Gut Microbiome and Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a leading cause of childhood blindness worldwide, is strongly associated with gestational age and weight at birth. Yet, many extremely preterm infants never develop ROP or develop only mild ROP with spontaneous regression. In addition, a myriad of other factors play a role in the retinal pathology, one of which may include the early gut microbiome. The complications associated with early gestational age include dysbiosis of the dynamic neonatal gut microbiome, as evidenced by the development of often concomitant conditions, such as necrotizing enterocolitis. Given this, alongside growing evidence for a gut-retina axis, there is an increasing interest in how the early intestinal environment may play a role in the pathophysiology of ROP. Potential mechanisms include dysregulation of vascular endothelial growth factor and insulin-like growth factor 1. Furthermore, the gut microbiome may be impacted by other known risk factors for ROP, such as intermittent hypoxia and sepsis treated with antibiotics. This mini-review summarizes the literature supporting these proposed avenues, establishing a foundation to guide future studies.

Use of an Artificial Intelligence-Generated Vascular Severity Score Improved Plus Disease Diagnosis in Retinopathy of Prematurity.

PURPOSE: To evaluate whether providing clinicians with an artificial intelligence (AI)-based vascular severity score (VSS) improves consistency in the diagnosis of plus disease in retinopathy of prematurity (ROP). DESIGN: Multireader diagnostic accuracy imaging study. PARTICIPANTS: Eleven ROP experts, 9 of whom had been in practice for 10 years or more. METHODS: RetCam (Natus Medical Incorporated) fundus images were obtained from premature infants during routine ROP screening as part of the Imaging and Informatics in ROP study between January 2012 and July 2020. From all available examinations, a subset of 150 eye examinations from 110 infants were selected for grading. An AI-based VSS was assigned to each set of images using the i-ROP DL system (Siloam Vision). The clinicians were asked to diagnose plus disease for each examination and to assign an estimated VSS (range, 1-9) at baseline, and then again 1 month later with AI-based VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye examination from the Imaging and Informatics in ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis. MAIN OUTCOME MEASURES: Mean linearly weighted κ value for plus disease diagnosis compared with RSD. Area under the receiver operating characteristic curve (AUC) and area under the precision-recall curve (AUPR) for labels 1 through 9 compared with RSD for plus disease. RESULTS: Expert agreement improved significantly, from substantial (κ value, 0.69 [0.59, 0.75]) to near perfect (κ value, 0.81 [0.71, 0.86]), when AI-based VSS was integrated. Additionally, a significant improvement in plus disease discrimination was achieved as measured by mean AUC (from 0.94 [95% confidence interval (CI), 0.92-0.96] to 0.98 [95% CI, 0.96-0.99]; difference, 0.04 [95% CI, 0.01-0.06]) and AUPR (from 0.86 [95% CI, 0.81-0.90] to 0.95 [95% CI, 0.91-0.97]; difference, 0.09 [95% CI, 0.03-0.14]). CONCLUSIONS: Providing ROP clinicians with an AI-based measurement of vascular severity in ROP was associated with both improved plus disease diagnosis and improved continuous severity labeling as compared with an RSD for plus disease. If implemented in practice, AI-based VSS could reduce interobserver variability and could standardize treatment for infants with ROP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

FULL-THICKNESS MACULAR HOLE CLOSURE WITH TOPICAL MEDICAL THERAPY.

PURPOSE: To examine the efficacy and clinical characteristics of successful full-thickness macular hole closure with topical therapy. METHODS: Retrospective case series of full-thickness macular holes managed by a single retinal physician (DS) diagnosed and treated from 2017 to 22. RESULTS: Of 168 patients with full-thickness macular holes, 71 patients were started on steroid, carbonic anhydrase inhibitor, and nonsteroidal antiinflammatory (NSAID) drops. 49 patients (mean 67 years, 59% women) were included in the analysis, and 22 patients were excluded for poor follow-up. In total, 7/49 were secondary post-PPV holes and 42/49 were idiopathic. In addition, 18/49 eyes (36.7%) achieved closure on topical therapy, of which 13 were idiopathic. Hole size was directly correlated with odds of closure: for every 10 µm decrease in size and odds of closure increased by 1.2× ( P = 0.001, CI 1.1-1.4). Average time to closure was 107.2 days (range 20-512 days) and was not correlated with hole size ( P = 0.217, CI -0.478 to +1.938). The presence of VMT was found to be inversely related to successful closure (OR 6.1, P = 0.029, CI 1.2-31.3). There was no significant difference in final best-corrected visual acuity for eyes undergoing primary pars plana vitrectomy versus those trialing drops before undergoing pars plana vitrectomy ( P = 0.318, CI -0.094 to +0.112). CONCLUSION: In the first study to date to report the overall efficacy and clinical characteristics of successful macular hole closure with topical therapy, drops achieved an overall closure rate of 36.7%, with higher efficacy in smaller holes and those without VMT. Rates of MH narrowing and reduction in central foveal thickness acted as predictors of effectiveness of drop therapy.

Cardiovascular involvement in alpha-n-acetyl neuraminidase deficiency syndromes (sialidosis type I and II).

Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with neonatal-onset type II sialidosis which was associated with left ventricular dysfunction. The clinical presentation and subsequent progression which culminated in his untimely death at 16 months of age are succinctly described. Early-onset cardiovascular involvement as noted in this patient is not well characterised. The case report is supplemented by a comprehensive review of the determinants, characteristics, and the clinical course of cardiovascular involvement in this rare condition.

Racial Differences in Choroidal Vascularity Index in Healthy Patients: Novel Insights.

BACKGROUND AND OBJECTIVE: Choroidal vascularity index (CVI) measures the ratio of blood vessels in the choroid to the total choroidal area. We aimed to compare CVI between young Black and White patients without a history of ocular or systemic disease. PATIENTS AND METHODS: We used a previously validated algorithm for shadow compensation and choroidal vessel binarization to measure CVI across the Early Treatment of Diabetic Retinopathy Study grid. RESULTS: Black patients had a lower CVI (ß = -0.05, P < 0.001) compared to White patients. Choroidal volume or luminal volume did not significantly differ with respect to race, whereas there was a trend for Black patients to have a greater stromal volume (ß = 3.08, P = 0.01). CONCLUSIONS: Black patients have a lower CVI than do White patients, likely due to a greater proportion of stromal volume. Further study of this parameter is warranted to validate the findings of this exploratory study. [Ophthalmic Surg Lasers Imaging Retina 2024;55:30-38.].

The impact of a multidisciplinary intervention to reduce severe retinopathy of prematurity in Kampala, Uganda.

BACKGROUND: To address the threat of retinopathy of prematurity (ROP) in Sub-Saharan Africa (SSA), the Stop Infant Blindness in Africa (SIBA) project introduced a comprehensive program, including subspecialty training and oxygen management equipment. METHODS: A before-and-after retrospective cohort study compared preterm infants < 1750 g or < 34 weeks' gestation before (2022) and after (2023) program implementation. Outcomes included: the proportion with severe ROP, the proportion with Zone III vascularization on first examination, and factors associated with severe ROP. RESULTS: Overall, 140 infants were screened before and 122 after program implementation. The proportion with Zone III vascularization increased from 16.1% (N = 11) pre-intervention to 44.9% (N = 32) post-intervention (p = 0.001). The proportion with severe ROP decreased from 27.8% (N = 19) to 12.8% (N = 9, p = 0.03). Factors predicting severe ROP on adjusted analyses were gestational age and blood transfusion. CONCLUSION: In SSA, introduction of a comprehensive program to prevent and treat ROP can decrease the risk of severe ROP.

Pediatric cataracts of different etiologies contain insoluble, calcified particles.

Our recent studies in mice suggest that a crucial event for the development of cataracts is the formation of calcium-containing deposits. To examine the generality of pathologic mineralization as a novel mechanism of cataract formation, we analyzed lens material from different human cataract surgeries. Human lens material was obtained from routine cataract surgeries performed on three patients with dense, white cataracts: a 10-month-old with congenital cataracts, a 9-year-old with a uveitic cataract, and a 17-year-old with a traumatic cataract. The aspirated material from the cataract surgeries contained insoluble material that could be isolated by centrifugation. Many particles within the insoluble fraction stained with Alizarin red, a dye that stains insoluble calcified material. The appearance of these human insoluble, Alizarin red-stained particles was similar to some of those detected in homogenates from cataractous mouse lenses. These results support the hypothesis that pathologic mineralization may have a mechanistic role in the formation of cataracts of different etiologies.

Racial differences in quantitative optical coherence tomography angiography findings between older non-diabetics with co-morbidities.

This cross-sectional study compared optical coherence tomography angiography (OCTA) parameters between older Black and White adults with systemic comorbidities in an effort to further understand racial differences in the retinal microvasculature. We analyzed vessel density at the superficial (SCP), intermediate (ICP), and deep capillary plexuses (DCP), foveal avascular zone (FAZ) parameters, and blood flow area (BFA) at the choriocapillaris. We used a mixed-effects linear regression model, controlling for hypertension and two eyes from the same subject, to compare OCTA parameters. Black subjects had lower foveal vessel density at the SCP and ICP, while no differences were observed at the parafovea or 3x3 mm macular area of any capillary layer. Black subjects had greater FAZ area, perimeter, and FD-300, a measurement of vessel density in a 300 µm wide ring around the FAZ. Black subjects also had lower BFA at the choriocapillaris. Within a cohort of subjects without hypertension, these differences remained statistically significant, with the exception of foveal vessel density at the SCP and foveal BFA of the choriocapillaris. These findings suggest that normative databases of OCTA parameters must strive to be diverse in nature to adequately capture differences across patient populations. Further study is required to understand if baseline differences in OCTA parameters contribute to epidemiological disparities in ocular diseases.

Retinopathy of Prematurity in the 21st Century and the Complex Impact of Supplemental Oxygen.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Not only do the epidemiologic determinants and distributions of patients with ROP vary worldwide, but clinical differences have also been described. The Third Edition of the International Classification of ROP (ICROP3) acknowledges that aggressive ROP (AROP) can occur in larger preterm infants and involve areas of the more anterior retina, particularly in low-resource settings with unmonitored oxygen supplementation. As sub-specialty training programs are underway to address an epidemic of ROP in sub-Saharan Africa, recognizing characteristic retinal pathology in preterm infants exposed to unmonitored supplemental oxygen is important to proper diagnosis and treatment. This paper describes specific features associated with various ROP presentations: oxygen-induced retinopathy in animal models, traditional ROP seen in high-income countries with modern oxygen management, and ROP related to excessive oxygen supplementation in low- and middle-income countries: oxygen-associated ROP (OA-ROP).

Laser Prophylaxis in Patients with Stickler Syndrome.

PURPOSE: To evaluate the association among laser prophylaxis treatment, retinal detachment (RD), and visual acuity (VA) in patients with Stickler syndrome (SS). DESIGN: Retrospective comparative case series. PARTICIPANTS: Patients with SS. METHODS: Patients received extended vitreous base laser (EVBL), nonprotocol laser (NPL), or no laser prophylaxis treatment of any kind. MAIN OUTCOME MEASURES: The 2 main outcome measures that were examined in these patients were rates of RD and VA. RESULTS: In this study, 230 eyes of 115 patients were included. Fifty-nine patients were women (51%). The median age at the time of laser prophylaxis treatment was 9.5 years (interquartile range [IQR], 6-13 years), and the median age of patients with RD was 11 years (IQR, 7-18 years). Of the 230 eyes, 92 did not undergo any laser treatment, 9 received NPL treatment, and 129 received EVBL treatment. Of the 129 eyes that underwent EVBL treatment, 4 (3%) had RD, compared with 74 eyes (73%) that had RD and did not receive laser or NPL treatment (P < 0.001). Eyes that received EVBL treatment had approximately 8 lines better vision, on average, compared with those that did not receive laser or NPL treatment (-0.86 logarithm of the minimum angle of resolution; 95% confidence interval,-1.1 to -0.64; P < 0.001). CONCLUSIONS: Treatment with EVBL seems to reduce the rate of subsequent RD and is associated with better VA in patients with SS.

Quantitative Optical Coherence Tomography Angiography (OCTA) Parameters in a Black Diabetic Population and Correlations with Systemic Diseases.

This is a cross-sectional, prospective study of a population of black diabetic participants without diabetic retinopathy aimed to investigate optical coherence tomography angiography (OCTA) characteristics and correlations with systemic diseases in this population. These parameters could serve as novel biomarkers for microvascular complications; especially in black populations which are more vulnerable to diabetic microvascular complications. Linear mixed models were used to obtain OCTA mean values ± standard deviation and analyze statistical correlations to systemic diseases. Variables showing significance on univariate mixed model analysis were further analyzed with multivariate mixed models. 92 eyes of 52 black adult subjects were included. After multivariate analysis; signal strength intensity (SSI) and heart disease had statistical correlations to superficial capillary plexus vessel density in our population. SSI and smoking status had statistical correlations to deep capillary plexus vessel density in a univariate analysis that persisted in part of the imaging subset in a multivariate analysis. Hyperlipidemia; hypertension; smoking status and pack-years; diabetes duration; creatinine; glomerular filtration rate; total cholesterol; hemoglobin A1C; and albumin-to-creatinine ratio were not significantly associated with any OCTA measurement in multivariate analysis. Our findings suggest that OCTA measures may serve as valuable biomarkers to track systemic vascular functioning in diabetes mellitus in black patients.

Two-Year Outcomes Comparing Anti-VEGF Injections to Laser for ROP Using a Commercial Claims Database.

BACKGROUND AND OBJECTIVE: To report ocular and neurodevelopmental outcomes among infants treated for retinopathy of prematurity (ROP) in a nationwide health insurance claims database. PATIENTS AND METHODS: Retrospective cohort study of 298 infants treated with laser or anti-vascular endothelial growth factor (VEGF) injection identified in the MarketScan database (2011-2017) with 2-year follow-up. RESULTS: A review of claims data found 298 patients with International Classification of Diseases and Common Procedural Technology codes for ROP treatment and 2 years of continuous insurance coverage. Of these, 63 infants received injections and 235 received laser. Overall, the anti-VEGF group had higher rates of underlying neurological comorbidities (35% vs. 23%; P = .05) and thrombocytopenia (17% vs. 8%; P = .02). Most ocular outcomes were similar, including retinal detachment (P = .87). There were higher rates of second procedures after injection (44% vs. 10%; P < .001). Rates of language, motor, and cognitive delays were similar. Rates of cerebral palsy were higher with injections but were not statistically significant after adjusting for comorbidities (odds ratio = 1.88; P = .10). CONCLUSIONS: The prevalence of retinal detachment after 2 years was similar comparing anti-VEGF to laser. Despite the higher rates of underlying neurologic comorbidity in the injection group, there were no differences in language, motor, or cognitive delays. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:486-493.].

Macular Sequelae Following Exudative Retinal Detachment After Laser Photocoagulation for Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE: To report a series of exudative retinal detachments (ERDs) following laser photocoagulation for retinopathy of prematurity (ROP). PATIENTS AND METHODS: Retrospective case series. RESULTS: Eleven eyes of seven infants were identified who developed ERD following laser. Median gestation age was 25 weeks (interquartile range [IQR]: 24-27 weeks), and median birth weight was 662 grams (IQR: 538-850 grams). Median postmenstrual age at time of laser was 35 weeks (IQR: 33-39 weeks). ERD was diagnosed at a median of 7 days (IQR: 5-7 days) after laser and was managed with steroids. Bevacizumab was also used for certain cases. Time to resolution ranged from 1 to 5 weeks. Macular pigment changes, atrophy, window defect on fluorescein angiography, and photoreceptor loss on optical coherence tomography were noted in some cases following ERD resolution. Excluding one patient who expired at 3 months, median length of follow-up was 10 years (IQR: 9-13.5 years). Overall, only one patient, who presented with less severe ERD, had normal vision. CONCLUSIONS: ERD is an uncommonly reported complication following laser for ROP. Macular changes following ERD resolution may have negative visual consequences. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:698-705.].