P-Score: A Reference-Image-Based Clinical Grading Scale for Vascular Change in Retinopathy of Prematurity.

PURPOSE: The International Classification of Retinopathy of Prematurity Third Edition (ICROP3) acknowledged that plus-like ROP vascular changes occur along a spectrum. Historically, clinician-experts demonstrate variable agreement for plus diagnosis. We developed a 9-photo reference-image set for grading plus-like changes and compared intergrader agreement of the set to standard grading with no-plus/pre-plus/plus. DESIGN: Retinal photographic grading and expert consensus opinion PARTICIPANTS: Development: 34 international ICROP3 committee members. VALIDATION: 30 ophthalmologists with ROP expertise (15 ICROP3 committee members, 15 non-ICROP3 members) METHODS: Nine ROP fundus images (P1 through P9) representing increasing degrees of zone I vascular tortuosity and dilation, based on ICROP3-committee's 34 members' gradings and consensus image review, were used to establish standard photographs for the "Plus (P) Score." Study participants graded 150 fundus photographs two ways, separated by a 1-week washout period: (1) no-plus/pre-plus/plus disease, (2) choosing the closest P-Score image. MAIN OUTCOME MEASURES: Intergrader agreement measured by intraclass correlation coefficient (ICC) RESULTS: Intergrader agreement was higher using P-Score (ICC 0.75, 95% CI 0.71-0.79) than no-plus/pre-plus/plus (ICC 0.67, 95% CI 0.62-0.72). Mean P-Scores for images whose mode gradings were no-plus, pre-plus, and plus, were 2.5 (SD 0.7), 4.8 (SD 0.8), and 7.4 (SD 0.8), respectively. CONCLUSIONS: Intergrader agreement of plus-like vascular change in ROP using the P-Score is high. We recommend incorporation of this 9-image reference set into ICROP3 and clinician daily practice alongside zone/stage/plus. P-score is not yet meant to replace plus diagnosis for treatment decisions, but its use at our institutions has permitted better comparison between examinations for progression and regression, communication between examiners, and documentation of vascular change without fundus imaging. P-score also could provide more detailed ROP classification for clinical trials, consistent with the spectrum of plus-like change that is now formally part of ICROP.

Inherited retinal disorders: a genotype-phenotype correlation in an Indian cohort and the importance of genetic testing and genetic counselling.

PURPOSE: Recent advances in sequencing technologies have enabled radical and rapid progress in the genetic diagnosis of inherited retinal disorders (IRDs). Although the list of gene variations continues to grow, it lacks the genetic etiology of ethnic groups like South Asians. Differences in racial backgrounds and consanguinity add to genetic heterogeneity and phenotypic overlaps. METHODS: This retrospective study includes documented data from the Gen-Eye clinic from years 2014 to 2019. Medical records and pedigrees of 591 IRD patients of Indian origin and genetic reports of 117 probands were reviewed. Genotype-phenotype correlations were performed to classify as correlating, non-correlating and unsolved cases. RESULTS: Among the 591 patients, we observed a higher prevalence of clinically diagnosed retinitis pigmentosa (38.9%) followed by unspecified diagnoses (28.5%). Consanguinity was reported to be high (55.6%) in this cohort. Among the variants identified in 117 probands, 36.4% of variants were pathogenic, 19.2% were likely pathogenic, and 44.4% were of uncertain significance. Among the pathogenic and likely pathogenic variants, autosomal recessive inheritance showed higher prevalence. About 35% (41/117) of cases showed genotype-phenotype correlation. Within the correlating cases, retinitis pigmentosa and Stargardt disease were predominant. Novel variants identified in RP, Stargardt, and LCA are reported here. CONCLUSION: This first-of-a-kind report on an Indian cohort contributes to existing knowledge and expansion of variant databases, presenting relevant and plausible novel variants. Phenotypic overlap and variability lead to a differential diagnosis and hence a clear genotype-phenotype correlation helps in precise clinical confirmation. The study also emphasizes the importance of genetic counselling and testing for personalized vision care in a tertiary eye hospital.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Optical coherence tomography angiography in preterm-born children with retinopathy of prematurity.

PURPOSE: To describe the foveal avascular zone (FAZ) and vessel density (VD) in the superficial and deep capillary plexus in children with a history of prematurity on optical coherence tomography angiography (OCTA) and their correlation with gestational age (GA) and birth weight (BW). METHODS: We enrolled 81 preterm- and eight term-born children in this prospective observational study. The Optovue RTVue AVANTI (Optovue Inc., Fremont, CA) was used to procure the OCTA images. The 3 × 3 mm scan protocol centered on the fovea and the central 1 mm of the grid along with the FAZ of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was acquired. RESULTS: The mean SCP-VD was comparable between the preterms and term controls (p = 0.315) in the central fovea (1-mm grid). However, the SCP-VD of the 3-mm grid was lower in the preterms born without ROP, with type 1 ROP, and with type 2 ROP (47.61, 47.90, and 48.82 respectively) compared to that in the term group (51.38; p = 0.031). The FAZ in the SCP (p = 0.003) and DCP (p = 0.003) was significantly smaller in the preterms compared to that in the controls. Based on the GA sub-analysis, the FAZ was significantly smaller in the SCP and DCP of preterms born < 31 weeks and > 31 weeks GA (p < 0.000, p < 0.035, respectively). Based on the BW, the difference between the FAZ in the SCP (p = 0.002) and DCP (p = 0.003) was significant. There was no association between the visual acuity and FAZ. CONCLUSION: Optical coherence tomography angiography findings in this study show an altered foveal morphology and vascularity in preterms with and without ROP.

Automated Detection and Classification of Telemedical Retinopathy of Prematurity Images.

Background: Retinopathy of prematurity (ROP) is a retinal disorder of low birth weight infants and it is the leading cause of childhood blindness. The capability of wide field digital imaging systems to capture the clinical features of ROP has greatly helped the physicians to assess the severity of ROP and prevent childhood blindness due to ROP. Currently there is a lack of automated systems to assess the severity of ROP to assist the ROP specialist to make treatment decision. Objective: To present an automated detection and classification approach to assess the severity of ROP using wide field telemedical images. Materials and Methods: A total of 160 telemedical ROP (tele-ROP) images were collected out, of which 36 images were Normal, 79 images were Stage 2, and 45 images were Stage 3. Hessian analysis and support vector machine (SVM) classifier have been used to detect and classify the severity of ROP from tele-ROP images. Results: Classified the Normal, Stage 2, and Stage 3 images using SVM. Achieved accuracy of 91.8%, sensitivity of 90.37%, specificity of 94.65%, false positive rate of 5.35%, and false negative rate of 9.63%. Conclusions: The automated approach of detecting and classifying ROP would support pediatric ophthalmologists for early treatment decisions with optimal care.

Aggressive posterior retinopathy of prematurity: a pilot study of quantitative analysis of vascular features.

PURPOSE: To evaluate aggressive posterior retinopathy of prematurity (AP-ROP) with regard to inter-expert diagnostic agreement and quantitative vascular features. METHODS: Eight ROP experts interpreted 15 retinal images for AP-ROP and plus disease. Inter-expert agreement was calculated by absolute agreement for AP-ROP and plus, and kappa statistic for each expert was compared with others. Retinal vessels were analyzed by a computer-based system to calculate diameter and integrated curvature (IC). Consensus reference standards for images were developed, and quantitative parameters for arterioles and venules were compared among images with AP-ROP vs. not AP-ROP, plus vs. not plus, and AP-ROP vs. plus. RESULTS: Mean kappa for each expert in AP-ROP diagnosis ranged from -0.15 (no agreement) to 0.42 (moderate agreement). Nine (30 %) of 30 total AP-ROP diagnoses were also classified as not plus disease. Analysis of images with AP-ROP vs. plus showed that images with AP-ROP had higher venular IC (p = 0.04). Arteriolar IC was statistically significant between images with AP-ROP vs. not AP-ROP (p = 0.01) and plus vs. not plus (p = 0.00003). There were no statistically significant differences in diameter between image groups. CONCLUSIONS: Inter-expert agreement with regard to AP-ROP diagnosis is imperfect. Venular curvature may be a distinguishing characteristic between AP-ROP and plus. Future studies involving quantitative features of AP-ROP will have benefits for clinical diagnosis and management.

COMPARING THE OUTCOME OF SINGLE VERSUS MULTIPLE SESSION LASER PHOTOABLATION OF FLAT NEOVASCULARIZATION IN ZONE 1 AGGRESSIVE POSTERIOR RETINOPATHY OF PREMATURITY: A Prospective Randomized Study.

PURPOSE: To compare single versus 2-session laser photoablation for flat neovascularization in cases with Zone 1 aggressive posterior retinopathy of prematurity. METHODS: Twenty-nine Asian Indian infants with aggressive posterior retinopathy of prematurity were randomized; each eye received 1 of 2 methods (29 each in Group A or B) proposed by the PHOTO-ROP group. Group A underwent single session laser to the avascular retina underlying the flat neovascularization by direct laser over the fronds. Group B underwent laser in 2 sessions; first, laser was delivered to the avascular periphery up to the flat neovascularization and 7 days later to the avascular bed exposed by the retraction of the fronds. Outcome and complications between the two groups were compared. RESULTS: Mean birthweight and gestational ages were 1,276 g and 30.1 weeks, respectively. All eyes showed favorable outcome at a minimum 12-month follow-up. Hemorrhages after laser (41.4% vs. 17.2%, P < 0.001) were more common in the single laser group. Large hemorrhages (>1 disk diameter) seen in Group A took longer than 8 weeks to resolve and developed focal fibrosis. CONCLUSION: This study demonstrates that the two-staged laser procedure produces fewer and smaller hemorrhages and no fibrosis compared with a single session. Both methods have comparable favorable outcomes in Asian Indian infants.

Role of Anti-Vascular Endothelial Growth Factor (Anti-VEGF) in the Treatment of Retinopathy of Prematurity: A Narrative Review in the Context of Middle-Income Countries.

The rise in preterm births and higher survival rates of premature infants have led to a global increase in retinopathy of prematurity (ROP), a vasoproliferative retinal disorder common in premature infants. ROP is one of the leading causes of childhood blindness. Clinical manifestation of ROP ranges from mild abnormal retinal neovascularization to bilateral retinal detachment and vision loss. The incidence of ROP is higher in middle income countries, including India, which has the highest number of global preterm births. Low birth weight and low gestational age are the primary risk factors for ROP; however, anemia, cardiac defects, blood transfusion, apnea, sepsis, respiratory distress syndrome, high exposure to oxygen and poor postnatal weight gain may also contribute to its development. India has stringent ROP screening guidelines revised in 2018, and screening of infants with either birth weight <2000 grams or gestational age <34 weeks is mandated. With an improved understanding of the pathogenesis of ROP in the past decades and advances in clinical research, treatment for ROP has evolved from cryotherapy to laser retinal ablation. Most recently, anti-vascular endothelial growth factor (anti-VEGF) drugs have emerged as a favorable treatment option for zone-I and II ROP. This article reviews the current approaches for ROP treatment in India with a particular focus on anti-VEGF drugs. The article also integrates the understanding of safety and risk-benefit evaluation of the current approaches in ROP management. The review concluded that there is a need to increase the ROP screening not only for preterm and low birth weight but also for optimal gestational age infants with healthy birth weight. Anti-VEGF therapies have shown improved efficacy, although studies are required to establish the long-term safety.

Retinopathy of prematurity in India - what can we learn from the polio legacy?

Retinopathy of prematurity (ROP) is a vasoproliferative disease of the preterm retina that has the potential to cause vision impairment and blindness. Timely screening and treatment are hence critical for infants at risk for ROP. Screening for ROP is challenging in India owing to the limited resources, a vast at-risk population and lack of awareness among paediatricians and the public. Addressing ROP in India requires a comprehensive approach involving multiple sectors, considering the magnitude of the problem and the expected increase in need for ROP services due to the increased survival of preterm infants following improvements in neonatal care. The success of the Global Polio Eradication Initiative (GPEI) offers valuable lessons for improving ROP services in developing nations by applying its strategies. An approach for primary and secondary prevention of ROP is proposed, and the current challenges and a neonatal-led care model for ROP are discussed.

Reducing the Impact of the COVID-19 Pandemic on Retinopathy of Prematurity Screening: Successful Strategies Learnt from a Multi-Center Tele-Medicine Program in India.

PURPOSE: Control of blindness due to retinopathy of prematurity (ROP) requires timely screening and treatment within 48-72 h. Anticipating that the coronavirus disease 2019 (COVID-19) pandemic would disrupt ROP services, we devised strategies ''on-the''-go"" to ameliorate this possiblity. We describe the successful outcomes of this approach in preventing infant blindness during the pandemic. METHODS: Data on the number of preemies recruited, screened and treated in the Karnataka Internet-assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program were collected in a retrospective (2019, interval 1) - prospective (2020, interval 2) manner. We summarize 10 key strategies that were developed as we faced logistic, operational and implementation challenges. These included pragmatic methods of enhancing enrolment, transporting for screening and ensuring timely treatment in the outreach. RESULTS: The total number of ROP screening sessions was 20,598 (7,197 new) and 14,371 (5,773 new) during interval 1 and 2 respectively. Of these, 166 (2.3%) and 157 (2.7%) infants required treatment during interval 1 and 2 respectively. All infants needing treatment during the COVID period, were treated on time which was possible due to successful implementation of the 'on-the-go' strategies throughout the state of Karnataka. The fiscal equivalent of the blindness prevented during this period is USD 15.6 million. CONCLUSION: The greater decline in the number of ROP screening episodes in neonatal units in government hospitals was because several were converted to 'COVID only" hospitals. KIDROP's multi-zonal, decentralized strategy, which uses non-physician-based imaging in a telemedicine network, ensured that essential ROP services continued even during the lockdown.

Early detection and correlation of tear fluid inflammatory factors that influence angiogenesis in premature infants with and without retinopathy of prematurity.

Purpose: To measure the levels of inflammatory factors in tear fluid of pre-term infants with and without retinopathy of prematurity (ROP). Methods: The cross-sectional pilot study included 29 pre-term infants undergoing routine ROP screening. Pre-term infants were grouped as those without ROP (no ROP; n = 14) and with ROP (ROP; n = 15). Sterile Schirmer's strips were used to collect the tear fluid from pre-term infants. Inflammatory factors such as interleukin (IL)-6, IL-8, MCP1 (Monocyte Chemoattractant Protein 1; CCL2), RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and soluble L-selectin (sL-selectin) were measured by cytometric bead array using a flow cytometer. Results: Birth weight (BW) and gestation age (GA) were significantly (P < 0.05) lower in pre-term infants with ROP compared with those without ROP. Higher levels of RANTES (P < 0.05) and IL-8 (P = 0.09) were observed in the tear fluid of pre-term infants with ROP compared with those without ROP. Lower levels of tear fluid IL-6 (P = 0.14) and sL-selectin (P = 0.18) were measured in pre-term infants with ROP compared with those without ROP. IL-8 and RANTES were significantly (P < 0.05) higher in the tear fluid of pre-term infants with stage 3 ROP compared with those without ROP. Tear fluid RANTES level was observed to be inversely associated with GA and BW of pre-term infants with ROP and not in those without ROP. Furthermore, the area under the curve and odds ratio analysis demonstrated the relevance of RANTES/BW (AUC = 0.798; OR-7.2) and RANTES/MCP1 (AUC = 0.824; OR-6.8) ratios in ROP. Conclusions: Distinct changes were observed in the levels of tear inflammatory factors in ROP infants. The status of RANTES in ROP suggests its possible role in pathobiology and warrants further mechanistic studies to harness it in ROP screening and management.

A Novel Method to Improve Inter-Clinician Variation in the Diagnosis of Retinopathy of Prematurity Using Machine Learning.

PURPOSE: Inter-clinician variation could cause uncertainty in disease management. This is reported to be high in Retinopathy of Prematurity (ROP), a potentially blinding retinal disease affecting premature infants. Machine learning has the potential to quantify the differences in decision-making between ROP specialists and trainees and may improve the accuracy of diagnosis. METHODS: An anonymized survey of ROP images was administered to the expert(s) and the trainee(s) using a study-designed user interface. The results were analyzed for repeatability as well as to identify the level of agreement in the classification. "Ground truth" was prepared for each individual and a unique classifier was built for each individual using the same. The classifier allowed the identification of the most important features used by each individual. RESULTS: Correlation and disagreement between the expert and the trainees were visualized using the Dipstick™ diagram. Intra-clinician repeatability and reclassification statistics were assessed for all. The repeatability was 88.4% and 86.2% for two trainees and 92.1% for the expert, respectively. Commonly used features differed for the expert and the trainees and accounted for the variability. CONCLUSION: This novel, automated algorithm quantifies the differences using machine learning techniques. This will help audit the training process by objectively measuring differences between experts and trainees. TRANSLATIONAL RELEVANCE: Training for image-based ROP diagnosis can be more objectively performed using this novel, machine learning-based automated image analyzer and classifier.

Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis.

Background: Retinopathy of prematurity (ROP) and abnormal brain development share similar risk factors and mechanisms. There has been contrasting evidence on the association of ROP with adverse neurodevelopmental outcomes. Objective: We analysed the association between ROP at levels of severity and treatment with all neurodevelopmental outcomes until adolescence. Data source: We followed PRISMA guidelines and searched Medline and Embase between 1 August 1990 and 31 March 2022. Study selection and participants: Randomised or quasi-randomised clinical trials and observational studies on preterm infants (<37 weeks) with ROP [type 1 or severe ROP, type 2 or milder ROP, laser or anti-vascular endothelial growth factor (VEGF) treated] were included. Data extraction and synthesis: We included studies on ROP and any neurocognitive or neuropsychiatric outcomes. Outcomes: The primary outcomes were as follows: cognitive composite scores evaluated between the ages of 18 and 48 months by the Bayley Scales of Infant and Toddler Development (BSID) or equivalent; neurodevelopmental impairment (NDI; moderate to severe NDI or severe NDI), cerebral palsy, cognitive impairment; and neuropsychiatric or behavioural problems. The secondary outcomes were as follows: motor and language composite scores evaluated between the ages of 18 and 48 months by BSID or equivalent; motor/language impairment; and moderate/severe NDI as defined by the authors. Results: In preterm infants, "any ROP" was associated with an increased risk of cognitive impairment or intellectual disability [n = 83,506; odds ratio (OR): 2.56; 95% CI: 1.40-4.69; p = 0.002], cerebral palsy (n = 3,706; OR: 2.26; 95% CI: 1.72-2.96; p < 0.001), behavioural problems (n = 81,439; OR: 2.45; 95% CI: 1.03-5.83; p = 0.04), or NDI as defined by authors (n = 1,930; OR: 3.83; 95% CI: 1.61-9.12; p = 0.002). Type 1 or severe ROP increased the risk of cerebral palsy (OR: 2.19; 95% CI: 1.23-3.88; p = 0.07), cognitive impairment or intellectual disability (n = 5,167; OR: 3.56; 95% CI: 2.6-4.86; p < 0.001), and behavioural problems (n = 5,500; OR: 2.76; 95% CI: 2.11-3.60; p < 0.001) more than type 2 ROP at 18-24 months. Infants treated with anti-VEGF had higher odds of moderate cognitive impairment than the laser surgery group if adjusted data (gestational age, sex severe intraventricular haemorrhage, bronchopulmonary dysplasia, sepsis, surgical necrotising enterocolitis, and maternal education) were analysed [adjusted OR (aOR): 1.93; 95% CI: 1.23-3.03; p = 0.04], but not for cerebral palsy (aOR: 1.29; 95% CI: 0.65-2.56; p = 0.45). All outcomes were adjudged with a "very low" certainty of evidence. Conclusion and relevance: Infants with "any ROP" had higher risks of cognitive impairment or intellectual disability, cerebral palsy, and behavioural problems. Anti-VEGF treatment increased the risk of moderate cognitive impairment. These results support the association of ROP and anti-VEGF treatment with adverse neurodevelopmental outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022326009.

Development and validation of an artificial intelligence based screening tool for detection of retinopathy of prematurity in a South Indian population.

Purpose: The primary objective of this study was to develop and validate an AI algorithm as a screening tool for the detection of retinopathy of prematurity (ROP). Participants: Images were collected from infants enrolled in the KIDROP tele-ROP screening program. Methods: We developed a deep learning (DL) algorithm with 227,326 wide-field images from multiple camera systems obtained from the KIDROP tele-ROP screening program in India over an 11-year period. 37,477 temporal retina images were utilized with the dataset split into train (n = 25,982, 69.33%), validation (n = 4,006, 10.69%), and an independent test set (n = 7,489, 19.98%). The algorithm consists of a binary classifier that distinguishes between the presence of ROP (Stages 1-3) and the absence of ROP. The image labels were retrieved from the daily registers of the tele-ROP program. They consist of per-eye diagnoses provided by trained ROP graders based on all images captured during the screening session. Infants requiring treatment and a proportion of those not requiring urgent referral had an additional confirmatory diagnosis from an ROP specialist. Results: Of the 7,489 temporal images analyzed in the test set, 2,249 (30.0%) images showed the presence of ROP. The sensitivity and specificity to detect ROP was 91.46% (95% CI: 90.23%-92.59%) and 91.22% (95% CI: 90.42%-91.97%), respectively, while the positive predictive value (PPV) was 81.72% (95% CI: 80.37%-83.00%), negative predictive value (NPV) was 96.14% (95% CI: 95.60%-96.61%) and the AUROC was 0.970. Conclusion: The novel ROP screening algorithm demonstrated high sensitivity and specificity in detecting the presence of ROP. A prospective clinical validation in a real-world tele-ROP platform is under consideration. It has the potential to lower the number of screening sessions required to be conducted by a specialist for a high-risk preterm infant thus significantly improving workflow efficiency.

Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants.

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Retinopathy of Prematurity: A Global Perspective and Recent Developments.

Retinopathy of prematurity (ROP) is a significant cause of potentially preventable blindness in preterm infants worldwide. It is a disease caused by abnormal retinal vascularization that, if not detected and treated in a timely manner, can lead to retinal detachment and severe long term vision impairment. Neonatologists and pediatricians have an important role in the prevention, detection, and management of ROP. Geographic differences in the epidemiology of ROP have been seen globally over the last several decades because of regional differences in neonatal care. Our understanding of the pathophysiology, risk factors, prevention, screening, diagnosis, and treatment of ROP have also evolved over the years. New technological advances are now allowing for the incorporation of telemedicine and artificial intelligence in the management of ROP. In this comprehensive update, we provide a comprehensive review of pathophysiology, classification, diagnosis, global screening, and treatment of ROP. Key historical milestones as well as touching upon the very recent updates to the ROP classification system and technological advances in the field of artificial intelligence and ROP will also be discussed.