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.

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.

Central Retinal Artery Occlusion in Rhino-Orbital-Cerebral Mucormycosis: An Inflammatory-Prothrombotic State.

PURPOSE: The aim was to evaluate patient profiles of rhino-orbital-cerebral mucormycosis (ROCM) cases with central retinal artery occlusion (CRAO) postcoronavirus disease 2019. DESIGN: A nonrandomized retrospective case-control study. METHODS: The ROCM cases presenting with CRAO were compared with a control ROCM group without CRAO at a tertiary care center. Demography, systemic status, clinical features, histopathology, imaging, and blood profile were assessed for any specific risk factors. RESULTS: A total of 12 patients were seen in the CRAO group and 16 in the non-CRAO group. The male-to-female ratio was 3:1 with a mean age of 49.5 years. In the CRAO group, 75% had diabetes mellitus with mean hemoglobin A1c of 9.03%, and 66.7% had received steroid treatment. All cases were histopathologically confirmed positive for mucor. There was a significant difference in mean D-dimer and serum ferritin between the 2 groups, with higher level in the CRAO group. All patients with CRAO had light perception-negative vision, with total ophthalmoplegia and proptosis seen in 66.7% of cases. Four patients had orbital apex involvement, 5 had cavernous sinus involvement, and 8 had intracranial involvement in the CRAO group. CONCLUSIONS: Inflammatory markers D-dimer and serum ferritin were significantly associated with CRAO, suggestive of hyperinflammatory and hypercoagulable state. A high index of suspicion should be maintained in cases with elevated markers and prophylactic anticoagulants can be started to prevent CRAO in a subset of patients.

Optical Coherence Tomography Features of Ocular Cysticercosis: A Review of Literature With Observer Variation.

Ocular cysticercosis is a sparsely reported condition, requiring urgent management. The gold standard for diagnosis is an in toto extraction of the cyst with subsequent histopathology. The procedure can be demanding in contrast to the frequently adopted practice of in vivo cyst lysis. The latter, however, obviates a conventional biopsy. We reviewed published optical coherence tomography (OCT) images of ocular cysticercosis for their suitability to surrogate a conventional biopsy and identified commonly reported features. We also used triple masking and ascertained the observer agreement on identification of these features. We found that the features of the parasite are much more clearly discernible as compared with features of the involved ocular tissue itself. The hyperreflective cyst wall and scolex and the hyporeflective cyst cavity had the highest frequency and observer agreement among all the analyzed features, suggesting their use for diagnosis. We could match many of the OCT features with the previously reported histopathological findings, supporting the role of OCT as a diagnostic adjunct and a substitute for conventional biopsy. Conversely, features of the ocular tissue could be judged poorly with low observer agreement, suggesting poor prognostic ability of OCT. [Ophthalmic Surg Lasers Imaging Retina 2022;53:446-454.].

Unconventional avenues to decelerate diabetic retinopathy.

Diabetic retinopathy (DR) is an important microvascular complication of diabetes mellitus (DM), causing significant visual impairment worldwide. Current gold standards for retarding the progress of DR include blood sugar control and regular fundus screening. Despite these measures, the incidence and prevalence of DR and vision-threatening DR remain high. Given its slowly progressive course and long latent period, opportunities to contain or slow DR before it threatens vision must be explored. This narrative review assesses the recently described unconventional strategies to retard DR progression. These include gut-ocular flow, gene therapy, mitochondrial dysfunction-oxidative stress, stem cell therapeutics, neurodegeneration, anti-inflammatory treatments, lifestyle modification, and usage of phytochemicals. These therapies impact DR directly, while some of them also influence DM control. Most of these strategies are currently in the preclinical stage, and clinical evidence remains low. Nevertheless, our review suggests that these approaches have the potential for human use to prevent the progression of DR.

Unmet Need for ROP Screening in Peripheral Rural Areas.

Aim: To study the incidence and risk factors associated with retinopathy of prematurity (ROP) at a tertiary care centre in Western India. Methods: A retrospective review of records of both referred and babies born in our hospital who were screened for ROP within the last 21 months at a tertiary care centre was done. The newborns were screened as per National Neonatology Forum of India guidelines. ROP was classified according to the International Classification for Retinopathy of Prematurity criteria. Results: A total of 167 neonates were screened with an incidence of ROP of 26.9%. The mean gestational age (GA) and mean birth weight (BW) were 31.89 ± 2.824 weeks and 1538.11 ± 530.84 gm. The mean BW of neonates having any ROP was significantly lower (1296.98gm, p < 0.001), and the mean GA was also significantly lower in ROP babies (30.67 weeks, p < 0.001). O2 supplementation, RDS, IVH, and NEC were the systemic risk factors that significantly correlated with ROP p-value <0.001. On analysis of the correlation of stage of ROP with BW and GA, a significant correlation of -0.307 (p < 0.001) and -0.283 (p < 0.001) was found. Conclusion: The incidence of ROP in this study is similar to that reported in the literature from other regions. Other than LBW and GA, oxygen supplementation, RDS, IVH, and NEC were significant risk factors associated with ROP.

Inflammatory mediators in diabetic retinopathy: Deriving clinicopathological correlations for potential targeted therapy.

The role of inflammation in diabetic retinopathy (DR) is well-established and dysregulation of a large number of inflammatory mediators is known. These include cytokines, chemokines, growth factors, mediators of proteogenesis, and pro-apoptotic molecules. This para-inflammation as a response is not directed to a particular pathogen or antigen but is rather directed toward the by-products of the diabetic milieu. The inflammatory mediators take part in cascades that result in cellular level responses like neurodegeneration, pericyte loss, leakage, capillary drop out, neovascularization, etc. There are multiple overlaps between the inflammatory pathways occurring within the diabetic retina due to a large number of mediators, their varied sources, and cross-interactions. This makes understanding the role of inflammation in clinical manifestations of DR difficult. Currently, mediator-based therapy for DR is being evaluated for interventions that target a specific step of the inflammatory cascade. We reviewed the role of inflammation in DR and derived a simplified clinicopathological correlation between the sources and stimuli of inflammation, the inflammatory mediators and pathways, and the clinical manifestations of DR. By doing so, we deliberate mediator-specific therapy for DR. The cross-interactions between inflammatory mediators and the molecular cycles influencing the inflammatory cascades are crucial challenges to such an approach. Future research should be directed to assess the feasibility of the pathology-based therapy for DR.

Recurrent unintentional filtering blebs after vitrectomy: A case report.

A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of sclerotomies. Filtering blebs were managed by suturing the sclerotomies. Targeted gene sequencing identified a variant of ASPH gene (p.Arg688Gln) which is not known to be associated with Traboulsi syndrome. But considering the paucity of cases with genetic analysis, it would be possible that p.Arg688Gln is a pathogenic variant. This is the first case report of Traboulsi syndrome due to an ASPH variant not reported earlier that can lead to recurrent filtering blebs.

Ultra-Wide Field Imaging Characteristics of Primary Retinal Vasculitis: Risk Factors for Retinal Neovascularization.

Aim: To evaluate patterns of retinal vasculitis with ultra-wide field imaging (UWF) and ascertain the risk factors for retinal neovascularization. Methods: Consecutive patients of retinal vasculitis were included prospectively. Patients with retinal vasculitis secondary to uveitis were excluded. UWF was done for all the patients. Retinal involvement was classified into three zones and area of capillary non-perfusion was stratified into clock hours. Results: Two hundred patients were included, 85% (n = 170) were male. Mean age was 28.99 ± 10.56 years. Clinical examination revealed 65% cases (n = 130) to be bilateral, while UWF angiography detected 72.5% (n = 145) to have bilateral involvement. Retinal neovascularization was present in 47% (n = 188).Presence of posterior disease had very high odds ratio for development of retinal neovascularization as compared to cases restricted to retinal periphery (OR = 45.03, CI = 6.10-332.30, p = < 0.001). Conclusion: UWF imaging is useful in detecting retinal vasculitis, which is otherwise obscure to clinical examination and assessing risk factors for retinal neovascularization.

Patterns of uveitis in patients with proven systemic (pulmonary and extrapulmonary) tuberculosis.

PURPOSE: To report patterns of uveitis in patients with systemic tuberculosis. METHODS: Records of patients presenting at uvea clinic of a tertiary eye care centre were evaluated retrospectively, and 47 cases with proven systemic tuberculosis were analyzed for patterns of uveitis. Tuberculosis had been proven with a combination of radio imaging and detection of acid fast bacilli in body fluids. All patients had been reviewed by a specialist as applicable before diagnosing tuberculosis. These patients had undergone a thorough ocular workup. Pattern of uveitis was the primary outcome measure. RESULTS: Mean age was 35.34 ± 15.56 years. Lung was the commonest systemic focus, seen in nearly 75% of the cases. Anterior uveitis was the most common presentation (48.9%), followed by posterior (25.5%), panuveitis (10.6%) and intermediate uveitis (10.6%). Multifocal serpiginoid choroidopathy (MSC) was seen in only one patient, while granulomatous choroiditis was the commonest type of posterior uveitis. CONCLUSIONS: Anterior uveitis is the most frequent type of uveitis seen in patients with proven systemic tuberculosis. Rarity of MSC in such patients indicates possibility of etiologies other than tuberculosis in causing MSC.