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.

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.

Tear Protein Markers for Diabetic Retinopathy and Diabetic Macular Edema - Towards an Early Diagnosis and Better Prognosis.

BACKGROUND: Diabetic eye disease is a highly prevalent and sight-threatening disorder. It is a disease of neuro-vascular unit of the retina, if left untreated can cause blindness. Therapeutic approaches followed for its treatment can only restrict the progression of the disease with highly variable results. There is no known biomarker for an early diagonsis of this disease, therefore by the time it is detected it goes beyond repair. This creates a massive demand for development of such biomarkers that help detect disease in its earlier stages. METHODS: PUBMED (https://pubmed.ncbi.nlm.nih.gov/) was searched for articles relevant to the topic published till November 2023. The search was made using keywords such as Diabetic Retinopathy, inflammation, tear, biomarker, proteomics etc. The studies providing relevant information to prove the importance of biomarker discovery were chosen. After compiling the data, the manuscript writing was planned under relevant headings and sub-headings. RESULTS: The review provides a comprehensive overview of all the tear protein biomarker studies in the field of DR and DME. Briefly, their potential in other diseases is also elucidated. While there are many studies pertaining to DR biomarkers, the identified markers lack validations which has restricted their usage in clinics. In case of DME, there was no such study towards biomarker discovery for its diagnosis and prognosis. CONCLUSIONS: The review highlights major studies and their lacunae in the field of biomarkers discovery for DR and DME.

Macular Pigment Assessment in Indian Population Using Degree of Polarization Threshold: Impact of Diet on Macular Pigment Density.

Purpose: To determine macular pigment (MP) density scores in healthy Indians and examine correlations with demographic and lifestyle variables. Methods: We observed 484 Indians without an ocular pathology. Body mass index (BMI) and self-reported lifestyle factors (sunglasses usage, physical activity, and smoking) were noted. MP density was assessed as the threshold of perception of the shadow of their macular pigments on their retina using a new MP assessment tool (MP-eye). Lutein and zeaxanthin intake was assessed using a prevalidated questionnaire regionally designed for the Indian diet. Clusters of participants were created for statistical analysis based on MP-eye scores secondarily to detect any relevant effects in very low, low, medium, and high ranges of MPs. Results: Data analyzed included 235 males and 249 females with mean age of 36.1 ± 12.9 years (range, 14-72). The median MP-eye score was 6 (range, 0-10, with 10 being high). Most were non-smokers (413, 85.3%) and did not use sunglasses (438, 90.5%), and 314 (64.9%) had low physical activity. Diabetes was present in 62 participants (12.8%) and hypertension in 53 (10.9%). Advancing age (r = -0.209; P < 0.000) and BMI (r = -0.094; P = 0.038) had weak negative correlation with MP-eye scores. Hypertension was less prevalent (7/88) in the cluster with the highest median MP-eye score (P = 0.033). Dietary intake of MPs and other lifestyle factors did not correlate significantly with MP-eye score overall or when analyzed in clusters. Conclusions: MP-eye scores of an Indian population were normally distributed. Higher age, high BMI, and presence of hypertension were weakly associated with lower MP-eye scores. The impact of diet on MPs requires further evaluation. Translational Relevance: This normative regional database enables risk stratification of macular degeneration.

Clinical Profile, Antibiotic Resistance and Outcomes in Bacterial Endophthalmitis: Coagulase-Negative Staphylococcus Endophthalmitis as Compared to Other Organisms.

BACKGROUND: To evaluate the clinical profile, outcomes and antibiotic resistance in bacterial endophthalmitis. METHODS: This was a post-hoc analysis of a study conducted at a tertiary centre, where 60 consecutive cases of culture-proven bacterial endophthalmitis were included prospectively. Group 1 included coagulase-negative Staphylococcus endophthalmitis (CNSE), while group 2 included the remaining cases. Clinical features, antibiotic resistance and visual outcomes were compared. Visual acuity >3/60 at six months of follow-up was defined as a good visual outcome. RESULTS: Group 1 had 31 cases, while group 2 had 29. Group 2 included 12 gram-positive and 17 gram-negative isolates. Among the groups, group 2 had more patients with presenting visual acuity below hand motions close to the face (25 vs. 12, p<0.001), poor visual outcomes (26 vs. 3, p<0.001) and retinal detachment (RD) (10 vs. 2, p=0.007). Pseudomonas was most commonly resistant to antibiotics, and ceftazidime (p=0.005) and cefazolin (p=0.009) resistance were higher in group 2 isolates. In group 1, five isolates were resistant to any one of the antibiotics, whereas in group 2, 13 isolates were resistant to any one of the antibiotics (p=0.024). CONCLUSIONS: In the current study, eyes in the group of endophthalmitis caused by CNSE achieved better visual acuities at the last follow-up compared to eyes with endophthalmitis caused by other bacteria. Antibiotic resistance in isolates other than CNSE is a cause of concern.

Real-world experience of full-thickness traumatic macular hole among young patients.

OBJECTIVE: To describe the demographics, clinical, and imaging characteristics, and visual outcomes in young patients with full-thickness traumatic macular hole (TMH). METHODS: This retrospective hospital-based study included patients with full-thickness TMH who presented between August 2010 and June 2021. Demographic data, clinical findings, and imaging characteristics were extracted from an electronic medical record system. Regression analyses were performed to determine significant associations among variables and to identify predictors of visual outcomes. RESULTS: 144 (0.005%) patients among 2,834,616 were diagnosed with Full thickness TMH. The majority of them were male (89.58%; odds ratio [OR] = 6.71) and the holes were unilateral. The mean age at presentation was 23.37 ± 8.19 years. Ball were the most common cause of injuries (22.22%), followed by stick (14.58%) and firecracker (12.50%). The mean LogMAR visual acuity (VA) at presentation was 1.18 ± 0.72, with 25.69% of eyes having VA < 20/400. The mean minimum hole diameter was 619.34 ± 336.16 µm. Sub-retinal fluid was present in 44.44%, followed by intraretinal fluid in 34.03% of eyes. Macular holes closed after vitrectomy in 66.67% of eyes, with mean final VA of 1.07 ± 0.85. Baseline VA was a strong predictor of final VA (R2 = 0.677; p = 0.000168). CONCLUSION: Traumatic macular hole is a unilateral condition with significant visual impairment that is mainly seen in males during the third decade of life. Surgery is successful in most cases but improvements in VA are modest.

Optical coherence tomography characteristics and factors affecting visual acuity in diabetic papillopathy.

PURPOSE: To analyse baseline imaging characteristics and factors affecting poor visual acuity in diabetic papillopathy. METHODS: This was a retrospective, observational study conducted at a tertiary eye care centre in eyes with a diagnosis of diabetic papillopathy. Demographic data including age, gender, duration of diabetes, type of diabetes, HbA1c values and other systemic co-morbidities were recorded. Baseline best corrected visual acuity (BCVA), and various imaging characteristics were noted. RESULTS: 37 eyes of 22 patients with diagnosis of diabetic papillopathy were included [mean age of 46.6 ± 13.5 years, five (22.7%) females and 17 (77.3%) males]. Bilateral involvement was seen in 15 (68.2%) patients. The mean baseline BCVA was 0.51 ± 0.49 logMAR (Snellen equivalent 20/60). Two eyes (5.4%) had features of concurrent mild NPDR, 9 eyes (24.3%) had moderate NPDR, 10 eyes (27.03%) had severe NPDR while 16 (43.2%) other had PDR. All eyes had optic disc edema while 4 had disc pallor at presentation. Telangiectatic vessels/ neovascularisation of disc was present in 17 eyes (45.9%) detected either clinically or on optical coherence tomography (OCT) angiography. 11 (29.7%) eyes had a peripapillary cuff of subretinal fluid accompanying the disc edema. Sixteen eyes (43.2%) had centre involving macular edema seen on OCT. In eyes with a macular edema, the mean central macular thickness was 407.4 ± 71.42 microns at baseline. On assessing the baseline factors that contribute to the final visual acuity, presenting visual acuity was the only variable found to be statistically significant. CONCLUSION: Although described to have good visual outcome, eyes presenting with poor visual acuity tend to have worse vision on follow up. This may aid in prognosticating and guiding management plan.

Hemi-retinal vein occlusion: Characterizing a rare retinal vasculopathy.

PURPOSE: To characterize hemi-retinal vein occlusion (HRVO) in patients presenting to a multi-tier ophthalmology hospital network. METHODS: This retrospective, hospital-based study analyzed 2,834,616 new patients between August 2010 and June 2021. Patients with a clinical diagnosis of HRVO in at least one eye were included as cases. Data were collected using an electronic medical record system. Data were compared to the findings noted in branch RVO (BRVO) and central RVO (CRVO) patients. RESULTS: HRVO constituted 0.9% ( n = 191) of all the retinal vein occlusions (RVOs), with the mean age being 60.55 ± 10.14 years. Most patients were male (125, 65.45%) with unilateral (92.67%) affliction. Majority presented during the sixth (31.41%) or seventh (32.46%) decade of life. Most patients reported mild (37.07%) or moderate (27.32%) visual impairment, with vision < 20/200 being less common in HRVO (25.8%) and BRVO (17.2%) compared to CRVO (44.1%) ( P < 0.00001). Glaucoma was diagnosed and treated in 49 (23.90%) eyes, which was much higher than CRVO (11.45%) and BRVO (5.04%) ( P < 0.001), though neovascular glaucoma was much less than CRVO (2.9% vs. 9.2%) ( P = 0.0037). On follow-up, HRVO eyes (12.2%) had lesser vision loss compared to CRVO eyes (13.7%) (this difference does not look very significant to me), though BRVO had the least (9.1%) vision loss. CONCLUSION: HRVO is a rare RVO, presenting more in males. It causes less-severe visual impairment compared to CRVO. Large majority of patients with HRVO do not have identifiable systemic risk factors other than age. Preexisting glaucoma was more associated with HRVO compared to other RVOs.

Clinical Profile, Demographic Distribution and Risk Factors of Parafoveal Telangiectasia: An Electronic Medical Record-Driven Big Data Analytics from a Multitier Eye Care Network.

OBJECTIVE: To describe the demographics and clinical profile of parafoveal telangiectasia (PFT) and compare risk factors for diabetic retinopathy (DR) among PFT and non-PFT patients. METHODS: This cross-sectional hospital-based study included 2,834,616 new patients presenting to a multi-tier ophthalmology hospital network in India between August 2010 and June 2021. Patients with a clinical diagnosis of PFT in at least one eye were included as cases. The data were collected using an electronic medical record system. RESULTS: Overall, 2,310 (0.081%) patients were diagnosed with PFT. Most of the patients were female (62.42%) with (odds ratio [OR] = 2.08), and had bilateral (84.85%) affliction. The most common age group at presentation was during the sixth decade of life with 825 (35.71%) patients. The overall prevalence was higher in patients from an upper socio economic status (0.242%) presenting from the metropolitan geography (0.113%; OR = 2.37). Systemic history of diabetes mellitus (DM) with a mean duration of 122.03 ± 95.59 months was seen in 849 (36.75%) and hypertension in 609 (26.36%) patients. Of the 4,270 eyes, 2,441 (57.17%) eyes had a visual impairment of mild or no visual impairment (<20/70) followed by moderate visual impairment (>20/70-20/200) in 1022 (23.93%) eyes. The risk of sight threatening diabetic retinopathy (STDR) among PFT patients was higher (OR = 1.43) compared to non-PFT cohort. Choroidal neovascular membrane (CNVM) was observed in 481 (11.26%) eyes. CONCLUSION: PFT is more common in females and is predominantly bilateral. PFT is more common in upper socio economic status and majority of the eyes had mild or moderate visual impairment. Diabetes and Hypertension are associated risk factors in PFT.

Outcomes of vitreoretinal surgery in eyes with retinitis pigmentosa without retinal detachment.

PURPOSE: Outcomes of retinal detachment (RD) have been discussed in detail in many reports of patients with retinitis pigmentosa (RP). This study tries to understand the outcomes of vitreoretinal (VR) surgery for indications other than RD in the eyes with RP. METHODS: This is a retrospective study that includes clinical data from January 2013 to December 2021. Patients with RP who were treated with a VR surgical intervention were included in the study. The primary outcome of the study was to assess the changes in best-corrected visual acuity. RESULTS: Forty-four eyes of 40 patients with RP were included in the study. Nearly half of the eyes (43%, 19/44) presented from 1 month to 1 year after the onset of diminished vision, with or without floaters. The mean ± standard deviation (SD) best-corrected visual acuity (BCVA) at presentation was 1.30 ± 0.79 logMAR (20/400 ± 20/125). The major surgical indications were vitreous opacities (43.2%, 19/44) and subluxated/dislocated cataractous lenses (25%, 11/44). The median follow-up duration was 8 months (interquartile range (IQR): 1.5-27). Approximately 77% (34/44) of the eyes had improvement in vision. The mean postoperative BCVA at the last follow-up was 0.95 ± 0.73 logMAR (p-value: 0.03). CONCLUSIONS: Most eyes with RP recovered well after VR surgical interventions, with short-term improvements in visual acuity. It may be crucial to address the vitreous opacities and membranes as they hinder the residual central island of vision in RP. However, appropriate counselling is required regarding the progressive nature of retinal neuronal degeneration.

Characterization of retinal hemorrhages delimited by the internal limiting membrane.

Clinically, hemorrhages at the vitreoretinal interface have been termed as 'pre-retinal' in location. However, there is a careful distinction to be made between sub-hyaloid and sub-internal limiting membrane (ILM) planes of blood collection. In the past half-century, a body of literature has accrued on sub-internal limiting membrane hemorrhage. We characterize the etiopathological, clinical, anatomical, and imaging characteristics of this entity (often misconstrued as sub-hyaloid hemorrhage). Management decisions are briefly described, and a unifying term of sub-internal limiting membrane macular hemorrhage is proposed to aid in further research.

Gene Therapy for Inherited Retinal Diseases: From Laboratory Bench to Patient Bedside and Beyond.

This comprehensive review provides a thorough examination of inherited retinal diseases (IRDs), encompassing their classification, genetic underpinnings, and the promising landscape of gene therapy trials. IRDs, a diverse group of genetic conditions causing vision loss through photoreceptor cell death, are explored through various angles, including inheritance patterns, gene involvement, and associated systemic disorders. The focal point is gene therapy, which offers hope for halting or even reversing the progression of IRDs. The review highlights ongoing clinical trials spanning retinal cell replacement, neuroprotection, pharmacological interventions, and optogenetics. While these therapies hold tremendous potential, they face challenges like timing optimization, standardized assessment criteria, inflammation management, vector refinement, and raising awareness among vision scientists. Additionally, translating gene therapy success into widespread adoption and addressing cost-effectiveness are crucial challenges to address. Continued research and clinical trials are essential to fully harness gene therapy's potential in treating IRDs and enhancing the lives of affected individuals.

Central retinal artery occlusion following pediatric blunt ocular trauma.

BACKGROUND: To analyze the clinical profile, presentation, possible pathophysiology, and outcomes of central retinal artery occlusion (CRAO) following blunt trauma in pediatric subjects. METHODOLOGY: The medical charts of subjects aged 18 years or less with a diagnosis of CRAO following blunt ocular trauma were analyzed retrospectively for demography, details of the trauma, ocular findings, additional imaging reports if any, and final outcome. A Medline search was done (key words like central retinal artery occlusion, blunt trauma, children, pediatric subjects, and adolescents) to gather information available in the literature on the subject. RESULTS: A total of 11 patients (11 eyes), mean age of 14.3 ± 3.4 years, and 100% male preponderance, with an average time duration from trauma to presentation to the hospital of 8.1 days were included. Visual acuity ranged from no light perception (four eyes) to finger count at a 1 m distance. Intraocular pressure was raised in three patients, of which two were suffering from sickle cell disease. In two eyes, the CRAO coexisted with optic nerve avulsion and the cilioretinal artery was spared. Disk pallor was seen in six eyes as early as 12 days from the trauma. None of the cases revealed any bony fracture in the CT scan. CONCLUSION: CRAO was observed to be an important primary or contributory cause of visual loss in children following blunt trauma, reflex vasospasm being the most common etiology. Early onset disk pallor could suggest an underlying vascular compromise of both retinal and optic disk circulation in addition to direct disk damage.

Clinical profile and demographic distribution of Stargardt disease phenotypes: An Electronic medical record-driven big data analytics from a multitier eye care network.

Purpose: To describe the demographics and clinical profile of Stargardt disease in patients presenting a multitier ophthalmology hospital network in India. Methods: This cross-sectional hospital-based study was performed among 2,834,616 new patients presenting between August 2010 and June 2021 in our network. Patients with a clinical diagnosis of Stargardt disease in at least one eye were included as cases. The data were collected using an electronic medical record system. Results: Overall, 1,934 (0.069%) patients were diagnosed with Stargardt disease. Most of the patients were male (63.14%). The most common age group at presentation was during the second decade of life, with 626 (31.87%) patients. The overall prevalence was higher in patients from a higher socioeconomic status (0.077%), in those presenting from the urban geography (0.079%), and in students (0.197%). Systemic history of hypertension was seen in 56 (2.85%) patients, while diabetes mellitus was seen in (2.49%) patients. Of the 3,917 eyes, 1,910 (48.76%) eyes had moderate visual impairment (>20/70-20/200) followed by severe visual impairment (>20/200 to 20/400) in 646 (16.49%) eyes. The most commonly associated retinal signs were retinal flecks in 1,260 (32.17%) eyes, followed by RPE changes in 945 (24.13%) eyes. The most documented investigations were autofluorescence (39.85%), followed by optical coherence tomography (23.90). Cataract surgery was the commonest performed surgical intervention in (0.66%) eyes, followed by intravitreal injection in 4 (0.10%) eyes. The family history of parent consanguinity marriage was reported by 212 (10.79%) patients. Conclusion: Stargardt disease was seen more commonly in males presenting during the second decade of life. It is predominantly a bilateral disease, with the majority of the eyes having moderate visual impairment.

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.

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.

Case Report: Poor Outcome Despite Aggressive Management in Pythium insidiosum Endophthalmitis.

Pythium insidiosum is a parasitic oomycete that can cause keratitis and closely resembles fungus, both clinically and morphologically. It requires a trained microbiologist for its differentiation from fungal filaments and has poor response to antifungal therapy. We present a case of primary isolation of the organism from the vitreous cavity in a case of endophthalmitis. The infection spread quickly and involved all the ocular tissues. The eye had poor visual outcome despite a sequence of rapidly completed retinal and corneal surgeries along with initiation of anti-Pythium therapy.