Retinopathy of prematurity (ROP) is a vasoproliferative disease occurring in premature infants that affects the blood vessels of the developing retina. ROP results in the development of vascular shunts, neovascularization, and in its most severe form tractional retinal detachment. The development of retinal vascular shunts and neovascularization in ROP is related to local ischemia in the immature and incompletely vascularized retina. Understanding the pathophysiology of ROP helps physicians both in the prevention and treatment of ROP and will be discussed in this review article. The role of oxygen in the pathophysiology of ROP will be reviewed with recent studies discussed.

Retinopathy of prematurity (ROP) remains the leading cause of childhood blindness worldwide. Recent advances in ROP imaging have significantly improved our understanding of the pathogenesis and pathophysiological course of ROP including the acute phase, regression, reactivation, and late complications, known as adult ROP. Recent progress includes various contact and noncontact wide-field imaging devices for fundus imaging, smartphone-based fundus photography, wide-field fluorescein angiography, handheld optical coherence tomography (OCT) devices for wide-field en face OCT images, and OCT angiography. Images taken by those devices were incorporated in the recently updated guidelines of ROP, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3). ROP imaging has also allowed the real-world adoption of telemedicine- and artificial intelligence (AI)-based screening. Recent study demonstrated proof of concept that AI has a high diagnostic performance for the detection of ROP in a real-world screening. Here, we summarize the recent advances in ROP imaging and their application for screening, diagnosis, and management of ROP.

Retinopathy of prematurity (ROP) remains among the leading causes of childhood blindness. It affects mainly premature infants who tend to be systematically and clinically unstable and are more prone to complications and anesthesia related adverse effects when undergoing examination or treatment. A better comprehension of different analgesic and anesthetic methods used during screening and treatment may help in choosing a suitable option for ROP screening and treatment. An electronic search was done using MEDLINE, PubMed, and Embase databases. Search terms used included ROP, ROP, ROP screening, ROP treatment, analgesia, and anesthesia. All randomized clinical trials, large case series, and surveys were included in the review. Topical proparacaine is the most commonly used anesthesia during ROP screening and may significantly ease pain during ROP screening. Different comfort measures during screening may help infants recover faster but do not abolish pain. Topical tetracaine seems an effective pain-relieving option during intravitreal injections for ROP treatment. Photocoagulation of the peripheral retina under general anesthesia is considered the most common practice in the treatment of ROP. Further work is necessary to better understand the options of anesthesia methods offered for the treatment of ROP patients. This is a comprehensive review highlighting the available anesthetic methods for ROP patients to aid ophthalmologists in determining the most common and current anesthetic and analgesic practices.

Laser photocoagulation can still be considered the gold standard for treatment for retinopathy of prematurity (ROP). However, anti-vascular endothelial growth factor (anti-VEGF) therapy has increasingly become an important option that plays a significant role in the treatment of ROP. Major clinical trials have been published regarding the anti-VEGF use in ROP, along with multiple other studies looking into the different agents, doses, techniques, and possible complications. Anti-VEGF therapies can be considered as a safe and effective option for managing ROP. More longitudinal randomized clinical trials are necessary to evaluate the preferred treatment agent, the appropriate dose, best follow-up protocol, and the long-term ocular and systemic outcomes following treatment.

This article provides information about late complications of retinopathy of prematurity (ROP), especially seen in adolescence and adulthood. The majority of ROP patients recover without complications and treatment, but severe ROP cases should be properly treated. Both prematurity itself and the treatment of ROP cause some changes in the anterior (refractive changes, cataract, and glaucoma) and posterior segments (tractional, rhegmatogenous and exudative retinal detachment, vitreous hemorrhage, etc.,) of the eye and predispose to significant lifelong complications. Awareness of these late complications can minimize severe vision loss with proper follow-up and appropriate treatment. Therefore, life-long ophthalmological follow-up is mandatory in all prematures with the diagnosis of ROP.

The Saudi Arabian Retinopathy of Prematurity National Telemedicine programme (SAROP) is a product of the National Committee for Retinopathy of Prematurity (ROP). The program includes ROP telescreening, diagnosis, and management of cases requiring treatment. Digital retinal images and filled ROP software requests were uploaded from 20 level-3 neonatal intensive care units (NICU) in the Kingdom of Saudi Arabia (KSA) to the King Khaled Eye Specialist Hospital server and the ROP telemedicine website. The data were accessed and reported by qualified retinal and pediatric ophthalmologists. Currently, retinal wide-angle digital cameras are available in 20 of the 31 level-3 NICUs of the Ministry of Health, Kingdom of KSA. This telemedicine approach is practical and effective in detecting and managing ROP cases. In the first 2.5 years, encouraging results were noticed with no unfavorable outcomes in the participating NICUs. Technical challenges were resolved promptly to ensure that the program ran smoothly. Therefore, this ideal state-of-the-art ROP telemedicine program could be also applied to similar and neighboring countries.

PURPOSE: Neonatal care in middle-income countries has improved over the last decade, leading to a “third epidemic” of retinopathy of prematurity (ROP). Without concomitant improvements in ROP screening infrastructure, reduction of ROP-associated visual loss remains a challenge worldwide. The emergence of teleophthalmology screening programs and artificial intelligence (AI) technologies represents promising methods to address this growing unmet demand in ROP screening. An improved understanding of current ROP screening programs may inform the adoption of these novel technologies in ROP care. METHODS: A critical narrative review of the literature was carried out. Publications that were representative of established or emerging ROP screening programs in high-, middle-, and low-income countries were selected for review. Screening programs were reviewed for inclusion criteria, screening frequency and duration, modality, and published sensitivity and specificity. RESULTS: Screening inclusion criteria, including age and birth weight cutoffs, showed significant heterogeneity globally. Countries of similar income tend to have similar criteria. Three primary screening modalities including binocular indirect ophthalmoscopy (BIO), wide-field digital retinal imaging (WFDRI), and teleophthalmology were identified and reviewed. BIO has documented limitations in reduced interoperator agreement, scalability, and geographical access barriers, which are mitigated in part by WFDRI. Teleophthalmology screening may address limitations in ROP screening workforce distribution and training. Opportunities for AI technologies were identified in the context of these limitations, including interoperator reliability and possibilities for point-of-care diagnosis. CONCLUSION: Limitations in the current ROP screening include scalability, geographical access, and high screening burden with low treatment yield. These may be addressable through increased adoption of teleophthalmology and AI technologies. As the global incidence of ROP continues to increase, implementation of these novel modalities requires greater consideration.

PURPOSE: Artificial intelligence (AI) offers considerable promise for retinopathy of prematurity (ROP) screening and diagnosis. The development of deep-learning algorithms to detect the presence of disease may contribute to sufficient screening, early detection, and timely treatment for this preventable blinding disease. This review aimed to systematically examine the literature in AI algorithms in detecting ROP. Specifically, we focused on the performance of deep-learning algorithms through sensitivity, specificity, and area under the receiver operating curve (AUROC) for both the detection and grade of ROP. METHODS: We searched Medline OVID, PubMed, Web of Science, and Embase for studies published from January 1, 2012, to September 20, 2021. Studies evaluating the diagnostic performance of deep-learning models based on retinal fundus images with expert ophthalmologists' judgment as reference standard were included. Studies which did not investigate the presence or absence of disease were excluded. Risk of bias was assessed using the QUADAS-2 tool. RESULTS: Twelve studies out of the 175 studies identified were included. Five studies measured the performance of detecting the presence of ROP and seven studies determined the presence of plus disease. The average AUROC out of 11 studies was 0.98. The average sensitivity and specificity for detecting ROP was 95.72% and 98.15%, respectively, and for detecting plus disease was 91.13% and 95.92%, respectively. CONCLUSION: The diagnostic performance of deep-learning algorithms in published studies was high. Few studies presented externally validated results or compared performance to expert human graders. Large scale prospective validation alongside robust study design could improve future studies.

PURPOSE: To understand conditional prognostic value of the Cancer Genome Atlas (TCGA) for uveal melanoma metastasis based on event-free survival at 1, 2, 3, 4, and 5 years. METHODS: A retrospective study of eyes with uveal melanoma categorized according to TCGA and studied for nonconditional and conditional risks for metastasis at 5 and 10 years. RESULTS: Of 1001 eyes with uveal melanoma, the nonconditional (standard, at presentation) 5-year/10-year metastatic rate was 18%/25%. The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed 10%/18% and the conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed 9%. The TCGA categories included Group A (n = 486, 49%), B (n = 141, 14%), C (n = 260, 26%), and D (n = 114, 11%). The non-conditional 5-year/10-year metastatic rate revealed Group A (4%/6%), Group B (12%/20%), Group C (23%/49%), and Group D (60%/68%). The conditional 5-year/10-year metastatic rate (for those without metastasis at 2 years) revealed Group A (2%/5%), Group B (8%/18%), Group C (21%/40%), and Group D (38%/50%). The conditional 10-year metastatic rate (for those without metastasis at 5 years) revealed Group A (2%), Group B (10%), Group C (33%), and Group D (20%). The peak incidence of metastasis for Groups A and B occurred during years 5–6, C during years 4–6, and D during years 1–2. CONCLUSION: Survival outcomes for uveal melanoma as non-conditional (at presentation) and conditional (event-free survival during follow-up) reveal reduction in metastatic rate over time. For those with 5-year metastasis-free survival, the 10-year conditional risk for metastasis was 9%.

PURPOSE: Patients with neovascular age-related macular degeneration (nAMD) have varying responses to anti-vascular endothelial growth factor injections. Limited early response (LER) after three monthly loading doses is associated with poor long-term vision outcomes. This study predicts LER in nAMD and uses feature importance analysis to explain how baseline variables influence predicted LER risk. METHODS: Baseline age, best visual acuity (BVA), central subfield thickness (CST), and baseline and 3 months intraretinal fluid (IRF) and subretinal fluid (SRF) for 286 eyes were collected in a retrospective clinical chart review. At month 3, LER was defined as the presence of fluid, while early response (ER) was the absence thereof. Decision tree classification and feature importance methods determined the influence of baseline age, BVA, CST, IRF, and SRF, on predicted LER risk. RESULTS: One hundred and sixty-seven eyes were LERs and 119 were ERs. The algorithm achieved area under the curve = 0.66 in predicting LER. Baseline SRF was most important for predicting LER while age, BVA, CST, and IRF were somewhat less important. Nonlinear trends were observed between baseline variables and predicted LER risk. Zones of increased predicted LER risk were identified, including age <74 years, and CST <290 or >350 μm, IRF >750 nL, and SRF >150 nL. CONCLUSION: These findings explain baseline variable importance for predicting LER and show SRF to be the most important. The nonlinear impact of baseline variables on predicted risk is shown, increasing understanding of LER and aiding clinicians in assessing personalized LER risk.

PURPOSE: In recent years, the prognostic nutritional index (PNI), an easily obtainable nutritional inflammatory marker, has been introduced as an independent prognostic indicator for various types of cancers and cardiovascular diseases. However, its clinical importance in the area of ophthalmology is not well known yet. We aimed to elucidate the association between the PNI and the occurrence of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, the PNI was applied to 128 consecutive patients with T2DM. The relationship between the PNI and the occurrence of DR was examined. PNI was calculated as 10× (serum albumin) + 0.005 × (total lymphocyte count). The risk factors for DR were evaluated using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve analysis of PNI for predicting DR was performed. RESULTS: Patients with DR had significantly lower levels of PNI than those without DR (41.20 ± 4.81 and 44.49 ± 3.10, respectively, P < 0.001). Multivariate regression analysis indicated that PNI, together with the duration of diabetes and creatinine, was an independent factor for DR occurrence (odds ratio, 0.885; 95% confidence interval: 0.735–0.971; P = 0.017). ROC curve analysis revealed that the best cutoff value of PNI was 43 (area under the curve: 0.713; sensitivity: 74%; specificity: 64%). CONCLUSION: A lower PNI value is common among T2DM patients with DR and is strongly associated with the occurrence of DR. The PNI might be a useful biomarker for identifying DR to improve the risk stratification and management of T2DM patients.

PURPOSE: To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1^st year of the pro re nata treatment regimen. METHODS: One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients. RESULTS: A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1^st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1^st month with AFL administration. CONCLUSION: Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.