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Aim: To evaluate the changes in choroidal vascular structures in patients with dry age-related macular degeneration (AMD) and healthy controls (No-AMD) after phacoemulsification. Methods: This prospective study was conducted in 34 eyes of 19 patients in the AMD group and 32 eyes of 20 patients in the no-AMD group who had uneventful phacoemulsification. Best-corrected visual acuity, slitlamp biomicroscopy, and intraocular pressure were recorded. Choroidal thickness (CT) measurements of the subjects were obtained using enhanced depth imaging optical coherence tomography (Edi-OCT) (RS-3000 Advance, Nidek, Japan), and choroidal vascular index (CVI) was calculated by using the binarization method at baseline and postoperatively at months 1 (M1) and 3 (M3) and the results were compared. Results: There was no significant difference between the patients in terms of age and gender (p=0.069, p=0.855 respectively). The mean CVI at baseline was 0.644 ± 0.019% in the AMD group and 0.657 ± 0.021% in the no-AMD group (p=0.025). In the AMD group, the CVI increased significantly in M3 compared to preoperative values (p=0.001). There was no significant difference between the two groups in terms of CT in baseline, M1, and M3 (p=0.05). There was a significant increase in CT in M1 compared to preoperative values in both groups (p=0.026 and p=0.050, respectively). Conclusion: Although the preoperative CVI was lower in the AMD group than in the no-AMD group, there was a greater increase in CVI after phacoemulsification in the AMD group. While CT values return to normal after phacoemulsification sooner, CVI remains elevated for a longer period. [ABSTRACT FROM AUTHOR]

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Anti-vascular endothelial growth factor (anti-VEGF) injections are a mainstay of treatment for retinal vascular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion. While anti-VEGF monotherapy has helped improve visual outcomes in patients with these conditions, the need for frequent injections and followup visits, as well as the varying response to therapy are notable shortcomings. To address this, novel therapies have been investigated as adjuncts or alternatives to anti-VEGF monotherapy. One such therapy is faricimab, the first US Food and Drug Administration-approved intravitreal injection designed to target both VEGF-A and angiopoietin-Tie-2 for the treatment of nAMD and DMO. Clinical trial data thus far support that faricimab produces non-inferior visual and anatomical outcomes to standard anti-VEGF therapy, with longer durability, in these diseases. In this review, details regarding faricimab's molecular development, clinical trial outcomes, and its prospect as the newest drug in the treatment landscape for retinal diseases will be discussed. [ABSTRACT FROM AUTHOR]

Tissue Engineering offers a novel, curative approach to treating Age-Related Macular degeneration (AMD), a disease characterized by excessive drusen deposition beneath the retinal surface and consequent vision loss. Preclinical studies in rats have shown that transplanted Retinal Pigment Epithelium (RPE) derived from human Embryonic Stem Cells (hESC) have not only slowed AMD but have also restored vision. There are two main methods of delivering RPE cells: direct injection and monolayer surgical insertion, the latter demonstrating long-term integration. Biocompatible scaffolds allow for better delivery of RPE cells, induced Pluripotent Stem Cells (iPSC), and Retinal Progenitor Cells (RPC). Unlike animal-derived extracellular matrix components, soft modulus biomaterials such as poly(lactic-co-glycolic acid) (PLGA) and poly(l-lactic acid) (PLLA) are ideal for AMD cell transplants because of fast degradation times, high cellular attachment proliferation, and strong adherence to Bruch's membrane. These biomaterials can also be created at a 10-100μm thickness so that vision is not distorted. Use of biomaterials could be improved by cross-linking them with anti-vascular endothelial growth factors (VEGFs) like Brolucizumab and retinal growth factors such as fibroblast growth factor (FGF). Similarly, hESC and iPSC cells can be genetically modified to secrete anti-VEGF factors. [ABSTRACT FROM AUTHOR]

To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4 mm diameter and a circle of 6 mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36 ± 8.39 mm2 at baseline to 37.77 ± 9.03 mm2 at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p < 0.001; ring: p < 0.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p < 0.001; ring: p < 0.001). Evaluation of CC parameters suggested significant group × time interaction effects for CC FD (p = 0.04) and mean intensity signal (p = 0.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5 years in both RPD-affected and RPD-unaffected macular areas. [ABSTRACT FROM AUTHOR]

Background: Blue blocking (BB) lenses, including spectacles and intraocular lenses, work by attenuating short-wavelength light. BB glasses are being marketed with the aim to reduce eye fatigue symptoms when using digital devices, improve sleep quality and potentially confer protection from retinal phototoxicity. BB intraocular lenses following cataract surgery may be implanted because they are thought to prevent age-related macular degeneration (AMD) progression. Methods: The present study is a systematic review aiming to analyze BB lenses clinical efficacy in preventing blue light-related ocular disorders, including AMD progression, eye fatigue, and their impact on sleep quality. We searched Medline, PubMed, Web of Science and the Cochrane Library until May 2020. Results:Although several studies have been performed investigating BB lenses, clinical efficacy for preventing or attenuating the above-mentioned ocular disorders is often theorical or based on laboratory or animal experiments. Conclusions: To date, there is a lack of consistent evidence for a larger-sclale introduction of BB lenses in the routine clinical practice. [ABSTRACT FROM AUTHOR]

Polypoidal choroidal vasculopathy (PCV) is difficult to diagnose subtype of neovascular age-related macular degeneration (nAMD). Although advances in optical coherence tomography (OCT) and OCT angiography (OCTA) have allowed much improved diagnosis of PCV when indocyanine green angiography (ICGA), a gold-standard for diagnosing PCV, is unavailable, the task may still represent a challenge even for the most experienced ophthalmologists. Numerous diagnostic errors (including failure in elicitation or interpretation of symptoms or signs) may be partially due to the absence of a universal algorithm for identification of the pathology. We believe that highlighting the pathological features of importance to confirm diagnosis, and developing a clearly defined sequence of steps for interpretation of OCT and OCTS results will be a valuable approach to improved diagnosis of this type of nAMD. Three nAMD cases that had OCT signs consistent with PCV and required further differential diagnostic assessment to confirm or exclude PCV are presented as examples demonstrating the efficacy of the proposed algorithm. In these example cases, the OCT findings suggestive of PCV are reported, and OCTA segmentation steps with the related actions as per the proposed algorithm are described. The example cases demonstrate that the stepwise assessment of OCT and OCTA results for patients with nAMD allows to determine reliably whether PCV is present or not (i.e., whether the diagnosis should be confirmed or refuted). [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the serum irisin level of patients with age-related macular degeneration (ARMD) and compared it with that of healthy individuals. Methods: The serum irisin level of 15 healthy controls (Group 1) and 15 dry ARMD patients (Group 2) and 15 wet ARMD patients (Group 3) were measured using the enzyme-linked immunosorbent assay (ELISA) method and compared. Results: There was no statistically significant difference between the groups in terms of age or gender (p>0.05). The mean serum irisin levels of Group 1, Group 2, and Group 3 were 25.81±24.04 ng/mL, 22.93±19.05 ng/mL, and 12.38±8.16 ng/mL, respectively. Although the mean irisin level in the wet ARMD patients was lower than that of the control and dry ARMD groups, there was no statistically significant difference between the groups (p>0.05). Conclusion: The results suggest that the serum irisin level in ARMD patients is not different from that of healthy individuals. Studies of larger groups that examine the irisin level in the vitreous and neovascular membranes will further elucidate any role in the pathogenesis of ARMD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is genetically associated with complement. Dendritic cells (DCs) play key roles during innate and adaptive immunity, and express complement components and their receptors. We investigated ocular DC heterogeneity and the role of DCs in the laser-induced choroidal neovascularization (CNV) model. In order to determine the function of DCs, we used two models of DC deficiency: the Flt3−/− and Flt3l−/− mouse. We identified three types of ocular DCs: plasmacytoid DC, classical DC-1, and classical DC-2. At steady-state, classical DCs were found in the iris and choroid but were not detectable in the retina. Plasmacytoid DCs existed at very low levels in iris, choroid, and retina. After laser injury, the number of each DC subset was up-regulated in the choroid and retina. In Flt3−/− mice, we found reduced numbers of classical DCs at steady-state, but each DC subset equally increased after laser injury between wildtype and Flt3−/− mice. In Flt3l−/− mice, each DC subsets was severely reduced after laser injury. Neither Flt3−/− or Flt3l−/− mice demonstrated reduced CNV area compared to wildtype mice. DCs do not play any significant role during the laser-induced CNV model of neovascular AMD. [ABSTRACT FROM AUTHOR]

Non-vascularized pigment epithelial detachments (PED) are usually associated with dry age-related macular degeneration (AMD). In this study, we aimed to investigate the correlation between visual function and morphologic parameters. Seventeen eyes of eleven patients with non-vascularized AMD were enrolled. In addition to conventional optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT) measurements were performed by evaluating the regularity of retinal pigment epithelium (RPE) entropy within the PED area. Retinal sensitivity was measured with MP-3 microperimetry, and retinal sensitivities within (RSin) and outside (RSout) the PED area were calculated. The relationship between OCT parameters and visual function was analyzed. As a result, there was a significant difference between the RSin and RSout (p < 0.001, Wilcoxon signed rank test). Moreover, RSin was significantly related to logMAR VA (p = 0.033, linear mixed model). The regularity of RPE entropy was significantly related to visual acuity and RSin (p = 0.00038, p = 0.031, linear mixed model), although neither the height nor area of PED correlated with visual function. Our results suggest that retinal sensitivity is significantly deteriorated within the PED area and RPE entropy measured with PS-OCT was closely related to visual function in eyes with non-vascularized PED. [ABSTRACT FROM AUTHOR]

Evidence indicates that age-related macular degeneration (AMD) is associated with the prior presence of allergic diseases; however, large-scale studies in the literature are limited. A case–control study was conducted to describe the relationship between premorbid allergic diseases and AMD using Taiwan's National Health Insurance database. Eligibility criteria for inclusion of new adult AMD cases from 2000 to 2013 were set up. We defined the year of diagnosis as the index year. Age-, gender-, index year- matched controls who were drawn from the same database. The case control ratio was 1:4. For all participants, all premorbid conditions staring 1996 to index year were documented. Binary logistic regression was used to describe factors related to AMD occurrence. The AMD group consisted of 10,911 patients, and the comparison group consisted of 43,644 individuals. Patients with AMD showed significant associations with premorbid allergic diseases (aOR 1.54, 95% CI 1.47–1.61), specifically with allergic conjunctivitis (aOR 2.07, 95% CI 1.94–2.20), allergic rhinitis (aOR 1.32, 95% CI 1.25–1.39), asthma (aOR 0.99, 95% CI 0.93–1.06), and atopic dermatitis (aOR 1.04, 95% CI 0.94–1.17). Further analyses indicated that patients with more concurrent allergic diseases have higher associations with AMD than those with fewer concurrent diseases. Patients with more annual medical visits for their allergic diseases also showed higher associations with AMD than those with fewer visits. AMD is significantly associated with premorbid allergic diseases. The underlying mechanisms must be further investigated. [ABSTRACT FROM AUTHOR]

Melanosomes, lipofuscin, and melanolipofuscin are the three principal types of pigmented granules found in retinal pigment epithelium (RPE) cells. Changes in the density of melanosomes and lipofuscin in RPE cells are considered hallmarks of various retinal diseases, including Stargardt disease and age-related macular degeneration (AMD). Herein, we report the potential of an in vivo multimodal imaging technique based on directional back-scattering and short-wavelength fundus autofluorescence (SW-FAF) to study disease-related changes in the density of melanosomes and lipofuscin granules in RPE cells. Changes in the concentration of these granules in Abca4−/− mice (a model of Stargardt disease) relative to age-matched wild-type (WT) controls were investigated. Directional optical coherence tomography (dOCT) was used to assess melanosome density in vivo, whereas the autofluorescence (AF) images and emission spectra acquired with a spectrometer-integrated scanning laser ophthalmoscope (SLO) were used to characterize lipofuscin and melanolipofuscin granules in the same RPE region. Subcellular-resolution ex vivo imaging using confocal fluorescence microscopy and electron microscopy was performed on the same tissue region to visualize and quantify melanosomes, lipofuscin, and melanolipofuscin granules. Comparisons between in vivo and ex vivo results confirmed an increased concentration of lipofuscin granules and decreased concentration of melanosomes in the RPE of Abca4−/− mice, and provided an explanation for the differences in fluorescence and directionality of RPE scattering observed in vivo between the two mouse strains. [ABSTRACT FROM AUTHOR]

Age‐related macular degeneration (AMD) is a blinding eye disease with no unifying theme for its etiology. We used single-cell RNA sequencing to analyze the transcriptomes of ~ 93,000 cells from the macula and peripheral retina from two adult human donors and bulk RNA sequencing from fifteen adult human donors with and without AMD. Analysis of our single-cell data identified 267 cell-type-specific genes. Comparison of macula and peripheral retinal regions found no cell-type differences but did identify 50 differentially expressed genes (DEGs) with about 1/3 expressed in cones. Integration of our single-cell data with bulk RNA sequencing data from normal and AMD donors showed compositional changes more pronounced in macula in rods, microglia, endothelium, Müller glia, and astrocytes in the transition from normal to advanced AMD. KEGG pathway analysis of our normal vs. advanced AMD eyes identified enrichment in complement and coagulation pathways, antigen presentation, tissue remodeling, and signaling pathways including PI3K-Akt, NOD-like, Toll-like, and Rap1. These results showcase the use of single-cell RNA sequencing to infer cell-type compositional and cell-type-specific gene expression changes in intact bulk tissue and provide a foundation for investigating molecular mechanisms of retinal disease that lead to new therapeutic targets. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (ARMD), a major cause of sight impairment for elderly people, is still not well understood despite intensive research. Measuring the size of the lesions in the fundus is the main biomarker of the severity of the disease and as such is widely used in clinical trials yet only relies on manual segmentation. Artificial intelligence, in particular automatic image analysis based on neural networks, has a major role to play in better understanding the disease, by analyzing the intrinsic optical properties of dry ARMD lesions from patient images. In this paper, we propose a comparison of automatic segmentation methods (classical computer vision method, machine learning method and deep learning method) in an unsupervised context applied on cSLO IR images. Among the methods compared, we propose an adaptation of a fully convolutional network, called W-net, as an efficient method for the segmentation of ARMD lesions. Unlike supervised segmentation methods, our algorithm does not require annotated data which are very difficult to obtain in this application. Our method was tested on a dataset of 328 images and has shown to reach higher quality results than other compared unsupervised methods with a F1 score of 0.87, while having a more stable model, even though in some specific cases, texture/edges-based methods can produce relevant results. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) and age-related macular degeneration (AMD) are both common diseases of the elderly people. COPD induced systemic inflammation and hypoxia may have an impact on the development of AMD. This study investigated the possible association between COPD and subsequent risk of AMD. A retrospective cohort study was conducted based on the data from the National Health Insurance Research Database in Taiwan. The COPD cohort comprised 24,625 adult patients newly diagnosed during 2000–2012, whereas age-, gender-, and the year of diagnosis-matched non-COPD cohort comprised 49,250 individuals. Incident AMD was monitored to the end of 2013. A Cox proportional hazards model was applied to evaluate the risk of AMD. The COPD cohort showed 1.25 times higher AMD incidence than the non-COPD cohort (4.80 versus 3.83 per 1000 person-years, adjusted hazard ratio (HR) = 1.20 [95% confident interval (CI) = 1.10–1.32]). Stratified analyses for age, gender, and presence of comorbidity resulted in significant adjusted HRs in most subgroups. Further analysis revealed that the COPD group had an increased risk of both the exudative and non-exudative types of AMD (adjusted HRs = 1.49 [95% CI = 1.13–1.96] and 1.15 [95% CI = 1.05–1.26], respectively). COPD patients have an increased risk for AMD development. Clinicians should provide adequate care for the ocular health to these patients. [ABSTRACT FROM AUTHOR]

Disturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β = + 0.18, p = 0.0007, β = + 0.18, p = 0.0008, respectively) and to dry AMD (β = + 0.17, p = 0.00003 for both ATC and AVC and β = − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs = − 0.13, p < 0.05; Rs = − 0.12; p < 0.05, Rs = − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs = − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease. [ABSTRACT FROM AUTHOR]

Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease's severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3–35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility. [ABSTRACT FROM AUTHOR]

The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (p = 0.021; odds ratio, 5.85), treatment modality (p = 0.019; odds ratio, 6.32), and total number of injections (p = 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP. [ABSTRACT FROM AUTHOR]

To compare the long-term effectiveness of intravitreal anti-vascular endothelial growth factor (VEGF) treatment for pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization (PCV/AT1), and typical neovascular age-related macular degeneration (nAMD). Forty-one eyes with PNV, 68 eyes with PCV/AT1, and 56 eyes with typical nAMD were retrospectively included for analysis. All patients were treatment-naïve and received a three-monthly loading injection of anti-VEGF, followed by further injections, as required. The visual and anatomical outcomes after treatment were evaluated up to 36 months from baseline. No significant intergroup difference was found in terms of best-corrected visual acuity (BCVA) and changes in central foveal thickness at 12, 24, and 36 months after the baseline. In addition, no significant difference was found between the groups regarding the proportions of improved or worsened (increased or decreased more than 3-lines) visual acuity. However, the PNV group participants received significantly fewer anti-VEGF injections (11.7 ± 6.9) than those in the PCV/AT1 (12.4 ± 7.0; P = 0.031) and typical nAMD groups (13.2 ± 7.4; P = 0.016). The incidence of macular atrophy (MA) development was also significantly lower for the PNV (4/41 eyes, 9.8%) than the typical nAMD (15/56 eyes, 26.8%; P = 0.033) eyes. There was no significant difference between PNV, PCV/AT1, and typical nAMD regarding visual acuity improvement after anti-VEGF treatment over 36 months. However, the number of injections for PNV was significantly lower compared to that for PCV/AT1 and typical nAMD, and the incidence of MA development was significantly lower than in typical nAMD. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a key role in proliferative retinal diseases such as age-related macular degeneration by contributing to subretinal fibrosis. To investigate the potential role of retinoic acid receptor-α (RAR-α) signaling in this process, we have now examined the effects of the RAR-α agonist Am580 on EMT induced by transforming growth factor-β2 (TGF-β2) in primary mouse RPE cells cultured in a three-dimensional type I collagen gel as well as on subretinal fibrosis in a mouse model. We found that Am580 inhibited TGF-β2-induced collagen gel contraction mediated by RPE cells. It also attenuated the TGF-β2-induced expression of the mesenchymal markers α-smooth muscle actin, fibronectin, and collagen type I; production of pro-matrix metalloproteinase 2 and interleukin-6; expression of the focal adhesion protein paxillin; and phosphorylation of SMAD2 in the cultured RPE cells. Finally, immunofluorescence analysis showed that Am580 suppressed both the TGF-β2-induced translocation of myocardin-related transcription factor-A (MRTF-A) from the cytoplasm to the nucleus of cultured RPE cells as well as subretinal fibrosis triggered by laser-induced photocoagulation in a mouse model. Our observations thus suggest that RAR-α signaling inhibits EMT in RPE cells and might attenuate the development of fibrosis associated with proliferative retinal diseases. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a disease of the macular area and is the most common cause of irreversible vision loss in people over 50 years of age. Many AMD risk factors, including aging, smoking, exposure to UV and blue light, chronic inflammation, and improper diet, can be associated with oxidative stress. In this regard, certain food ingredients and supplements that have antioxidant properties may contribute to the prevention of AMD and it's progression. Polyphenols can be considered as preventive and therapeutic compounds in the prevention of diseases associated with aging due to the antioxidant properties. For example, quercetin, present in onions, improves anti-VEGF therapy, which is the only effective drug for the wet form of AMD, while resveratrol, found in grape skin, red wine, blueberries and mulberries, neutralizes the negative effects of anti-VEGF therapy. Blueberry anthocyanins have a protective effect on induced damage of retina caused by blue light. Carotenoids that are part of the macular pigment; lutein and zeaxanthin, found in leafy green vegetables and eggs, have the ability to filter light ("natural sunglasses"), but also have direct antioxidant properties. Zinc and copper homeostasis in the retina-choroid complex also play a role in retinal health and AMD prevention. Adequate intake of omega-3 fatty acids, which are found in blue fish, nuts and seeds, reduces the risk of progression to the late stage of AMD. Oxidative stress can be exacerbated by improper diet, and thus increase the possibility of the occurrence and progression of AMD, which is why during the eye examination of persons at risk, it is necessary to advise on proper nutrition and appropriate supplementation. [ABSTRACT FROM AUTHOR]

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in the foveal avascular zone (FAZ) area and retinal vessel density (VD) in the macula of patients receiving multiple anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (N-AMD).Methods: This study included 54 eyes of 54 treatment-naïve N-AMD patients. Thirty-three eyes were treated with intravitreal aflibercept injections, and 21 eyes were treated with intravitreal ranibizumab injections. Unaffected fellow eyes (54 eyes) were used as controls. All image scans were acquired after the macular architecture had recovered with drying up of the subretinal fluid/hemorrhage after treatment.Results: Both the superficial and deep FAZ areas were significantly larger in the aflibercept group than in the control group. The VD was also significantly reduced in the aflibercept group.Conclusions: Prolonged and repeated anti-VEGF therapy may cause an increase in the FAZ area and a decrease in the VD in patients with N-AMD, indicating ischemic damage. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model's ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a highly prevalent degenerative disease and a leading cause of vision loss worldwide. Evidence for an inflammatory component in the development of AMD exists, yet the exact mechanisms remain unclear. Bisretinoid N-retinylidene-N-retinylethanolamine (A2E) in retinal pigmental epithelial (RPE) cells, and in extracellular deposits constitutes a hallmark of AMD, but its role in the pathology of AMD is elusive. Here, we tested the hypothesis that A2E is responsible for the heightened inflammatory activity in AMD. To this end, we measured ex vivo mRNA expression of the cytokines TNF-α, IL-6, and IL-10 in whole blood samples after stimulation with A2E in a clinical sample of 27 patients with neovascular AMD and 24 patients with geographic atrophy secondary to AMD. Patients' spouses (n = 30) were included as non-affected controls. After stimulation with A2E, no statistical differences were found in the median expression level of TNF-α, IL-6, IL-10 between the control group, and the neovascular AMD and the geographic atrophy group. Our findings do not support evidence for the hypothesis, that A2E per se contributes to heightened inflammatory activity in AMD. [ABSTRACT FROM AUTHOR]

In age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (~ 20–30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at α = 0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently. [ABSTRACT FROM AUTHOR]

Deep learning (DL) has the potential to transform medical diagnostics. However, the diagnostic accuracy of DL is uncertain. Our aim was to evaluate the diagnostic accuracy of DL algorithms to identify pathology in medical imaging. Searches were conducted in Medline and EMBASE up to January 2020. We identified 11,921 studies, of which 503 were included in the systematic review. Eighty-two studies in ophthalmology, 82 in breast disease and 115 in respiratory disease were included for meta-analysis. Two hundred twenty-four studies in other specialities were included for qualitative review. Peer-reviewed studies that reported on the diagnostic accuracy of DL algorithms to identify pathology using medical imaging were included. Primary outcomes were measures of diagnostic accuracy, study design and reporting standards in the literature. Estimates were pooled using random-effects meta-analysis. In ophthalmology, AUC's ranged between 0.933 and 1 for diagnosing diabetic retinopathy, age-related macular degeneration and glaucoma on retinal fundus photographs and optical coherence tomography. In respiratory imaging, AUC's ranged between 0.864 and 0.937 for diagnosing lung nodules or lung cancer on chest X-ray or CT scan. For breast imaging, AUC's ranged between 0.868 and 0.909 for diagnosing breast cancer on mammogram, ultrasound, MRI and digital breast tomosynthesis. Heterogeneity was high between studies and extensive variation in methodology, terminology and outcome measures was noted. This can lead to an overestimation of the diagnostic accuracy of DL algorithms on medical imaging. There is an immediate need for the development of artificial intelligence-specific EQUATOR guidelines, particularly STARD, in order to provide guidance around key issues in this field. [ABSTRACT FROM AUTHOR]

Purpose: To find out the factors predisposing to rhegmatogenous retinal detachment. Study Design: Descriptive cross sectional study. Place and Duration of Study: Liaquat National Hospital, Karachi, from October 2017 to April 2018. Methods: After approval from ethical review committee 117 patients presenting with Rhegmatogenous retinal detachment (RRD) were included in the study. A detailed history was taken including previous surgery and trauma. Complete ocular examination was performed including dilated fundus examination. Data was analyzed using SPSS version 21. Mean and standard deviation were computed for quantitative variable i.e. age and frequency. Percentages were calculated for qualitative variables i.e. gender, eye involved, lattice degeneration, trauma and intraocular surgery. Stratification was done with regards to age, gender, eye involved to see the effect of these modifiers on individual factor (lattice degeneration, trauma, intraocular surgery) by using chi square test and considering p value ≤ 0.05 as significant. Results: There were 117 patients including 91 males and 26 females. Sixty four were right eyes and fifty three were left eyes. Mean age was 37.30 ± 8.97 years. Lattice Degeneration was observed in 29.1% patents, Trauma was 37.6% and intraocular surgery was observed in 33.3% patients. There was a significant association of age with trauma (p = 0.045) and intraocular surgery (p = 0.001), which had statistically significant association with RRD. Conclusion: Intraocular surgery, trauma were significantly associated with age and RRD. However, although lattice degeneration is an established risk factors for Rhegmatogenous retinal detachment it was not associated with increased age. [ABSTRACT FROM AUTHOR]

Iron is an essential component in many biological processes in the human body. It is critical for the visual phototransduction cascade in the retina. However, excess iron can be toxic. Iron accumulation and reduced efficiency of intracellular antioxidative defense systems predispose the aging retina to oxidative stress-induced cell death. Age-related macular degeneration (AMD) is characterized by retinal iron accumulation and lipid peroxidation. The mechanisms underlying AMD include oxidative stress-mediated death of retinal pigment epithelium (RPE) cells and subsequent death of retinal photoreceptors. Understanding the mechanism of the disruption of iron and redox homeostasis in the aging retina and AMD is crucial to decipher these mechanisms of cell death and AMD pathogenesis. The mechanisms of retinal cell death in AMD are an area of active investigation; previous studies have proposed several types of cell death as major mechanisms. Ferroptosis, a newly discovered programmed cell death pathway, has been associated with the pathogenesis of several neurodegenerative diseases. Ferroptosis is initiated by lipid peroxidation and is characterized by iron-dependent accumulation. In this review, we provide an overview of the mechanisms of iron accumulation and lipid peroxidation in the aging retina and AMD, with an emphasis on ferroptosis. [ABSTRACT FROM AUTHOR]

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) share some similarity in clinical imaging manifestations. However, their disease entity and treatment strategy as well as visual outcomes are very different. To distinguish these two vision-threatening diseases is somewhat challenging but necessary. In this study, we propose a new artificial intelligence model using an ensemble stacking technique, which combines a color fundus photograph-based deep learning (DL) model and optical coherence tomography-based biomarkers, for differentiation of PCV from nAMD. Furthermore, we introduced multiple correspondence analysis, a method of transforming categorical data into principal components, to handle the dichotomous data for combining with another image DL system. This model achieved a robust performance with an accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of 83.67%, 80.76%, 84.72%, and 88.57%, respectively, by training nearly 700 active cases with suitable imaging quality and transfer learning architecture. This work could offer an alternative method of developing a multimodal DL model, improve its efficiency for distinguishing different diseases, and facilitate the broad application of medical engineering in a DL model design. [ABSTRACT FROM AUTHOR]

A remarkable proportion of neovascular age-related macular degeneration (nAMD) patients respond rather poorly to ranibizumab treatment, in spite of the minimum 4-week follow-up and treatment interval. Usually, retreatments are based on nAMD activity as evaluated by Spectral-domain Optical coherence Tomography (SD-OCT), biomicroscopic fundus examination and visual acuity changes. In this prospective pilot study, we aimed to study SD-OCT changes in a high-frequent follow-up manner (weekly (month 0–6), biweekly (month 7–12)) throughout the first year, which consequently led to intravitreal ranibizumab being administered up to biweekly. Best corrected visual acuity (BCVA) was already significantly improved at week 2. Central retinal thickness (CRT), intraretinal and subretinal fluid (SRF) were significantly improved from week 1 onwards. Half of the patients showed nAMD activity at week 2 or 3 and received the first retreatment earlier than 4 weeks after baseline injection. In total, 46% of retreatments were already applied 2 or 3 weeks after the previous treatment. Greater range of CRT and SRF fluctuation during follow-up was associated with lower final BCVA. Lower baseline BCVA and better SRF improvement at week 2 was associated with greater BCVA improvement. In conclusion, high-frequency SD-OCT follow-up provided a good option for adapting treatment in nAMD individually. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the predominant cause of vision loss in the elderly with a major impact on ageing societies and healthcare systems. A major challenge in AMD management is the difficulty to determine the disease stage, the highly variable progression speed and the risk of conversion to advanced AMD, where irreversible functional loss occurs. In this study we developed an optical coherence tomography (OCT) imaging based spatio-temporal reference frame to characterize the morphologic progression of intermediate age-related macular degeneration (AMD) and to identify distinctive patterns of conversion to the advanced stages macular neovascularization (MNV) and macular atrophy (MA). We included 10,040 OCT volumes of 518 eyes with intermediate AMD acquired according to a standardized protocol in monthly intervals over two years. Two independent masked retina specialists determined the time of conversion to MNV or MA. All scans were aligned to a common reference frame by intra-patient and inter-patient registration. Automated segmentations of retinal layers and the choroid were computed and en-face maps were transformed into the common reference frame. Population maps were constructed in the subgroups converting to MNV (n=135), MA (n=50) and in non-progressors (n=333). Topographically resolved maps of changes were computed and tested for statistical significant differences. The development over time was analysed by a joint model accounting for longitudinal and right-censoring aspect. Significantly enhanced thinning of the outer nuclear layer (ONL) and retinal pigment epithelium (RPE)–photoreceptorinner segment/outer segment (PR-IS/OS) layers within the central 3 mm and a faster thinning speed preceding conversion was documented for MA progressors. Converters to MNV presented an accelerated thinning of the choroid and appearance changes in the choroid prior to MNV onset. The large-scale automated image analysis allowed us to distinctly assess the progression of morphologic changes in intermediate AMD based on conventional OCT imaging. Distinct topographic and temporal patterns allow to prospectively determine eyes with risk of progression and thereby greatly improving early detection, prevention and development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

This study aimed to identify the clinical characteristics and longitudinal changes in exudative pachychoroid neovasculopathy (PNV) and non-exudative PNV. This retrospective cohort study involved 81 eyes of PNV diagnosed by multimodal imaging including optical coherence tomography angiography. At baseline, they were divided into exudative PNV group and non-exudative PNV group depending on the presence of subretinal fluid. The clinical features of both groups and the longitudinal changes were investigated and compared. There were 55 eyes with non-exudative PNV and 26 eyes with exudative PNV. Individuals with non-exudative PNV were older, more frequently asymptomatic and had a higher prevalence of polypoidal choroidal vasculopathy in the opposite eye (all P's < 0.05). Whereas individuals with exudative PNV showed thicker choroid and more frequent history of central serous chorioretinopathy (all P's < 0.001). During about 12 months of longitudinal observation, the transformation into polypoidal choroidal vasculopathy was noted in 4 eyes of non-exudative PNV group, whereas in none of the exudative PNV group. Exudative PNV and non-exudative PNV seem to be separate entities with different epidemiological parameters. Non-exudative PNV, which is frequently found without symptoms at an older age, is suspected to be the significant precursor lesion of polypoidal choroidal vasculopathy. In contrast, exudative PNV may share the same pathophysiology as central serous chorioretinopathy. [ABSTRACT FROM AUTHOR]

Polypoidal choroidal vasculopathy (PCV) is a distinctive type of neovascular age-related macular degeneration prevalent in many Asian countries. However, there is still some controversy in how the subtypes of PCV are classified. This post-hoc study redefined the branching vascular network (BVN) and PCV subtypes through retrospective review of indocyanine green angiography (ICGA) and fluorescein angiography images from two observational studies (RENOWNED/REAL). Of the visual outcomes for each angiographic subtype and treatment pattern investigated, BVN was identified in 56.3% of PCV patients. The proportions and features of the re-defined PCV subtypes were 43.8%, 10.4%, and 45.8% for subtype A (without distinctive features of BVN), B (with BVN but no leakage), and C (with BVN and leakage), respectively. Subtype A had better visual outcomes when compared to subtype C. This possibly resulted from a better baseline visual acuity in subtype A. Moreover, combination therapy [photodynamic therapy plus anti-vascular endothelial growth factor (VEGF)] may lead to better visual improvement than mono-anti-VEGF treatment alone. This study provides the prevalence of PCV subtypes in Taiwan and may serve as a reference for PCV treatment strategies in a real-world setting, especially for the combination therapy and patients without distinctive features of BVN. [ABSTRACT FROM AUTHOR]

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is standard care for neovascular age-related macular degeneration (nAMD), but the recommended monthly injection regimen is burdensome. Evidence suggests low injection/monitoring frequencies in clinical practice and suboptimal vision outcomes. This observational cohort study uses administrative claims data from the French national healthcare system to assess anti-VEGF treatment patterns and nAMD-specific healthcare resource demands and costs. nAMD patients ≥50 years initiating intravitreal ranibizumab, aflibercept or bevacizumab treatment (2014‒2015), and propensity score-matched non-nAMD patients (controls), were identified from the Echantillon Généraliste de Bénéficiaires database. Outcomes of interest included anti-VEGF treatment patterns, and healthcare resource utilization and associated costs of patients vis-à-vis controls over 24 months. Study patients (n = 355) received (mean) 5.2 and 2.4 anti-VEGF injections over 0‒12 and 12‒24 months, respectively. Most patients (79.0%) remained on their initial anti-VEGF agent; among treatment switchers, the most common transition was from ranibizumab to aflibercept. During follow-up, nAMD patients were more likely than controls to require ophthalmology visits (99.7% vs. 44.8%), ocular procedures (optical coherence tomography/angiography/fundoscopy) (96.9% vs. 27.2%), cataract surgery (13.0% vs. 6.7%), and medical transports (38.0% vs. 31.9%). Mean numbers of ophthalmology visits (25.1 vs. 1.2) and medical transports (6.0 vs. 3.5) were higher (p<.01) among nAMD patients. Total reimbursed costs were two-fold higher for nAMD patients than controls (mean €16,799 vs. €8,255) due to higher treatment costs (€6,847 vs. €1,156), medical fees (€1,858 vs. €295), hospital fees (€6,396 vs. €5,235), and transport costs (€358 vs. €259). Excess total healthcare cost was (mean) €5,279 and €7,918 over the first 12 and 24 months of treatment, respectively. Current intravitreal anti-VEGF treatment and monitoring requirements place a considerable economic burden on the French healthcare system. New intravitreal therapies with extended dosing intervals and predictable efficacy might reduce demand for ophthalmology services. [ABSTRACT FROM AUTHOR]

The aim of this observational study was to assess the use and outcome of intravitreal aflibercept in a treat and extend regimen in treatment-naïve neovascular AMD patients in routine practice. This both retrospective and prospective study was conducted in four larger Swiss retina clinics (ASTERIA study). The primary endpoint was the mean change in best-corrected visual acuity (BCVA) in ETDRS letters from baseline to 12 months. Between December 2017 and August 2018, 160 patients were included. For patients with available data, the mean change in BCVA was + 8.4 (± 14.4) letters at month 12 (n = 139) and + 5.0 (± 11.4) letters at month 24 (n = 95). A mean number of 8.3 (± 2.4) injections were administered within the first year and 5.4 (± 2.9) injections during the second year. On average, the observed treatment interval at month 12 was 63.3 (± 22.0) days and increased to 69.1 (± 28.6) days at month 24. For 37% of the patients, a treatment interval ≥ 12 weeks was attained at month 24. In conclusion, intravitreal aflibercept in a Swiss real-life treat and extend regimen resulted in comparable anatomic and functional outcomes as were observed in the prospective registration trials of aflibercept for nAMD treatment. [ABSTRACT FROM AUTHOR]

Epigenetics has been recognized to play an important role in physiological and pathological processes of the human body. Accumulating evidence has indicated that epigenetic mechanisms contribute to the pathogenesis of age-related macular degeneration (AMD). Although the susceptibility related to genetic variants has been revealed by genome-wide association studies, those genetic variants may predict AMD risk only in certain human populations. Other mechanisms, particularly those involving epigenetic factors, may play an important role in the pathogenesis of AMD. Therefore, we briefly summarize the most recent reports related to such epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA, and the interplay of genetic and epigenetic factors in the pathogenesis of AMD. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) affects the central part of the retina and causes blindness. In developed countries, AMD occurs in people over 50 years old. Important factors for AMD pathogenesis are an immune response, inflammation, and genetic factors. This study aimed to determine the impact of IL1RL1 rs1041973 and IL1RAP rs4624606 single nucleotide polymorphisms (SNPs) on the occurrence of AMD and the outcome of treatment with aflibercept and bevacizumab. Patients and Methods: 563 patients with AMD and 281 healthy candidates were evaluated. Patients with exudative AMD were treated with intravitreal bevacizumab and aflibercept and, after 6 months based on the changes in bestcorrected visual acuity and central macular thickness, were classified as ‘responders’ or ‘poor-responders’. Genotyping of IL1RL1 rs1041973 and IL1RAP rs4624606 was accomplished using real-time PCR. Age was compared using the Mann-Whitney U-test. Categorical data (gender, genotype, and allele distributions) compared between groups using the χ2 test or the Fisher’s exact test. Associations of gene polymorphisms were calculated using logistic regression analysis with adjustment for age in exudative and atrophic AMD analysis. An adjusted significance threshold for multiple comparisons α=0.025 was applied. Results: Statistically significant differences in the distribution of IL1RAP rs4624606 genotypes (TT, TA and AA) were found between males with atrophic AMD and controls: 50%, 42.9% and 7.1% vs. 69.7%, 30.3% and 0%, respectively, p=0.015. Moreover, we found that ‘responders’ had a significantly better best-corrected visual acuity than ‘poor-responders’ before treatment (p=0.032). The central macular thickness was significantly lower in exudative AMD patients with IL1RL1 rs1041973 AA genotype than in wild type and heterozygous (CC+CA) genotype carriers before treatment (p=0.017). Conclusion: IL1RAP rs4624606 may be associated with atrophic AMD in males while IL1RL1 rs1041973 may play a protective role against macular thickening in exudative AMD patients. [ABSTRACT FROM AUTHOR]

Polymorphisms in the Complement Factor H (CFH) gene, coding for the Factor H protein (FH), can increase the risk for age-related macular degeneration (AMD). AMD-associated CFH risk variants, Y402H in particular, impair FH function leading to complement overactivation. Whether this alone suffices to trigger AMD pathogenesis remains unclear. In AMD, retinal homeostasis is compromised due to the dysfunction of retinal pigment epithelium (RPE) cells. To investigate the impact of endogenous FH loss on RPE cell balance, we silenced CFH in human hTERT-RPE1 cells. FH reduction led to accumulation of C3, at both RNA and protein level and increased RPE vulnerability toward oxidative stress. Mild hydrogen-peroxide exposure in combination with CFH knock-down led to a reduction of glycolysis and mitochondrial respiration, paralleled by an increase in lipid peroxidation, which is a key aspect of AMD pathogenesis. In parallel, cell viability was decreased. The perturbations of energy metabolism were accompanied by transcriptional deregulation of several glucose metabolism genes as well as genes modulating mitochondrial stability. Our data suggest that endogenously produced FH contributes to transcriptional and metabolic homeostasis and protects RPE cells from oxidative stress, highlighting a novel role of FH in AMD pathogenesis. [ABSTRACT FROM AUTHOR]

Wet age-related macular degeneration (AMD), which can cause progressive blindness, is characterised by choroid neovascularization (CNV) in the macular area. Although close attention has been paid to AMD, and anti-vascular endothelial growth factor (VEGF) drugs are available, its complex pathogenesis is still elusive. Tie2-expressing macrophages (TEMs) have been found to promote angiogenesis in remodel tissues and tumours. This study aimed to elucidate the role of macrophage Tie2 signalling in laser-induced CNV (LCNV). We observed that TEMs were responsible for the severity of CNV. Mechanistically, TEM deletion resulted in impaired LCNV due to the suppression of inflammatory angiogenesis and the promotion of apoptosis. We also observed that TEMs prevented apoptosis of b.End3 cells, but promoted their migration, proliferation and tube formation via VEGF, extracellular signal-regulated kinase (ERK) and v-akt murine thymoma viral oncogene (AKT)-dependent signalling pathways. The flow cytometry results comparing dry AMD patients and healthy controls with wet AMD patients showed that the percentage of Tie2+CD14+ cells was higher in the wet AMD patients' peripheral blood. This study demonstrates that Tie2 expression by macrophages intensifies CNV in LCNV murine models, thereby proposing an additional intervention option to inhibit CNV. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this retrospective study was to evaluate the efficacy of the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents to treat choroidal neovascularization (CNV) caused by a pathology other than exudative type age-related macular degeneration (AMD). Methods: This was a retrospective study of 43 treatment naive eyes of 35 patients who had been diagnosed with CNV caused by a pathology other than exudative- type AMD and who underwent intravitreal injection of anti-VEGF agents. Primary and secondary outcome measures were the best corrected visual acuity (BCVA) and the central macular thickness (CMT). Results: The mean patient age was 44.6±13.1 years. The mean number of injections was 3.3±1.8. The mean logarithm of minimal angle of resolution BCVA at baseline and the 12th month follow-up was 0.89±0.50 and 0.73±0.57, respectively (p=0.120). In all, 44.2% of the eyes gained =15 letters of BCVA, whereas 14% lost =15 letters of BCVA. The mean CMT at baseline and the 12th month follow-up was 381±121 and 311±73 microns, respectively (p=0.001). Conclusion: Stabilized functional and improved anatomic outcomes following intravitreal anti-VEGF agent injection for CNV unrelated to AMD were seen at the 12th month of follow-up. [ABSTRACT FROM AUTHOR]

Müller cells (MCs) are the most common glial cell found in the human retina. MCs have an important role in architectural and metabolic functions in the retina. Additionally, there has been consideration that MC dysfunction might contribute to the pathogenesis of some retinal diseases, such as proliferative vitreoretinopathy, diabetic retinopathy, macular edema, retinal vein occlusion, macular telangiectasia type 2, age-related macular degeneration, retinal degeneration, hepatic and methanol-induced retinopathy, and glaucoma. This review is a summary of the functions of MCs and a discussion of the importance of these glial cells. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries. It is estimated that about 196 million people worldwide suffer from AMD. So far, despite many studies, no causative treatment that can be used large scale has been discovered. In order to slow down, the progression of the disease, a change of the modifiable risk factors such as diet and prophylaxis in the form of nutritional supplements are recommended. The purpose of this work is to present types of supplementation and draw attention to the proper diet containing products rich in substances such as lutein and zeaxanthin protecting the eye against the rapid progression of dry AMD. [ABSTRACT FROM AUTHOR]

In the healthy organism, there is a constant balance between the formation and neutralization of free radicals. Oxidative stress is a result of free radicals' production and naturalization imbalance, in favor of the free radicals' high concentration. Literature suggests the existence of the relationship between decreased intraocular antioxidant capacity and ocular diseases. Retina and the photoreceptors in particularl, are susceptible to oxygen deficiency due to their great oxygen consumption. The aim of this review was to describe the relationship between oxidative stress and the most common vitreoretinal disorders. The authors focused on four ocular diseases such as vitreous degeneration, rhegmatogenous retinal detachment, age-related macular degeneration and diabetic retinopathy. It was widely proven that high oxidative stress damages retina by the acceleration of photoreceptors and ganglion cells apoptosis. Available data suggesting that substances scavenging oxidative stress may be effective in slowing down the progression of these degenerative ocular diseases. However, the effects of antioxidants treatment are ambiguous, successful results of experimental studies lead straight to clinical use in human in the future. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to analyze the numbers and the economic burden of intravitreal anti-VEGF agents and intravitreal dexamethasone (IVD) implants administered to patients with diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). Material and methods: The retrospective case-control study included 1525 patients diagnosed with DME, neovascular AMD and RVO, and received intravitreal anti-VEGF and IVD between January 2016 and December 2018. Intravitreal anti-VEGF administration was performed within the framework of the Pro Re Nata (PRN) regimen. The prices of anti-VEGF agents and IVDs were calculated on the average of the prices in the relevant year. Results: The total number of intravitreal injections in 3 years was 5864. During the 3-year follow-up, on average, ranibizumab (Lucentis) was applied 3.56 ± 2.25 times, alfibercept (Eylea) was applied 3.31 ± 2.16 times, and IVD (Ozurdex) was applied 1.70 ± 0.83 times. The anti-VEGF numbers in 2016, 2017 and 2018 were 1997, 1801, 2066, respectively. In total, the 3-year drug cost was 3,587,812.44 USD. Conclusions: The economic burden of intravitreal anti-VEGF and IVD treatment for retinal diseases is so important to developing countries such as Turkey. The economic burden created by anti-VEGF agents and IVDs in Turkey will reduce in a serious sense, and the legal concerns of physicians will decrease thanks to the decision taken by the Turkish Medicines and Medical Devices Agency (TMMDA). [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to compare the visual acuity (VA) score obtained in both normal subjects and patients with different eye diseases by using TOPCON CP-22 electronic ETDRS charts (i.e. E-ETDRS) and standard ETDRS charts (S-ETDRS). Material and methods: The primary outcome of this observational prospective study was the difference in median VA score (in letters) recorded in 60 patients by using both E-ETDRS and S-ETDRS. There were 60 subjects enrolled in the study: 20 normal, 20 with diabetic retinopathy and 20 with age-related macular degeneration. Results: Median number of letters read was 72.5 S-ETDR and 77 for E-ETDR (p < 0.01). A subgroup analysis disclosed that the difference in VA score between the 2 devices was more pronounced (p < 0.01) when considering healthy subjects compared to patients affected by diabetic retinopathy (p = 0.02) or age-related macular degeneration (p = 0.04). Conclusions: Small but significant discrepancies between the 2 devices have been detected, especially when recording high VA values. [ABSTRACT FROM AUTHOR]

We investigated the association of visual outcome in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) with or without pachychoroid with lesion areas on optical coherence tomography (OCT) quantified by convolutional neural network (CNN) analysis. Treatment-naïve 132 nAMD and 45 PCV eyes treated with ranibizumab or aflibercept for at least 12 months were retrospectively reviewed. Significant factors, including intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED) and subretinal hyperreflective material (SHRM) area quantified by CNN at baseline and 12 months, were analyzed by logistic regression analyses for 3-line visual gain or maintenance of 20/30 Snellen vision. Visual gain at the final visit in nAMD was associated with a smaller SHRM at baseline (OR 0.167, P = 0.03), greater decrease in SRF and SHRM from baseline to month 12 (OR 1.564, P = 0.02; OR 12.877, P = 0.01, respectively). Visual gain in nAMD without pachychoroid was associated with a greater decrease in SRF and SHRM (OR 1.574, P = 0.03, OR 1.775, P = 0.04). No association was found in nAMD with pachychoroid and any type of PCV. Greater decrease in SRF and SHRM from baseline to month 12 was associated with favorable visual outcomes in nAMD without pachychoroid but not in nAMD with pachychoroid and PCV. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) is a complex and multi-factorial disease, and low-grade inflammation is associated with pathogenesis of nAMD. Aqueous humor could reflect intraocular immune environments in various eye diseases. The research so far used aqueous humor samples and revealed that inflammation is involved in pathophysiology of nAMD, although immunological roles of cytokines were evaluated inadequately with aspect to individual effects. Here we used 27 kinds of cytokines covering general immunologic reactions, examined specific expression patterns of cytokines, and assessed relationships between inflammation and pathophysiology of nAMD by multivariate analyses. In nAMD eyes, principal component analysis showed that IL-7, MCP-1, MIP-1β and VEGF had high principal component loadings of over 0.6 in the first principal component constituting 32.6% of all variability of the data. In exploratory factor analysis, IL-6, MCP-1 and MIP-1β had high factor loadings (FL) of over 0.5 in Factor 1 constituting 32.6% of all variability, while VEGF had FL of over 1.0 in Factor 3 constituting 10.7% of all variability. In hierarchical cluster analysis, MCP-1 and VEGF were located in the cluster of first proximate mutual distance to central retinal thickness. These data could suggest that low-grade inflammation is a principal contributor in nAMD. [ABSTRACT FROM AUTHOR]