Integrin ß4 induced epithelial-to-mesenchymal transition involves miR-383 mediated regulation of GATA6 levels.

BACKGROUND: The process of transdifferentiating epithelial cells to mesenchymal-like cells (EMT) involves cells gradually taking on an invasive and migratory phenotype. Many cell adhesion molecules are crucial for the management of EMT, integrin ß4 (ITGB4) being one among them. Although signaling downstream of ITGB4 has been reported to cause changes in the expression of several miRNAs, little is known about the role of such miRNAs in the process of EMT. METHODS AND RESULTS: The cytoplasmic domain of ITGB4 (ITGB4CD) was ectopically expressed in HeLa cells to induce ITGB4 signaling, and expression analysis of mesenchymal markers indicated the induction of EMT. ß-catenin and AKT signaling pathways were found to be activated downstream of ITGB4 signaling, as evidenced by the TOPFlash assay and the levels of phosphorylated AKT, respectively. Based on in silico and qRT-PCR analysis, miR-383 was selected for functional validation studies. miR-383 and Sponge were ectopically expressed in HeLa, thereafter, western blot and qRT-PCR analysis revealed that miR-383 regulates GATA binding protein 6 (GATA6) post-transcriptionally. The ectopic expression of shRNA targeting GATA6 caused the reversal of EMT and ß catenin activation downstream of ITGB4 signaling. Cell migration assays revealed significantly high cell migration upon ectopic expression ITGB4CD, which was reversed upon ectopic co-expression of miR-383 or GATA6 shRNA. Besides, ITGB4CD promoted EMT in in ovo xenograft model, which was reversed by ectopic expression of miR-383 or GATA6 shRNA. CONCLUSION: The induction of EMT downstream of ITGB4 involves a signaling axis encompassing AKT/miR-383/GATA6/ß-catenin.

Tuberculosis Pathways to Care and Transmission of Multidrug Resistance in India.

Rationale: India is experiencing a regional increase in cases of multidrug-resistant tuberculosis (MDR-TB). Objectives: Given the complexity of MDR-TB diagnosis and care, we sought to address key knowledge gaps in MDR risk factors, care delays, and drivers of delay to help guide disease control. Methods: From January 2018 to September 2019, we conducted interviews with adults registered with the National TB Elimination Program for MDR (n = 128) and non-MDR-TB (n = 269) treatment to quantitatively and qualitatively study care pathways. We collected treatment records and GeneXpert-TB/RIF diagnostic reports. Measurements and Main Results: MDR-TB was associated with young age and crowded residence. GeneXpert rifampicin resistance diversity was measured at 72.5% Probe E. Median time from symptom onset to diagnosis of MDR was 90 days versus 60 days for non-MDR, Wilcoxon P < 0.01. Delay decreased by a median of 30 days among non-MDR patients with wider access to GeneXpert, Wilcoxon P = 0.02. Pathways to care were complex, with a median (interquartile range) of 4 (3-5) and 3 (2-4) encounters for MDR and non-MDR, respectively. Of patients with MDR-TB, 68% had their first encounter in the private sector, and this was associated with a larger number of subsequent healthcare encounters and catastrophic expenditure. Conclusions: The association of MDR with young age, crowding, and low genotypic diversity raises concerns of ongoing MDR transmission fueled by long delays in care. Delays are decreasing with GeneXpert use, suggesting the need for routine use in presumptive TB. Qualitatively, we identify the need to improve patient retention in the National TB Elimination Program and highlight patients' trust relationship with private providers.

Correlating the patterns of diabetic macular edema, optical coherence tomography biomarkers and grade of diabetic retinopathy with stage of renal disease.

PURPOSE: To correlate optical coherence tomography (OCT)-based morphological patterns of diabetic macular edema (DME), biomarkers and grade of diabetic retinopathy (DR) in patients with various stages of chronic kidney disease (CKD) secondary to diabetes. DESIGN: Multicentric retrospective cross-sectional study was conducted at seven centers across India. METHODS: Data from medical records of patients with DME and CKD were entered in a common excel sheet across all seven centers. Staging of CKD was based on estimated glomerular filtration rate (eGFR). RESULTS: The most common morphological pattern of DME was cystoid pattern (42%) followed by the mixed pattern (31%). The proportion of different morphological patterns did not significantly vary across various CKD stages (p = 0.836). The presence of external limiting membrane-ellipsoid zone (ELM-EZ) defects (p < 0.001) and foveal sub-field thickness (p = 0.024) showed a direct correlation with the stage of CKD which was statistically significant. The presence of hyperreflective dots (HRD) and disorganization of inner retinal layers (DRIL) showed no significant correlation with the stage of CKD. Sight threatening DR was found to increase from 70% in CKD stage 3 to 82% in stages 4 and 5 of CKD, and this was statistically significant (p = 0.03). CONCLUSION: Cystoid morphological pattern followed by mixed type was the most common pattern of DME on OCT found in patients suffering from stage 3 to 5 of CKD. However, the morphological patterns of DME did not significantly vary across various CKD stages. ELM-EZ defects may be considered as an important OCT biomarker for advanced stage of CKD.

BjuWRR1, a CC-NB-LRR gene identified in Brassica juncea, confers resistance to white rust caused by Albugo candida.

KEY MESSAGE: BjuWRR1, a CNL-type R gene, was identified from an east European gene pool line of Brassica juncea and validated for conferring resistance to white rust by genetic transformation. White rust caused by the oomycete pathogen Albugo candida is a significant disease of crucifer crops including Brassica juncea (mustard), a major oilseed crop of the Indian subcontinent. Earlier, a resistance-conferring locus named AcB1-A5.1 was mapped in an east European gene pool line of B. juncea-Donskaja-IV. This line was tested along with some other lines of B. juncea (AABB), B. rapa (AA) and B. nigra (BB) for resistance to six isolates of A. candida collected from different mustard growing regions of India. Donskaja-IV was found to be completely resistant to all the tested isolates. Sequencing of a BAC spanning the locus AcB1-A5.1 showed the presence of a single CC-NB-LRR protein encoding R gene. The genomic sequence of the putative R gene with its native promoter and terminator was used for the genetic transformation of a susceptible Indian gene pool line Varuna and was found to confer complete resistance to all the isolates. This is the first white rust resistance-conferring gene described from Brassica species and has been named BjuWRR1. Allelic variants of the gene in B. juncea germplasm and orthologues in the Brassicaceae genomes were studied to understand the evolutionary dynamics of the BjuWRR1 gene.

Knowledge, attitude and practices on diabetes, hypertension and diabetic retinopathy and the factors that motivate screening for diabetes and diabetic retinopathy in a pyramidal model of eye health care.

INTRODUCTION: To report the results of a knowledge, attitude and practice (KAP) study related to diabetes mellitus (DM), hypertension and diabetic retinopathy (DR) of patient populations in India at different levels (Tertiary (T), Secondary (S) and Primary (P)) of a pyramidal model of eye health care. METHODS: In total, 202 participants, composed of equal numbers of diabetic and non-diabetic patients at a Tertiary urban facility (T), a Secondary rural facility (S) and a Primary (P) community-screening program, were surveyed on their knowledge, knowledge sources, attitudes, practices and factors that motivate use of eye health services. RESULTS: People with diabetes had a higher mean knowledge and attitude score about DM, hypertension and DR (67.3% T, 59.4% S, 47.0% P) than non-diabetics (41.8% T, 29.0% S, 23.5% P; p<0.001). Awareness of DR was more 65.3% among diabetics compared with 22.0% among non-diabetics at all locations. Most participants in all locations were aware of hypertension (84.0% T, 65.3% S, 52.9% P), but few knew it could affect the eyes (30.0% T, 12.2% S, 13.7% P) or be associated with diabetic complications (30.0% T, 32.7% S, 21.8% P). Many participants had never previously had a dilated eye examination (2% T, 40% S, 50% P). Participants were motivated to visit an eye facility for a routine checkup (70.6%), poor vision (22.6%) or a glucose/blood pressure test (17.7%) at a Primary-level facility and for follow-up or poor vision at the other facilities (28% and 42% Tertiary, 50% and 30% Secondary). CONCLUSION: Practice-oriented education and advertising of facilities tailored for the relevant populations at each level of an eye health pyramid and continuation of fundus, glucose and blood pressure screening programs can help in creating awareness about diabetes, hypertension and diabetic retinopathy.

Management of perisylvian arteriovenous malformations: a retrospective institutional case series and review of the literature.

OBJECT: Sylvian arteriovenous malformations (sAVMs) are challenging lesions of the central nervous system. The natural history of these unique lesions as well as clinical outcomes following treatment of sAVMs has been limited to case series owing to the rarity of these lesions. The authors present their experience with sAVMs and review the literature. METHODS: In accordance with the Henry Ford Institutional Review Board, medical records of patients with sAVMs treated from 2000 to 2012 were reviewed. Clinical data were retrospectively collected to calculate pre- and posttreatment modified Rankin Scale scores for all patients. RESULTS: The authors identified 15 patients with sAVMs who received treatment. Of these, 12 were female and 3 were male, and the average age at presentation was 39.6 ± 12.94 years (± SD). Two patients (13.3%) had Spetzler-Martin Grade I lesions, 6 patients (40%) had Grade II lesions, 5 patients (33.3%) had Grade III lesions, and another 2 (13.3%) harbored Grade IV arteriovenous malformations (AVMs). According to the Sugita classification, 6 patients (40%) had medial lesions, 6 (40%) had lateral lesions, 2 (13.3%) had deep lesions, and 1 patient (6.67%) had a pure sAVM. Eight patients (53.3%) underwent stereotactic radiosurgery while 7 patients (46.7%) had microsurgical resection; 1 patient underwent surgical extirpation after incomplete response following radiosurgery. After treatment, 9 patients were unchanged from pretreatment (60%), 3 patients worsened, and 2 patients had improved functional outcome (20% and 13.3%, respectively). The authors' literature search yielded 348 patients with sAVMs, most of them harboring Spetzler-Martin Grade II and III lesions. Approximately 98% of the patients underwent resection with excellent outcomes. CONCLUSIONS: While the ideal choice of therapeutic modality for cerebral AVMs remains controversial in light of the recent publication of the ARUBA (A Randomized trial of Unruptured Brain AVMs) trial, a multidisciplinary treatment approach for the management of sAVMs can lead to acceptable neurological outcome.

Health transition and eye care policy planning for people with diabetic retinopathy in south Asia.

The prevalence of type 2 diabetes (T2D), associated systemic disorders, diabetic retinopathy (DR) and current health policies in south Asian countries were analysed to assess country-specific preparedness to meet the 2030 Sustainable Development Goals. The south Asian countries were classified by human development index, socio-demographic index, multidimensional poverty indices, and eye health resources for epidemiological resource-level analysis. In south Asia, the prevalence of diagnosed and undiagnosed T2D in adults aged 40 years or above, was higher in Pakistan (26.3%) and Afghanistan (71.4%), respectively; India has the highest absolute number of people with DR, and Afghanistan has the highest prevalence of DR (50.6%). In this region, out-of-pocket spending is high (∼77%). This Health Policy is a situational analysis of data available on the prevalence of DR and common eye diseases in people with T2D in south Asia and available resources to suggest tailored health policies to local needs. The common issues in the region are insufficient human resources for eye health, unequal distribution of available workforce, and inadequate infrastructure. Addressing these challenges of individuals with T2D and DR, a 10-point strategy is suggested to improve infrastructure, augment human resources, reduce out-of-pocket spending, employ targeted screening, and encourage public-private partnerships.

Late postoperative vitreous cavity hemorrhage after vitrectomy for proliferative diabetic retinopathy-observation versus intervention.

PURPOSE: To analyze the outcome of intervention versus observation for vitreous cavity hemorrhage occurring after a 2-month period of blood-free cavity (late postoperative vitreous cavity hemorrhage-POVCH) in eyes operated by vitrectomy for complications of proliferative diabetic retinopathy (PDR). METHODS: This study was a 10-year retrospective, observational, multi-center study involving eight major vitreoretinal surgical centers across India from January 2010 to December 2019. The primary objective of the study was to assess the visual and clinical outcomes of various management approaches for late POVCH. The key secondary objective was to determine the best management option that prevented recurrence. Patients with follow-up of less than 6 months of POVCH management were excluded. RESULTS: The occurrence of late POVCH was studied in 261 eyes. The median time to occurrence was 7 months (range: 2-87) postvitrectomy/silicone oil removal. The majority (58%) experienced a single, nonrecurring POVCH event. Visual acuity outcome was independent of all management approaches (P = 0.179; mean follow-up 20.7 ± 14.1 months). With watchful observation, spontaneous resolution was noted in 83% (60/72 eyes) of eyes in 81.5 days (interquartile range, 169.75). Silicone oil injection was most effective in preventing recurrence (P < 0.001). CONCLUSION: The current treatment practice of late POVCH management in PDR suggests that watchful observation for at least 3 months could be as efficacious as any surgical intervention.

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.

Multifocal electroretinography in type 2 idiopathic macular telangiectasia.

BACKGROUND: To characterize the electroretinographic response of the macula by multifocal electroretinography (mfERG) in patients with type 2 idiopathic macular telangiectasia (MacTel). METHODS: A prospective study of mfERG in patients with type 2 MacTel was conducted from April 2009 to November 2009. mfERGs were recorded using a visual evoked response imaging system (MonElec2, Metrovision, Perenchies, France). The International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines were followed. Patients with type 2 MacTel confirmed by fundus fluorescein angiography without subretinal neovascularisation were included. For recording purposes, 61 stimulus hexagonal elements were used. The first-order kernel mfERG responses were analyzed. Individual mfERG responses for the hexagons were grouped into concentric rings centered on the fovea for analysis (< 2, 5-10, 10-15 and >15°). Student's t-test and Mann-Whitney U test and linear regression analysis was performed with STATA ver 11.1 (StataCorp, College Station , TX, USA). RESULTS: Twenty eight eyes of 14 patients and 20 eyes of ten normal controls were included in the study. The mean logMAR visual acuity of the patients was 0.51 (Snellen equivalent 20/63). The mean N1 amplitude (nv/deg(2)) of patients were significantly reduced compared to controls and were as follows: 8.91 ± 14.00 vs 43.44 ± 9.55 (p < 0.0001) in less than 2°, 9.24 ± 10.47 vs 22.00 ± 3.87 (p < 0.0001) in 5-10°, 8.57 ± 10.02 vs 15.24 ± 1.89 (p < 0.0001) in 10-15°, and 7.03 ± 6.52 vs 12.47 ± 2.62 in > 15° (p < 0.001). The mean P1 amplitude (nv/deg(2)) was also significantly reduced in patients compared to controls and was as follows: 27.66 ± 37.44 vs 96.20 ± 12.41 (p < 0.0001) in less than 2°, 22.61 ± 19.38 vs 53.78 ± 9.79 (p < 0.0001) in 5-10°, 18.75 ± 20.21 vs 35.22 ± 4.16 (p < 0.001) in 10-15°, and 17.10 ± 12.54 vs 25.71 ± 3.93 (p < 0.001). The implicit time of N1 and P1 were also delayed significantly in all the rings. The mean central foveal thickness assessed by optical coherence tomography (OCT) scan was 84.78 ± 45.12 µm. There was poor correlation between mfERG amplitudes or implicit times with either the visual acuity or OCT central thickness. CONCLUSION: mfERG showed significant reduction in amplitudes and implicit times of the waveforms in patients with type 2 MacTel in all the rings, suggesting a more generalized affection of the macula. The maximum reductions were seen in the <2(o) rings. Although there was poor correlation between the visual acuity and the amplitudes a of the waveforms, mfERG is a useful investigative modality for functional assessment of macula in type 2 MacTel patients.

Seeing beyond Gaucher disease: Early detection and treatment of ocular complications.

Background: Gaucher disease is a rare genetic disorder caused by a deficiency in the enzyme glucocerebrosidase, which impairs the body's ability to break down certain fats. This leads to the accumulation of glucosyl sphingosine and glucosyl ceramide in the liver, spleen, and bone marrow. Gaucher disease has two major types: nonneuropathic (Type 1) and neuropathic (Type 2 and Type 3). Gaucher disease can have various ophthalmologic manifestations, particularly in Type 3, including posterior segment abnormalities, such as vitreous opacities, condensations, and/or preretinal white dots. We present a case of a patient with Gaucher disease Type 3 who had severe bilateral vitreous and extensive retinal deposits, leading to challenges during surgery. Purpose: This video reports surgical outcomes for an uncommon ophthalmologic manifestation in a patient with Gaucher disease Type 3. We focus on the challenges and results of surgery for severe bilateral vitreous and extensive retinal deposits. Synopsis: A 16-year-old female patient with a history of Gaucher's disease since birth presented with a one-year history of blurred vision in both eyes. Her best-corrected visual acuity was 20/200 in the right eye and 20/100 in the left eye, as measured by Snellen's chart. Intraocular pressure was normal in both eyes, and anterior segment examinations were unremarkable. However, fundus evaluation revealed extensive vitreous deposits that obscured the details of the fundus. Additionally, an epiretinal membrane was observed over the macula in both eyes. Optical coherence tomography (OCT) confirmed the presence of deposits in the vitreous cavity and on the surface of the retina. The patient underwent pars plana vitrectomy with epiretinal membrane removal. A transconjunctival 23-G pars plana vitrectomy was performed to the extent possible. Multiple instruments were used to remove the fluffy vitreous deposits, as they were extremely adherent to the underlying surface of the retina, and brilliant blue dye was used to stain the internal limiting membrane. The epiretinal membrane and internal limiting membrane were removed from the macular area, and the entire cassette fluid was sent for histopathological examination to identify Gaucher cells. At one week postoperative, the patient's visual acuity improved to 20/125 in the right eye, and the fundus picture showed a cleared macular area. OCT showed a reduction in deposits over the retina. The histopathological examination revealed crumpled, barrel-like cytoplasm with an oval nucleus in a hemorrhagic background, suggestive of Gaucher cells. Highlights: Early detection and treatment of ocular manifestations of Gaucher's disease are important to prevent permanent damage to vision. An ophthalmological assessment involving a dilated fundus examination and optical coherence tomography can facilitate early diagnosis and follow-up of ocular manifestations. Timely surgery may be required to preserve functional vision in patients with severe ocular disease. Video Link: https://youtu.be/KR-kfgfDoqM.

Peering into the eye: A comprehensive look at ultrasound biomicroscopy (UBM) and its diagnostic value in anterior segment disorders.

Background: Ultrasound biomicroscopy (UBM) is a noninvasive imaging modality that enables in-vivo visualization of the structures of the anterior segment of the eye. Unlike routine ophthalmic diagnostic ultrasound which uses frequencies of 5-10 MHz, UBM utilizes ultrasound frequencies in the range of 50-100 MHz. The high-frequency probes in UBM allows for higher resolution and better visualization of subsurface ocular structures, even in the presence of anatomic or pathological obscuration. UBM has qualitative as well as quantitative applications in various disorders affecting the anterior segment of the eye. Despite its huge importance, many clinicians lack in knowledge about the technique and its clinical usefulness. The current educational video aims to address this gap in knowledge by highlighting the technique and various clinical indications of UBM. Purpose: The purpose of this video is to demonstrate the technique of UBM and showcase its quantitative and qualitative implications and importance through various clinical cases. Synopsis: UBM is an imaging technique that assesses the depth of tissue structures by measuring the time delay of the returning ultrasound signal. This modality is capable of measuring the size of various structures within the eye, such as the cornea, iris, ciliary body, sclera, and the depth of the anterior and posterior chamber. To perform a UBM, a transducer is inserted into a specially designed eye cup filled with distilled water, creating a water bath environment. Axial and longitudinal scans can be performed in a similar fashion as in routine diagnostic B-scan ultrasound. Quantitative indications for UBM depicted in this video include measurements of corneal thickness, depth of the anterior chamber, and the width of the angle. The video also showcases how UBM can aid in the diagnosis and management of various anterior segment disorders like angle-closure glaucoma, plateau iris configuration, secondary glaucoma, and anterior uveitis with complicated cataract. Qualitative indications for UBM highlighted in this video include its role in intermediate uveitis, ocular hypotony, ocular surface tumors, cystic lesions of iris, and identifying the location and type of intraocular foreign bodies in the anterior segment based on the type of artifact seen. Additionally, the video shows the applications of UBM in scleral and episcleral pathologies. Highlights: This video will educate clinicians about the technique of UBM and showcase a bouquet of UBM findings in various case scenarios, helping one to better understand the potential of this modality in clinical practice. Video link: https://youtu.be/F626TMbJXoU.

Using deep learning to detect diabetic retinopathy on handheld non-mydriatic retinal images acquired by field workers in community settings.

Diabetic retinopathy (DR) at risk of vision loss (referable DR) needs to be identified by retinal screening and referred to an ophthalmologist. Existing automated algorithms have mostly been developed from images acquired with high cost mydriatic retinal cameras and cannot be applied in the settings used in most low- and middle-income countries. In this prospective multicentre study, we developed a deep learning system (DLS) that detects referable DR from retinal images acquired using handheld non-mydriatic fundus camera by non-technical field workers in 20 sites across India. Macula-centred and optic-disc-centred images from 16,247 eyes (9778 participants) were used to train and cross-validate the DLS and risk factor based logistic regression models. The DLS achieved an AUROC of 0.99 (1000 times bootstrapped 95% CI 0.98-0.99) using two-field retinal images, with 93.86 (91.34-96.08) sensitivity and 96.00 (94.68-98.09) specificity at the Youden's index operational point. With single field inputs, the DLS reached AUROC of 0.98 (0.98-0.98) for the macula field and 0.96 (0.95-0.98) for the optic-disc field. Intergrader performance was 90.01 (88.95-91.01) sensitivity and 96.09 (95.72-96.42) specificity. The image based DLS outperformed all risk factor-based models. This DLS demonstrated a clinically acceptable performance for the identification of referable DR despite challenging image capture conditions.

Diabetes, Diabetic Retinopathy, and Inflammatory Disorders.

This review summarizes the impact of systemic and ocular inflammatory disorders on diabetes mellitus (DM) and diabetic retinopathy (DR). Local inflammation is a key pathology in diabetic retinopathy (DR) and is also an evolving target for clinical therapy. The legacy effects of local inflammation at the intracellular level make DR a persistent self-driven vicious process. Ocular inflammation is accompanied as well as incited by systemic inflammation due to diabetes mellitus (DM) itself. Over the years, a multitude of studies have evaluated the impact of systemic inflammatory disorders (SIDs, like rheumatoid arthritis, lupus, psoriasis, etc.) and anti-inflammatory drugs prescribed for managing them on manifestations of DM. Recent studies have indicated increased insulin resistance to be a result of chronic inflammation, and the anti-inflammatory drugs to have a protective effect towards DM. Very few studies have evaluated the impact of SIDs on DR. Furthermore, the evidence from these studies is conflicting, and while local anti-inflammatory therapy has shown a lot of clinical potential for use in DR, the results of systemic anti-inflammatory therapies have been inconsistent. The impact of local ocular inflammation due to uveitis on DR is a crucial aspect that has not been evaluated well at present. Initial pre-clinical studies and small-sized clinical reports have shown a strong and positive relationship between the presence of uveitis and the severity of DR as well as its progression, while larger cross-sectional patient surveys have refuted the same. The long term impact of ocular inflammation due to uveitis on DR needs to be studied while adjusting for confounders.

Flanged intraocular lens (IOL) implantation with scleral pockets - A modification of flanged IOL technique (E-Flanged IOL) for secondary lens implantation.

The current technique for implanting flangedintraocular lens (IOL) suffers from complications like haptic exposure and tilting of the implanted IOL. We describe a modification of the currently described technique to obviate its shortcomings. Five eyes of five patients with a minimum of 1 year of follow-up were included. In this technique, two scleral pockets were made nasal and temporal to embed the flanged haptics. The primary outcome measure was the improvement in visual acuity (VA) postoperatively and the secondary outcome measures were postoperative complications. The primary objective of this current modification is to simplify the surgical technique for secondary IOL implantation and make it more replicable and predictive. The mean age of the patients was 19.44 years. The mean preoperative VA was 0.44 logMAR which improved to 0.26 logMAR at the 6-week postoperative visit. The mean follow-up was 496+/- 80 days. The maximum follow-up was 647 days. There were no postoperative complications such as haptic exposure, hypotony, or IOL tilt in any cases. The new E-flanged IOL technique has good visual outcomes and does not have postoperative complications. It has less intraoperative manipulation and complications.

Tele-rehabilitation for persons with vision impairment during COVID-19: Experiences and lessons learned.

Purpose: The COVID-19 pandemic imposed challenges to access rehabilitation intervention to individuals with visual impairment, thereby increasing their disability effects. This study explored the viability maintaining the continuum of care through telerehabilitation. Methods: This study is a retrospective analysis of individuals with vision impairment who underwent telerehabilitation at the center of excellence in eye care at Hyderabad, Telangana, India, between April and September 2020. The International Classification of Functioning, Disability and Health framework was followed to provide services such as counseling for mental well-being, information and resources, educational interventions, Assistive Technology programs, therapeutic interventions for children with multiple disabilities, access to digital audio books and rehabilitation helpline.A team of professionals involved in the service care. Phone and what's app calls were used to facilitate the training.The duration and the number of training sessions were individual need-based with an average of 45 minutes per session and 175 training sessions. Results: Three hundred and fifty individuals and their families benefited. The service include early intervention (n = 129), and low vision care (n = 176) inclusive of computer training (n = 53), soft skills (n = 53), digital books (n = 55).Nearly two-thirds of the participants were male (n = 205). Conclusion: Evidence from this study suggests telerehabilitation as a successful model of care.A well-planned telerehabilitation approach can expand the scope of reaching the visually impaired from geographically isolated areas where scarcity of service providers and service centers.

Development of Diabetic retinopathy screening guidelines in South-East Asia region using the context, challenges, and future technology.

OBJECTIVE: To formulate guidelines for screening of diabetic retinopathy (DR) for the World Health Organization (WHO) South-East Asia Region (SEAR) aligned with the current infrastructure and human resources for health (HRH). DESIGN: A consultative group discussion of technical experts of the International Agency for the Prevention of Blindness (IAPB) from SEAR. PARTICIPANTS: IAPB country chairs and DR technical experts from SEAR countries. METHODS: Data related to DR in SEAR was collected from published literature on available DM and DR guidelines and the participating experts. The 10 SEAR countries (the Democratic Republic of Korea was not included for lack of sufficient data) were divided into 3 resource levels (low, medium, and high) based on gross national income/per capita, cataract service indicators (cataract surgical rate and cataract surgical service), current infrastructure and available HRH. Two countries each were assigned to low (Myanmar, Timor-Leste) and high resource (India, Thailand) levels, and the remaining 6 countries (Bangladesh, Bhutan, Indonesia, Maldives, Nepal, Sri Lanka) were assigned the medium resource level. The DR care system was divided into 3 levels of care (essential, recommended, and desirable) and 3 levels of service delivery (primary, secondary, and tertiary). MAIN OUTCOME MEASURES: Primary, secondary, and tertiary level guidelines for screening of DR. RESULTS: Nine WHO SEAR countries participated in the formulation of the new country-specific DR screening guidelines. The DR screening recommendations were: advocacy at the community level, visual acuity measurement, and non-mydriatic fundus photography at the primary level, comprehensive eye examination and retinal laser at the secondary level, and intravitreal therapy and vitrectomy at the tertiary level. The systemic care of DM and hypertension are recommended at all levels commiserating with their care capabilities. CONCLUSIONS: The DR guidelines for the SEAR region are the first region-specific and resource-aligned recommendations for comprehensive DR care in each country of the region. In the future, the new technological advances in retinal camera technology, teleophthalmology, and artificial intelligence should be included within the structure of the public DR care system.

Prevalence of diabetic retinopathy in India stratified by known and undiagnosed diabetes, urban-rural locations, and socioeconomic indices: results from the SMART India population-based cross-sectional screening study.

BACKGROUND: National and subnational estimates of the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy (VTDR) are needed to inform the stepwise implementation of systematic retinal screening for people with diabetes in India to decrease the rate of blindness. We aimed to assess these national and subnational estimates and to stratify the prevalence of diabetic retinopathy and VTDR on the basis of people with known versus undiagnosed diabetes, urban versus rural residence, and epidemiological transition level (ETL) and Socio-demographic Index (SDI) categories of states. METHODS: We did a multicentre cross-sectional screening study for diabetic retinopathy using a complex cluster sampling design in people aged 40 years or older in ten Indian states and one union territory between Dec 20, 2018, and March 20, 2020. We did non-mydriatic retinal screening and assessed risk factor burden for people with diabetes. We estimated nationally weighted prevalence of diabetic retinopathy and VTDR for individuals with known and undiagnosed diabetes by urban versus rural residence, and by state categorisation by ETL and SDI. We also assessed adjusted risk factors. FINDINGS: From 42 146 participants screened, 7910 (18·8%) were identified to have diabetes. Of these, 6133 (77·5%; 4350 with known diabetes and 1783 with undiagnosed diabetes) had gradable retinal images. 3411 (56%) participants were women and 2722 (44%) were men, and the median age was 56 years (IQR 49-65). The estimated national prevalence was 12·5% (95% CI 11·0-14·2) for diabetic retinopathy and 4·0% (3·4-4·8) for VTDR, with no significant differences between urban and rural residence for diabetic retinopathy. Compared with individuals with undiagnosed diabetes, we observed a higher prevalence of diabetic retinopathy (15·5% [13·4-17·8] vs 8·0% [6·3-10·1]) and VTDR (5·3% [4·5-6·3] vs 2·4% [1·6-3·6]) in individuals with known diabetes. The prevalence was significantly lower in low ETL-SDI states compared with high and middle ETL-SDI states for diabetic retinopathy (by 7·0%, 1·9-12·2, p=0·024) and VTDR (by 4·8%, 3·0-6·6, p<0·0001). Hyperglycaemia was the strongest modifiable risk factor. INTERPRETATION: We estimate that, in absolute numbers, approximately 3 million people aged 40 years or older have VTDR in India, with a higher prevalence in those with known diabetes residing in high and middle ETI-SDI states. FUNDING: UKRI Global Challenge Research Fund.

Training of nonophthalmologists in diabetic retinopathy screening.

The burden of diabetes mellitus (DM) and diabetic retinopathy (DR) is at alarming proportions in India and around the globe. The number of people with DM in India is estimated to increase to over 134 million by 2045. Screening and early identification of sight-threatening DR are proven ways of reducing DR-related blindness. An ideal DR screening model should include personalized awareness, targeted screening, integrated follow-up reminders, and capacity building. The DR screening technology is slowly shifting from direct examination by an ophthalmologist to remote screening using retinal photographs, including telescreening and automated grading of retinal images using artificial intelligence. The ophthalmologist-to-patient ratio is poor in India, and there is an urban-rural divide. The possibility of screening all people with diabetes by ophthalmologists alone is a remote possibility. It is prudent to use the available nonophthalmologist workforce for DR screening in tandem with the technological advances. Capacity-building efforts are based on the principle of task sharing, which allows for the training of a variety of nonophthalmologists in DR screening techniques and technology. The nonophthalmologist human resources for health include physicians, optometrists, allied ophthalmic personnel, nurses, and pharmacists, among others. A concurrent augmentation of health infrastructure, conducive health policy, improved advocacy, and increased people's participation are necessary requirements for successful DR screening. This perspective looks at the characteristics of various nonophthalmologist DR screening models and their applicability in addressing DR-related blindness in India.

Effect of COVID-19 Pandemic on Presentation of Patients With Diabetic Retinopathy in a Multitier Ophthalmology Network in India.

OBJECTIVE: This study aimed to describe the demographics and clinical profile of patients with diabetic retinopathy (DR) presenting during the novel coronavirus disease 2019 (COVID-19) lockdown and unlock phases in India. METHODS: This hospital-based cross-sectional study included patients presenting from March 25, 2019, to March 31, 2021. All patients who presented with DR were included as cases. The data were collected using an electronic medical record system. RESULTS: In total, 88,012 patients diagnosed with retinal diseases were presented to the network and included for analysis. There were 21,271 (24%) DR patients during the study period and the majority were men (71%) from the urban area (45%). An increasing number of patients with proliferative DR (56%), sight-threatening DR (79%), need for vitreoretinal procedures (31%), and intravitreal injections (19%) were seen during the lockdown (phase one-four). There was a significant increase in the number of patients with blindness in pre-lockdown (20%), lockdown (32%), and post-lockdown (26%). Patterns of sight-threatening DR and blindness were similar in both fresh and follow-up patients. CONCLUSION: The presentation of DR patients in hospital is evolving because of the COVID-19 pandemic. The footfalls of patients during the unlock (phase 1-10) regained to two-thirds of the pre-COVID-19 level. There was an increase in patients with sight-threatening DR and the need for vitreoretinal surgery and intravitreal injections during the lockdown (phase 1-4).