HVDROPDB datasets for research in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a retinal disorder that may bring about blindness in preterm infants. Early detection and treatment of ROP can prevent this blindness. The gold standard technique for ROP screening is indirect ophthalmoscopy performed by ophthalmologists. The scarcity of medical professionals and inter-observer heterogeneity in ROP grading are two of the screening concerns. Researchers employ artificial intelligence (AI) driven ROP screening systems to assist medical experts. A major hurdle in developing these systems is the unavailability of annotated data sets of fundus images. Anatomical landmarks in the retina, such as the optic disc, macula, blood vessels, and ridge, are used to identify ROP characteristics. HVDROPDB is the first dataset to be published for the retinal structure segmentation of fundus images of preterm infants. It is prepared from two diverse imaging systems on the Indian population for segmenting the lesions mentioned above and annotated by a group of ROP experts. Each dataset contains retinal fundus images of premature infants with the ground truths prepared manually to assist researchers in developing explainable automated screening systems.

Natural course of non-center-involving diabetic macular edema progression in patients under initial observation.

PURPOSE: We aim to report the natural course of non-center involving diabetic macular edema (NCIDME) progression to center involving diabetic macular edema (CIDME) and associated risk factors. METHODS: This is a multicenter retrospective comparative study. Data was collected from electronic medical records from 8 centers in India covering. We included patients with type 2 diabetes above 18 years of age with treatment-naïve NCIDME on OCT and best-corrected visual acuity at baseline of 6/12 or better who were under observation for NCIDME and had 2 years follow-up data. RESULTS: Out of 72 patients with NCIDME, 26.38% patients progressed to CI DME by 2 years, and the visit wise proportion was 11.11% at 6 months, 7% at 1st year and 8.3% at 2 years. The change in CST was statistically significant at 2 years in patients who developed CIDME, the mean difference was 137.73 ± 48.56 microns p = 0.045. Duration of diabetes mellitus > 10 years was the only risk factor for conversion to CIDME. CONCLUSION: A quarter of eyes with NCIDME developed CIDME and 15% progressed from NPDR to PDR by 2 years, highlighting the disease burden in these patients with NCIDME.

A comparative clinical study of postoperative care by teleophthalmology and in-person consultation at hospital outpatient department after an uncomplicated cataract surgery.

BACKGROUND: Teleophthalmology provides an opportunity to conduct consultations in far-flung and remote areas that have no access to specialized eye care. However, there is a paucity of studies to assess the effect of missing in-person follow-up on initial postoperative visits. The study thus aims to compare postoperative satisfaction and uncorrected distance visual activity after an uneventful phacoemulsification cataract surgery in patients with teleconsultation approach to those with hospital visit. MATERIALS AND METHODS: The prospective observation study (n = 240) was conducted in patients who underwent surgery for cataract. Pre- and post-operative data were collected and divided into two groups based on the type of postoperative follow-up. All patients were scheduled for ophthalmic reviews in the hospital on day 1, day 7, and day 30-40 (hospital visit group) or through teleconsultation on days 1 and 7 followed by a hospital visit on days 30-40 (teleconsultation group). Outcomes evaluated in both groups were complications, patient satisfaction, and uncorrected distance visual acuity. RESULTS: Most patients in both groups were in the age group of 51-70 years. Overall satisfaction was comparable in teleconsultation and hospital visit groups (3.74 ± 0.23 vs. 3.72 ± 0.27; P = 0.22). The majority of patients had visual acuity 6/18-6/6 on postoperative day 1, day 7, and day 30-40 in both groups. Lid edema, pain, redness, watering, and congestion complications were more in the hospital visit group on postoperative day 1. CONCLUSION: The study concludes that patients with no preexisting ocular and systemic comorbidity undergoing an uneventful phacoemulsification cataract surgery teleconsultation approach can be used for follow-up without any impact on the postoperative visual outcome and patient satisfaction, thereby increasing the efficiency and productivity of health-care system.

TMEM16A partners with mTOR to influence pathways of cell survival, proliferation, and migration in cholangiocarcinoma.

Expression of transmembrane protein 16 A (TMEM16A), a calcium activated chloride channel, is elevated in some human cancers and impacts tumor cell proliferation, metastasis, and patient outcome. Evidence presented here uncovers a molecular synergy between TMEM16A and mechanistic/mammalian target of rapamycin (mTOR), a serine-threonine kinase that is known to promote cell survival and proliferation in cholangiocarcinoma (CCA), a lethal cancer of the secretory cells of bile ducts. Analysis of gene and protein expression in human CCA tissue and CCA cell line detected elevated TMEM16A expression and Cl- channel activity. The Cl- channel activity of TMEM16A impacted the actin cytoskeleton and the ability of cells to survive, proliferate, and migrate as revealed by pharmacological inhibition studies. The basal activity of mTOR, too, was elevated in the CCA cell line compared with the normal cholangiocytes. Molecular inhibition studies provided further evidence that TMEM16A and mTOR were each able to influence the regulation of the other's activity or expression respectively. Consistent with this reciprocal regulation, combined TMEM16A and mTOR inhibition produced a greater loss of CCA cell survival and migration than their individual inhibition alone. Together these data reveal that the aberrant TMEM16A expression and cooperation with mTOR contribute to a certain advantage in CCA.NEW & NOTEWORTHY This study points to the dysregulation of transmembrane protein 16 A (TMEM16A) expression and activity in cholangiocarcinoma (CCA), the inhibition of which has functional consequences. Dysregulated TMEM16A exerts an influence on the regulation of mechanistic/mammalian target of rapamycin (mTOR) activity. Moreover, the reciprocal regulation of TMEM16A by mTOR demonstrates a novel connection between these two protein families. These findings support a model in which TMEM16A intersects the mTOR pathway to regulate cell cytoskeleton, survival, proliferation, and migration in CCA.

Social determinants of diabetic retinopathy and impact of sight-threatening diabetic retinopathy: A study from Pune, India.

Purpose: Diabetes-related retinopathy is the leading cause of blindness in India. The study was carried out with the purpose of studying the association of sight-threatening diabetic retinopathy (STDR) with socioeconomic factors and demonstrating the impact of STDR on the affected individual. Methods: A mixed methods (quantitative and qualitative) research design was used. The study participants were divided into two groups for quantitative analysis. The control group consisted of non-sight-threatening diabetic retinopathy, whereas the study group consisted of sight-threatening diabetic retinopathy. Apart from demographics, data on comorbidities, type and duration of diabetes mellitus (DM), health insurance status, and socioeconomic data were collected from each individual. A statistical test (Chi-square) was performed to study the association between socioeconomic (SE) classes and STDR. For the qualitative part, a few people were chosen. Face-to-face interviews were conducted in depth. Results: A total of 207 individuals, were recruited, of which 69 had STDR and the remaining 138 had non-STDR. The incidence of STDR was high among patients with lower socioeconomic class (SEC) (upper lower and lower), and univariate analysis revealed a strong association between STDR and SEC, the presence of comorbidities, presence of health insurance, type and duration of DM, and P value <0.05. SEC, in contrast, emerged as an independent risk factor for STDR in multivariate analysis. STDR had a devastating effect on all patients interviewed. The financial impact was most likely the most severe. Conclusion: People with lower SEC are more likely to suffer from STDR-related vision loss. The impact of such vision loss on individuals is multifaceted, including a negative impact on social and work life, psychological well-being, and, most importantly, a significant financial impact.

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.

Comparative study of anatomical and functional recovery of eye along with patient satisfaction score after small-incision cataract surgery and phacoemulsification cataract surgery.

Purpose: Functional recovery after cataract surgery depends on the anatomical recovery of the eye. This study compared the improvement in visual function parameters after uniocular manual small-incision cataract surgery (MSICS) and phacoemulsification cataract surgery. Methods: This study included 310 patients divided randomly into two groups: 155 who received MSICS (MSICS group) and 155 who underwent phacoemulsification (phaco group) for cataract treatment. Outcome measures assessed included vertical and horizontal keratometry reading. The mean corneal astigmatism tear function measured using Schirmer 1 test results were recorded preoperatively, and on postoperative day 1, day 7, and day 30. Optical coherence tomography (OCT) was done to record the average central macular thickness (µm) on day 7 and day 30. Results: The mean corneal astigmatism and anterior chamber inflammation were more in the MSICS group than in the phaco group immediately postoperatively. However, no statistically significant difference was found between the groups with respect to corneal sensation, mean corneal astigmatism, tear film function, and visual outcomes on postoperative day 30. Uncorrected visual acuity was better in the phacoemulsification group than in the manual SICS group on postoperative day 1, day 7, and day 30 (P < 0.001). Conclusion: Both phacoemulsification cataract surgery and manual small-incision sutureless cataract surgery (MSICS) are safe and effective for visual rehabilitation. Phacoemulsification is the preferred technique where resources are available with the advantages of less mean corneal astigmatism, less anterior chamber inflammation, and better uncorrected visual acuity (UCVA) in the immediate postoperative period.

The impact of early intervention on a child with vision loss in infancy - A parental perspective.

Purpose: : To assess the impact of early intervention services provided to children with visual loss and to report how parents perceive them in terms of a child's development and the family dynamics. Methods: : A qualitative descriptive study was conducted on a purposively selected sample of 15 children with severe visual impairment, availing early intervention services at a tertiary care facility in Pune, Maharashtra. Data were collected by conducting in-depth interviews of the parents with the help of a semi-structured interview topic guide. Participants were asked in detail about how and whether various components of the early intervention program (EIP) had an impact on their child. The interviews were audio-recorded, transcribed, and translated into English, and the resultant textual data were analyzed using the qualitative research software NVIVO 12 to identify themes and sub-themes under each domain. Results: : A total of 15 children were included in the study, with ages ranging from 13 months to 5 years. All the children included in the study suffered from severe visual impairment in infancy (Vision 3/60 - PL). In the course of this EIP, the majority of the children showed consistent progress in various aspects of child development. According to the parents, the most beneficial components of EIP were visual stimulation exercises, an improvised teaching methodology, and counseling services. Conclusion: : Almost all the parents included in the study reported a positive change in the behavior and development of the child as well as improved family dynamics after implementation of EIP.

Preferred practice guidelines for retinopathy of prematurity screening during the COVID-19 pandemic.

Retinopathy of prematurity (ROP) is the leading cause of preventable infant blindness in the world and predominantly affects babies who are born low birth weight and premature. India has the largest number of surviving preterm births born annually. ROP blindness can be largely prevented if there is a robust screening program which detects treatment requiring disease in time. ROP treatment must be provided within 48 h of reaching this threshold of treatment making it a relative emergency. During the severe acute respiratory syndrome-coronavirus disease 2019 pandemic in 2020 ROP screening was disrupted throughout the world due to lockdowns and restriction of movement of these infants, their families, specialists and healthcare workers. The Indian ROP Society issued guidelines for ROP screening and treatment in March 2020, which was aimed at preserving the chain-of-care despite the potential limitations and hazards during the (ongoing) pandemic. This preferred practice guideline is summarized in this manuscript.

Cost analysis of pediatric cataract surgery in a tertiary eye care hospital in Western India.

PURPOSE: To assess the cost of pediatric cataract surgery in a tertiary eye care hospital from a provider's perspective. METHODS: Retrospective review of direct costs incurred for pediatric cataract surgery for the financial year April 1, 2018, to March 31, 2019. The cost analysis was done by standard costing methods. The fixed cost included the cost of land, buildings, construction, maintenance, personnel, operation theater (OT), and Out patient department (OPD) equipment. The variable cost included the cost of consumables used during surgery. The indirect costs were not considered. RESULTS: The per-patient fixed facility cost was INR 1.52 ($0.02), maintenance cost was INR 39.06 ($0.55), OPD equipment and consultation were INR 19.64 ($0.28), OT equipment was INR 467.95 ($6.61), the cost for personnel was INR 5,300.33 ($74.92), and the cost of consumables varied between INR 16,418 ($314.44) and INR 22,313 ($397.76), with the choice of intraocular lenses (IOL) being the main determining factor. The net average cost for a pediatric cataract surgery varied between INR 22,246.50 ($ 314.44) and INR 28,141.50 ($ 397.76). CONCLUSION: Pediatric cataract surgeries are cost-intensive. High-volume surgeries and an increase in the number of patients in OPD reduce the fixed facility cost. But there is an overall increase in human resource (HR) and consumable cost owing to economic and technological reforms. However, the impact of operating a child, thereby, increasing his/her blindness-free years probably outweighs the cost and justifies it. High patient inflow, increased number of surgeries, and bulk purchase of consumables help in decreasing the cost.

Visual impairment and blindness among children from schools for the blind in Maharashtra state, India: Changing trends over the last decade.

PURPOSE: To determine the causes of severe visual impairment and blindness in children in schools for the blind in Maharashtra, India. METHODS: Children aged <16 years, enrolled in the schools for the blind in Maharashtra state, India were examined between October 2018 and December 2019. The anatomical sites and etiology for blindness were recorded using the World Health Organization's standard reporting form. Causes of blindness were compared among different regions of the state and also by different age groups. RESULTS: Of the 1,969 students examined from 39 schools for the blind, 188 children (9.5%) had severe visual impairment and 1,666 children (84.6%) were blind. Whole globe anomalies (794, 42.8%) were the most common anatomical site of vision loss in children, followed by corneal (289, 15.6%) and retinal abnormalities (280, 15.2%). Corneal causes were second most common in the poorer districts of Vidarbha (15.3%) and Marathwada (14.6%), whereas retinal causes were second most common in the wealthier regions of western Maharashtra (18.3%) and Khandesh (24.1%). Nearly one-third (593, 32%) of children were blind from potentially avoidable causes. Preventable blindness consisting of corneal causes and retinopathy of prematurity was seen in 281 (15.2%) cases, whereas treatable causes comprising of lens-related causes, glaucomas, refractive errors, amblyopia, and uveitis accounted for another 311 (16.8%). Among the younger children (≤10 years), the proportion of corneal blindness was lower (83/623, 13.3% vs. 206/1232, 16.7%) and that of retinal blindness was higher (119/623, 19% vs. 163/1232, 13.2%) than the older children. CONCLUSION: Whole globe anomalies constitute a major cause of SVI and blindness in Maharashtra. There seems to be an increase in the proportion of retinal blindness, especially retinopathy of prematurity, suggesting a need for increased screening coverage.

Fungal Endophthalmitis: Analysis of 730 Consecutive Eyes from 7 Tertiary Eye Care Centers in India.

PURPOSE: To evaluate the clinical and microbiological features of a large cohort with culture-confirmed fungal endophthalmitis across India. DESIGN: Cross-sectional, hospital-based, retrospective medical record review. PARTICIPANTS: Seven large tertiary eye care centers from different regions of India. METHODS: Patient data were pooled from electronic or physical medical records of each participating center. Fellowship-trained vitreoretinal specialists clinically managed all patients, and in-house microbiology laboratories performed all microbiological workups. The clinical and microbiological procedures were broadly uniform across all participating centers. The essential treatment consisted of vitreous surgery as well as intravitreal and systemic therapies with antifungal agents. MAIN OUTCOME MEASURES: Clinical outcome of the causative event and causative fungus. RESULTS: In the period from 2005 to 2020, 7 centers treated 3830 cases of culture-proven endophthalmitis, and of these, 19.1% (n = 730) were cases of culture-confirmed fungal endophthalmitis. It included 46.9% cases of postoperative (87.4% postcataract surgery), 35.6% of traumatic, and 17.5% of endogenous endophthalmitis. The fungi included 39.0% of Aspergillus (high prevalence in central, east, and south zones), 15.1% of Candida (high prevalence in west zone), and 15.9% of Fusarium (high prevalence in north and west zones). The time to symptom development was between 1 week and 4 weeks in more than one third of the patients, except in patients with traumatic endophthalmitis. Less than half of the patients had hypopyon on presentation. The presenting visual acuity (PVA) in most patients was <20/400. Nearly all patients needed vitrectomy and an average of 2 intravitreal injections of antifungal agents. At least 10% of eyes needed therapeutic keratoplasty, and up to 7% of eyes were eviscerated. After treatment, the final (best corrected) visual acuity (FVA) was >20/400 in 30.5% (n = 222) of eyes and >20/40 in 7.9% (n = 58) of eyes, and 12% (n = 88) of eyes lost light perception. A post hoc analysis showed the male sex to be significantly more associated with traumatic endophthalmitis than with postoperative (P < 0.0001) and endogenous (P = 0.001) endophthalmitis, more isolation of Candida species in patients with endogenous endophthalmitis than in those with postoperative (P = 0.004) and traumatic (P < 0.0001) endophthalmitis, better PVA in eyes with Candida species infection (P < 0.0001), and poorer FVA in eyes with Aspergillus species infection. CONCLUSIONS: Fungal endophthalmitis is not uncommon in India. The inclusion of antifungal agents with antibiotics as the first empirical intravitreal therapy before microbiological confirmation should be considered when a fungal infection is suspected.

UNC-16 alters DLK-1 localization and negatively regulates actin and microtubule dynamics in Caenorhabditis elegans regenerating neurons.

Neuronal regeneration after injury depends on the intrinsic growth potential of neurons. Our study shows that UNC-16, a Caenorhabditis elegans JIP3 homolog, inhibits axonal regeneration by regulating initiation and rate of regrowth. This occurs through the inhibition of the regeneration-promoting activity of the long isoform of DLK-1 and independently of the inhibitory short isoform of DLK-1. We show that UNC-16 promotes DLK-1 punctate localization in a concentration-dependent manner limiting the availability of the long isoform of DLK-1 at the cut site, minutes after injury. UNC-16 negatively regulates actin dynamics through DLK-1 and microtubule dynamics partially via DLK-1. We show that post-injury cytoskeletal dynamics in unc-16 mutants are also partially dependent on CEBP-1. The faster regeneration seen in unc-16 mutants does not lead to functional recovery. Our data suggest that the inhibitory control by UNC-16 and the short isoform of DLK-1 balances the intrinsic growth-promoting function of the long isoform of DLK-1 in vivo. We propose a model where UNC-16's inhibitory role in regeneration occurs through both a tight temporal and spatial control of DLK-1 and cytoskeletal dynamics.

Severity of diabetic retinopathy and its relationship with age at onset of diabetes mellitus in India: A multicentric study.

PURPOSE: To present clinical profile and risk factors of sight-threatening diabetic retinopathy (STDR) among people with age of onset of diabetes (AOD) <25 versus ≥25 years. METHODS: A retrospective chart analysis of consecutive patients with diabetic retinopathy (DR) n = 654) treated at 14 eye care centers across India between 2018 and 2019 was performed. Patients were divided into two groups, Group 1: AOD <25 years and Group 2: AOD ≥25 years. DR and diabetic macular edema (DME) were classified using the International Clinical Classification of DR severity scale. STDR included severe nonproliferative DR (NPDR), proliferative DR (PDR), and moderate to severe DME. A multilevel mixed-effects model was used for comparison between two groups: 1) Patients with DR and AOD <25 years and 2) Patients with DR and AOD ≥25 years. Bivariate and multivariate regression analyses were used to evaluate risk factors between the two groups. RESULTS: A total of 654 patients were included, 161 (307 eyes) in AOD <25 and 493 (927 eyes) in AOD >25 group. There was a higher prevalence of PDR with high-risk characteristics in AOD <25 group (24% vs. 12%) at baseline and 12-month follow-up (25% vs. 6%); P < 0.001. Systolic hypertension and poor glycemic control were risk factors in both groups, with no difference in these modifiable risk factors between groups. CONCLUSION: People with youth-onset DM are likely to present with severer form of STDR despite similar modifiable risk factors. Therefore, strict control of systolic blood pressure, glycemic status, and regular screening for DR are recommended to reduce the risk of STDR irrespective of the age of onset of diabetes.

Improving Retinopathy of Prematurity Care: A Medico-Legal Perspective.

ABSTRACT: Retinopathy of prematurity (ROP) is the leading cause of preventable infant blindness in the world. India leads all nations with the highest number of premature infants born each year. Asia has the highest estimated incidence, where visual loss from ROP is over twice as high per million live births compared to established market economies. The problems of ROP management in these countries are compounded by a large cohort of babies who require screening, relatively few ROP specialists, and more recently medico-legal challenges. The authors share the Indian jurisprudence literature from the past decade relating to ROP, summarizing key clinical lessons learned from these legal judgments. The authors endeavor to enlist good clinical practices for various key steps involved in ROP care to help mitigate future litigations as well as protect the clinical interest of the infants who require ROP screening and treatment.

Exploring the barriers for eye care among transgenders and commercial sex workers in Pune, Maharashtra.

PURPOSE: To explore all possible barriers faced by transgenders (TG) and commercial sex workers (CSW) in accessing eye care in Pune city in western India. METHODS: This qualitative study was conducted at a tertiary eye care center in Pune. Interview topic guides for face-to-face interviews and focused group discussions were developed. Comprehensive eye check-up was organized in the residential localities of TG and CSW communities in Pune. Those with severe visual impairment or blindness were identified. A sample of TGs and CSWs from this group was purposively selected and invited to participate in this study. Face-to-face interviews were conducted with each TG and CSW. A group of health care providers and NGO workers serving these communities were invited to participate in focused group discussions. All interviews/discussions were audio recorded, transcribed, and translated into English. A qualitative software (N vivo 12, QRS International, Australia) was used to identify various themes and subthemes under each domain of barriers. RESULTS: A total of 24 people (6 each from TGs, CSWs, health care provider, and NGO worker groups) participated in this study. The most common barriers reported were social stigma, discrimination, poverty, financial exclusion, and mental health factors. Non availability of gender-neutral facilities in clinics was a unique barrier reported by TGs. CONCLUSION: Marginalized communities of TGs and CSWs in Pune face several previously unexplored and unique barriers for access to eye care despite the availability of services in the vicinity.

Assistive Framework for Automatic Detection of All the Zones in Retinopathy of Prematurity Using Deep Learning.

Retinopathy of prematurity (ROP) is a potentially blinding disorder seen in low birth weight preterm infants. In India, the burden of ROP is high, with nearly 200,000 premature infants at risk. Early detection through screening and treatment can prevent this blindness. The automatic screening systems developed so far can detect "severe ROP" or "plus disease," but this information does not help schedule follow-up. Identifying vascularized retinal zones and detecting the ROP stage is essential for follow-up or discharge from screening. There is no automatic system to assist these crucial decisions to the best of the authors' knowledge. The low contrast of images, incompletely developed vessels, macular structure, and lack of public data sets are a few challenges in creating such a system. In this paper, a novel method using an ensemble of "U-Network" and "Circle Hough Transform" is developed to detect zones I, II, and III from retinal images in which macula is not developed. The model developed is generic and trained on mixed images of different sizes. It detects zones in images of variable sizes captured by two different imaging systems with an accuracy of 98%. All images of the test set (including the low-quality images) are considered. The time taken for training was only 14 min, and a single image was tested in 30 ms. The present study can help medical experts interpret retinal vascular status correctly and reduce subjective variation in diagnosis.