The role of cadre in the community on diabetic retinopathy management and its challenges in low-middle income countries: a scoping review.

INTRODUCTION: Diabetes is a serious public health problem, with low- and middle-income countries (LMICs) bearing over 80% of the burden. Diabetic retinopathy (DR) is one of the most prevalent diabetic microvascular problems, and early diagnosis through eye screening programs for people with diabetes is critical to prevent vision impairment and blindness. Community-based treatments, including non-physician cadres have been recommended to enhance DR care. METHODS: The review protocol was determined and scoping review was conducted.The population, concept, and context were "cadre", "role of cadre in the management of DR", and LMICs". Data were collected from databases and searches, including grey literature. RESULTS: Cadre can motivate people to attend a diabetic eye screening event when the rate of eye examinations is about six times higher than before the start of the intervention. Health education is a possible area for task sharing, and the cadre reported could also perform the task of vision testing. The cadre could be a good supporter and a good reminder for society. However, several challenges have been faced in this study and inadequate infrastructure is the foremost challenge found in this study. Other challenges encountered in the studies include poverty, lack of community awareness, trust issues, and low education levels contributing to poor health. CONCLUSION: The current study highlighted significant gaps in the literature, which focus on the role of cadre as a community-based intervention in managing DR in LMICs. Further research is needed to develop evidence to support cost-effective screening services and cadre-related policy development in LMICs.

Comparison of micropulse subthreshold laser plus anti-VEGF versus anti-VEGF alone in diabetic macular edema: Systematic review.

Intravitreal injection of anti- Vascular Endothelial Growth Factor (VEGF)is commonly used to treat patients with diabetic macular edema (DME). However, the injection alone requires high cost and compliance. Combining micropulse subthreshold laser (MPSL) and anti-VEGF is a new approach to treating DME. This study intended to answer the question of whether MPSL plus anti-VEGF is effective compared to anti-VEGF alone. The following terms were used in PubMed, clinicaltrial.gov, and Google Scholar: anti-VEGF, DME, MPSL, and diabetic retinopathy. All studies of DME comparing the intervention of MPSL plus anti-VEGF and VEGF alone between the years 2017-2021 were included. Studies with no comparison between the intervention and control group, abstract-only papers, case reports, case series, and systematic review studies were excluded. Five Randomized Controlled Trial (RCTs) and three retrospective studies were analyzed. Four studies found that best-corrected visual acuity (BCVA) improved in both therapies. Central macular thickness in six studies was also improved. The improvement differences between both therapies were insignificant and the number of anti-VEGF injections was significantly lower in combination therapy. These studies show equal outcomes of both therapies. The reduced number of anti-VEGF injections of the combination therapy could improve the management of DME in terms of cost-effectiveness. Further analysis should be conducted to pool the data from the studies and evaluate the overall outcome.

Recurrence risk of myopic choroidal neovascularisation: a systematic review of current study.

INTRODUCTION: The rising prevalence of myopia is a concern in ophthalmology, with myopic choroidal neovascularisation (m-CNV) significantly affecting vision. However, long-term outcomes of m-CNV management have been unsatisfactory, leading to high recurrence rates. These studies aim to identify risk factors for m-CNV recurrence. METHODS: Comprehensive review followed a pre-registered plan in the International Prospective Register of Systematic Reviews (PROSPERO). The search strategy used various databases including PubMed, Cochrane Library, Embase, Scopus and ScienceDirect using the keywords 'Myopic Choroidal Neovascularization', 'Recurrence' and 'Risk'. Eligible studies were identified and analysed based on predetermined criteria. This study was registered on PROSPERO (CRD4202343461). RESULTS: The systematic review included three retrospective studies investigating risk factors associated with m-CNV recurrence. These factors are: (1) requiring three or more injections for initial disease control, (2) older age, (3) larger myopic macular neovascularisation, (4) juxtafoveal CNV, (5) larger height of hyper-reflective foci (HRF) and (6) destruction or absence of the ellipsoid zone (EZ) and retinal pigment epithelium (RPE). CONCLUSION: Risk factors for m-CNV recurrence include a greater number of required injections, older age, large macular CNV, juxtafoveal location, increased HRF height and changes in EZ and RPE structure. Understanding these factors can inform personalised treatment approaches and improve patient outcomes by identifying individuals at higher risk of recurrence and implementing proactive measures to mitigate the impact of m-CNV recurrence and progression. Further investigation is needed to enhance our understanding of the underlying mechanisms and develop innovative therapeutic approaches for effective m-CNV management. PROSPERO REGISTRATION NUMBER: CRD4202343461.

Efficacy of Prophylactic Anti-VEGF in Preventing Radiation Retinopathy: A Systematic Review and Meta-Analysis.

Background: In patients predisposed to radiation retinopathy (RR), administration of therapy after apparent clinical signs and symptoms are considered too late, resulting in substantial vision loss and blindness. Early initiation of anti-vascular endothelial growth factor (anti-VEGF) might serve as a strategy to slow disease progression and prolong good eyesight. Objective: To evaluate the efficacy of prophylactic anti-VEGF in preventing RR and preserving vision in patients at high risk of radiation-induced vision loss. Methods: A systematic literature search was performed from inception to 4 June 2023 using Cochrane Library, EMBASE, PubMed (MEDLINE), and Scopus. Eligible studies were clinical trials and observational studies investigating the incidence of radiation maculopathy (RM), radiation optic neuropathy (RON), moderate vision loss (loss of more than or equal to 3 lines of baseline visual acuity [VA]) and final VA, whether good (20/40 or better) or poor (20/200 or worse), following prophylactic anti-VEGF. Three reviewers independently conducted article screening, data extraction and risk of bias assessment. Random effects models were used to determine the cumulative effects of each outcome. Results: Four studies (one clinical trial and three observational studies), involving 2109 patients, were included in our analysis. Across all studies, there were significant reductions in the events of RM (pooled odds ratio [OR] 0.50; 95% CI, 0.34-0.74; p = 0.001), RON (pooled OR 0.62; 95% CI, 0.42-0.90; p = 0.012) and poor final VA (pooled OR 0.50; 95% CI, 0.37-0.68; p = 0.003). The association of moderate vision loss and good final VA with the use of prophylactic anti-VEGF between the groups was unclear owing to the high level of heterogeneity. Conclusion: Prophylactic anti-VEGF therapy might delay RM and RON, preventing high-risk patients from developing poor VA by approximately 50%. However, this evidence should be interpreted with caution because of its low level of certainty. Future robust studies are warranted to confirm this finding.

Incidence and clinical characteristic of ocular surface manifestation: an evaluation of conjunctival swab results in Corona Virus 2019 (COVID-19) patients in Jakarta, Indonesia.

OBJECTIVES: This study aimed to investigate the spectrum of ocular characteristics and viral presence in the conjunctival swab of patients with COVID-19. METHODS: In this cross-sectional study, fifty-three patients were recruited from two COVID-19 referral hospitals in Jakarta (Cipto Mangunkusumo Hospital and Persahabatan Hospital) from July 2020 to March 2021. The inclusion criteria were patients who were suspected of or confirmed cases of COVID-19 with or without ocular symptoms. Demographic data, history of COVID-19 exposure, underlying medical condition, systemic symptoms, ocular symptoms, supporting laboratory results, reverse-transcriptase polymerase chain reaction (RT-PCR) of naso-oropharyngeal (NOP) swab and conjunctival swab were collected. RESULTS: Fifty-three patients who were suspected, probable or confirmed cases of Covid-19 were included. Forty-six out of 53 patients (86.79%) tested positive for either Covid-19 antibody rapid test or naso-oropharyngeal (NOP) swab. Forty-two patients tested positive for NOP swab. Fourteen out of 42 patients (33.33%) experienced symptoms of ocular infection including red eye, epiphora, itchy eyes, and eye discharge. None of these patients were tested positive for conjunctival swab. Two out of 42 patients (4.76%), who were tested positive for conjunctival swab, did not experience any ocular symptoms. CONCLUSIONS: Establishing the relationship between Covid-19 infection, ocular symptoms, and presence of SARS-CoV-2 virus on the ocular surface proves to be challenging. In Covid-19 patients, ocular symptoms did not warrant a positive conjunctival swab result. On the contrary, a patient without ocular symptoms can also have detectable presence of SARS-CoV-2 virus on the ocular surface.

Pro re nata versus fixed aflibercept regimen for neovascular age-related macular degeneration: a systematic review and meta-analysis.

BACKGROUND: Aflibercept is a relatively new anti-VEGF used to treat neovascular age-related macular degeneration (AMD). The purpose of this review is to evaluate the effect of pro re nata (PRN) and fixed regimen (bimonthly) of aflibercept injection for neovascular AMD on visual outcomes at 12 months of follow-up. METHODS: We conducted a systematic search in PubMed (MEDLINE), Embase, Scopus, and Web of Science, EBSCOHost, and ClinicalTrials.gov databases. Number of injections, number of hospital visit, mean change of best corrected visual acuity (BCVA), mean change of central macular thickness (CMT), and adverse effects of the included studies were evaluated. Meta-analysis were performed using Review Manager 5.4. RESULTS: Four studies were selected for meta-analyses synthesis (3 RCT, 1 retrospective study). A total of 197 eyes in PRN group and 241 eyes in the fixed group. All four studies favored fixed regimen with standardized mean difference of 0.56 (95% CI 0.36-0.75, I2 = 0%, p < 0.00001). There was no significant difference in CMT between both group with SMD of 0.17 (95% CI - 0.14-0.48, I2 = 26%, p = 0.28). CONCLUSION: The present meta-analysis shows that bimonthly injection of aflibercept for neovascular AMD is superior compared to PRN injection, shown by better improvement in BCVA at 12 months follow-up. However, high risk of bias downgrade the certainty of evidence.

Pars-plana vitrectomy combined with retinectomy in severe open-globe injuries: A systematic review and meta-analysis.

BACKGROUND: This review summarized prophylactic retinectomy technique and its effect on anatomic and functional outcomes in severe open globe injuries (OGIs). METHODS: A comprehensive search in PubMed (MEDLINE), Embase, Scopus, and EuropePMC databases was performed up until 8 January 2020. Enrolled studies include case series, studies involving pars plana vitrectomy (PPV) combined with retinectomy in severe penetrating injuries with or without IOFB, perforating injuries, and globe ruptures. Primary outcome was best-corrected visual acuity (BCVA) ⩾20/200 at the end of the study. Secondary outcomes were the rate of proliferative retinopathy (PVR), globe survival rate and retinal reattachment rate. RESULTS: A total of seven studies, involving 275 eyes with severe OGIs, is included in this study. Meta-analysis indicates that final BCVA ⩾20/200 was achieved in 61% (95% CI 49%-73%). Meta-regression analysis showed that improvement was inversely affected by the presence of pre-operative direct macular injury (p = 0.001) and corneal scar (p = 0.015). The proportion of pre-operative BCVA <20/200 was statistically insignificant to the final BCVA ⩾20/200 (p = 0.569). One study showed that the rate is higher in the retinectomy group than the non-retinectomy group (54% vs 11%). Meta-analysis showed that anatomical success can be achieved in 85% (95% CI 78%-91%) of the patients. Meta-regression analysis indicates that the anatomical success did not vary with age (p = 0.653), retinal detachment (p = 0.525), corneal scar (p = 0.596), and lens involvement (p = 0.450). CONCLUSION: Early PPV combined with retinectomy was associated with acceptable visual improvement and anatomical success.

Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?

PURPOSE: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis. METHODS: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef. RESULTS: The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment. CONCLUSION: Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.

Intravitreal ranibizumab versus dexamethasone implant in macular edema due to branch retinal vein occlusion: Systematic review and meta-analysis.

PURPOSE: Intravitreal ranibizumab (RNB) and dexamethasone intravitreal implant (DII) were developed in the recent past and has been widely used for macular edema secondary to BRVO. We aimed to assess the efficacy and safety of intravitreal ranibizumab (RNB) compared to dexamethasone intravitreal implant (DII) in patients with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: We performed a comprehensive search on topics that assess RNB and DII in patients with macular edema secondary to BRVO from several electronic databases. RESULTS: There were 678 subjects from five studies. Ranibizumab was associated with a greater increase in best-corrected visual acuity (BCVA; mean difference 9.13, I2: 0%) compared to DII. Ranibizumab also demonstrated a greater ⩾10 (OR 2.76, I2: 0%) and ⩾15 letters (OR 2.78, I2: 0%) gain. RNB has better BCVA (logMAR scale) improvement at 6 months' follow up (mean difference -0.15, I2: 64%) in favor of RNB. Higher IOP was found in DII group on follow-up (mean difference -2.92, I2: 89%) and RNB has lesser IOP ⩾10 mmHg increase compared to DII (OR 0.08, I2: 0%). Cataract formation and/or progression was less in RNB (OR 0.53, I2: 75%). The need for rescue laser was similar the two groups. CONCLUSION: Intravitreal RNB was more effective with less pronounced effect on IOP and cataract formation and/or progression compared to DII for patients with macular edema secondary to BRVO.

Statin reduces the incidence of diabetic retinopathy and its need for intervention: A systematic review and meta-analysis.

PURPOSE: We aimed to perform a systematic literature search on the latest evidence of the role of statin in reducing diabetic retinopathy and its need for intervention. METHODS: A comprehensive search on cohort studies/clinical trials that assess statins and diabetic retinopathy up until August 2019 was performed. The outcome measured was the incidence of diabetic retinopathy and its need for intervention. RESULTS: There were 558.177 patients from six studies. Statin was associated with a lower incidence of diabetic retinopathy (hazard ratio: 0.68 (0.55, 0.84), p < 0.001; I2: 95%). For the subtypes of diabetic retinopathy, statin lowers the incidence of proliferative diabetic retinopathy (hazard ratio: 0.69 (0.51, 0.93), p = 0.01; I2: 90%), non-proliferative diabetic retinopathy (hazard ratio: 0.80 (0.66, 0.96), p = 0.02; I2: 93%), and diabetic macular edema (hazard ratio: 0.56 (0.39, 0.80), p = 0.002; I2: 82%). Statin was associated with a reduced need for retinal laser treatment with a hazard ratio of 0.70 (0.64, 0.76) (p < 0.001; I2: 0%), intravitreal injection with a hazard ratio of 0.82 (0.79, 0.85) (p < 0.001; I2: 0%), and vitrectomy with a hazard ratio of 0.64 (0.48, 0.85) (p < 0.001; I2: 75%). Overall, statin was associated with a reduced need for intervention for diabetic retinopathy with a hazard ratio of 0.72 (0.64, 0.80) (p < 0.001; I2: 73%). The regression-based Egger's test showed statistically significant small-study effects for non-proliferative diabetic retinopathy (p = 0.011) outcomes. CONCLUSION: Statin was associated with a decreased risk of diabetic retinopathy and its subtypes. Statin also reduced the need for intervention with retinal laser treatment, intravitreal injection, and vitrectomy.

Ganglion cells apoptosis in diabetic rats as early prediction of glaucoma: a study of Brn3b gene expression and association with change of quantity of NO, caspase-3, NF-κB, and TNF-α.

AIM: To find a new concept to show whether or not apoptosis of retinal ganglion cells (RGCs) can be determined in the histology of acute hyperglycemia in the role of expressed Brn3b gene related to nitric oxide (NO), caspase-3, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-α (TNF-α) as an early predictor of primary open angle glaucoma (POAG) eyes and their associations. METHODS: Experimental in vivo study was carried out using adult male, white Sprague-Dawley rats aged ≥2mo, weighing 150-200 g. The animals were divided into two groups, one group receiving intraperitoneal injection of streptozotociz 50 mg/kg in 0.01 mol/L citric buffer and pH 4.5 and a comparison made with the control group. Retinal tissue was divided into two parts (both experimental and control groups respectively): a) right retina for immunohistochemistry (IHC; caspase-3 and TNF-α); b) left retina was divided into two parts for the purpose of real-time polymerase chain reaction (PCR) test (RNA extraction for Brn3b gene expression analysis) and ELISA test (NO and NF-κB). RESULTS: The experimental group showed a decrease in Brn3b gene expression compared to the control group (1.3-fold lower in 2nd month; 1.1-fold lower in 4th month and 2.5-fold lower in 6th month). However, there was a decrease of NO, caspase-3, and an increase of NF-κB and TNF-α quantity. CONCLUSION: The expression of mRNA Brn3b gene is inversely proportional to apoptosis in RGCs. The quantity of NO, caspase-3, NF-κB and TNF-α is influential in expression of Brn3b in RGCs caused by hyperglycemia in diabetic rats.