Purpose: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age‐related macular degeneration (nAMD) receiving long‐term treatment in the real world.Methods: An ambispective 36‐month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best‐corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed.Results: After 36 months of follow‐up and an average of 13.8 anti‐VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85–12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09–3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23–0.71) and its progression (OR = 0.44, 95% CI = 0.26–0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14–0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36‐month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29–0.81) and its progression (OR = 0.50, 95% CI = 0.31–0.81).Conclusion: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms. For this reason, we designed an in vitro study to compare 10 formulations of DHA and EPA supplements from different origins and combined in different proportions, evaluating their effect on cell viability, cell proliferation, reactive oxygen species production, and cell migration using ARPE-19 cells. Furthermore, we assessed their ability to rescue RPE cells from the oxidative conditions seen in diabetic retinopathy. Our results showed that the different formulations of n3-PUFAs have a beneficial effect on cell viability and proliferation and are able to restore oxidative induced RPE damage. We observed that the n3-PUFA provided different results alone or combined in the same supplement. When combined, the best results were obtained in formulations that included a higher proportion of EPA than DHA. Moreover, n3-PUFA in the form of ethyl-esters had a worse performance when compared with triglycerides or phospholipid based formulations.

Age related macular degeneration (AMD) is the main cause of legal blindness in developed countries. It is a multifactorial disease in which a combination of genetic and environmental factors contributes to increased risk of developing this vision-incapacitating condition. Oxidative stress plays a central role in the pathophysiology of AMD and recent publications have highlighted the importance of mitochondrial dysfunction and endoplasmic reticulum stress in this disease. Although treatment with vascular endothelium growth factor inhibitors have decreased the risk of blindness in patients with the exudative form of AMD, the search for new therapeutic options continues to prevent the loss of photoreceptors and retinal pigment epithelium cells, characteristic of late stage AMD. In this review, we explain how mitochondrial dysfunction and endoplasmic reticulum stress participate in AMD pathogenesis. We also discuss a role of several antioxidants (bile acids, resveratrol, melatonin, humanin, and coenzyme Q10) in amelioration of AMD pathology.

The purpose of this study was to evaluate the long-term evolution of retinal changes in COVID-19 patients with bilateral pneumonia. A total of 17 COVID-19 patients underwent retinal imaging 6 months after hospital discharge with structural optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The parafoveal retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly thinner in COVID-19 patients at 6 months compared to 0 months (p = <0.001 in both cases). In the optic nerve analysis, a significantly thinner RNFL was observed (p = 0.006) but persisted significantly thickened, compared to controls (p = 0.02). The vascular density (VD) at 6 months persisted significantly decreased when compared to the control group, and no significant differences were found with the 0 months evaluation; in addition, when analyzed separately, women showed a worsening in the VD. Moreover, a significantly greater foveal area zone (FAZ) (p = 0.003) was observed in COVID-19 patients at 6 months, compared to 0 months. The cotton wool spots (CWSs) observed at baseline were no longer present at 6 months, except for one patient that developed new ones. This study demonstrates that some of the previously known microvascular alterations resulting from COVID-19, persist over time and are still evident 6 months after hospital discharge in patients who have suffered from bilateral pneumonia.

Age-related macular degeneration (AMD) is a multifactorial disease of the retina featured by dysfunction of retinal pigmented epithelial (RPE) and loss of photoreceptor cells under oxidative stress and inflammatory conditions. Vitamin D and antioxidants have beneficial effects against retinal degenerative diseases, such as AMD. We investigated the impact of associating vitamin D (ND) with a nutritional antioxidant complex (Nutrof Total^®; N) on oxidative stress and inflammation-like induced conditions by H₂O₂ and LPS, respectively, in human retinal epithelial (ARPE-19) and human retinal endothelial (HREC) cells. Application of either N or ND treatments to H₂O₂-induced media in ARPE-19 cells counteracted late apoptosis, attenuated oxidative DNA damage, and increased cell proliferation. Significant reduction in the expression levels of MCP1, IL-8, and IL6 cytokines was observed following application of either N or ND treatments under LPS-induced conditions in ARPE-19 cells and in MCP-1 and IL12p70 cytokine levels in HREC cells. ND and not N revealed significant downregulation of IFNγ in ARPE-19 cells, and of IL-6 and IL-18 in HREC cells. In conclusion, adding vitamin D to Nutrof Total^® protects in a synergistic way against oxidative and inflammatory stress-induced conditions in retinal epithelial and endothelial cells.