The scope of artificial intelligence in retinopathy of prematurity (ROP) management.

Artificial Intelligence (AI) is a revolutionary technology that has the potential to develop into a widely implemented system that could reduce the dependence on qualified professionals/experts for screening the large at-risk population, especially in the Indian scenario. Deep learning involves learning without being explicitly told what to focus on and utilizes several layers of artificial neural networks (ANNs) to create a robust algorithm that is capable of high-complexity tasks. Convolutional neural networks (CNNs) are a subset of ANNs that are particularly useful for image processing as well as cognitive tasks. Training of these algorithms involves inputting raw human-labeled data, which are then processed through the algorithm's multiple layers and allow CNN to develop their own learning of image features. AI systems must be validated using different population datasets since the performance of the AI system would vary according to the population. Indian datasets have been used in AI-based risk model that could predict whether an infant would develop treatment-requiring retinopathy of prematurity (ROP). AI also served as an epidemiological tool by objectively showing that a higher ROP severity was in Neonatal intensive care units (NICUs) that did not have the resources to monitor and titrate oxygen. There are rising concerns about the medicolegal aspect of AI implementation as well as discussion on the possibilities of catastrophic life-threatening diseases like retinoblastoma and lipemia retinalis being missed by AI. Computer-based systems have the advantage over humans in not being susceptible to biases or fatigue. This is especially relevant in a country like India with an increased rate of ROP and a preexisting strained doctor-to-preterm child ratio. Many AI algorithms can perform in a way comparable to or exceeding human experts, and this opens possibilities for future large-scale prospective studies.

Impact of RB1 gene screening from blood collected on a single day from 411 family members of 113 Retinoblastoma survivors in India.

OBJECTIVES: To analyse the profile and implication of genetic testing in a cohort of retinoblastoma (RB) patients and their families conducted on a single day during World Retinoblastoma Awareness Week 2017. METHODS: Retrospective analysis of blood samples were collected from 411 subjects, including 113 probands at a camp organised for RB awareness and were analysed for RB1 mutations by Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). If germline mutations were detected, the parents and siblings of the proband were tested for the same mutation. RESULTS: Germline RB1 mutations were identified in 61/113(54%) probands with a mutation detection rate of 96% (47/49) and 22% (14/64) for bilateral and unilateral RB, respectively. Ten novel pathogenic mutations were identified. Splice mutation was most common (31%) followed by nonsense mutation (26%). The mean age at RB diagnosis was significantly lower in patients having germline RB1 mutation (mean 10.7 months ±2.5) compared to those without (mean 27.2 months ±6.5) (p = <0.0001). Parental transmission of the mutant allele was detected in 15/61(25%) cases of which 11(18%) parents were unaffected indicating incomplete penetrance. The origin of the variant allele was both paternal (n = 7) and maternal (n = 4) wherein 5 were bilateral and 6 unilateral. CONCLUSIONS: The detection of a germline mutation impacts the proband and family members due to its implications on change in prognosis, frequency of subsequent evaluations, screening for ocular and non-ocular cancers, and surveillance of family and future progeny.

Efficacy of Smartphone-Based Telescreening for Retinopathy of Prematurity With and Without Artificial Intelligence in India.

Importance: Retinopathy of prematurity (ROP) telemedicine screening programs have been found to be effective, but they rely on widefield digital fundus imaging (WDFI) cameras, which are expensive, making them less accessible in low- to middle-income countries. Cheaper, smartphone-based fundus imaging (SBFI) systems have been described, but these have a narrower field of view (FOV) and have not been tested in a real-world, operational telemedicine setting. Objective: To assess the efficacy of SBFI systems compared with WDFI when used by technicians for ROP screening with both artificial intelligence (AI) and human graders. Design, Setting, and Participants: This prospective cross-sectional comparison study took place as a single-center ROP teleophthalmology program in India from January 2021 to April 2022. Premature infants who met normal ROP screening criteria and enrolled in the teleophthalmology screening program were included. Those who had already been treated for ROP were excluded. Exposures: All participants had WDFI images and from 1 of 2 SBFI devices, the Make-In-India (MII) Retcam or Keeler Monocular Indirect Ophthalmoscope (MIO) devices. Two masked readers evaluated zone, stage, plus, and vascular severity scores (VSS, from 1-9) in all images. Smartphone images were then stratified by patient into training (70%), validation (10%), and test (20%) data sets and used to train a ResNet18 deep learning architecture for binary classification of normal vs preplus or plus disease, which was then used for patient-level predictions of referral warranted (RW)- and treatment requiring (TR)-ROP. Main Outcome and Measures: Sensitivity and specificity of detection of RW-ROP, and TR-ROP by both human graders and an AI system and area under the receiver operating characteristic curve (AUC) of grader-assigned VSS. Sensitivity and specificity were compared between the 2 SBFI systems using Pearson χ2testing. Results: A total of 156 infants (312 eyes; mean [SD] gestational age, 33.0 [3.0] weeks; 75 [48%] female) were included with paired examinations. Sensitivity and specificity were not found to be statistically different between the 2 SBFI systems. Human graders were effective with SBFI at detecting TR-ROP with a sensitivity of 100% and specificity of 83.49%. The AUCs with grader-assigned VSS only were 0.95 (95% CI, 0.91-0.99) and 0.96 (95% CI, 0.93-0.99) for RW-ROP and TR-ROP, respectively. For the AI system, the sensitivity of detecting TR-ROP sensitivity was 100% with specificity of 58.6%, and RW-ROP sensitivity was 80.0% with specificity of 59.3%. Conclusions and Relevance: In this cross-sectional study, 2 different SBFI systems used by technicians in an ROP screening program were highly sensitive for TR-ROP. SBFI systems with AI may be a cost-effective method to improve the global capacity for ROP screening.

Unusual presentation of a vascularized iris lesion in an infant.

We report an unusual presentation of a 10-month-old girl with left eye (LE) redness and watering. Evaluation showed an iris vascular lesion and lens opacity in her LE. Child underwent USG B-scan and ultrasound biomicroscopy, by which an extensive mass lesion arising from iris and ciliary body with absent calcification was revealed. Following extensive evaluation, child underwent cataract extraction and trans-scleral total excision of the mass lesion. Histopathology proved it as juvenile xanthogranuloma (JXG) with vascular proliferation. JXG is a rare benign self-limiting dermatologic disorder affecting mainly infants and small children. Ocular lesions are the most common extracutaneous manifestation. Cataract in JXG is less frequently reported. This case is reported due to its rarity and as it presented solely as an intraocular lesion with combined diffuse infiltration into ciliary body and cataract which is unusual. Early recognition and systematic approach helped in sight saving and organ salvaging.

Management of Recurrence in Retinoblastoma Based on the Source of Tumor Cells.

PURPOSE: The aim was to study the characteristics of recurrence patterns in the form of scar recurrence, new lesions, and vitreous seeds which is necessary in anticipating future events for the management of retinoblastoma (RB). METHODS: This retrospective analytical observational study was conducted in a tertiary care hospital in South India; we included 64 eyes of 45 patients having RB from January 2019 to July 2020. The inclusion criterion was treatment-naïve patients with > 12 months of follow-up period. Recurrence patterns were defined as Pattern 1a and Pattern 1b: local and diffuse dissemination of vitreous seeds, respectively. Pattern 2: Scar recurrences: these are new tumor growths over chemoreduced lesions. Pattern 3: New lesions: local dissemination of subretinal seeds leading to new lesions elsewhere in the retina. RESULTS: A noncomparative analysis of 64 eyes of 45 patients having 108 lesions was studied; of which 28/45 (62.22%) were male and 17/45 (37.78%) were female. The mean time of presentation since the first clinical sign was 40 days (range: 10-180). The most common sign at presentation was leukocoria 42/64 (65.6%), followed by squint 4/64 (6.34%). Nineteen patients (42.22%) had bilateral RB, while 26 patients (57.78%) had unilateral RB. Primary enucleation was done for 19/26 eyes with advanced unilateral disease. Out of the total 32 eyes with subretinal tumor seeds at presentation, 17/32 eyes had a recurrence in the form of new lesions (Pattern 3) and 22/32 eyes had scar recurrence (Pattern 2). All of these 32 eyes were salvaged by local tumor consolidation methods. Recurrence due to vitreous seed dissemination was found in 18/64 eyes, in which diffuse dissemination (Pattern 1b) was present in 8/18 eyes (44.4%); all required enucleation even after local and systemic chemotherapeutic measures. Rest 10/18 eyes with local vitreous seeds (Pattern 1a) were cured at the end of the follow-up. Globe salvage was more with Pattern 1a rather than Pattern 1b even after additional intravitreal chemotherapy. CONCLUSION: All eyes with Patterns 2 and 3 were salvaged at the end of follow-up with local tumor consolidation methods, while the globe salvage rate with Pattern 1 was poor even with multiple doses of intravitreal chemotherapy. The rate of successful treatment for managing these recurrence patterns depends on early identification by regular follow-ups with detailed retina examination.

Pediatric choroidal neovascularization: Etiology and treatment outcomes with anti-vascular endothelial growth factors.

PURPOSE: To describe the etiology and treatment outcomes of choroidal neovascularization (CNV) in a pediatric population with intravitreal anti-vascular endothelial growth factors (VEGF). METHODS: Retrospective single center interventional case series. A total of 26 eyes of 23 consecutive pediatric patients with CNV of various etiologies were treated with intravitreal injection of anti-VEGF agents. RESULTS: There were 15 males (65.2%) and eight females (34.8%), diagnosed with CNV during the study period. The mean age at presentation with CNV was 11.7 ± 3.3 years, (range 4-16 years) and the mean follow was 28.1 ± 18 months, (range 8-72 months). Inflammatory CNV was the most common etiology. The mean best corrected visual acuity (BCVA) and mean central macular thickness (CMT) at presentation, were logMAR 0.8 ± 0.3 and 367.6 ± 134.8 µm respectively. At the final visit, CNV in all eyes remained regressed with significant improvement in mean BCVA to logMAR 0.4 ± 0.4 (p < 0.0001) and mean CMT to 242.5 ± 82.4 µm (p < 0.0001). A mean of two intravitreal injections per eye was required for CNV regression. CONCLUSION: Intravitreal anti-VEGF therapy for pediatric CNV is an effective treatment in majority of affected eyes.

Coincidental ocular findings during retinopathy of prematurity telescreening of 9105 neonates.

PURPOSE: To describe the magnitude and spectrum of abnormal ocular findings other than retinopathy of prematurity (ROP) detected during an ROP telescreening programme. METHODS: Retrospective review of the records of all premature babies screened for ROP from August 2015 to December 2019. RESULTS: A total 9105 babies were screened during the study period with total 17,075 imaging sessions. Non-ROP ocular abnormalities were seen in 566 eyes of 383 babies (4.2%) including 207 male (54%) and 176 female babies (46%). Posterior segment abnormalities were seen in 88.2% babies (338/383) with haemorrhage being the most common (77%, 295/383). Anterior segment pathologies were seen in 12% babies (46/383) with congenital cataract being the most common pathology requiring surgical intervention. Other findings included globe abnormalities in 0.8% babies (3/383), adnexal disorders in 0.5% babies (2/383) and squint in 0.3% babies (1/383). Rare life-threatening conditions such as retinoblastoma and lipaemia retinalis were also detected. Eighty-seven babies (22.7%) were diagnosed with referral-warranted non-ROP pathologies, with an overall prevalence of 1% (87/9105). Prompt surgical intervention was advised for 7.3% babies (28/383), 3.4% babies (13/383) were treated medically and 4.2% babies (16/383) needed visual rehabilitation for non-amenable pathologies. CONCLUSION: This is the largest study describing the magnitude and spectrum of neonatal ocular pathologies other than ROP in a cohort of premature babies. Digital imaging has a significant impact on early detection and timely intervention for various vision as well as life-threatening non-ROP pathologies, which would have been missed or delayed otherwise.

Design and development of model eye for retina laser by using additive manufacturing.

Surgical skill of the surgeon can be improved by surgical simulation. Especially in ophthalmology, it is impossible to use real human/non-human primate eyes for ophthalmology surgery practice. However, surgical practice is most important for ophthalmologist. The retina laser surgery is one of the ophthalmology surgeries and it requires more surgical practice for surgeons to use the laser beam precisely to coagulate and fuse small areas of tissue. Dealing with the prospect of vision reduction or vision loss presents a peculiar problem and that can be highly stressful and frustrating for both doctors and patients. In this regard, training for indirect ophthalmoscopy and retinal photocoagulation is undergone using model eyes instead of real eyes. Properties and functioning of an existing model eye are huge and they differ from real human eye such as casings are completely rigid and focusing of retinal fundus is not completely covered. Therefore, this research concentrates to develop a model eye that assimilates close to the human eye by focussing on the maximum viewing area that is not done at the moment. Finally, the design and development of re-engineered model eye for retina laser is fabricated by additive manufacturing. Compared to existing plastic model eye, viewing area and viewing angle of the re-engineered model eye is increased by 16.66% and 6.14%, respectively. Due to design modifications and elimination of the insert, it can be reduced by 18.99% and 13.95% of height and weight of the top casing respectively. Developed re-engineered model eye will improve the surgical and diagnostic skill of the surgeon and increase their confidence and proficiency. It also augments the effective use of essential ophthalmic instruments. Additionally, it can reduce the surgical error and meet the existing demand of actual eyes for surgical practices.

Coexistent Retinoblastoma and Retinopathy of Prematurity in a Preterm Infant.

[Ophthalmic Surg Lasers Imaging Retina. 2020;51:732.].

Ocular oncology practice guidelines during COVID-19 pandemic-An expert consensus.

The outbreak of rapidly spreading COVID-19 pandemic in December 2019 has witnessed a major transformation in the health care system worldwide. This has led to the re-organization of the specialty services for the effective utilization of available resources and ensuring the safety of patients and healthcare workers. Suspension of oncology services will have major implications on cancer care due to delayed diagnosis and treatment leading to irreversible adverse consequences. Therefore various oncology organizations have called for a continuation of cancer care during this crisis with diligence. The COVID-19 pandemic has forced the clinicians to transform the components of care from screening to outpatient care and primary management. The purpose of this article is to establish guidelines and recommendations for ocular oncology in the management of ocular tumors set by a multidisciplinary team of experts including ocular, medical and radiation oncologists, and pathologists. As the pandemic is evolving fast, it will require constant updates and reformation of health strategies and guidelines for safe and quality health care.

Aggressive posterior retinopathy of prematurity in two cohorts of patients in South India: implications for primary, secondary, and tertiary prevention.

BACKGROUND: Aggressive posterior retinopathy of prematurity (APROP), which has a poor visual prognosis, is common in low- and middle-income countries (LMICs) as a result of suboptimal oxygen monitoring (primary prevention). The purpose of this study was to compare outcomes in APROP eyes treated with laser to eyes treated with antivascular endothelial growth factor (anti-VEGF) therapy. METHODS: The medical records of a cohort of APROP eyes treated with anti-VEGF (2010-2018) and another of eyes treated with laser photocoagulation (2002-2010) at the same institution in South India were reviewed retrospectively and compared. The main outcome was the proportion of eyes developing retinal detachment during resolution of acute ROP. RESULTS: A total of 398 eyes of 199 preterm babies with APROP were included: 168 eyes were treated with photocoagulation; 230, with anti-VEGF. From 2002 to 2010, compared to the more recent cohort, babies diagnosed with APROP tended to be heavier (P < 0.001), older (P < 0.001), and exposed to fewer days of oxygen (P = 0.02). In the laser-treated cohort, 17 of 168 eyes (10%) developed retinal detachment (7, stage 5; 12, stage 4), compared with 3 of 230 (1%) in the anti-VEGF cohort (all stage 4 [P = 0.002]). CONCLUSIONS: The incidence of retinal detachment was significantly lower in eyes treated with anti-VEGF compared with laser-.treated eyes In the absence of a randomized trial, these data suggest that anti-VEGF may lead to better anatomic outcomes, although questions remain concerning dosage, timing, and risks.

Refractive, sensory, and biometric outcome among retinopathy of prematurity children with a history of laser therapy: A retrospective review from a tertiary care center in South India.

Purpose: Ocular morbidities like high refractive error, strabismus, and amblyopia are common among laser-treated retinopathy of prematurity children (ROP). Long-term optical status and refractive outcomes including the sensory outcomes were less investigated in these children from this region. The purpose of our study is to evaluate the long-term outcome (refractive, biometric profile, sensory) of treatment for ROP using laser. Methods: This study is a retrospective, cross-sectional, observational, and intervention research among 6-15-year-old children who underwent laser for ROP with a minimum of 6-year follow-up. Results: Eighty lasered eyes of 41 children were assessed. Mean age was 9.71 years (±3.39). Seventy-three eyes (91.2%) achieved visual acuity better than 20/40. The mean visual acuity in LogMAR was 0.18 (20/30). The mean spherical equivalence was -5.29 D ± 4.9. Mean astigmatism measured was -1.53 DC (range: +0.50 DC to -4.5DC). Fifty-three eyes (66.25%) had significant astigmatism. The mean axial length was 23.5 ± 1.35 (21-26) mm. Mean lens thickness was 3.76 ± 0.30 (3.03-4.34) mm. Correlation analysis among the low and high spherical equivalent group signified that axial length (P value = 0.001), visual acuity (P value = 0.0002), and myopic shift (P value = 0.0006) were found to be statistically significant. Stereopsis better than 480 s of arc for near was observed in 41% children. Structural posterior pole sequelae developed in 3 eyes (3.75%). Conclusion: A significant number of children with high myopia, astigmatism, and strabismus had satisfactory visual outcome observed at long-term follow-up after treatment for ROP using laser. Our study revealed that myopia was influenced by an increase in axial length than the lens thickness.

Curious case of retrolental mass: An unusual tele-screening artifact.

We are presenting a case of premature baby born at 32 weeks of gestation who was under regular follow-up with our retinopathy of prematurity (ROP) tele-screening team. During final follow-up at 41 weeks of postconceptional age, anterior segment image captured with RetCam showed a retrolental mass lesion in right eye resembling retinoblastoma or medulloepithelioma. The baby was referred to our base hospital for further evaluation, where a detailed examination showed no retrolental lesion or intraocular mass. This is the first case where imaging artifact, despite use of high-quality imaging system by well-trained staff, during ROP tele-screening appeared like a retrolental mass lesion and resulted in false-positive referral.

Telemedicine for ROP.

With the increasing survival of preterm babies in the Asia-Pacific region, there has been an increase in the incidence of retinopathy of prematurity (ROP). There is also a lack of trained ophthalmologists to screen for this disease. New strategies for screening of ROP are required, wherein the load on the ophthalmologist can be reduced. Telemedicine is an excellent tool to address this need. This paper reviews the initial studies comparing digital imaging with indirect ophthalmoscopy, the current active ROP telescreening programs in the world, and ends with studies dealing with automated diagnosis of ROP.

Outcomes of transconjuctival sutureless 27-gauge vitrectomy for stage 4 retinopathy of prematurity.

AIM: To report our initial experience with lens-sparing vitrectomy for stage 4 retinopathy of prematurity using the 27-gauge (G) system. METHODS: This retrospective case series involved nine eyes of five babies with active stage 4 ROP, who underwent 27-G lens-sparing vitrectomy. Surgery was done using 27-G valved cannulas and sclerotomies were made 1.5 mm from the limbus. Bilateral sequential vitrectomy was done in eight eyes. RESULTS: At one-year follow-up, anatomical outcome was favourable in all nine (100%) eyes. High-speed cutting and smaller sclerotomies were helpful in reducing the intra and post-operative complications. CONCLUSION: 27-G vitrectomy is well suited for stage 4 ROP surgeries.