optic atrophy-13 with retinal and foveal abnormalities (OPA13) (MIM #165510) is a mitochondrial disease in which apparent bilateral optic atrophy is present and sometimes followed by retinal pigmentary changes or photoreceptors degeneration. OPA13 is caused by heterozygous mutation in the SSBP1 gene, associated with variable mitochondrial dysfunctions. Results: We have previously reported a 16-year-old Taiwanese male diagnosed with OPA13 and SSBP1 variant c.320G>A (p.Arg107Gln) was identified by whole exon sequence (WES). This variant was assumed to be de novo since his parents were clinically unaffected. However, WES and Sanger sequencing further revealed the proband’s unaffected mother carrying the same SSBP1 variant with a 13% variant allele frequency (VAF) in her peripheral blood. That finding strongly indicates the maternal gonosomal mosaicism contributing to OPA13, which has not been reported before. Conclusions: In summary, we described the first case of OPA13 caused by maternal gonosomal mosaicism in SSBP1 . Parental mosaicism could be a serious issue in OPA13 diagnosis, and appropriate genetic counseling should be considered.

Systemic Cytokines in Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.

Central Retinal Vein Occlusion in a Young Woman with Diabetes and Hypertension after mRNA-Based COVID-19 Vaccination-A Case Report and Brief Review of the Literature.

A 25-year-old female with diabetes and hypertension presented with progressive painless blurred vision in her left eye ten days after she received her third dose of the SARS-CoV-2 mRNA vaccine BNT162b2 (Pfizer-BioNTech). The clinical examination confirmed the diagnosis of Central Retinal Vein Occlusion (CRVO) complicated with macular edema. Three doses of anti-vascular endothelial growth factor (VEGF) were injected intravitreally. Visual acuity was improved from 20/100 to 20/30, but recurrence was noted at 6 months. Several cases of retinal vein occlusion (RVO) after COVID-19 vaccination have been reported. However, the present case is the youngest female individual documented to have CRVO after SARS-CoV-2 vaccination. This case demonstrates that the macular edema might be recurrent in patients with risk factors for CRVO who receive SARS-CoV-2 vaccination, suggesting the need for careful consideration of the treatment strategy and close follow-up. Although the definite pathogenesis still needs to be carefully determined, this report highlights the possible association between RVO and mRNA-based COVID-19 vaccination, even in young individuals.

HIF2α activation and mitochondrial deficit due to iron chelation cause retinal atrophy.

Iron accumulation causes cell death and disrupts tissue functions, which necessitates chelation therapy to reduce iron overload. However, clinical utilization of deferoxamine (DFO), an iron chelator, has been documented to give rise to systemic adverse effects, including ocular toxicity. This study provided the pathogenic and molecular basis for DFO-related retinopathy and identified retinal pigment epithelium (RPE) as the target tissue in DFO-related retinopathy. Our modeling demonstrated the susceptibility of RPE to DFO compared with the neuroretina. Intriguingly, we established upregulation of hypoxia inducible factor (HIF) 2α and mitochondrial deficit as the most prominent pathogenesis underlying the RPE atrophy. Moreover, suppressing hyperactivity of HIF2α and preserving mitochondrial dysfunction by α-ketoglutarate (AKG) protects the RPE against lesions both in vitro and in vivo. This supported our observation that AKG supplementation alleviates visual impairment in a patient undergoing DFO-chelation therapy. Overall, our study established a significant role of iron deficiency in initiating DFO-related RPE atrophy. Inhibiting HIF2α and rescuing mitochondrial function by AKG protect RPE cells and can potentially ameliorate patients' visual function.