Optical coherence tomography angiography in diabetic retinopathy: A major review.

Diabetic retinopathy (DR) is characterized by retinal vasculopathy and is a leading cause of visual impairment. Optical coherence tomography angiography (OCTA) is an innovative imaging technology that can detect various pathologies and quantifiable changes in retinal microvasculature. We briefly describe its functional principles and advantages over fluorescein angiography and perform a comprehensive review on its clinical applications in the screening or management of people with prediabetes, diabetes without clinical retinopathy (NDR), nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME). OCTA reveals early microvascular alterations in prediabetic and NDR eyes, which may coexist with sub-clinical neuroretinal dysfunction. Its applications in NPDR include measuring ischemia, detecting retinal neovascularization, and timing of early treatment through predicting the risk of retinopathy worsening or development of DME. In PDR, OCTA helps characterize the flow within neovascular complexes and evaluate their progression or regression in response to treatment. In eyes with DME, OCTA perfusion parameters may be of predictive value regarding the visual and anatomical gains associated with treatment. We further discussed the limitations of OCTA and the benefits of its incorporation into an updated DR severity scale.

Vision-related quality of life in patients with retinal vein occlusion.

PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.

Safety and Efficacy of Topical Vitamin D in the Management of Dry Eye Disease Associated With Meibomian Gland Dysfunction: A Placebo-Controlled Double-Blind Randomized Controlled Trial.

PURPOSE: The aim of this study was to investigate the safety and efficacy of topical vitamin D in the management of dry eye disease associated with meibomian gland dysfunction (MGD). METHODS: In this randomized controlled trial, patients with symptomatic MGD were divided into 2 groups to receive topical vitamin D drops or placebo in their randomized eyes. The exclusion criteria consisted of patients with vitamin D deficiency, previous ocular surgery, and patients with ocular diseases affecting the tear film. Patients and researchers were masked to the study groups. The outcomes included the score of Dry Eye Questionnaire (DEQ) 5 and Ocular Surface Disease Index (OSDI), corneal and conjunctival staining score, tear breakup time (TBUT), Schirmer, and MG expressibility score evaluated at baseline and weeks 4 and 8. RESULTS: Twenty-eight eyes of 28 patients were recruited in each group. In addition to the improvement of subjective parameters in both groups, there was a statistically significantly greater improvement in the vitamin D group compared with control for average scores of OSDI (13.38 ± 7.32 vs. 27.94 ± 7.49) and DEQ5 (9.67 ± 1.86 vs. 14.14 ± 2.45) at week 8 (Ps <0.001). In addition, a significant improvement in TBUT and Schirmer test was observed in both groups in weeks 4 and 8 ( P value <0.05). There was a significant difference between the treatment and control groups after 8 weeks for OSDI, DEQ5, Schirmer, TBUT, corneal fluorescein staining, and MG expressibility score ( P value <0.05). CONCLUSIONS: The preliminary results of this randomized controlled trial suggested that use of topical vitamin D drops with a lipid vehicle could be safe and might significantly improve the symptoms and signs of dry eye associated with MGD.

Intravitreal Injection of Anti-Vascular Endothelial Growth Factors Combined with Corticosteroids for the Treatment of Macular Edema Secondary to Retinal Vein Occlusion: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the efficacy and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) and corticosteroid combination therapy for the management of treatment-naïve or recurrent/refractory macular edema caused by retinal vein occlusion (RVO) in comparison with anti-VEGF monotherapy. METHODS: In this systematic review and meta-analysis study, the data from publications in the electronic databases including PubMed, Embase, Cochrane Library Central Register of Controlled Trials, ISI and Scopus from January 1, 2007, through November 20, 2020, were compiled. Heterogeneity was statistically quantified by the I2 statistic, and meta-analysis was performed using a random-effects model. RESULTS: Twenty-four related studies were identified, including a total of 1280 eyes, which consisted of 685 and 507 patients with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), respectively. This study demonstrated a greater improvement in best-corrected visual acuity (BCVA) in the combination group compared to anti-VEGF monotherapy for both CRVO and BRVO cases at 6 months after initiating therapy. The improvement in vision was more notable in BRVO cases than in CRVO cases. However, the changes in central macular thickness (CMT) did not differ significantly between the different treatment approaches, and the results were inconclusive. Including all cases with RVO, there was no inferiority in terms of BCVA improvement and CMT reduction in the triamcinolone subgroup compared with the slow-release dexamethasone implant subgroup. A greater improvement was noticed in terms of BCVA in the sequentially treated subgroup compared to the simultaneous treatment subgroup, while there was a greater reduction in CMT in the simultaneous subgroup with the highest reduction recorded at 1 month after treatment. CONCLUSIONS: This study suggests that combination therapy with intravitreal anti-VEGF and corticosteroid (such as intravitreal or subtenon triamcinolone or dexamethasone implant) has a slightly better effect on improving BCVA in cases with BRVO or CRVO at 6 months compared to monotherapy.

Prevalence of refractive errors in population aged 50 years and over: The Gilan eye study.

PURPOSE: To describe the prevalence of refractive error (RE) and its association with other environmental and health factors among population aged ≥50 years who lived in Gilan, Iran in 2014. METHODS: In this population-based cross-sectional study, 3281 individuals aged ≥50 years living in Gilan for at least 6 months were enrolled. The prevalence of different types of REs including myopia (spherical equivalent (SE)≤-0.50D), high myopia (SE ≤ -6.00D), hyperopia (SE≥ + 0.50D), high hyperopia (SE≥ + 3.00D), astigmatism (cylinder < -0.50D) and high astigmatism (cylinder < -2.25D) were determined. Anisometropia was defined as the SE difference of ≥1.00D between the two eyes. Associated factors including age, body mass index (BMI) and education were also studied. RESULTS: 2587 eligible individuals (58% female subjects) with the mean age of 62.6 ± 8.8 years participated (87.6% response rate). The prevalence of myopia, hyperopia and astigmatism was 19.2%, 48.6% and 57.4%, respectively. 3.6% high hyperopia, 0.5% high myopia and 4.5% high astigmatism were identified. The positive simultaneous effects3 of older age (Odds Ratio (OR) = 3.14), nuclear (OR = 1.71) and posterior subcapsular (OR = 1.61) cataracts as well as the negative effects of higher levels of education (OR = 0.28) were obtained on myopia. Higher BMI was found as a risk factor for hyperopia (OR = 1.67), while older patients were less likely to be hyperopic (OR = 0.31). CONCLUSION: Higher incidence of myopia and astigmatism was found in patients aged over 70 years. It was also found that patients at older ages who suffered with cataracts were at a higher risk of myopia, while elderly people with greater BMI were at a higher risk of hyperopia.

CLOSURE OF IDIOPATHIC FULL-THICKNESS MACULAR HOLE AFTER INTRAVITREAL C3F8 INJECTION WITHOUT VITREOMACULAR TRACTION RELEASE: A CASE REPORT AND REVIEW OF LITERATURE.

BACKGROUND: The purpose of this study was to describe a successful closure of macular hole without release of vitreomacular traction after intravitreal perfluoropropane (C3F8) gas injection. CASE PRESENTATION: A 54-year-old woman was referred to our clinic with the history of declined vision after a period of distorted vision in her right eye. After dilated fundus examination and performing optical coherence tomography, a V-shaped vitreomacular traction complicated by full-thickness macular hole was diagnosed and she underwent pneumatic vitreolysis using intravitreal C3F8 gas injection. After 12 weeks, her visual acuity was significantly improved and fundus examination and optical coherence tomography revealed that the macular hole was completely resolved despite persisted vitreomacular traction. CONCLUSION: Intravitreal gas injection would be a promising option to manage idiopathic macular holes not only by releasing the vitreous traction on the macula but also through some not proven or even unknown mechanisms.

Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment in the elderly. The current management of nAMD is limited and involves regular intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF). However, the effectiveness of these treatments is limited by overlapping and compensatory pathways leading to unresponsiveness to anti-VEGF treatments in a significant portion of nAMD patients. Therefore, a system view of pathways involved in pathophysiology of nAMD will have significant clinical value. The aim of this study was to identify proteins, miRNAs, long non-coding RNAs (lncRNAs), various metabolites, and single-nucleotide polymorphisms (SNPs) with a significant role in the pathogenesis of nAMD. To accomplish this goal, we conducted a multi-layer network analysis, which identified 30 key genes, six miRNAs, and four lncRNAs. We also found three key metabolites that are common with AMD, Alzheimer's disease (AD) and schizophrenia. Moreover, we identified nine key SNPs and their related genes that are common among AMD, AD, schizophrenia, multiple sclerosis (MS), and Parkinson's disease (PD). Thus, our findings suggest that there exists a connection between nAMD and the aforementioned neurodegenerative disorders. In addition, our study also demonstrates the effectiveness of using artificial intelligence, specifically the LSTM network, a fuzzy logic model, and genetic algorithms, to identify important metabolites in complex metabolic pathways to open new avenues for the design and/or repurposing of drugs for nAMD treatment.

A health terminological system for inherited retinal diseases: Content coverage evaluation and a proposed classification.

PURPOSE: To present a classification of inherited retinal diseases (IRDs) and evaluate its content coverage in comparison with common standard terminology systems. METHODS: In this comparative cross-sectional study, a panel of subject matter experts annotated a list of IRDs based on a comprehensive review of the literature. Then, they leveraged clinical terminologies from various reference sets including Unified Medical Language System (UMLS), Online Mendelian Inheritance in Man (OMIM), International Classification of Diseases (ICD-11), Systematized Nomenclature of Medicine (SNOMED-CT) and Orphanet Rare Disease Ontology (ORDO). RESULTS: Initially, we generated a hierarchical classification of 62 IRD diagnosis concepts in six categories. Subsequently, the classification was extended to 164 IRD diagnoses after adding concepts from various standard terminologies. Finally, 158 concepts were selected to be classified into six categories and genetic subtypes of 412 cases were added to the related concepts. UMLS has the greatest content coverage of 90.51% followed respectively by SNOMED-CT (83.54%), ORDO (81.01%), OMIM (60.76%), and ICD-11 (60.13%). There were 53 IRD concepts (33.54%) that were covered by all five investigated systems. However, 2.53% of the IRD concepts in our classification were not covered by any of the standard terminologies. CONCLUSIONS: This comprehensive classification system was established to organize IRD diseases based on phenotypic and genotypic specifications. It could potentially be used for IRD clinical documentation purposes and could also be considered a preliminary step forward to developing a more robust standard ontology for IRDs or updating available standard terminologies. In comparison, the greatest content coverage of our proposed classification was related to the UMLS Metathesaurus.

Prevalence of cataract and its contributing factors in Iranian elderly population: the Gilan eye study.

PURPOSE: To report the prevalence and the associated factors leading to cataract among the Iranian population living in Gilan Province, Iran. METHODS: This population-based cross-sectional study was performed from June to November 2014 on 2,975 residents aged ≥ 50 years old living in urban and rural regions of the Gilan Province in Iran. A representative sample of residents in the province was recruited into the study through door-to-door visiting, and baseline data were collected by questionnaire. All participants were referred to the medical center for comprehensive ophthalmic examination, laboratory tests, and blood pressure measurement. RESULTS: Among the population, 2,588 (86.99%) subjects were eligible to be included in this study, categorized either into the cataract or the non-cataract group. The mean age of participants was 62.59 ± 8.92 years, and 57.5% were female. Higher prevalence of cataract was found in individuals of older ages (odds ratio (OR) = 1.13; 95% confidence interval (CI) = 1.10 to 1.16; P < 0.001) and a history of previous ocular surgery (OR = 5.78; 95% CI = 2.28 to 14.63; P < 0.001). At the same time, a lower prevalence of cataract was seen in patients exposed to sunlight for more than 4 h per day (OR = 0.49; 95% CI = 0.32 to 0.73; P = 0.001). CONCLUSION: Cataract affects 50.50% of the study population, especially those over 80. The mildest form of cataract, grade zero, is the most common. Surgery for cataract has good outcomes. The risk of cataract is higher for those older or who have had eye surgeries. People not affected by cataract tend to be exposed to more sunlight.

microRNA-96 targets the INS/AKT/GLUT4 signaling axis: Association with and effect on diabetic retinopathy.

Background: miR-96-5p is a highly expressed microRNA in the retina of subjects with diabetes. The INS/AKT/GLUT4 signaling axis is the main cell signaling pathway of glucose uptake in cells. Here, we investigated the role of miR-96-5p in this signaling pathway. Methods: Expression levels of miR-96-5p and its target genes were measured under high glucose conditions, in the retina of streptozotocin-induced diabetic mice, in the retina of AAV-2-eGFP-miR-96 or GFP intravitreal injected mice and in the retina of human donors with diabetic retinopathy (DR). MTT, wound healing, tube formation, Western blot, TUNEL, angiogenesis assays and hematoxylin-eosin staining of the retinal sections were performed. Results: miR-96-5p expression was increased under high glucose conditions in mouse retinal pigment epithelial (mRPE) cells, in the retina of mice receiving AAV-2 carrying miR-96 and STZ-treated mice. Expression of the miR-96-5p target genes related to the INS/AKT/GLUT4 signaling pathway was reduced following miR-96-5p overexpression. mmu-miR-96-5p expression decreased cell proliferation and thicknesses of retinal layers. Cell migration, tube formation, vascular length, angiogenesis, and TUNEL-positive cells were increased. Conclusions: In in vitro and in vivo studies and in human retinal tissues, miR-96-5p regulated the expression of the PIK3R1, PRKCE, AKT1, AKT2, and AKT3 genes in the INS/AKT axis and some genes involved in GLUT4 trafficking, such as Pak1, Snap23, RAB2a, and Ehd1. Because disruption of the INS/AKT/GLUT4 signaling axis causes advanced glycation end product accumulation and inflammatory responses, the inhibition of miR-96-5p expression could ameliorate DR.

Sensitivity and specificity of optical coherence tomography angiography for diagnosis and classification of diabetic retinopathy; a systematic review and meta-analysis.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a noninvasive imaging method that can be used for the staging of diabetic retinopathy. In addition, alterations in OCTA parameters can precede the clinical fundus changes. In this review, we aimed to assess the accuracy of OCTA in diagnosis and staging of diabetic retinopathy. METHODS: Two independent reviewers participated in the literature search using electronic databases (PubMed, Embase, Cochrane Library Central Register of Controlled Trials, ISI, and Scopus) from inception till December 2020. The heterogeneity of data was assessed by Q statistics, Chi-square test and I2 index. RESULTS: Forty-four articles published from 2015 to the end of 2020 were included in this meta-analysis. Of these, 27 were case-control studies, 9 were case series, and 8 were cohort studies. In total, 4284 eyes of 3553 patients were assessed in this study. OCTA could differentiate diabetic retinopathy from diabetes without diabetic retinopathy with a sensitivity of 88% (95% CI: 85% to 92%) and specificity of 88% (95% CI: 85% to 91%). In addition, it could differentiate proliferative diabetic retinopathy from non-proliferative diabetic retinopathy with a sensitivity of 91% (95% CI: 86% to 95%) and specificity of 91% (95% CI:86% to 96%). The sensitivity of OCTA for diagnosing diabetic retinopathy was increased by the size of scan (3 × 3 mm: 85%; 6 × 6 mm: 91%, 12 × 12 mm: 96%). CONCLUSION: OCTA, as a non-invasive method, has acceptable sensitivity and specificity for diagnosis and classification of diabetic retinopathy. A larger scan size is associated with more sensitivity for discriminating diabetic retinopathy.

Choroidal structure investigated by choroidal vascularity index in patients with inherited retinal diseases.

PURPOSE: To evaluate the choroidal structure in patients with inherited retinal diseases (IRDs) by investigating the choroidal vascularity index (CVI). METHODS: The present study was conducted on 113 IRD patients and 113 sex- and age-matched healthy individuals. Patients' data was extracted from the Iranian National Registry for IRDs (IRDReg®). Total choroidal area (TCA) was determined between retinal pigment epithelium and choroid-scleral junction,1500 microns on either side of the fovea. Luminal area (LA) was considered as the black area corresponding to the choroidal vascular spaces, following Niblack binarization. CVI was calculated as the ratio of the LA to the TCA. CVI and other parameters were compared among different types of IRD and the control group. RESULTS: The IRD diagnosis included retinitis pigmentosa (n = 69), cone-rod dystrophy (n = 15), Usher syndrome (n = 15), Leber congenital amaurosis (n = 9), and Stargardt disease (n = 5). Sixty-one (54.0%) individuals of each of the study and control groups were male. The average CVI was 0.65 ± 0.06 in the IRD patients and 0.70 ± 0.06 in the control group (P < 0.001). Accordingly, the average of TCA and LA were 2.32 ± 0.63 and 1.52 ± 0.44 mm [1] in patients with IRDs, respectively. The measurements for the TCA and the LA were significantly lower in all subtypes of IRD (P-values < 0.05). CONCLUSION: CVI is significantly lower in patients with IRD than in healthy age-matched individuals. Choroidal changes in IRDs may be related to the changes in the lumen of the choroidal vessels rather than the stromal changes.

Retinal ischemic cascade: New insights into the pathophysiology and imaging findings.

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of ischemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accompanying risk factors, the middle and inner retinal vasculature and blood flow, and the vulnerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resembles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible associations between the middle and inner retinal ischemic patterns.

Design, construction and in vivo functional assessment of a hinge truncated sFLT01.

Gene therapy for the treatment of ocular neovascularization has reached clinical trial phases. The AAV2-sFLT01 construct was already evaluated in a phase 1 open-label trial administered intravitreally to patients with advanced neovascular age-related macular degeneration. SFLT01 protein functions by binding to VEGF and PlGF molecules and inhibiting their activities simultaneously. It consists of human VEGFR1/Flt-1 (hVEGFR1), a polyglycine linker, and the Fc region of human IgG1. The IgG1 upper hinge region of the sFLT01 molecule makes it vulnerable to radical attacks and prone to causing immune reactions. This study pursued two goals: (i) minimizing the immunogenicity and vulnerability of the molecule by designing a truncated molecule called htsFLT01 (hinge truncated sFLT01) that lacked the IgG1 upper hinge and lacked 2 amino acids from the core hinge region; and (ii) investigating the structural and functional properties of the aforesaid chimeric molecule at different levels (in silico, in vitro, and in vivo). Molecular dynamics simulations and molecular mechanics energies combined with Poisson-Boltzmann and surface area continuum solvation calculations revealed comparable free energy of binding and binding affinity for sFLT01 and htsFLT01 to their cognate ligands. Conditioned media from human retinal pigment epithelial (hRPE) cells that expressed htsFLT01 significantly reduced tube formation in HUVECs. The AAV2-htsFLT01 virus suppressed vascular development in the eyes of newborn mice. The htsFLT01 gene construct is a novel anti-angiogenic tool with promising improvements compared to existing treatments.

Augmented Expression of NOGO-A and Its Receptors in Human Retinal Pigment Epithelial Cells Following Treatment with Human Amniotic Fluid.

Background: Nogo-A, a myelin-associated inhibitor for neurite outgrowth, has important role in visual system development. Trans-differentiation ability of human amniotic fluid (HAF) on human retinal pigment epithelial cells (hRPEs) towards neural progenitor cells has been observed in several studies. We aimed to investigate the expression of NOGO-A gene and its receptors as a marker of neural differentiation in HAF-treated hRPE cells. Methods: hRPE cells were cultivated and immune characterized via RPE65 and cytokeratin 8/18 protein markers. Also, the cytotoxicity effect of 30% HAF on hRPE cells was evaluated using ELISA cell death assay. Finally, expression of NOGO-A and its receptors, RTN4R and LINGO1 was evaluated in the cells treated with HAF in comparison with FBS-treated cells using quantitative real-time PCR. Results: Harvested cells showed immunoreactivity for cytokeratin 8/18 and RPE65, confirming the hRPE cell identity. Besides, HAF had no cytotoxic effect on hRPE cells compared with FBS-treated cells. Results showed that NOGO-A and its receptors were expressed in cultured hRPE cells. Besides, comparative gene expression analysis revealed significant increased expression of the investigated genes in HAF-treated hRPE cells compared to FBS-treated cells. Conclusion: Augmented expression of NOGO-A and its receptors can support neural differentiation of hRPE when the cells are treated with HAF. Our outcomes provide more evidences on the trans-differentiation ability of HAF on hRPE cells into neural progenitors and retinal neural cells, but further studies are needed to elucidate the exact mechanism.

Optical Coherence Tomography Angiography in Patients with Amblyopia.

To determine the optical coherence tomography angiography (OCTA) parameters including foveal avascular zone (FAZ) and vessel density (VD) in the amblyopic eyes compared with the fellow sound eyes and the eyes of the non-amblyopic subjects. In this case-control study, a total of 23 eyes from unilateral amblyopic children were included as cases. The sound eye of the amblyopic children was considered as the internal control and the right eyes of the non-amblyopic children were considered as the external control. All participants underwent image recording with OCTA. In the present study, an equal number of 23 unilateral amblyopic eyes and 23 right eyes of non-amblyopic age- and sex-matched children were included as the cases and controls, respectively. The average age of participants in the case and controls were 9.86 ± 3.12 and 8.5 ± 2.35 years, respectively. Twelve patients (52.2%) in the case group and 14 subjects (60.9%) in the control group were female. Whole vascular density of the macula in superficial capillary plexuses (SCP) was significantly lower in the external controls compared with the other studied groups (P = .026). However, the VD of the deep capillary plexuses (DCP) was significantly greater in the external controls than cases and internal controls (P= .029). The average FAZ area was 0.26 ± 0.06 mm2 in amblyopic eyes that was significantly higher compared with fellow eyes (0.21 ± 0.07 mm2; P= .022), but it was not different with non-amblyopic eyes (0.22 ± 0.118 mm2). Based on our findings, there were no significant difference in the cases of foveal, parafoveal, and perifoveal in both superficial and deep vascular densities among amblyopic and non-amblyopic eyes, whereas deep whole density of the amblyopic eyes showed lower percent compared to non-amblyopic ones that indicates decrease blood supply of the amblyopic eyes in this region. Additionally, FAZ was larger in amblyopic eyes than internal controls.

Combined intravitreal injection of bevacizumab and a ROCK inhibitor (fasudil) for refractory macular edema secondary to retinal vein occlusion: a pilot study.

BACKGROUND: To investigate the adjunctive effect of an intravitreal ROCK inhibitor (fasudil) in combination with intravitreal bevacizumab (IVB) on refractory macular edema secondary to retinal vein occlusion (RVO). METHODS: In this prospective interventional case series, 17 eyes of 17 patients (10 men, 7 women) with refractory RVO-related macular edema underwent three consecutive intravitreal injections of bevacizumab plus fasudil. Monthly evaluation was continued up to 12 months and IVB injection was performed if needed during the follow-up. Changes in the best corrected visual acuity (BCVA) was the primary outcome measure. The secondary outcome measures included central macular thickness (CMT) changes and any adverse events. RESULTS: BCVA significantly improved (mean change: -0.15 LogMAR; P = 0.017) after 3 consecutive intravitreal injections of fasudil in combination with bevacizumab. CMT significantly decreased (mean change: -206 µm; P = 0.028). The anatomical and functional improvement was maintained during the 12 month follow-up. No adverse effects were noticed. CONCLUSION: Intravitreal ROCK inhibitors may break the resistance to anti-VEGF therapy and improve the RVO induced macular edema via affecting the VEGF-independent pathways.

Erratum: Carrier Status for p.Gly61Glu and p.Arg368His CYP1B1 Mutations Causing Primary Congenital Glaucoma in Iran.

[This corrects the article DOI: 10.18502/jovr.v16i4.9747.].

A Systematic Literature Review and Bibliometric Analysis of Ophthalmology and COVID-19 Research.

This review is proposed to summarize the updates on COVID-19 and ophthalmology along with the bibliometric features of articles that have been published since the beginning of the COVID-19 outbreak. The databases, including PubMed, Scopus, and Web of Science, were searched using "Coronavirus," "COVID-19," "SARS-CoV-2," "pandemic," "ophthalmology," "ophthalmic," and "eye" keywords. All published articles except commentaries, errata, and corrigenda up to April 2021 were included. Titles and abstracts were screened, and ophthalmology-focused articles were collected. The bibliographic information of the articles, such as the name and country of the first author, type of study, date of publication, language, and journal name, were extracted. Included studies were assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. After systematic searching, 2,669 distinct articles were screened by title/abstract, and 1,174 ophthalmology-focused articles were selected to be reviewed. Ophthalmology-focused publications accounted for less than 0.5 percent of the total COVID-19-related articles. Most of the articles were published in the Indian Journal of Ophthalmology, and the main publication type was "original article." Almost 88% of the publications were in English. There was a decline in the publication rate during the initial months of 2021 compared with the middle and last months of 2020. Most of the publications were affiliated with the United States of America. However, Singapore and the United Kingdom were the countries with the highest number of publications after population adjustment. Furthermore, a comprehensive review on major topics including SARS-CoV-2 ocular tropism, ophthalmic manifestations, ocular complications due to COVID-19 treatment strategies, the pandemic effect on ophthalmology care and operations, myopia progression during the pandemic, and telemedicine was conducted.