Mechanistic and therapeutic perspectives of non-coding RNA-modulated apoptotic signaling in diabetic retinopathy.

Diabetic retinopathy (DR), a significant and vision-endangering complication associated with diabetes mellitus, constitutes a substantial portion of acquired instances of preventable blindness. The progression of DR appears to prominently feature the loss of retinal cells, encompassing neural retinal cells, pericytes, and endothelial cells. Therefore, mitigating the apoptosis of retinal cells in DR could potentially enhance the therapeutic approach for managing the condition by suppressing retinal vascular leakage. Recent advancements have highlighted the crucial regulatory roles played by non-coding RNAs (ncRNAs) in diverse biological processes. Recent advancements have highlighted that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), act as central regulators in a wide array of biogenesis and biological functions, exerting control over gene expression associated with histogenesis and cellular differentiation within ocular tissues. Abnormal expression and activity of ncRNAs has been linked to the regulation of diverse cellular functions such as apoptosis, and proliferation. This implies a potential involvement of ncRNAs in the development of DR. Notably, ncRNAs and apoptosis exhibit reciprocal regulatory interactions, jointly influencing the destiny of retinal cells. Consequently, a thorough investigation into the complex relationship between apoptosis and ncRNAs is crucial for developing effective therapeutic and preventative strategies for DR. This review provides a fundamental comprehension of the apoptotic signaling pathways associated with DR. It then delves into the mutual relationship between apoptosis and ncRNAs in the context of DR pathogenesis. This study advances our understanding of the pathophysiology of DR and paves the way for the development of novel therapeutic strategies.

Baseline predictors of short-term visual outcomes after intravitreal conbercept injection for neovascular age-related macular degeneration / Preditores iniciais de desfechos visuais de curto prazo com injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade

ABSTRACT Purpose: Neovascular age-related macular degeneration is the leading cause of vision loss in the elderly. We aimed to identify baseline predictors of visual prognosis after intravitreal conbercept injection for neovascular age-related macular degeneration. Methods: We conducted a retrospective review of 58 patients with neovascular age-related macular degeneration who were treated with intravitreal injections of conbercept 0.5 mg in routine clinical practice. Basic information such as age, sex, intraocular pressure, and disease course was collected. Best-corrected visual acuity, mean retinal sensitivity, and optical coherence tomography findings were recorded at baseline and 6 months after treatment. Logistic regression analysis was used to identify independent predictors of best-corrected visual acuity at 6 months after treatment. Results: After the 6-month treatment, the mean best-corrected visual acuity improved from 1.10 ± 0.42 logarithm of the minimum angle of resolution (logMAR) to 0.41 ± 0.18 logMAR, the mean retinal sensitivity increased from 5.13 ± 0.86 dB to 7.32 ± 1.21 dB, the mean central retinal thickness decreased from 440.38 ± 61.05 μm to 260.01 ± 24.86 μm, and the total number of hyperreflective dots and the number of hyperreflective dots in each retina layer were significantly reduced as compared with those before treatment (all p<0.05). Twenty-two patients showed improved vision, and 36 had unimproved vision. Multivariate analyses revealed that the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age were independent predictors of best-corrected visual acuity (all p<0.05). Conclusion: Poor recovery of patients after intravitreal conbercept injection may be related to the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age, which may be used as predictors of short-term visual outcomes and should be fully evaluated before operation.

RESUMO Objetivo: A degeneração macular neovascular relacionada à idade é a principal causa de perda de visão em idosos. O objetivo deste estudo foi identificar os preditores iniciais que afetam o prognóstico visual após a injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade. Métodos: Esta é uma revisão retrospectiva de 58 pacientes com degeneração macular neovascular relacionada à idade que foram tratados com injeções intravítreas de 0,5 mg de combercepte na prática clínica de rotina. Foram coletadas informações básicas, tais como idade, sexo, pressão intraocular e evolução da doença. A melhor acuidade visual corrigida, as sensibilidades retinianas médias e varreduras de tomografia de coerência óptica foram registradas no início do estudo e 6 meses após o tratamento. Foi efetuada uma análise de regressão logística para determinar os preditores independentes da melhor acuidade visual corrigida 6 meses após o tratamento. Resultados: Após 6 meses de tratamento, a média da acuidade visual melhor corrigida melhorou de 1,10 ± 0,42 para 0,41 ± 0,18 logMAR; as sensibilidades retinianas médias aumentaram de 5,13 ± 0,86 para 7,32 ± 1,21 dB; a espessura retiniana central média diminuiu de 440,38 ± 61,05 para 260,01 ± 24,86 μm; e os pontos hiper-reflexivos, tanto em números totais quanto em cada camada de retina, foram significativamente reduzidos em comparação com os valores de antes do tratamento (todos com p<0,05). Houve 22 pacientes com visão melhorada e 36 pacientes com visão não melhorada. As análises multivariadas mostraram que o número de pontos hiper-reflexivos sub-retinianos, o estado da membrana limitante externa, a melhor acuidade visual corrigida inicial e a idade foram preditores independentes para a melhor acuidade visual corrigida (todos com p<0,05). Conclusão: A má recuperação de pacientes após a injeção de combercepte intravítreo pode estar relacionada ao número de pontos hiper-reflexivos sub-retinianos, ao estado da membrana limitante externa, à acuidade visual corrigida inicial e à idade, parâmetros que podem ser usados como preditores de resultados visuais de curto prazo e devem ser totalmente avaliados antes da cirurgia.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept.

AIM: To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and MP-3 microperimetry. METHODS: Twenty-eight patients (42 eyes) diagnosed with DME were treated with intravitreal injection of aflibercept. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), foveal avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1), 4° fixation rate (P2), and other indicators 1mo after treatment were compared; of these, BCVA was converted into logarithm of the minimum angle of resolution (logMAR), and the correlation among the factors was analyzed. RESULTS: After treatment, logMAR BCVA was 0.47±0.24, which was significantly better than that before treatment (0.63±0.28, P<0.001). The CRT was 359.21±107.87 µm after treatment, which was significantly lower than before treatment (474.10±138.20 µm, P<0.001). The FAZ area, SVD, and DVD were not significantly changed after treatment compared with the baseline. MLS was 22.16±4.20 dB after treatment, which was significantly higher than before treatment (19.63±4.23 dB, P<0.001). P2 significantly increased after treatment than before treatment (P=0.007). P1 had no significant change after treatment than before treatment (P=0.086). CONCLUSION: A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity, fixation stability, and visual acuity, possibly without causing significant changes in the retinal vascular condition in a short time.

Baseline predictors of short-term visual outcomes after intravitreal conbercept injection for neovascular age-related macular degeneration.

PURPOSE: Neovascular age-related macular degeneration is the leading cause of vision loss in the elderly. We aimed to identify baseline predictors of visual prognosis after intravitreal conbercept injection for neovascular age-related macular degeneration. METHODS: We conducted a retrospective review of 58 patients with neovascular age-related macular degeneration who were treated with intravitreal injections of conbercept 0.5 mg in routine clinical practice. Basic information such as age, sex, intraocular pressure, and disease course was collected. Best-corrected visual acuity, mean retinal sensitivity, and optical coherence tomography findings were recorded at baseline and 6 months after treatment. Logistic regression analysis was used to identify independent predictors of best-corrected visual acuity at 6 months after treatment. RESULTS: After the 6-month treatment, the mean best-corrected visual acuity improved from 1.10 ± 0.42 logarithm of the minimum angle of resolution (logMAR) to 0.41 ± 0.18 logMAR, the mean retinal sensitivity increased from 5.13 ± 0.86 dB to 7.32 ± 1.21 dB, the mean central retinal thickness decreased from 440.38 ± 61.05 µm to 260.01 ± 24.86 µm, and the total number of hyperreflective dots and the number of hyperreflective dots in each retina layer were significantly reduced as compared with those before treatment (all p<0.05). Twenty-two patients showed improved vision, and 36 had unimproved vision. Multivariate analyses revealed that the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age were independent predictors of best-corrected visual acuity (all p<0.05). CONCLUSION: Poor recovery of patients after intravitreal conbercept injection may be related to the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age, which may be used as predictors of short-term visual outcomes and should be fully evaluated before operation.

Nimbolide ameliorates the streptozotocin-induced diabetic retinopathy in rats through the inhibition of TLR4/NF-κB signaling pathway.

BACKGROUND: Diabetic retinopathy (DR) is a common problem in the diabetic patients due to the high blood glucose level. DR affects more number of diabetic patients worldwide with irreversible vision loss. OBJECTIVE: The current investigation was focused to reveal the therapeutic actions of nimbolide against the streptozotocin (STZ)-provoked DR in rats through inhibition of TLR4/NF-κB pathway. METHODOLOGY: DR was provoked to the rats through administering a single dose of STZ (60 mg/kg) intraperitoneally. The DR rats were then supplemented with the 50 mg/kg of nimbolide for 60 days. The bodyweight and blood glucose level was measured using standard methods. The lipid profiles (cholesterol, TG, LDL, and HDL), inflammatory markers, and antioxidants level was detected using respective kits. The level of MCP-1, VEGF, and MMP-9 was quantified using kits. The morphometric analysis of retinal tissues were done. The mRNA expressions of target genes were studied using RT-PCR assay. RESULTS: Nimbolide treatment effective decreased the food intake and blood glucose, and improved the bodyweight of STZ-provoked animals. The levels of pro-inflammatory mediators, cholesterol, TG, LDL, and HDL, MCP-1, VEGF, and MMP-9 was remarkably suppressed by the nimbolide treatment. Nimbolide also improved the antioxidants, retinal thickness and cell numbers. The TLR4/NF-κB pathway was appreciably inhibited by the nimbolide. CONCLUSION: Overall, our findings demonstrated that the nimbolide attenuated the STZ-provoked DR in rats through inhibiting the TLR4/NF-κB pathway.

Assessment of Foveal Avascular Zone and Macular Vascular Plexus Density in Children With Unilateral Amblyopia: A Systemic Review and Meta-Analysis.

Purpose: To examine the quantitative measurements of OCTA in children with amblyopia using the meta-analysis methodology. Methods: PubMed, Embase, and Cochrane library were searched for available papers up to March 2021. Weighted mean differences (WMD) were used to compare the retina parameters between the eyes with amblyopia and the contralateral eyes or healthy control eyes. Results: Twelve studies were included. When considering the parafovea, the microvessel density was reduced in amblyopic eyes compared with healthy control eyes in the superficial capillary plexus (SCP) in 6 × 6 volume scan (WMD = -2.12, 95%CI: -3.24, -0.99) but not SCP in 3 × 3 volume scan (WMD = -1.43, 95%CI: -2.96, 0.11). In the deep capillary plexus (DCP), amblyopia did not decrease vessel density in the 6 × 6 volume scan (WMD = -2.22, 95%CI: -5.86, 1.42; I 2 = 79.6%, P = 0.008), but a difference was observed in the whole eye 3 × 3 (WMD = -1.95, 95%CI: -3.23, -0.67; I 2 = 27.5%, P = 0.252). There were no significant differences in the foveal avascular zone area and foveal thickness between amblyopic eyes and healthy control eyes. There were no significant differences in microvessel density, foveal avascular zone area, and foveal thickness between amblyopic eyes and fellow eyes. Conclusion: According to OCTA, amblyopic eyes had lower vessel density in parafoveal SCP and DCP compared with healthy control eyes, but not compared with fellow eyes. There were no significant differences regarding the foveal avascular zone area and foveal thickness between amblyopic and non-amblyopic eyes.

Clinical efficacy of intravitreal ranibizumab in early and mid-idiopathic choroidal neovascularization.

Background. To compare visual outcomes and spectral-domain optical coherence tomography results following intravitreal ranibizumab treatment for early and mid-idiopathic choroidal neovascularization (ICNV). Methods. This retrospective, case-controlled study examined 44 patients with ICNV in one eye initially treated with intravitreal ranibizumab (0.5 mg). Further intravitreal treatments were administered as necessary. Patients were divided into two groups according to disease duration, that is, ≤3 months or 3-6 months (early and mid-groups), and the data were compared. Results. All patients completed at least 12 months of follow-up. Significant differences were observed between the groups in best-corrected visual acuity and in central macular thickness (CMT) reduction at all five follow-up visits. At the last follow-up (12 months), 19 early group eyes (79.1%) and 10 mid group eyes (50.0%) had statistically significant visual gains of >15 early treatment diabetic retinopathy study (ETDRS) letters (χ (2) = 4.130, P = 0.042). The mean number of injections was significantly higher (P = 0.0001) in the mid group (2.53 ± 1.76) than in the early group (1.22 ± 1.01). Conclusions. Early intravitreal ranibizumab for ICNV can result in better visual prognoses, more obvious decreases in CMT, and fewer injections.