Use of an artificial intelligence-generated vascular severity score improved plus disease diagnosis in retinopathy of prematurity.

OBJECTIVE: To evaluate whether providing clinicians with an artificial intelligence-based vascular severity score (AI-VSS) improves consistency in diagnosis of plus disease in retinopathy of prematurity (ROP). DESIGN: This is a multi-reader diagnostic accuracy imaging study. PARTICIPANTS: Eleven ROP experts (4 pediatric ophthalmologists, 7 retina specialists), 9 of which had been in practice for 10 or more years. 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 exams, a subset of 150 eye exams from 110 infants were selected for grading. An AI-VSS was assigned to each set of images using the i-ROP DL system. The clinicians were asked to diagnose plus disease for each exam and assign an estimated VSS (range 1-9) at baseline, and then again one month later with AI-VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye exam from the i-ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis. MAIN OUTCOME MEASURE: Mean linearly weighted kappa for plus disease diagnosis compared to the RSD. Area under the receiver operating characteristic and precision-recall curves (AUROC, AUPR) for 1-9 labels compared to RSD for plus disease. RESULTS: Expert agreement improved significantly from substantial (κ: 0.69 [0.59, 0.75]) to near perfect (κ: 0.81 [0.71, 0.86]) when AI-VSS was integrated. Additionally, there was a significant improvement in plus disease discrimination as measured by mean [95% confidence interval] AUROC (0.94 [0.92, 0.96] to 0.98 [0.96, 0.99], difference: 0.04 [0.01, 0.06]) and AUPR (0.86 [0.81, 0.90] to 0.95 [0.91, 0.97], difference: 0.09 [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 to a reference standard diagnosis for plus disease. If implemented in practice, AI-VSS could reduce inter-observer variability and standardize treatment for infants with ROP.

Impact of postnatal steroids on peripheral avascular retina and severity of retinopathy of prematurity.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

Reduction of Glut1 in the Neural Retina But Not the RPE Alleviates Polyol Accumulation and Normalizes Early Characteristics of Diabetic Retinopathy.

Hyperglycemia is a key determinant for development of diabetic retinopathy (DR). Inadequate glycemic control exacerbates retinopathy, while normalization of glucose levels delays its progression. In hyperglycemia, hexokinase is saturated and excess glucose is metabolized to sorbitol by aldose reductase via the polyol pathway. Therapies to reduce retinal polyol accumulation for the prevention of DR have been elusive because of low sorbitol dehydrogenase levels in the retina and inadequate inhibition of aldose reductase. Using systemic and conditional genetic inactivation, we targeted the primary facilitative glucose transporter in the retina, Glut1, as a preventative therapeutic in diabetic male and female mice. Unlike WT diabetics, diabetic Glut1+/- mice did not display elevated Glut1 levels in the retina. Furthermore, diabetic Glut1+/- mice exhibited ameliorated ERG defects, inflammation, and oxidative stress, which was correlated with a significant reduction in retinal sorbitol accumulation. Retinal pigment epithelium-specific reduction of Glut1 did not prevent an increase in retinal sorbitol content or early hallmarks of DR. However, like diabetic Glut1+/- mice, reduction of Glut1 specifically in the retina mitigated polyol accumulation and diminished retinal dysfunction and the elevation of markers for oxidative stress and inflammation associated with diabetes. These results suggest that modulation of retinal polyol accumulation via Glut1 in photoreceptors can circumvent the difficulties in regulating systemic glucose metabolism and be exploited to prevent DR.SIGNIFICANCE STATEMENT Diabetic retinopathy affects one-third of diabetic patients and is the primary cause of vision loss in adults 20-74 years of age. While anti-VEGF and photocoagulation treatments for the late-stage vision threatening complications can prevent vision loss, a significant proportion of patients do not respond to anti-VEGF therapies, and mechanisms to stop progression of early-stage symptoms remain elusive. Glut1 is the primary facilitative glucose transporter for the retina. We determined that a moderate reduction in Glut1 levels, specifically in the retina, but not the retinal pigment epithelium, was sufficient to prevent retinal polyol accumulation and the earliest functional defects to be identified in the diabetic retina. Our study defines modulation of Glut1 in retinal neurons as a targetable molecule for prevention of diabetic retinopathy.

The U.S. National Trend for Retinopathy of Prematurity.

OBJECTIVE: The use of supplemental oxygen in premature infants is essential for survival. However, its use has been associated with unintended complications. The restricted use of oxygen is associated with increased mortality and necrotizing enterocolitis (NEC), whereas its liberal use is associated with increased risk for retinopathy of prematurity (ROP). Although there is no clear consensus on the acceptable oxygen saturation range, clinicians have recently become more liberal with the use of oxygen. We aim to assess (1) the national trends for ROP in very low birth weight preterm infants, and (2) the associated trends in mortality, NEC, intraventricular hemorrhage (IVH), and length of hospital stay (LOS). STUDY DESIGN: We analyzed deidentified patient data from the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) from 2002 to 2017. All infants with gestational age ≤32 weeks and birth weight <1,500 g were included. Trends in ROP, severe ROP, mortality, NEC, IVH, severe IVH, and LOS were analyzed using Jonckheere-Terpstra test. RESULTS: A total of 818,945 neonates were included in the study. The overall mortality was 16.2% and the prevalence of ROP was 17.5%. There was a significant trend for increased ROP over the years (p < 0.001). Severe ROP was also significantly increased (p < 0.001). This was associated with a significant trend for increased median LOS in survived infants (p < 0.001). Mortality was significantly decreased (p < 0.001), whereas NEC and severe NEC did not change over time (p = 0.222 and p = 0.412, respectively). CONCLUSION: There is a national trend for increased ROP and severe ROP over the 16 years of the study period. This trend was associated with a significant increase in the LOS in survived infants without change in NEC. KEY POINTS: · Prevalence of ROP and severe ROP has increased in VLBW infants over the 16-year study period.. · The prevalence of NEC did not change over the same time period.. · Increased ROP and severe ROP were consistent in all three GA and BW subgroups..

VITREOUS SEEDING OF CHOROIDAL MELANOMA.

PURPOSE: To report a case of vitreous seeding in a medium-sized choroidal melanoma and review the literature. METHODS: Observational case report and review of literature for pathogenesis, role of vitreous biopsy, and treatment outcomes. RESULTS: A case of 57-year-old man diagnosed with vitreous seeding in the left eye 1 year after episcleral brachytherapy for medium-sized choroidal melanoma. The patient was initially diagnosed to have subretinal and vitreous hemorrhage due to rupture of a retinal artery macroaneurysm for which focal laser and intravitreal antivascular endothelial growth factor injections were administered. Over the next 9 months, the vitreous hemorrhage cleared and choroidal melanoma with retinal invasion became evident. One year after brachytherapy, the primary tumor regressed with resolution of surrounding subretinal fluid and hemorrhage. However, gradual decline in the visual acuity from 20/50 to 20/500 with increase of pigmented debris over the retinal surface and in the vitreous cavity was noted. A vitreous biopsy confirmed the presence of viable melanoma cells (epithelioid type), and the eye was enucleated. Histopathology showed microscopic persistence of primary tumor with diffuse vitreous seeding. CONCLUSION: Vitreous seeding of choroidal melanoma poses a diagnostic and management challenge.

Stickler syndrome: exploring prophylaxis for retinal detachment.

PURPOSE OF REVIEW: The literature regarding prophylactic treatment of rhegmatogenous retinal detachment in Stickler syndrome remains controversial. We review major published clinical studies and offer a critical analysis of this subject. SUMMARY: Stickler syndrome is a systemic collagenopathy affecting multiple organ systems including the eye, ear, and skeleton. Stickler syndrome is probably the most common cause of genetically determined pediatric rhegmatogenous retinal detachment. Congenital developmental anomalies constitute over half rhegmatogenous detachments (RRD) in patients less than 10 years. The majority are caused by hereditary vitreoretinopathies associated with Stickler syndrome. Sixty percent of patients with Stickler syndrome develop RRD's over their lifetime with possible severe visual loss and subsequent lifelong morbidity. In view of these complications, some have emphasized the importance of prophylactic laser treatment to the retina of patients with Stickler syndrome to reduce the occurrence of and/or prevent future rhegmatogenous retinal detachment, but there appears to be insufficient data to support the absolute benefit of such prophylactic treatment. Guidelines regarding the age at prophylactic treatment as well as type and frequency of intervention are scarce and would benefit from additional clinical investigations.

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG). Although both molecules conferred a protective phenotype, gene expression analysis by RNA sequencing found that Roxadustat can prevent OIR by two pathways: direct retinal HIF stabilization and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilization and increased serum angiokines. As predicted by pathway analysis, Roxadustat rescued the hepatic HIF-1 knockout mouse from retinal oxygen toxicity, whereas DMOG could not. The simplicity of systemic treatment that targets both the liver and the eye provides a rationale for protecting the severely premature infant from oxygen toxicity.

Long-Term Outcomes of Total Exudative Retinal Detachments in Stage 3B Coats Disease.

PURPOSE: To evaluate the long-term outcomes of treatment of total exudative retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of vitrectomy. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to Coats disease with at least 5 years of follow-up. METHODS: We reviewed the records of patients with stage 3B Coats disease. The interventions, including the timing of vitrectomy if used, and clinical course were recorded. MAIN OUTCOME MEASURES: The primary outcome measures were visual acuity at the most recent appointment, whether there was progression to neovascular glaucoma (NVG) or phthisis bulbi, and need for enucleation. RESULTS: All patients received ablative treatment (photocoagulation or cryotherapy), with 8 having scleral buckling (SB) and 6 having external drainage of subretinal fluid (XD). Of the 12 patients who had pars plana vitrectomy (PPV), 8 had early PPV (EV) in the first year after presenting, and 4 of 8 in the expectant management group had late PPV (late vitrectomy) at a mean of 4.3 years post-presentation for treatment of significant traction retinal detachment (TRD). The other 4 patients of 8 in the expectant management group did not require vitrectomy. Mean follow-up overall was 9 1/2 years. At the date of last follow-up, 50% had no light perception or light perception vision, which was consistent across the subgroups that underwent EV (4/8), late vitrectomy (2/4), or no PPV (2/4). A total of 4 of 16 patients had progression to NVG or phthisis, 1 of whom required enucleation. CONCLUSIONS: In this retrospective series of patients with Stage 3B Coats disease, ablative therapy with a combination of PPV, XD, or SB was effective in preventing progression to NVG or phthisis in the majority of patients, thus preserving the globe. Half of the patients (4/8) in this series who did not undergo PPV in the early vitrectomy group developed late-onset TRD, suggesting a possible role for early prophylactic vitrectomy with possible SB and XD; however, this is balanced by the other half (4/8) in the expectant management group who did not require any vitrectomy.

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study.

PURPOSE: To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. DESIGN: International, multicenter, interventional, retrospective case series. PARTICIPANTS: Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. METHODS: Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. MAIN OUTCOME MEASURES: Ocular and systemic adverse events. RESULTS: A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. CONCLUSIONS: This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Evolutionarily conserved long intergenic non-coding RNAs in the eye.

The discovery that the mammalian transcriptome encodes thousands of long intergenic non-coding (linc) RNA transcripts, together with recent evidence that lincRNAs can regulate protein-coding genes, has added a new level of complexity to cellular transcriptional/translational regulation. Indeed several reports now link mutations in lincRNAs to heritable human disorders. Here, we identified a subset of lincRNAs in terminally differentiated adult human retinal neurons based on their sequence conservation across species. RNA sequencing of eye tissue from several mammalian species with varied rod/cone photoreceptor content identified 18 lincRNAs that were highly conserved across these species. Sixteen of the 18 were conserved in human retinal tissue with 14 of these also conserved in the macular region. A subset of lincRNAs exhibited restricted tissue expression profiles in mice, with preferential expression in the retina. Mouse models with different populations of retinal cells as well as in situ hybridization provided evidence that these lincRNAs localized to specific retinal compartments, most notably to the photoreceptor neuronal layer. Computational genomic loci and promoter region analyses provided a basis for regulated expression of these conserved lincRNAs in retinal post-mitotic neurons. This combined approach identified several lincRNAs that could be critical for retinal and visual maintenance in adults.

Inducing a visceral organ to protect a peripheral capillary bed: stabilizing hepatic HIF-1α prevents oxygen-induced retinopathy.

Activation of hypoxia-inducible factor (HIF) can prevent oxygen-induced retinopathy in rodents. Here we demonstrate that dimethyloxaloylglycine (DMOG)-induced retinovascular protection is dependent on hepatic HIF-1 because mice deficient in liver-specific HIF-1α experience hyperoxia-induced damage even with DMOG treatment, whereas DMOG-treated wild-type mice have 50% less avascular retina (P < 0.0001). Hepatic HIF stabilization protects retinal function because DMOG normalizes the b-wave on electroretinography in wild-type mice. The localization of DMOG action to the liver is further supported by evidence that i) mRNA and protein erythropoietin levels within liver and serum increased in DMOG-treated wild-type animals but are reduced by 60% in liver-specific HIF-1α knockout mice treated with DMOG, ii) triple-positive (Sca1/cKit/VEGFR2), bone-marrow-derived endothelial precursor cells increased twofold in DMOG-treated wild-type mice (P < 0.001) but are unchanged in hepatic HIF-1α knockout mice in response to DMOG, and iii) hepatic luminescence in the luciferase oxygen-dependent degradation domain mouse was induced by subcutaneous and intraperitoneal DMOG. These findings uncover a novel endocrine mechanism for retinovascular protection. Activating HIF in visceral organs such as the liver may be a simple strategy to protect capillary beds in the retina and in other peripheral tissues.

Early treatment response of fluocinolone (retisert) implantation in patients with uveitic macular edema: an optical coherence tomography study.

PURPOSE: To analyze the early spectral domain optical coherence tomography changes after fluocinolone implantation in eyes with baseline uveitic macular edema. METHODS: Patients with uveitic macular edema and who received fluocinolone implantations by 2 surgeons (R.P.S. and J.E.S.) at the Cole Eye Institute (Cleveland Clinic, Cleveland, OH) from September 2009 to July 2010 were eligible for this study. Best-corrected visual acuity, intraocular pressure, central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade were recorded before implantation and in the early postoperative period (median: 3 months postimplantation). Changes in these variables were analyzed using the Wilcoxon signed-rank test for paired comparisons of clustered data. P values were 2 sided, and alpha was set at 0.05. RESULTS: Twelve eyes of seven patients were included in the study. The median best-corrected visual acuity improved in the early postoperative period after implantation (20/80 before implantation and 20/50 after implantation), but this improvement was not found to be significant (P = 0.12). However, the spectral domain optical coherence tomography measurements-central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade-were all significantly reduced (median changes: -234 µm [P = 0.02], -1 mm [P = 0.04], -39 µm [P = 0.04], and -3 [P = 0.03], respectively). CONCLUSION: Fluocinolone implantation is associated with a significant reduction in macular edema as measured by spectral domain optical coherence tomography in the early postoperative period, a result that is consistent with the proposed mechanism of the drug.

Trans-tamponade optical coherence tomography: postoperative imaging in gas-filled eyes.

PURPOSE: To investigate the feasibility of trans-tamponade optical coherence tomography and evaluate factors contributing to image quality and acquisition success. METHODS: Retrospective case series of eyes receiving Postoperative Day 1 optical coherence tomography imaging after vitrectomy and gas tamponade. The quality of the scans was graded by three independent expert readers. Clinical and surgical variables were recorded and correlated with scan quality. RESULTS: Eighty eyes were included in the study. An image quality classification scheme was developed (0-4, 0 = no image and 4 = comparable quality to trans-fluid optical coherence tomography). In 51 scans (64%), visualization of the inner retina and retinal pigment epithelium was achieved (Grades 2-4) but with variable image quality of the retinal layers. Twenty-nine scans (36%) achieved visualization of all retinal layers (Grades 3-4). Only 9 scans (11%) were of comparable quality to fluid-filled eyes (Grade 4). Pseudophakia (P = 0.0001), shorter operative times (P = 0.007), and macular surgery (P = 0.002) correlated with scan quality. An optimum scan protocol was developed to facilitate maximum quality images. CONCLUSION: Successful trans-tamponade optical coherence tomography through gas on Postoperative Day 1 is possible but significant variability exists in scan quality.

Coats Plus Syndrome in a Premature Infant, With a Focus on Management.

Purpose: A premature infant was diagnosed with Coats plus syndrome based on a genetic evaluation showing biallelic heterozygous pathogenic CTC1 variants. Methods: A case study was performed, including findings and interventions. Results: A premature infant born 30 weeks gestational age weighing 817 g was evaluated for retinopathy of prematurity at 35 weeks corrected gestational age. An initial dilated fundus examination showed an exudative retinal detachment (RD) in the right eye and avascularity post-equatorially in the left eye with telangiectasias and aneurysmal dilations. Genetic evaluation showed biallelic heterozygous pathogenic CTC1 variants, diagnostic of Coats plus syndrome. Sequential examination under anesthesia with fluorescein showed progressive ischemia despite confluent photocoagulation. Conclusions: CTC1 gene variants manifest as Coats plus syndrome, which has a clinical appearance consistent with retinovascular ischemia, capillary remodeling, aneurysmal dilation, and exudative RD. Systemic and local corticosteroids in conjunction with peripheral laser ablation decreased vascular exudation and avoided intraocular intervention.

Hyperoxia Induced Hypomyelination.

We asked whether hyperoxia might induce hypomyelination of the corpus callosum, clinically described as periventricular leukomalacia (PVL) of the severely preterm infant. Mouse pups and their nursing dams were placed in 80% oxygen from P4-P8, then removed to room air until P11. Corpus callosal sections were probed myelin immunofluorescence, tested for myelin basic protein concentration by Western blot, and both glial fibrillary acidic protein levels and apoptosis quantified. Density of corpus callosal capillaries were measured after lectin staining and hypoxia measured by Hypoxyprobe. Numbers of oligodendrocytes were quantified by immunohistochemistry. We next used hypoxiamimesis as a surrogate to hypoxia by comparing cerebral hypoxia inducible factor (HIF) stabilization to hepatic HIF stabilization. Hyperoxia induced hypomyelination and a reduction of corpus callosal capillaries. Hyperoxia decreased numbers of oligodendrocytes with an increase in corpus callosal fibrosis and apoptosis. Cerebral hypoxiamimesis induced hypomyelination whereas hepatic hypoxiamimesis alone increased myelination, oligodendrocyte numbers, and corpus callosal capillary density. Hepatic HIF-1 dependence on myelination was confirmed using the cre/lox hepatic HIF-1 knockout. These findings suggest that hyperoxia can induce hypomyelination through vasoobliteration and subsequent ischemia, adding a potential oxygen induced mechanism to the diverse causes of periventricular leukomalacia of the severely preterm infant. Targeting hepatic HIF-1 alone led to increased myelination.

Referable Macular Hemorrhage-A Clinically Meaningful Screening Target in Newborn Infants. Position Statement of the Association of Pediatric Retina Surgeons.

Universal newborn eye screening facilitates early diagnosis of ocular abnormalities and mitigates vision loss. "Referral warranted" eye disease is present at birth in about 5.5% of term infants, with "macular hemorrhage impinging on the fovea" representing about 50% of referral warranted disease. The Association of Pediatric Retina Surgeons held a symposium on February 9, 2021 that culminated in a position statement on "referable macular hemorrhage" (RMH) in newborn infants. RMH is meaningful in that in can cause amblyopia through deprivation, can be readily captured with wide-angle photography in a safe and efficient manner, and may lead to early intervention with mitigation of vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:3-6.].

Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy.

Oxygen-induced retinopathy (OIR) in the mouse, like the analogous human disease retinopathy of prematurity, is an ischemic retinopathy dependent on oxygen-induced vascular obliteration. We tested the hypothesis that chemically overriding the oxygen-induced downregulation of hypoxia-inducible factor (HIF) activity would prevent vascular obliteration and subsequent pathologic neovascularization in the OIR model. Because the degradation of HIF-1alpha is regulated by prolyl hydroxylases, we examined the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in the OIR model. Our results determine that stabilizing HIF activity in the early phase of OIR prevents the oxygen-induced central vessel loss and subsequent vascular tortuosity and tufting that is characteristic of OIR. Overall, these findings imply that simulating hypoxia chemically by stabilizing HIF activity during the causative ischemia phase (hyperoxia) of retinopathy of prematurity may be of therapeutic value in preventing progression to the proliferative stage of the disease.