2023

PURPOSE: Genetic variants in regions that include the mitochondrial genes TXNRD2 and ME3 are associated with primary open-angle glaucoma (POAG) in genome-wide association studies (GWAS). To assess their clinical impact, we investigated whether TXNRD2 and ME3 genetic risk scores (GRSs) are associated with specific glaucoma phenotypes. DESIGN: Cross-sectional study PARTICIPANTS: 2617 POAG cases and 2634 controls from the NEIGHBORHOOD consortium. METHODS: All POAG-associated single nucleotide polymorphisms (SNPs) in the TXNRD2 and ME3 loci were identified using GWAS data (p<0.05). Of these, 20 TXNRD2 and 24 ME3 SNPs were selected after adjusting for linkage disequilibrium. The correlation between SNP effect size and gene expression levels was investigated using the Gene-Tissue Expression (GTEx) database. GRSs were constructed for each individual using the unweighted sum of TXNRD2, ME3, and TXNRD2+ME3 combined risk alleles. Age and gender-adjusted odds ratios (ORs) for POAG diagnosis were calculated per decile for each GRS. Additionally, the clinical features of POAG cases in the top 1, 5, and 10% of each GRS were compared to the bottom 1, 5, and 10%, respectively. MAIN OUTCOME MEASURES: POAG OR per GRS decile; maximal treated intraocular pressure (IOP) and prevalence of paracentral visual field loss among POAG cases with high vs. low GRSs. RESULTS: Increased SNP effect size strongly correlated with higher TXNRD2 and lower ME3 expression levels (r=0.95 and -0.97, respectively, p<0.05 for both). Individuals in decile 10 of TXNRD2+ME3 GRS had the highest odds of POAG diagnosis (OR=1.79 compared to decile 1, p<0.001). POAG cases in the top 1% of TXNRD2 GRS had higher mean maximal treated IOP compared to the bottom 1% (19.9 mmHg vs 15.6 mmHg, adjusted p=0.03). POAG cases in the top 1% of ME3 and TXNRD2+ME3 GRS had a higher prevalence of paracentral field loss compared to the bottom 1% (72.7-88.9% vs 14.3-33.3%; adjusted p=0.03 for both). CONCLUSIONS: POAG patients with higher TXNRD2 and ME3 GRSs had higher treated IOP and a greater prevalence of paracentral field loss. Functional studies exploring how these variants impact mitochondrial function in glaucoma patients are warranted.

Rare missense and nonsense variants in the Angiopoietin-like 7 (ANGPTL7) gene confer protection from primary open-angle glaucoma (POAG), though the functional mechanism remains uncharacterized. Interestingly, a larger variant effect size strongly correlates with in silico predictions of increased protein instability (r = -0.98), suggesting that protective variants lower ANGPTL7 protein levels. Here, we show that missense and nonsense variants cause aggregation of mutant ANGPTL7 protein in the endoplasmic reticulum (ER) and decreased levels of secreted protein in human trabecular meshwork (TM) cells; a lower secreted:intracellular protein ratio strongly correlates with variant effects on intraocular pressure (r = 0.81). Importantly, accumulation of mutant protein in the ER does not increase expression of ER stress proteins in TM cells (P > 0.05 for all variants tested). Cyclic mechanical stress, a glaucoma-relevant physiologic stressor, also significantly lowers ANGPTL7 expression in primary cultures of human Schlemm's canal (SC) cells (-2.4-fold-change, P = 0.01). Collectively, these data suggest that the protective effects of ANGPTL7 variants in POAG stem from lower levels of secreted protein, which may modulate responses to physiologic and pathologic ocular cell stressors. Downregulation of ANGPTL7 expression may therefore serve as a viable preventative and therapeutic strategy for this common, blinding disease.

Stroke is the most common cause of acquired epilepsy, but treatment for preventing the development of post-stroke epilepsy is still unavailable. Since stroke results in neuronal damage and death as well as initial loss of activity in the affected brain region, homeostatic plasticity may be trigged and contribute to an increase in network hyperexcitability that underlies epileptogenesis. Correspondingly, enhancing brain activity may inhibit hyperexcitability from enhanced homeostatic plasticity and prevent post-stroke epileptogenesis. To test these hypotheses, we first used in vivo two-photon and mesoscopic imaging of activity of cortical pyramidal neurons in Thy1-GCaMP6 transgenic mice to determine longitudinal changes in excitatory activity after a photothrombotic ischemic stroke. At 3-days post-stroke, there was a significant loss of neuronal activity in the peri-injury area as indicated by reductions in the frequency of calcium spikes and percentage of active neurons, which recovered to baseline level at day 7, supporting a homeostatic activity regulation of the surviving neurons in the peri-injury area. We further used optogenetic stimulation to specifically stimulate activity of pyramidal neurons in the peri-injury area of Thy-1 channelrhodopsin transgenic mice from day 5 to day 15 after stroke. Using pentylenetetrazole test to evaluate seizure susceptibility, we showed that stroke mice are more susceptible to Racine stage V seizures (time latency 54.3 ± 12.9 min) compared to sham mice (107.1 ± 13.6 min), but optogenetic stimulation reversed the increase in seizure susceptibility (114.0 ± 9.2 min) in mice with stroke. Similarly, administration of D-cycloserine, a partial N-methyl-d-aspartate (NMDA) receptor agonist that can mildly enhance neuronal activity without causing post-stroke seizure, from day 5 to day 15 after a stroke significantly reversed the increase in seizure susceptibility. The treatment also resulted in an increased survival of glutamic acid decarboxylase 67 (GAD67) positive interneurons and a reduced activation of glial fibrillary acidic protein (GFAP) positive reactive astrocytes. Thus, this study supports the involvement of homeostatic activity regulation in the development of post-stroke hyperexcitability and potential application of activity enhancement as a novel strategy to prevent post-stroke late-onset seizure and epilepsy through regulating cortical homeostatic plasticity.

PURPOSE: To demonstrate the use of a novel measure of neighborhood quality, the Child Opportunity Index (COI), for investigating health disparities in pediatric ophthalmology. METHODS: This study included children 2-12 years of age from a registry of patients diagnosed with amblyopia at an urban pediatric hospital between 2010 and 2014. Children previously treated for amblyopia were excluded. Patient demographics, residential addresses, and logMAR visual acuities were collected. The association between visual acuity at presentation and COI was examined using linear mixed-effects models adjusting for individual-level factors, including age, sex, race, ethnicity, and insurance type. RESULTS: This study included 1,050 amblyopic children, of whom 317 (37%) were non-White and 149 (19%) were Hispanic; 461 (44%) had public insurance. Regarding residence, 129 (12%) lived in areas of very low opportunity (COI <20); 489 (47%) in areas of very high opportunity (COI ≥80). Children residing in the lowest opportunity neighborhoods correctly identified approximately two fewer letters at presentation with their better-seeing eye compared with children from the highest opportunity neighborhoods after adjusting for individual-level factors (-0.0090 logMAR per 20 unit increase in COI; 95% CI, -0.0172 to -0.0008; P = 0.031). No difference was appreciated in the worse-seeing eye. CONCLUSIONS: Amblyopic children residing in communities with low neighborhood opportunity had slightly worse visual acuity in the better-seeing eye at presentation. Although statistically significant in the better-seeing eye, the two-letter difference attributable to neighborhood environment may not be clinically significant, and the impact of this disparity on treatment outcomes deserves further investigation.

PURPOSE: The purpose of this systematic review is to identify techniques used for quantification of choriocapillaris (CC) flow in eyes with uveitis using optical coherence tomography angiography (OCTA), report reliability and level of correlation with techniques such as indocyanine green angiography (ICGA). METHODS: A systematic search of several databases was done. The studies were analyzed for techniques of measurement, reliability, and correlation with other modalities. Risk of bias assessment was performed. RESULTS: Thirteen studies were included. CC vessel density (7 studies) and flow deficit area (4 studies) were the most used indices. There was significant heterogeneity in the studies due to differences in the scan protocol, thresholding strategy, and analysis. Comparison with ICGA was performed by only one study, and reliability indices were reported by only two studies. CONCLUSION: OCTA is a useful tool to measure the CC vascularity in eyes with uveitis. However, standardized acquisition and analysis protocols are needed.

An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.

OBJECTIVE: To introduce the Collaborative Ocular Tuberculosis Study (COTS) Calculator, an online clinical scoring system for initiating antitubercular therapy (ATT) in patients with ocular tuberculosis (TB). METHOD: The COTS Calculator was derived from COTS Consensus (COTS CON) data, which has previously published consensus guidelines. Using a two-step Delphi method, 81 experts evaluated 486 clinical scenario-based questions, ranking their likelihood of initiating ATT in each specific scenario. Each scenario was a permutation of the results and/or availability of five following components-clinical phenotype, endemicity, two immunological (tuberculin skin test, interferon-γ release assay) and one radiological (chest X-Ray) test results-and a sixth component further stratifying three of the clinical phenotypes. The median scores and interquartile ranges (IQR) of each scenario were tabulated, representing the expert consensus on whether to initiate ATT in that scenario. The consensus table was encoded to develop the COTS Calculator. RESULTS: The COTS Calculator can be accessed online at: https://www.oculartb.net/cots-calc . The attending physician can select the conditions present in the patient, which will generate a median score from 1 to 5. 114 out of 486 scenarios (24%) deliberated had a median score of 5 indicating expert consensus to initiate ATT. CONCLUSION: The COTS Calculator is an efficient, low-cost, evidence and experience-based clinical tool to guide ATT initiation. While it holds substantial promise in improving standard-of-care for ocular-TB patients, future validation studies can help to as certain its clinical utility and reliability.

PURPOSE: To provide an overview of the impact of retinopathy of prematurity (ROP), and the challenges in the screening, diagnosis, and treatment of ROP worldwide. METHODS: A comprehensive search was conducted using the PubMed database from January 2011 to October 2021 using the following keywords: retinopathy of prematurity, laser, and anti-vascular endothelial growth factor (VEGF). Data on patient characteristics, ROP treatment type, and recurrence rates were collected. The countries included in these studies were classified based on 2021-2022 World Bank definitions of high, upper-middle, lower-middle, and low-income groups. Moreover, a search for surgical outcomes for ROP and screening algorithms and artificial intelligence for ROP was conducted. RESULTS: Thirty-nine studies met the inclusion criteria. ROP treatment and outcomes showed a trend towards intravitreal anti-VEGF injections as the initial treatment for ROP globally and the treatment of recurrent ROP in high-income countries. However, laser remains the treatment of choice for ROP recurrence in middle-income countries. Surgical outcomes for ROP stage 4A, 4B and 5 are similar worldwide. The incidence of ROP and ROP-related visual impairment continue to increase globally. Although telemedicine and artificial intelligence offer potential solutions to ROP screening in resource-limited areas, the current models require further optimization to reflect the global diversity of ROP patients. CONCLUSION: ROP screening and treatment paradigms vary widely based on country income group due to disparities in resources, limited access to care, and lack of universal guidelines.

PURPOSE: To determine the effect of combined macular optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. UWFI and SD-OOCT were independently evaluated for diabetic macular edema (DME) and non-diabetic macular pathology. Sensitivity and specificity were calculated with SD-OCT as gold standard. RESULTS: 422 eyes from 211 diabetic patients were evaluated. DME severity by UWFI: no DME 93.4%, non-center involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular pathology was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. DME represented only 38.6% of referable macular pathology identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared to SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared to SDOCT was 3%/98% for ERM. CONCLUSIONS: Addition of SD-OCT increased the identification of macular pathology by 29.4%. Over 58.3% of the eyes thought to have any DME on UWF imaging alone were false positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false positive assessments of DME and macular pathology in a teleophthalmology program.

PURPOSE: To determine the effect of combined macular spectral-domain optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program. METHODS: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. Ultrawide field retinal imaging and SD-OOCT were independently evaluated for diabetic macular edema (DME) and nondiabetic macular abnormality. Sensitivity and specificity were calculated with SD-OCT as the gold standard. RESULTS: Four hundred twenty-two eyes from 211 diabetic patients were evaluated. Diabetic macular edema severity by UWFI was as follows: no DME 93.4%, noncenter involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular abnormality was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. Diabetic macular edema represented only 38.6% of referable macular abnormality identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared with SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared with SDOCT was 3%/98% for epiretinal membrane. CONCLUSION: Addition of SD-OCT increased the identification of macular abnormality by 29.4%. More than 58.3% of the eyes believed to have any DME on UWF imaging alone were false-positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false-positive assessments of DME and macular abnormality in a teleophthalmology program.

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.

PURPOSE: To test the hypothesis that a simple model having properties consistent with activation and deactivation in the rod approximates the whole time course of the photoresponse. METHODS: Routinely, an exponential of the form f = α·(1 - exp(-(τ·(t - teff)s-1))), with amplitude α, rate constant τ (often scaled by intensity), irreducible delay teff, and time exponent s-1, is fit to the early period of the flash electroretinogram. Notably, s (an integer) represents the three integrating stages in the rod amplification cascade (rhodopsin isomerization, transducin activation, and cGMP hydrolysis). The time course of the photoresponse to a 0.17 cd·s·m-2 conditioning flash (CF) was determined in 21 healthy eyes by presenting the CF plus a bright probe flash (PF) in tandem, separated by interstimulus intervals (ISIs) of 0.01 to 1.4 seconds, and calculating the proportion of the PF a-wave suppressed by the CF at each ISI. To test if similar kinetics describe deactivation, difference of exponential (DoE) functions with common α and teff parameters, respective rate constants for the initiation (I) and quenching (Q) phases of the response, and specified values of s (sI, sQ), were compared to the photoresponse time course. RESULTS: As hypothesized, the optimal values of sI and sQ were 3 and 2, respectively. Mean ± SD α was 0.80 ± 0.066, I was 7700 ± 2400 m2·cd-1·s-3, and Q was 1.4 ± 0.47 s-1. Overall, r2 was 0.93. CONCLUSIONS: A method, including a DoE model with just three free parameters (α, I, Q), that robustly captures the magnitude and time-constants of the complete rod response, was produced. Only two steps integrate to quench the rod photoresponse.

PURPOSE: To evaluate the retinal vasculature in pediatric patients with X-linked retinoschisis (XLRS). DESIGN: Retrospective consecutive case series. SUBJECTS: Pediatric patients with a diagnosis of XLRS who had undergone widefield fluorescein angiography (FA). METHODS: The electronic medical records of pediatric patients with XLRS at a tertiary referral eye center were reviewed from January 2015 to December 2021. Fluorescein angiography images were reviewed for anomalies of the retinal vasculature. MAIN OUTCOMES MEASURES: Vascular anomalies on FA were recorded, including capillary dropout/ischemia, terminal supernumerary vessels, vascular leakage, abnormal vascular loops, straightening of vessels, aberrant circumferential vessels, and neovascularization. RESULTS: In total, 29 eyes of 15 patients were included in the study (1 patient had a phthisical eye). On FA, the most common findings were capillary dropout/ischemia (21 of 29 eyes, 72.4%), terminal supernumerary vessels (21 eyes, 72.4%), abnormal vascular loops (20 eyes, 69%), and vascular leakage (17 eyes, 58.6%). Of the 17 eyes with leakage, the most posterior zone of involvement was zone 1 in 11 eyes (64.7%) and zone 2 in 6 eyes (35.3%). All eyes demonstrated ≥ 1 vascular anomaly on FA. Among the 29 eyes, 23 (79.3%) demonstrated peripheral bullous schisis or retinal detachment (RD) with a mean of 5.6 clock hours of involvement. The presence of either RD or bullous retinal schisis was associated with the incidence of capillary dropout (91.3% in schisis/RD eyes vs. 0% in nonschisis/RD eyes, P < 0.001). Among those with RD or bullous schisis, a higher degree of involvement correlated with more severe capillary dropout (Pearson 0.49, P = 0.025). CONCLUSION: The present study demonstrates consistent vascular changes in pediatric patients with XLRS using widefield FA. Although the presence of capillary ischemia was associated with the severity of bullous schisis or RD, other vascular anomalies were observed in patients both with and without peripheral schisis. Although further research is needed to understand the etiology of these vascular anomalies, FA should be considered in the evaluation of these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

PURPOSE: To report a case of proliferative vitreoretinopathy (PVR) in a man with recurrent retinal detachment successfully managed without surgical intervention following the initiation of intravitreal methotrexate injections to arrest progression of PVR. METHODS: Report of a case. RESULTS: A 60-year-old man presented to the retina clinic 4 weeks after undergoing vitrectomy for rhegmatogenous retinal detachment and was found to have an inferior recurrent retinal detachment. He underwent repeat vitrectomy and scleral buckling with successful reattachment of the retina in the immediate postoperative period. At postoperative Week 2, preretinal membranes were noted inferiorly with stretching of the causative retinal break and localized subretinal fluid, consistent with early PVR. The patient underwent immediate laser barricade, and a course of intravitreal methotrexate injections was started. At the final follow-up 7 months later, the retina was fully attached without progression of PVR. CONCLUSION: Intravitreal methotrexate may play a role in arresting progression of early postoperative PVR and obviating the need for surgical intervention.

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1 and 3, and weekly for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation and immunostaining were used to examine corneal cross-sections collected at the completion of follow-up. A biphasic ocular injury was observed in mice exposed to NM, most prominent in the corneal epithelium and anterior stroma. Following exposure, mice experienced central corneal epithelial erosions and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma. The epithelium was recovered by day 3, followed by exacerbated punctuate erosions alongside persistent stromal edema that arose and continued onward to four weeks post-exposure. The endothelial cell density was reduced on the first day after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at this time included dysmorphic basal epithelial cells, and in the limbal cornea included decreased cellular layers and p63+ area, along with increased DNA oxidization. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas. Our research suggests DNA oxidation contributes to the long-term effects of nitrogen mustard on limbal stem cells.

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.

Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 μL solution of 0.25 mg/mL or 5 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1, 3, 7, 14, and 28 for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation was used to examine corneal cross-sections collected at the completion of follow-up. Following exposure, mice experienced central corneal epithelial erosion and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma in both dosages. The epithelium was recovered by day 3 in the low dose group, followed by exacerbated punctuate erosions alongside persistent corneal edema that arose and continued onward to four weeks post-exposure. The high dose group showed persistent epitheliopathy throughout the study. The endothelial cell density was reduced, more prominent in the high dose group, early after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at 4 weeks post-exposure included dysmorphic basal epithelial cells and reduced epithelial thickness, and in the limbal cornea included decreased cellular layers. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas.

BACKGROUND: Intermittent exotropia (IXT) is one of the most common forms of strabismus usually seen in the pediatric age group, the prevalence of IXT is higher in Africa and the Middle East. IXT treatment strategies include both surgical and non-surgical methods, non-surgical management is preferred in general as it is less invasive and avoids the risks associated with surgery and anesthesia. AIMS: This study aims to determine the effectiveness of patching therapy for the treatment of IXT in different age groups and to compare the success of patching therapy in preventing surgery in IXT patients in different age groups. METHODOLOGY: A retrospective chart review was conducted from September 2022 until February 2023 at King Abdulaziz University Hospital in Riyadh. The data was collected retrospectively from electronic medical records from 2016 to 2021 of all patients diagnosed with IXT and were managed by patching therapy fitting the inclusion criteria. RESULTS: A total of 76 patients with IXT enrolled in the study with 56.5% of the participants were older than 7 years old. Overall, there was no improvement in the angle of deviation but 34% of patients had improved control over the follow-up period. 55.3% of the participants didn't require surgery. Younger age, longer duration of patching per month, and good compliance were significantly associated with treatment success. CONCLUSION: Younger age groups were more likely to benefit from patching therapy than older age groups, and good compliance to patching therapy is an important factor in preventing the need for surgery.

The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.