Metabolic memory and diabetic retinopathy: Legacy of glycemia and possible steps into future.

The response of retinal pathology to interventions in diabetic retinopathy (DR) is often independent of the glycated hemoglobin (HbA1c) values at the point of care. This is despite glucose control being one of the strongest risk factors for the development and progression of DR. Previous preclinical and clinical research has indicated metabolic memory, whereby past cumulative glucose exposure may continue to impact DR for a prolonged period. Preclinical studies have evaluated punitive metabolic memory through poor initial control of DM, whereas clinical studies have evaluated protective metabolic memory through good initial control of DM. In this narrative review, we evaluate the preclinical and clinical evidence regarding metabolic memory and discuss how this may form the basis of preventive care for DR by inducing "metabolic amnesia" in people with a history of uncontrolled diabetes in the past. While our review suggested mitochondrial biology may be one such target, research is still far from a possible clinical trial. We discuss the challenges in such research.

Surgical approach to endophthalmitis: an overview.

Endophthalmitis is one of the most severe ocular emergencies faced by ophthalmologists worldwide. Without prompt treatment significant visual loss is inevitable. With increased understanding of the science of endophthalmitis, recent studies have shown a clear role of early and more definitive surgery to achieve better visual and anatomic outcomes. Surgery in endophthalmitis encompasses a whole gamut of interventions. There are diagnostic procedures like anterior chamber tap and vitreous biopsy or therapeutic procedures like complete pars plana vitrectomy and retinal detachment repair. Current literature is deficient on a detailed description of the spectrum of surgical interventions in endophthalmitis. In the current communication, we summarize the studies based on various surgical interventions in endophthalmitis. We also elaborate in detail on each surgical maneuver, taking the reader through the nuances of each surgery via an exhaustive description and appropriate photos and surgical video clips.

National prevalence of vision impairment and blindness and associated risk factors in adults aged 40 years and older with known or undiagnosed diabetes: results from the SMART-India cross-sectional study.

BACKGROUND: National estimates of the prevalence of vision impairment and blindness in people with diabetes are required to inform resource allocation. People with diabetes are more susceptible to conditions such as diabetic retinopathy that can impair vision; however, these are often missed in national studies. This study aims to determine the prevalence and risk factors of vision impairment and blindness in people with diabetes in India. METHODS: Data from the SMART-India study, a cross-sectional survey with national coverage of 42 147 Indian adults aged 40 years and older, collected using a complex sampling design, were used to obtain nationally representative estimates for the prevalence of vision impairment and blindness in people with diabetes in India. Vulnerable adults (primarily those who did not have capacity to provide consent); pregnant and breastfeeding women; anyone deemed too ill to be screened; those who did not provide consent; and people with type 1 diabetes, gestational diabetes, or secondary diabetes were excluded from the study. Vision impairment was defined as presenting visual acuity of 0·4 logMAR or higher and blindness as presenting a visual acuity of 1·0 logMAR or higher in the better-seeing eye. Demographic, anthropometric, and laboratory data along with geographic distribution were analysed in all participants with available data. Non-mydriatic retinal images were used to grade diabetic retinopathy, and risk factors were also assessed. FINDINGS: A total of 7910 people with diabetes were included in the analysis, of whom 5689 had known diabetes and 2221 were undiagnosed. 4387 (55·5%) of 7909 participants with available sex data were female and 3522 (44·5%) participants were male. The estimated national prevalence of vision impairment was 21·1% (95% CI 15·7-27·7) and blindness 2·4% (1·7-3·4). A higher prevalence of any vision impairment (29·2% vs 19·6%; p=0·016) and blindness (6·7% vs 1·6%; p<0·0001) was observed in those with ungradable images. In known diabetes, diabetic retinopathy (adjusted odds ratio [aOR] 3·06 [95% CI 1·25-7·51]), vision-threatening diabetic retinopathy (aOR 7·21 [3·52-14·75]), and diabetic macular oedema (aOR 5·41 [2·20-13·33]) were associated with blindness in adjusted analysis. Common sociodemographic risk factors for vision impairment and blindness include older age, lower educational attainment, and unemployment. INTERPRETATION: Based on the estimated 101 million people with diabetes in 2021 and the interpretation of the data from this study, approximately 21 million people with diabetes have vision impairment in India, of whom 2·4 million are blind. Higher prevalence is observed in those from lower socio-economic strata and policy makers should focus on these groups to reduce inequalities in health care. FUNDING: Global Challenge Research Fund of United Kingdom Research and Innovation through the Medical Research Council.

OUTCOME OF EYES TREATED FOR RETINOPATHY OF PREMATURITY IN POSTERIOR ZONE I: An Eastern India Study.

PURPOSE: To analyze the outcomes of eyes treated for retinopathy of prematurity in posterior Zone I. METHODS: In a part retrospective (9 years) and part prospective (1 year) interventional study, we analyzed eyes treated for retinopathy of prematurity in posterior Zone I with a minimum follow-up for 6 months. RESULTS: This study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) g, respectively. The treatment included intravitreal anti-vascular endothelial growth factor as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in eight eyes, either alone (n = 3) or in combination with surgery (n = 5). With anti-vascular endothelial growth factor alone, 30.68% (n = 27) eyes responded favorably, and the remaining 69.32% (n = 59) eyes needed retreatment (laser in the majority). At the final follow-up, 89.9% (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation ( P < 0.0001) and the presence of well-defined central vascular trunks ( P = 0.001). CONCLUSION: Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior Zone I retinopathy of prematurity.

Outcome of real-time telescreening for retinopathy of prematurity using videoconferencing in a community setting in Eastern India.

PURPOSE: To evaluate the feasibility and outcome of a real-time retinopathy of prematurity (ROP) telescreening strategy using videoconferencing in a community setting in India. METHOD: In a prospective study, trained allied ophthalmic personnel obtained the fundus images in the presence of the parents and local childcare providers. Analysis of images and parental counseling were done in real time by an ROP specialist located at a tertiary center using videoconferencing software. A subset of babies was also examined using bedside indirect ophthalmoscopy by an ROP care-trained ophthalmologist. The data were analyzed using descriptive statistics, sensitivity, specificity, positive and negative predictive values, and correlation coefficient. RESULTS: Over 9 months, we examined 576 babies (1152 eyes) in six rural districts of India. The parents accepted the model as they recognized that a remotely located specialist was evaluating all images in real time. The strategy saved the travel time for ROP specialists by 477 h (47.7 working days) and for parents (47,406 h or 1975.25 days), along with the associated travel cost. In a subgroup analysis (100 babies, 200 eyes), the technology had a high sensitivity (97.2%) and negative predictivity value (92.7%). It showed substantial agreement (k = 0.708) with the bedside indirect ophthalmoscopy by ROP specialists with respect to the detection of treatment warranting ROP. Also, the strategy helped train the participants. CONCLUSION: Real-time ROP telescreening using videoconferencing is sensitive enough to detect treatment warranting ROPs and saves skilled workforce and time. The real-time audiovisual connection allows optimal supervision of imaging, provides excellent training opportunities, and connects ophthalmologists directly with the parents.

Antibiotic susceptibility in Endophthalmitis Management Study and intravitreal antibiotic practice trend in India-EMS Report #5.

AIM: Analyze antibiotic susceptibility in the Endophthalmitis Management Study (EMS) and compare it with the current intravitreal antibiotic practice trend of members of the Vitreoretinal Society of India (VRSI) practicing in India. METHODS: The microbiology work-up of undiluted vitreous included microscopy, culture-susceptibility, polymerase chain reaction (PCR), and next-generation sequencing (NGS). VRSI members were invited to the survey. The EMS conventional culture-susceptibility (PCR and NGS excluded) results were compared vis-a-vis gram-positive cocci (GPC), gram-negative bacilli (GNB), and less commonly used antibiotics with the current recommended intravitreal antibiotics. p < 0.05 was considered significant. RESULTS: Culture and positivity (culture + PCR/NGS) positivity was 28.8% and 56.1%, respectively. GPC was most susceptible to cefazolin, linezolid, and vancomycin; GNB was most susceptible to amikacin, ceftazidime, colistin, and imipenem. There was no susceptibility difference between cefazolin and vancomycin (p = 0.999) and between ceftazidime and imipenem (p = 1.0). Colistin was superior to ceftazidime (p = 0.047) against GNB. The GNB resistant to amikacin (n = 14) were equally susceptible to ceftazidime and colistin; resistant to ceftazidime (n = 16) were susceptible to colistin; and resistant to colistin (n = 7) were susceptible to ceftazidime. The preference of VRSI members (n = 231) practicing in India was a vancomycin-ceftazidime combination (82%), vancomycin for GPC (94%), ceftazidime for GNB (61%), and voriconazole for fungi (74%). CONCLUSION: In EMS, GPC had good susceptibility to vancomycin; GNB had good susceptibility to ceftazidime and colistin. Given the lower resistance of colistin, a vancomycin-colistin combination could be an alternative empiric treatment in post-cataract endophthalmitis in India.

Seasonal Hyperacute Panuveitis (SHAPU) in Bhutan.

PURPOSE: To report the first series of Seasonal Hyperacute Pan Uveitis (SHAPU) from Bhutan. METHODS: We retrospectively analyzed the patients with clinically diagnosed SHAPU treated in the referral center in the last 5 years. Data included demographics (age, sex, laterality), region, time of presentation (year, season) and treatment received. RESULTS: The series included 3 males and 2 females. The mean age was 16 years. Three patients had presented in autumn of 2021, and two in autumn of 2019. Four patients presented within 2 weeks of the onset of symptoms. All patients had either exposure or contact with white moths. All patients presented with unilateral sudden painless reduction in vision and low Intraocular pressure. Four patients required vitrectomy. The final visual acuity of 3 patients was >6/36, and one patient was 6/60. CONCLUSIONS AND IMPORTANCE: The time of presentation and early treatment intervention are crucial in achieving good visual prognosis in SHAPU.

Evaluating the utility of inflammation score in post-cataract surgery endophthalmitis. Results from a prospective study in India. EMS Report #4.

PURPOSE: To investigate if inflammation score (IS), calculated from the cornea, anterior chamber, iris, and vitreous, indicates endophthalmitis severity. METHODS: In a prospective study, consecutive adults with a clinical diagnosis of post-cataract endophthalmitis within 6 weeks of surgery were recruited. Patients were allocated to IS-based primary treatment (IS < 10: intravitreal injection and IS ≥ 10: vitrectomy) and randomized to two intravitreal antibiotics combinations (vancomycin + ceftazidime and vancomycin + imipenem). Undiluted vitreous microbiology work-up included culture susceptibility, polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing. RESULTS: The average age of 175 people was 63.4 ± 10.7 years and included 52.6% small incision cataract surgery and 47.4% phacoemulsification surgery. Severe endophthalmitis (IS ≥ 20), diagnosed in 27.4% of people, had a shorter time to symptoms (average 5.4 vs 8.7 days; P = 0.018), poorer presenting vision (all ≤ hand motion), higher culture positivity (50% vs 30.7%; P = 0.032), and higher Gram-negative bacterial infection (70.8% vs 46.2%; P = 0.042). For IS ≥ 20 discriminant and Gram-negative infection, Spearman's coefficient was 0.7 [P < 0.0001, 95% confidence interval (CI) 0.59-0.82], with an area under the receiver operating characteristic curve of 0.9 (95% CI 0.85-0.94, P < 0.0001), a Youden index J of 0.74, a sensitivity of 87.2%, and a specificity of 87.5%. The final vision of >20/400 and >20/100 was regained in 50.2% and 29.1% of people, respectively. The susceptibility of common Gram-positive cocci and Gram-negative bacilli was the highest for vancomycin (95.0%) and colistin (88.6%), respectively. NGS detected polymicrobial infection in 88.5% of culture-negative endophthalmitis. CONCLUSIONS: Higher inflammation scores indicated severe disease and Gram-negative infection in post-cataract endophthalmitis.

Endophthalmitis Management Study-A Prospective Randomized Clinical Trial on Postoperative Endophthalmitis Management in India: An Interim Analysis. Endophthalmitis Management Study Report #3.

PURPOSE: An interim analysis of the Endophthalmitis Management Study to examine the outcome of inflammation score (IS)-based treatment and antibiotic susceptibility. DESIGN: A prospective randomized study. PATIENTS AND METHODS: IS was measured on a 0-4 scale from presenting signs in 4 cardinal ocular tissues. The eyes with IS <10 received vitreous tap and intravitreal antibiotics, whereas eyes with IS ≥10 received vitrectomy and intravitreal antibiotics. These eyes were randomized to 2 intravitreal antibiotic combinations: (1) vancomycin and ceftazidime and (2) vancomycin and imipenem. Microbiology workup of undiluted vitreous included microscopy, culture-susceptibility, Sanger, and targeted next-generation sequencing. The clinical and microbiology outcomes were analyzed for advanced (IS = ≥20) and less advanced (IS = <10) endophthalmitis. RESULTS: Interim analysis was performed after the Endophthalmitis Management Study recruited 56.85% (248/436) of patients and completed 54.6% (238/436) of microbiology workup. A 90-day follow-up was completed in 90.8% (168/185) of eligible people. In eyes with IS ≥20, the time to symptoms was shorter (5.8 ± 6.7 vs 8.5 ± 9.1 d; P = 0.015), and the need for additional treatment was higher (95.8% vs 53.1%; P = 0.0267). Good final vision was associated with good presenting vision (r = 0.30) and IS-based treatment decisions (r = 0.170). Microbiology positivity was 55.9%. Eyes with IS <10 had a higher Gram-positive cocci (33.9% vs 4.8%; P = 0.013) infection. Gram-positive cocci were most susceptible to vancomycin (95.7%), and Gram-negative bacilli to colistin (95.7%). CONCLUSIONS: Considering both IS and presenting vision, rather than only one of them, helps in making appropriate management decisions for acute postoperative endophthalmitis.

Consensus and controversies in the science of endophthalmitis management: Basic research and clinical perspectives.

Infectious endophthalmitis is a severe intraocular infection caused by bacteria, or less commonly by fungi. It can occur after penetrating eye procedures, trauma, or the spread of infection from contiguous structures or via emboli from distant organs. Because of the time-critical nature of the treatment, endophthalmitis is treated with the clinical diagnosis and modified by the microbiological report of the intraocular contents. The current strategy for managing endophthalmitis relies on pre-clinical literature, case series, and one large multi-center randomized clinical trial on post-cataract surgery endophthalmitis. Culture-susceptibility of the microorganisms from undiluted vitreous guides the definitive treatment in non-responsive cases. Strategies to reduce the incidence of endophthalmitis after penetrating eye procedures have been developed concurrently with refined means of treatment. Despite these advances, outcomes remain poor for many patients. Although consensus articles have been published on managing endophthalmitis, treatment patterns vary, and controversies remain. These include (1) the use of newer methods for early and precise microbiological diagnosis; (2) the choice of intravitreal antibiotics; (3) the need for systemic therapy; (4) early and complete vitrectomy. Here, we review the current consensus and address controversies in diagnosing and managing endophthalmitis. This review is intended to familiarize physicians and ophthalmologists with different aspects of endophthalmitis management to make informed decisions.

Prevalence and causes of visual impairment in Dongaria indigenous (tribal) community. Tribal Odisha eye disease study # 12.

Purpose: To document the spectrum and magnitude of eye disorders and visual impairment in the Dongaria-a Particularly Vulnerable Tribal Group in the Rayagada district of Odisha, India. Methods: A door-to-door screening protocol included a record of basic health parameters, visual acuity for distance, and near and flashlight examination of the eyes. Spectacles were dispensed to those who improved; those who failed the screening were referred to fixed (primary and secondary) eye care centers. Results: We examined 89% (n = 9872/11,085) of people who consented for screening. The mean age was 25.5 ± 18.8 years; 55% (n = 5391) were female; 13.8% (n = 1361) were under-five children, and 39% (n = 3884) were 6 to 16 years. 86% (n = 8515) were illiterate. 12.4% (n = 1224) were visually impaired, of which 9.9% had early moderate VI, and 2.5% had severe VI and blindness. Uncorrected refractive error was detected in 7.5% (n = 744) and cataracts in 7.6% (n = 754); among the adults, 41.5% (n = 924/2227) had presbyopia. In children, 20% (n = 790) had vitamin A deficiency, 17% (n = 234) had global acute malnutrition, and 18% (n = 244) were stunted for their age. Almost two-thirds (62%, n = 6144) confirmed habitual intake of alcohol, and 4% (n = 389) of adults had essential hypertension. Following the screening, 43.5% (n = 837) of referred patients reported to the fixed centers, and 55% (134/243) of people advised underwent cataract surgery. Spectacles were dispensed to 1496 individuals. Conclusion: Visual impairment and malnutrition are high in Dongaria indigenous community. Permanent health facilities and advocacy would improve this community's health and health-seeking behavior.

Burden of undiagnosed and suboptimally controlled diabetes in selected regions of India: Results from the SMART India population-level diabetes screening study.

AIMS: To estimate the prevalence of undiagnosed diabetes and suboptimally controlled diabetes and the associated risk factors by community screening in India. METHODS: In this multi-centre, cross-sectional study, house-to-house screening was conducted in people aged ≥40 years in urban and rural areas across 10 states and one union territory in India between November 2018 and March 2020. Participants underwent anthropometry, clinical and biochemical assessments. Capillary random blood glucose and point-of-care glycated haemoglobin (HbA1c ) were used to diagnose diabetes. The prevalence of undiagnosed diabetes and suboptimal control (HbA1c ≥53 mmol/mol [≥7%]) among those with known diabetes was assessed. RESULTS: Among the 42,146 participants screened (22,150 urban, 19,996 rural), 5689 had known diabetes. The age-standardised prevalence of known diabetes was 13.1% (95% CI 12.8-13.4); 17.2% in urban areas and 9.4% in rural areas. The age-standardised prevalence of undiagnosed diabetes was 6.0% (95% CI 5.7-6.2); similar in both urban and rural areas with the highest proportions seen in the East (8.0%) and South (7.8%) regions. When we consider all people with diabetes in the population, 22.8% of individuals in urban areas and 36.7% in rural areas had undiagnosed diabetes. Almost 75% of the individuals with known diabetes had suboptimal glycaemic control. CONCLUSIONS: High prevalence of undiagnosed diabetes and suboptimally controlled diabetes emphasises the urgent need to identify and optimally treat people with diabetes to reduce the burden of diabetes.

Prevalence of refractive error among Dongarias and use of Folding Phoropter (FoFo) as a field device enabling implementation research in this indigenous community. Tribal Odisha Eye Disease Study (TOES) Report # 13.

PURPOSE: To evaluate the prevalence of uncorrected refractive error (URE) among Dongarias-a particularly vulnerable tribal group in Rayagada, Odisha, India and evaluate if folding phoropter (FoFo) can help achieve on-site correction of URE. METHODS: This was a cross-sectional study. FoFo was used for people with URE. Spherical equivalent (SE) spectacles based on the FoFo refraction were dispensed when distance visual acuity improved to > 6/12. Others were referred to fixed eye centres. Multivariable logistic regression evaluated the relationship of URE with sociodemographic characters and factors predicting acceptance of FoFo. RESULTS: In the study, 7.5% (95% confidence interval [CI]:7-8) people had URE, and included 4% with severe vision impairment and 36% with moderate visual impairment. URE was less common in children. Simple hyperopia was more common in females (25.3% vs 19.3%); compound myopic astigmatism was more common in males (27.4% vs 20.2%). People older than 50 years (p <0.0001) and females (p <0.0001) were more likely to have URE. Ninety-four people accepted FoFo on-site refraction and received SE spectacles; the acceptance was better in the younger (15-29 years old) and literate people (p <0.0001). CONCLUSIONS: URE was the second most common cause of visual impairment in older adults and was higher in females. Within its technological limit, FoFo could be used in the field for correcting URE and obviating the need for travel, thus bridging the know-do gap for the marginalised Dongaria community.

Characteristics of posterior zone I retinopathy of prematurity.

OBJECTIVE: To report the demographic profile and clinical characteristics of retinopathy of prematurity (ROP) in posterior Zone I. METHODS: In a partly retrospective (ten years) and partly prospective (one year) study, we analysed the demographic profile and clinical characteristics of babies with ROP in posterior Zone I. RESULTS: The study included 130 eyes of 67 infants with a mean gestational age and birth weight of 29.3 (±2.2) weeks and 1217.3 (±381.9) grams, respectively. All babies had received unblended oxygen. In 47 of 51 (91.1%) babies, the weekly weight gain was <100 g (details were not available in 16 babies). The ROP subtypes included aggressive, threshold, hybrid, stage 4, and atypical types in 78 (60%), 20 (15.4%), 11 (8.5%), 15 (11.5%), and 6 (4.6%) eyes, respectively. Fibrovascular proliferation, when present, was prominent nasally, occasionally overriding the disc margin. Extensive arteriovenous tortuosity was more prominent than vascular dilatation. Atypical observations included bleb-like detachment (6 eyes; 4.6%) and candle wax-like preretinal deposits (23 eyes; 17.7%). CONCLUSIONS: Retinopathy of Prematurity in posterior Zone I in this cohort was strongly associated with 100% unblended oxygen supplementation, poor weight gain, and multiple systemic co-morbidities. ROP in posterior zone 1 has a distinct profile with several atypical characteristics different from ROP in other zones.

Mumbai metropolitan region eye care facility survey: Mumbai Eye Disease Study (MEDiS) report #1.

Purpose: To examine the eye care practice in the Mumbai Metropolitan Region (MMR). Methods: This study consisted of primary and secondary research conducted in five zones of MMR. The primary research included interviews with the patients, eye care providers, and key opinion leaders. The secondary research included analyzing data from the professional ophthalmology societies, public health domain, and health insurance providers. We divided people into three economic classes by annual income - low (1.8 m). We analyzed the collected data to estimate the eye care demand-supply, quality of eye care, health-seeking behavior, gap in eye care delivery, and eye care expenditure. Results: We examined 473 key eye care facilities and interviewed 513 people. The ophthalmologist density in MMR was 80/million, and it was the highest in North MMR. Most ophthalmologists visited several facilities. Cataract surgery and glaucoma care coverage were better than other specialties; it was poor for oncology and oculoplastic services. Annual eye examination practice was poor in the low- and middle-income groups than in the high-income group (48%-50% vs. 85%). Most people preferred visiting eye care facilities within 5 km of their residence. Out-of-pocket spending was between 60% and 83%. Lower-income group people preferred public facilities. Conclusion: MMR eye care needs further improvement in affordable and accessible eye care, health literacy, public health surveillance, research into the application of newer technologies to provide less-expensive home care for the elderly and minimize their hospital visits, and collection and analysis of big data to address city-specific eye health issues.

Risk Stratification on Systemic Target Organ Involvement Associated with Hypertensive Retinopathy.

BACKGROUND: Hypertensive retinopathy is a common complication among people with hypertension. The current study assessed the risk stratification on systemic target organ involvement of people with hypertensive retinopathy. METHODS: In a hospital- based cross-sectional study conducted at a tertiary referral eye institute in Nepal, we included consecutive people ≥ 31 years with essential hypertension. Details of histories and systemic target organ involvements were documented. People with un-gradable retinal findings of hypertensive retinopathy and prior retinal surgery were excluded. All participants underwent comprehensive eye examination, including dilated fundus examination. Hypertensive retinopathy was classified by Modified Scheie classification. Multivariate analysis was performed to identify the risks for hypertensive retinopathy and target organ involvement. RESULTS: The study recruited 312 subjects. The mean age was 63.68 ± 12.63 years. The mean duration of hypertension was 7.0 ± 6.5 years. Hypertensive retinopathy was detected in 83.7% (n=261) people and 63.5% (n= 198) had grade 1 hypertensive retinopathy. Target organ involvement was detected in 20.5% (n =64) people. These included cardiac (12.5%; n=39), central nervous (5.1%; n= 16), and renal (4.5%; n=14) systems. In multivariate analysis, concurrent hyperlipidaemia was significantly associated with hypertensive retinopathy and target organ involvement. Target organ involvement increased with the severity of hypertensive retinopathy. CONCLUSIONS: Over four-fifths of people with hypertension had hypertensive retinopathy and one-fifth had other systemic target organ involvements. Severity of hypertensive retinopathy and concurrent hyperlipidaemia were associated with target organ involvement. Hypertensive retinopathy can be considered for risk stratification to other target organ involvement in a clinical setting.

Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data.

Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.

Electronic medical records driven big data analytics in retinal diseases, report number 1: non-oncological retinal diseases in children and adolescents in India.

PURPOSE: To describe the spectrum and demographic distribution of non-oncological retinal diseases in children and adolescents presenting to a multi-tier ophthalmic hospital network in India. METHODS: This is a cross-sectional hospital-based retrospective study over nine years (March 2011-March 2020) from a pyramidal eye care network in India. The analysis included 477,954 new patients (0-21 years), collected from an International Classification of Diseases (ICD) coded electronic medical record (EMR) system. Patients with a clinical diagnosis of retinal disease (non-oncological) in at least one eye were included. Age-wise distribution of these diseases in children and adolescents was analysed. RESULTS: In the study, 8.44% (n = 40,341) of new patients were diagnosed with non-oncological retinal pathology in at least one eye. The age group-specific distribution of retinal diseases was 47.4%, 11. 8%, 5.9%, 5.9%, 6.4%, 7.6% in infants (< 1 year), toddlers (1-2 years), early childhood (3-5 years), middle childhood (6-11 years), early adolescents (12-18 years) and late adolescents (18-21 years), respectively. 60% were male, and 70% had bilateral disease. The mean age was 9.46 ± 7.52 years. The common retinal disorders were retinopathy of prematurity (ROP, 30.5%), retinal dystrophy (19.5%; most commonly, retinitis pigmentosa), and retinal detachment (16.4%). Four-fifth of the eyes had moderate to severe visual impairment. Nearly one-sixth of patients needed low vision and rehabilitative services, and about 1 in 10 patients required surgical intervention (n = 5960, 8.6%). CONCLUSION AND RELEVANCE: About 1 in 10 children and adolescents seeking eye care in our cohort had non-oncological retinal diseases; the common ones were ROP (in infants) and retinitis pigmentosa (in adolescents). This information would help future strategic planning of eye health care in the institution in pediatric and adolescent age groups.

Application and validation of a novel inflammatory score in the clinical grading of infectious endophthalmitis: The endophthalmitis management study - Report 2.

Purpose: This study was conducted to describe and validate a novel inflammatory score (IS) system in the management of infectious endophthalmitis. Methods: This was a prospective comparative non-interventional observational study. The study included the patients with clinical signs and symptoms of acute post-cataract surgery endophthalmitis (surgery within 6 weeks) with visual acuity from 6/18 to light perception. IS was scored by the clinical picture at two-levels of four ocular tissues on a scale of 0 (normal) to 4 (severe). Four masked graders of different levels of experience evaluated slit-lamp photographs. The concordance correlation coefficient was assessed between the slit-lamp clinical grading and photographic grading. We measured the concordance correlation coefficient, Pearson's correlation (indicating precision), and the bias correction factor (indicating the accuracy). Results: The study included 43 eyes of 43 patients. The concordance correlation coefficient was 0.99 (95% CI 0.995 to 0.998). Both Pearson's correlation coefficient and the bias correction were 0.99. The interclass correlation coefficient (ICC) was measured. The intra-rater ICC was 0.833 with good agreement (95% CI, 0.711 to 0.906; P < 0.001). Inter-rater ICC for consistency was 0.92 (95% CI 0.87 to 0.95). Inter-rater ICC for absolute agreement was 0.86 (95% CI 0.66 to 0.93). Conclusion: Currently used IS scoring in the study is a reliable, reproducible, and easy-to-apply scale to measure inflammation severity in endophthalmitis. We propose that it can have applications in decision-making for primary treatment and monitoring progression in acute infectious endophthalmitis.

Intraocular Microbiome in Diabetes and Diabetic Retinopathy: A Pilot Study.

INTRODUCTION: The objective of this study was to compare the microbiome in the aqueous humour and gut of people with diabetes mellitus (DM) with and without diabetic retinopathy (DR). METHODS: This was a prospective controlled study. The study included 17 people undergoing intraocular surgery in their naïve eyes. Stool samples were obtained in the perioperative period; aqueous humour samples of sufficient quantity were obtained in 12 people during intraocular surgery. Dietary information was obtained using a previously validated questionnaire. The gut and aqueous humour samples were assessed for microbiome using 16S rRNA gene sequencing coupled with QIIME and R software. RESULTS: Aqueous humour was analysed in 12 people: 4 each healthy controls, people with DM, and people with DR. There were minor differences at the phyla levels, but the aqueous humour microbiomes of healthy controls, DM, and DR formed three distinct clusters on heat map analysis with discriminatory genera. This genera-level clustering was more apparent for the intraocular than the gut microbiome. In people with DM and DR, we identified genera unique to the eye or the gut. There was a consistent reduction in the abundance of anti-inflammatory bacteria in people with DR than DM. CONCLUSIONS: There is a difference in intraocular and gut microbiome regardless of disease or health. Our preliminary findings indicate distinctive features of the intraocular microbiome in people with DR compared with those without it. While this distinctiveness appears more evident in aqueous humour than in the gut, it needs further confirmation with larger studies.