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.     

Articular degeneration after subchondral cementation for giant cell tumors at the knee

PurposeTo quantify joint degeneration and the clinical outcome after curettage and cementation in subchondral giant cell tumors of the bone (GCTB) at the knee.MethodsWe conducted a retrospective analysis of 14 consecutive patients (seven female, seven male) with a mean age of 34 years (range 19–51) who underwent curettage and subchondral cementation for a biopsy-confirmed GCTB at the distal femur or the proximal tibia between August 2001 and August 2017, with a mean follow-up period of 54.6 months (range 16.1–156 months). The Whole-Organ Magnetic Resonance Imaging Score (WORMS), Kellgren-Lawrence (KL) classification, and Musculo-Skeletal Tumor Society (MSTS) score were assessed.ResultsRadiological degeneration progressed from preoperative to the latest follow-up, with a median WORMS from 2.0 to 4.0 (p = 0.006); meanwhile, the median KL score remained at 0 (p = 0.102). Progressive degeneration (WORMS) tended to be associated with the proximity of the tumor to the articular cartilage (mean 1.57 mm; range 0–12 mm) (p = 0.085). The most common degenerative findings were cartilage lesions (n = 11), synovitis (n = 5), and osteophytes (n = 4). Mean MSTS score increased from 23.1 (preoperatively) to 28.3 at the latest follow-up (p < 0.01).Seven patients (50%) were treated for a local recurrence, with six revision surgeries performed. Removal of the cement spacer and filling of the cavity with a cancellous autograft was performed in seven patients. Conversion to a total knee arthroplasty was performed in one patient for local tumor control.ConclusionsCementation following the curettage of GCTB around the knee is associated with slight degeneration at medium-term follow-up and leads to a significant reduction in pain. Removal of the cement and reconstruction with an autograft may be beneficial in the long term.     

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.