Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.     

Efficacy and safety of anti-vascular endothelial growth agents for the treatment of polypoidal choroidal vasculopathy: A systematic review and meta-analysis

There remains limited agreement regarding the efficacy and safety of different antivascular endothelial growth factor (anti-VEGF) agents for the management of polypoidal choroidal vasculopathy (PCV). Our meta-analysis compares different anti-VEGF agents for PCV treatment. Ovid MEDLINE, EMBASE, and Cochrane Library were systematically searched from January 2000 to July 2022. We included articles comparing the efficacy and safety of different anti-VEGF agents, specifically bevacizumab (BEV), ranibizumab (RAN), aflibercept AFL), and brolucizumab (BRO), for patients with PCV. 10,440 studies were identified, 122 underwent full-text review, and seven were included. One study was a randomized trial, and six were observational studies. Ranibizumab and aflibercept were associated with a similar best-corrected visual acuity (BCVA) at the last visit in three observational studies (P = 0.10), similar retinal thickness at the last visit in two observational studies (P = 0.85). One observational study comparing BEV versus RAN found comparable outcomes for final BCVA, retinal thickness, and polyp regression. One randomized trial on BRO versus AFL found comparable outcomes for improvement in BCVA, while anatomical outcomes favored BRO. The available evidence suggests that final BCVA is comparable across different anti-VEGF agents, however, further investigation is warranted due to paucity of evidence.     

Clinical observation of vitrectomy combined with endolaser photocoagulation at the edge of posterior scleral staphyloma for macular hole retinal detachment in high myopia

AIM: To observe the clinical effect of pars plana vitrectomy (PPV) and silicone oil filling surgery combined with intraoperative posterior scleral staphyloma (PS) marginal retinal photocoagulation in the treatment of high myopic macular hole retinal detachment (MHRD) with PS. METHODS: This was a retrospective clinical study. From May 2017 to March 2020, 62 MHRD patients with PS (62 eyes) were enrolled in the study. Patients were divided into 23G PPV combined with PS marginal retina intraoperative photocoagulation group (combined group) and conventional surgery group (conventional group), with 31 eyes in each. Triamcinolone acetonide and indocyanine green were used to remove the epiretinal membrane and the posterior macular inner limiting membrane (ILM). In the combined group, 2 to 3 rows of retinal photocoagulation were performed on the edge of the PS. The patients were followed up for an average of 8.34±3.21mo. The first retinal reattachment rate, macular hole closure rate, Duration of silicone oil tamponade, best corrected visual acuity (BCVA) and average number of operations were observed and compared between the two groups. RESULTS: The first retinal reattachment rates of the eyes in the combined group and the conventional group were 96.7% (29/31) and 67.7% (21/31), respectively (χ2=6.613, P=0.010). The macular hole closure rates in the combined group and the conventional group were 74.2% (23/31) and 67.7% (21/31), respectively (χ2=0.128, P=0.721). The Duration of silicone oil tamponade of the patients in the combined group was lower than that of the routine group (t=-41.962, P≤0.001). Postoperative logMAR BCVA values of patients in the combined group and the conventional group were 1.27±0.12 and 1.26±0.11, compared with the logMAR BCVA before surgery, each group was improved (t=19.947, t=-19.517, P≤0.001, P≤0.001). There was no significant difference in the logMAR BCVA between the eyes of the two groups (t=-0.394, P=0.695). The average numbers of operations on the eyes in the conventional group and the combined group were 2.39±0.62 and 2.06±0.25 times, the combined group had fewer operations on average (t=-2.705, P=0.009). CONCLUSION: Intraoperative PPV treatment of MHRD with PS combined with PS marginal endolaser photocoagulation can effectively increase the rate of retinal reattachment after the first operation, reduce the number of repeated operations, and reduce the postoperative duration of silicone oil tamponade.     

Reticular pseudodrusen: A critical phenotype in age-related macular degeneration

Reticular pseudodrusen (RPD), or subretinal drusenoid deposits (SDD), refer to distinct lesions that occur in the subretinal space. Over the past three decades, their presence in association with age-related macular degeneration (AMD) has become increasingly recognized, especially as RPD have become more easily distinguished with newer clinical imaging modalities. There is also an increasing appreciation that RPD appear to be a critical AMD phenotype, where understanding their pathogenesis will provide further insights into the processes driving vision loss in AMD. However, key barriers to understanding the current evidence related to the independent impact of RPD include the heterogeneity in defining their presence, and failure to account for the confounding impact of the concurrent presence and severity of AMD pathology. This review thus critically discusses the current evidence on the prevalence and clinical significance of RPD and proposes a clinical imaging definition of RPD that will help move the field forward in gathering further key knowledge about this critical phenotype. It also proposes a putative mechanism for RPD formation and how they may drive progression to vision loss in AMD, through examining current evidence and presenting novel findings from preclinical and clinical studies.     

Neutrophils and neutrophil extracellular trap components: Emerging biomarkers and therapeutic targets for age-related eye diseases

Age-related eye diseases, including dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy, represent a major global health issue based on their increasing prevalence and disabling action. Unraveling the molecular mechanisms underlying these diseases will provide novel opportunities to reduce the burden of age-related eye diseases and improve eye health, contributing to sustainable development goals achievement. The impairment of neutrophil extracellular traps formation/degradation processes seems to be one of these mechanisms. These traps formed by a meshwork of DNA and neutrophil cytosolic granule proteins may exacerbate the inflammatory response promoting chronic inflammation, a pivotal cause of age-related diseases. In this review, we describe current findings that suggest the role of neutrophils and their traps in the pathogenesis of the above-mentioned age-related eye diseases. Furthermore, we discuss why these cells and their constituents could be biomarkers and therapeutic targets for dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy. We also examine the therapeutic potential of some neutrophil function modulators and provide several recommendations for future research in age-related eye diseases.