Progression Of Age-related Macular Degeneration Research Articles

Лечение «сухой» формы возрастной макулярной дегенерации: изученное настоящее и перспективное будущее

Age-related macular degeneration (AMD) is the main cause of central vision loss in elder group of patients. At the same time, annually, the number of people with detected changes in the retina corresponding to different forms of macular dystrophy is steadily growing. The disease is considered to be a highly significant medical, social and economic problem, since a deterioration of the central vision negatively affects the life quality and work capacity of patients. The article presents an analysis of modern views concerning the current therapy possibilities for the dry form of AMD, including the use of nutraceuticals, consisting of lutein, zeaxanthin, mesoseaxanthin, as well as an overview of the directions of development and clinical trials. The use of lutein- and zeaxanthin-containing compounds can be recommended for prevention both the AMD progression and the presence of risk factors for its development, especially in persons over 50 years of age, as well as in the presence of high visual workload. Keywords: age-related macular degeneration, nutraceuticals, carotenoids, lutein, zeaxanthin, mesoseaxanthin. For citation: Glazko N.G., Kanaeva O.A., Rabadanova M.H. Treatment of the dry form of age-related macular degeneration: the studied present and promising future. Russian Journal of Clinical Ophthalmology. 2022;22(4):240–246 (in Russ.). DOI: 10.32364/2311-7729-2022- 22-4-240-246.

Towards the Development of Longer and More Efficacious Therapies for Wet and Dry Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of vision loss in developed countries. The advanced stages of AMD are characterized by the onset and progression of macular neovascularization or geographic atrophy. Several treatments are currently available for managing the neovascular form of AMD, based on intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs. Although these agents are efficient in inducing fluid regression and preserving visual function, their limited duration of action and treatment burden are stimulating the development of new molecules with more prolonged pharmacological activity. The future of exudative AMD therapies will include new generations of anti-VEGF drugs, surgical anti-VEGF port delivery systems and novel molecules acting on other AMD pathogenic pathways. In contrast, dry AMD and geographic atrophy have no approved treatments; nutraceutical approaches still represent the only way to reduce the probability of AMD progression and the onset of complications. Several ongoing clinical trials are testing different molecules that have been developed to slow the progression of geographic atrophy, including complement system inhibitors, integrin inhibitors, gene therapies and cell-based therapies. In this review, we provide an overview of the current state of the art and future perspectives for the management of dry and wet AMD.

Predicting Age-related Macular Degeneration Progression with Longitudinal Fundus Images Using Deep Learning.

Accurately predicting a patient's risk of progressing to late age-related macular degeneration (AMD) is difficult but crucial for personalized medicine. While existing risk prediction models for progression to late AMD are useful for triaging patients, none utilizes longitudinal color fundus photographs (CFPs) in a patient's history to estimate the risk of late AMD in a given subsequent time interval. In this work, we seek to evaluate how deep neural networks capture the sequential information in longitudinal CFPs and improve the prediction of 2-year and 5-year risk of progression to late AMD. Specifically, we proposed two deep learning models, CNN-LSTM and CNN-Transformer, which use a Long-Short Term Memory (LSTM) and a Transformer, respectively with convolutional neural networks (CNN), to capture the sequential information in longitudinal CFPs. We evaluated our models in comparison to baselines on the Age-Related Eye Disease Study, one of the largest longitudinal AMD cohorts with CFPs. The proposed models outperformed the baseline models that utilized only single-visit CFPs to predict the risk of late AMD (0.879 vs 0.868 in AUC for 2-year prediction, and 0.879 vs 0.862 for 5-year prediction). Further experiments showed that utilizing longitudinal CFPs over a longer time period was helpful for deep learning models to predict the risk of late AMD. We made the source code available at https://github.com/bionlplab/AMD_prognosis_mlmi2022 to catalyze future works that seek to develop deep learning models for late AMD prediction.

An integrated analysis of clinical and morphometric indications of atrophic forms of age-related macular degeneration

The atrophic form of late age-related macular degeneration (AMD) is a common cause of severe vision loss. Recently, a new classification system has been proposed, which identifies two types of atrophy in the late stage of AMD that require a more detailed study: (1) drusenassociated geographic atrophy (GA), which is the final stage of progression of dry AMD, and (2) macular atrophy (MA), which occurs in wet AMD, including the period of AMD treatment with angiogenesis inhibitors. Purpose: an integrated analysis of clinical and morphometric signs of atrophic AMD forms. Material and methods. 48 people (61eyes) aged 48–84 with GA (group 1) and MA (group 2) and a control group, recruited from age-matching 25 healthy volunteers (35 eyes), underwent standard ophthalmological examinations, fundus autofluorescence (FAF) with lesion area measurement, fundus photography, optical coherence tomography (OCT) in the standard mode and Enhanced Depth Imagine Mode, Multicolor, and OCT angiography. Results. The comparative analysis of two atrophic AMD forms showed that in GA eyes, foci of atrophy capturing the fovea were significantly more common, while, contrariwise in MA eyes atrophic foci not capturing the fovea were more frequent (p < 0.05). Photoreceptor tubulation was diagnosed mainly in eyes with GA (p < 0.05). The morphometric analysis showed a significant decrease in the subfoveal thickness of the choroid in the groups with GA and MA as compared to the control (p < 0.05), whilst no significant differences between two groups were noted. The assessment of the frequency of occurrence of types of fundus AF patterns in groups 1 and 2 followed by a comparative analysis, showed the presence of all types of patterns in GA patients, including the heterogeneous and the bordering pattern (p < 0.05). In the MA group, diffuse and focal types of patterns were revealed, while the frequency of the diffuse pattern turned out to be significantly more frequent (p < 0.05). Conclusion. The integrated analysis revealed the main semiological signs and morphometric parameters, their features and prevalence in GA and MA, which may have diagnostic and prognostic importance for the management and treatment of patients with AMD.

Inhibition of prolyl oligopeptidase: A promising pathway to prevent the progression of age-related macular degeneration

Dry age-related macular degeneration (AMD) is a currently untreatable vision threatening disease. Impaired proteasomal clearance and autophagy in the retinal pigment epithelium (RPE) and subsequent photoreceptor damage are connected with dry AMD, but detailed pathophysiology is still unclear. In this paper, we discover inhibition of cytosolic protease, prolyl oligopeptidase (PREP), as a potential pathway to treat dry AMD. We showed that PREP inhibitor exposure induced autophagy in the RPE cells, shown by increased LC3-II levels and decreased p62 levels. PREP inhibitor treatment increased total levels of autophagic vacuoles in the RPE cells. Global proteomics was used to examine the phenotype of a commonly used cell model displaying AMD characteristics, oxidative stress and altered protein metabolism, in vitro. These RPE cells displayed induced protein aggregation and clear alterations in macromolecule metabolism, confirming the relevance of the cell model. Differences in intracellular target engagement of PREP inhibitors were observed with cellular thermal shift assay (CETSA). These differences were explained by intracellular drug exposure (the unbound cellular partition coefficient, Kpuu). Importantly, our data is in line with previous observations regarding the discrepancy between PREP’s cleaving activity and outcomes in autophagy. This highlights the need to further explore PREP’s role in autophagy so that more effective compounds can be designed to battle diseases in which autophagy induction is needed. The present work is the first report investigating the PREP pathway in the RPE and we predict that the PREP inhibitors can be further optimized for treatment of dry AMD.

MTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in Energy Metabolism Caused by FH Loss in RPE Cells.

Age-related macular degeneration (AMD) is a complex degenerative disease of the retina with multiple risk-modifying factors, including aging, genetics, and lifestyle choices. The combination of these factors leads to oxidative stress, inflammation, and metabolic failure in the retinal pigment epithelium (RPE) with subsequent degeneration of photoreceptors in the retina. The alternative complement pathway is tightly linked to AMD. In particular, the genetic variant in the complement factor H gene (CFH), which leads to the Y402H polymorphism in the factor H protein (FH), confers the second highest risk for the development and progression of AMD. Although the association between the FH Y402H variant and increased complement system activation is known, recent studies have uncovered novel FH functions not tied to this activity and highlighted functional relevance for intracellular FH. In our previous studies, we show that loss of CFH expression in RPE cells causes profound disturbances in cellular metabolism, increases the vulnerability towards oxidative stress, and modulates the activation of pro-inflammatory signaling pathways, most importantly the NF-kB pathway. Here, we silenced CFH in hTERT-RPE1 cells to investigate the mechanism by which intracellular FH regulates RPE cell homeostasis. We found that silencing of CFH results in hyperactivation of mTOR signaling along with decreased mitochondrial respiration and that mTOR inhibition via rapamycin can partially rescue these metabolic defects. To obtain mechanistic insight into the function of intracellular FH in hTERT-RPE1 cells, we analyzed the interactome of FH via immunoprecipitation followed by mass spectrometry-based analysis. We found that FH interacts with essential components of the ubiquitin-proteasomal pathway (UPS) as well as with factors associated with RB1/E2F signalling in a complement-pathway independent manner. Moreover, we found that FH silencing affects mRNA levels of the E3 Ubiquitin-Protein Ligase Parkin and PTEN induced putative kinase (Pink1), both of which are associated with UPS. As inhibition of mTORC1 was previously shown to result in increased overall protein degradation via UPS and as FH mRNA and protein levels were shown to be affected by inhibition of UPS, our data stress a potential regulatory link between endogenous FH activity and the UPS.

Hyporeflective Cores within Drusen: Association with Progression of Age-Related Macular Degeneration and Impact on Visual Sensitivity

To examine the association between hyporeflective cores within drusen (HCD) and disease progression in age-related macular degeneration (AMD) and with visual function. Longitudinal observational study. Two hundred and eighty eyes from 140 participants with bilateral large drusen, without late AMD. Multimodal imaging and microperimetry were performed at baseline and subsequently every 6 months for up to 3 years. Baseline OCT scans were graded for the presence of HCD and used to calculate drusen volume. The total area of the drusenoid lesions containing hyporeflective cores (HCD extent) on color fundus photographs (CFPs) was calculated. CFPs were also graded for the presence of pigmentary abnormalities. The association between HCD extent with progression to late AMD (including OCT signs of atrophy) and visual sensitivity measured using microperimetry at baseline and its rate of change over time was evaluated with and without adjustment for confounders of drusen volume, pigmentary abnormalities, and age. Time to develop late AMD and visual sensitivity. Twenty (7%) eyes from 12 (9%) individuals were found to have HCD at baseline, which was associated with a nonsignificantly increased rate of progression to late AMD (unadjusted P= 0.050). HCD extent was significantly associated with an increased rate of progression to late AMD (unadjusted P= 0.034) and lower visual sensitivity at baseline (unadjusted P < 0.001). However, these associations were no longer significant (P ≥ 0.264 for both) after adjusting for known risk factors for AMD progression. HCD extent was also not associated with a faster rate of visual sensitivity decline before the development of late AMD, with or without adjustment (P ≥ 0.674 for both). Increasing age and larger drusen volume were associated with HCD extent (P ≤ 0.041). In a cohort with bilateral large drusen, HCD presence and extent were not independently associated with an increased rate of progression to late AMD over 3 years, nor with lower visual sensitivity or an increased rate of visual sensitivity decline before the development of late AMD, after adjusting for known risk factors for disease progression.

Отдаленные результаты применения комбинированного лазерного лечения друзеноидной отслойки ретинального пигментного эпителия

Drusenoid pigment epithelial detachment is a condition characterized by separation of the retinal pigment epithelium from the underlying Bruch’s membrane due to formation of drusenoid deposits. The disorder represents the intermediate stage of the age-related macular degeneration, and is a risk factor for the age-related macular degeneration progression to late stage characterized by geographic atrophy, which results in the irreversible central vision loss. Management of patients with this disorder is in most cases limited to follow-up. The feasibility of using the multimodality low power mode laser therapy for treatment of drusenoid pigment epithelial detachment is reported. The results of laser photocoagulation of the retina demonstrate the morphological and functional recovery: retinal pigment epithelial detachment sealing, improvement of visual function, and restored retinal architecture.

Interferon-γ induces retinal pigment epithelial cell Ferroptosis by a JAK1-2/STAT1/SLC7A11 signaling pathway in Age-related Macular Degeneration.

Retinal pigment epithelium (RPE) cell damage is implicated in the pathogenesis of age-related macular degeneration (AMD). An increase of interferon-γ (IFN-γ) levels was observed in patients with AMD, but whether inflammatory factors are causally related to AMD progression is unclear. Here, we demonstrate a direct causal relationship between IFN-γ and RPE cell death. IFN-γ induced human retinal pigment epithelial cell (ARPE-19) death accompanied by increases in Fe2+ , reactive oxygen species, lipid peroxidation, and glutathione (GSH) depletion, which are main characteristics of ferroptosis. Mechanistically, IFN-γ upregulates the level of intracellular Fe2+ through inhibiting Fe2+ efflux protein SLC40A1 and induces GSH depletion by blocking cystine/glutamate antiporter, System xc-. At the same time, treatment with IFN-γ decreases the level of glutathione peroxidase 4 (GPx4), rendering the cells more sensitive to ferroptosis. JAK1/2 and STAT1 inhibitors could reverse the reduction of SLC7A11, GPx4 and GSH expression induced by IFN-γ, indicating IFN-γ induces ARPE-19 cell ferroptosis via activation of the JAK1-2/STAT1/SLC7A11 signaling pathway. The above results were largely confirmed in IFN-γ-treated mice in vivo. Finally, we used sodium iodate (NaIO3 )-induced retinal degeneration to further explore the role of ferroptosis in AMD in vivo. Consistent with the role of IFN-γ, treatment with NaIO3 decreased SLC7A11, GPx4 and SLC40A1 expressions. NaIO3 -induced RPE damage was accompanied by increased iron, lipid peroxidation products (4-hydroxynonenal, malondialdehyde), and GSH depletion, and ferroptosis inhibitors could reverse the above phenomenon. Taken together, our findings suggest that inhibiting ferroptosis or reducing IFN-γ may serve as a promising target for AMD.

Evidence-based vitamin supplements for age-related macular degeneration: an analysis of available products

ABSTRACT Clinical Relevance A wide range of supplements are available for age-related macular degeneration (AMD); however, clinicians may not be aware of which supplements contain an evidence-based formula. Background Vitamin and antioxidant supplementation has been shown to be effective in slowing the progression of AMD. The Age-Related Eye Disease Studies (AREDS) group reported an evidence-based formula in the AREDS 2 trials. Commercially available products carry varying degrees of resemblance to this formula. Methods A review of commercially available supplements in pharmacies and websites across Australasia, the United States, the United Kingdom, and Canada was undertaken. Supplements containing all the ingredients of the AREDS 2 recipe were included. The dose, formulation, and cost of the supplements were reviewed. Results Sixty-six products were reviewed. Forty-three products contained all the AREDS 2 ingredients and were therefore included for analysis. Twenty products contained all ingredients at 100% or more of the recommended dose, and 23 products contained some ingredients at a lower dose. The cost of the products varied from Australian dollar (AUD) $0.12 to AUD $6.72 per day. Seven (35%) products were available online only and 13 (65%) products were available both online and in pharmacies. Eight products were available in the United States pharmacies, five products were available in Canadian pharmacies, three products were available in the United Kingdom pharmacies, and one product was available in Australasian pharmacies. Conclusions Commercially available AMD supplements vary widely in price and resemblance to the AREDS 2 formulation. Clinician awareness of this information is important when counselling patients on which supplement is most suitable. The categorisation of products in Table 1 may assist with patient counselling of vitamin supplementation for AMD.

Personalized Atrophy Risk Mapping in Age-Related Macular Degeneration.

PurposeTo develop and validate an automatic retinal pigment epithelial and outer retinal atrophy (RORA) progression prediction model for nonexudative age-related macular degeneration (AMD) cases in optical coherence tomography (OCT) scans.MethodsLongitudinal OCT data from 129 eyes/119 patients with RORA was collected and separated into training and testing groups. RORA was automatically segmented in all scans and additionally manually annotated in the test scans. OCT-based features such as layers thicknesses, mean reflectivity, and a drusen height map served as an input to the deep neural network. Based on the baseline OCT scan or the previous visit OCT, en face RORA predictions were calculated for future patient visits. The performance was quantified over time with the means of Dice scores and square root area errors.ResultsThe average Dice score for segmentations at baseline was 0.85. When predicting progression from baseline OCTs, the Dice scores ranged from 0.73 to 0.80 for total RORA area and from 0.46 to 0.72 for RORA growth region. The square root area error ranged from 0.13 mm to 0.33 mm. By providing continuous time output, the model enabled creation of a patient-specific atrophy risk map.ConclusionsWe developed a machine learning method for RORA progression prediction, which provides continuous-time output. It was used to compute atrophy risk maps, which indicate time-to-RORA-conversion, a novel and clinically relevant way of representing disease progression.Translational RelevanceApplication of recent advances in artificial intelligence to predict patient-specific progression of atrophic AMD.

Assessing bidirectional associations between cognitive impairment and late age-related macular degeneration in the Age-Related Eye Disease Study 2.

We aimed to investigate bidirectional associations between cognitive impairment and late age-related macular degeneration (AMD). Participants in the Age-Related Eye Disease Study 2 (AREDS2) received annual eye examinations and cognitive function testing (e.g., Modified Telephone Interview for Cognitive Status [TICS-M]). We examined bidirectional associations between cognitive impairment (e.g., a TICS-M score<30) and late AMD at 5 and 10 years. Five thousand one hundred eighty-nine eyes (3157 participants; mean age 72.7 years) were analyzed and followed for a median of 10.4 years. Eyes of participants with cognitive impairment at baseline were more likely to progress to late AMD at 5 years (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.08-1.43) and 10 years (HR, 1.20; 95% CI, 1.05-1.37) than eyes of participants without cognitive impairment. Worse baseline AMD severity was not associated with developing cognitive impairment. Cognitive impairment is associated with late AMD progression in AREDS2. Our finding highlights the importance of eyecare for people with cognitive impairment.

Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.

Age‐related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen‐associated proteins are released as cargo of extracellular vesicles secreted by RPE cells in a polarised apical:basal mode. Notably, drusen‐associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors. These observations underpin the existence of a finely‐tuned mechanism regulating directional apical:basal sorting and secretion of drusen‐associated proteins via EVs, and its modulation in response to mechanisms involved in AMD pathophysiology. Collectively, our results strongly support an active role of RPE‐derived EVs as a key source of drusen proteins and important contributors to drusen development and growth.

Dietary Antioxidants in Age-Related Macular Degeneration and Glaucoma.

Age-related macular degeneration (AMD) and glaucoma are ophthalmic neurodegenerative diseases responsible for irreversible vision loss in the world population. Only a few therapies can be used to slow down the progression of these diseases and there are no available treatment strategies for reversing the degeneration of the neural retina. In AMD, the pathological process causes the malfunction and damage of the retinal pigmented epithelium and photoreceptors in the macula. In glaucoma, damage of the retinal ganglion cells and their axons is observed and treatment strategies are limited to intraocular pressure lowering. Therefore, other prophylactic and/or therapeutic methods are needed. Oxidative stress is involved in the neurodegenerative process accompanying both AMD and glaucoma; therefore, the use of antioxidant agents would clearly be beneficial, which is supported by the decreased prevalence and progression of AMD in patients adherent to a diet naturally rich in antioxidants. Dietary antioxidants are easily available and their use is based on the natural route of administration. Many preclinical studies both in vitro and using animal models of retinal degeneration showed the efficacy of dietary antioxidants, which was further proved in clinical trials. Resveratrol is beneficial both in AMD and glaucoma animal models, but confirmed only among AMD patients. For AMD, carotenoids and omega-3 fatty acids were also proved to be sufficient in preventing neurodegeneration. For glaucoma, coenzyme Q10 and alpha-lipoic acid showed efficacy for decreasing retinal ganglion cell loss and inhibiting the accompanying destructive processes. Interestingly, the benefits of vitamins, especially vitamin E was not confirmed, neither in preclinical nor in clinical studies.

Low-Reflectivity Drusen With Overlying RPE Damage Revealed by Spectral-Domain OCT: Hint for the Development of Age-Related Macular Degeneration.

Purpose: To observe the relationship between the characteristic changes in the drusen morphology revealed by the spectral-domain optical coherence tomography (SD-OCT) and the progression of age-related macular degeneration (AMD).Methods: A total of 380 drusen in 45 eyes in 35 patients with the intermediate drusen were longitudinally followed up every 6 months by SD-OCT for a period of 24 months. The drusen were divided into the dynamic group and stable group according to the following parameters: number, volume, concurrent retinal pigment epithelium (RPE)/ellipsoid zone (EZ) damage, and the development of advanced AMD. The morphological characteristics of the progressive or stable drusen were further analyzed. Odds ratios (ORs) and the risk for the drusen progression were calculated.Results: The level of interobserver and intraobserver agreement for each drusen tomographic morphological parameters ranged from 82.7 to 90%. At the end of an average follow-up of 15.92 ± 6.99 months, six patients developed choroidal neovascularization and no patients developed geographic atrophy. Finally, 139 drusen changed and 241 drusen remained stable. The drusen with low reflectivity (p < 0.001; OR: 5.26; 95% CI: 2.24–12.36), non-homogeneity without a core (p < 0.001; OR: 4.31; 95% CI: 2.08–8.92), RPE damage (p < 0.001; OR: 28.12; 95% CI: 9.43–83.85), and the EZ damage (p < 0.001; OR: 14.01; 95% CI: 5.28–37.18) were significantly associated with active change; the drusen with low reflectivity (p = 0.01; OR: 2.95; 95% CI: 1.29–6.75) and decreased overlying RPE reflectivity (p < 0.001; OR: 21.67; 95% CI: 9.20–51.02) were the independent predictors for progression. The drusen with high reflectivity were significantly associated with stabilization (p = 0.03; OR: 0.17; 95% CI: 0.04–0.84).Conclusion: Spectral-domain optical coherence tomography is an optimized, accurate, and efficient method to follow-up the drusen. The intermediate non-exudative AMD prognosis of the patient was most strongly correlated with the drusen reflectivity and disruption of the overlying RPE layer. The drusen with low reflectivity and overlying RPE damage were more likely to progress and required frequent follow-up.

Physical Activity, Incidence, and Progression of Age-Related Macular Degeneration: A Multicohort Study

To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population. Meta-analysis of longitudinal cohort studies. We included 14,630 adults with no or early AMD at baseline from 7 population-based studies and examined associations of PA with AMD incidence and progression using multistate models (MSM) per study and subsequent random effects meta-analysis. Age effects were assessed using meta-regression. The main outcome measure was the hazard ratio (HR) for incident early or progression to late AMD. At baseline, mean age was 60.7 ± 6.9 to 76.4 ± 4.3 years, and prevalence of early AMD was 7.7% (range, 3.6%-16.9%) between cohorts. During follow-up, 1461 and 189 events occurred for early and late AMD, respectively. In meta-analyses, no or low to moderate PA (high PA as reference) was associated with an increased risk for incident early AMD (HR, 1.19; 95% CI, 1.01-1.40; P=.04), but not for late AMD. In subsequent meta-regression, we found no association of age with the effect of PA on incident AMD. Our study suggests high levels of PA to be protective for the development of early AMD across several population-based cohort studies. Our results establish PA as a modifiable risk factor for AMD and inform further AMD prevention strategies to reduce its public health impact.

No association between cataract surgery and mitochondrial DNA damage with age-related macular degeneration in human donor eyes.

To determine whether age-related macular degeneration (AMD) severity or the frequency of retinal pigment epithelium mitochondrial DNA lesions differ in human donor eyes that have undergone cataract surgery compared to phakic eyes. Eyes from human donors aged ≥ 55 years were obtained from the Minnesota Lions Eye Bank. Cataract surgery status was obtained from history provided to Eye Bank personnel by family members at the time of tissue procurement. Donor eyes were graded for AMD severity using the Minnesota Grading System. Quantitative PCR was performed on DNA isolated from macular punches of retinal pigment epithelium to quantitate the frequency of mitochondrial DNA lesions in the donor tissue. Univariable and multivariable analyses were performed to evaluate for associations between (1) cataract surgery and AMD severity and (2) cataract surgery and mitochondrial DNA lesion frequency. A total of 157 subjects qualified for study inclusion. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that only age was associated with AMD grade. Multivariable analysis with age, sex, smoking status, and cataract surgery status showed that none of these factors were associated with retinal pigment epithelium mitochondrial DNA lesion frequency. In this study of human donor eyes, neither retinal pigment epithelium mitochondrial DNA damage nor the stage of AMD severity are independently associated with cataract surgery after adjusting for other AMD risk factors. These new pathologic and molecular findings provide evidence against a relationship between cataract surgery and AMD progression and support the idea that cataract surgery is safe in the setting of AMD.

RESVEGA, a Nutraceutical Omega-3/Resveratrol Supplementation, Reduces Angiogenesis in a Preclinical Mouse Model of Choroidal Neovascularization.

Age-related macular degeneration (AMD) is an eye disease that is characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. At an advanced stage, a blind spot grows in the center of vision, severely handicapping patients with this degenerative condition. Despite therapeutic advances thanks to the use of anti-VEGF, many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether supplementation with Resvega®, a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, a well-known polyphenol in grapes, was able to counteract laser-induced choroidal neovascularization (CNV) in mice. We highlight that Resvega® significantly reduced CNV in mice compared with supplementations containing omega-3 or resveratrol alone. Moreover, a proteomic approach confirmed that Resvega® could counteract the progression of AMD through a pleiotropic effect targeting key regulators of neoangiogenesis in retina cells in vivo. These events were associated with an accumulation of resveratrol metabolites within the retina. Therefore, a supplementation of omega-3/resveratrol could improve the management or slow the progression of AMD in patients with this condition.

Dietary omega-3 polyunsaturated fatty acids and fish intake and risk of age-related macular degeneration

Epidemiologic studies are inconsistent regarding the association of dietary omega-3 polyunsaturated fatty acids (PUFA) and/or fish intake with risk of age-related macular degeneration (AMD) incidence and progression. The objective was to determine these associations by conducting a meta-analysis of available studies. Three electronic databases were searched for studies that quantified dietary omega-3 PUFA and/or fish intake from inception to December 2020 without language restriction. Three investigators independently assessed for inclusion and extracted data. Study-specific risk estimates were combined using random-effects model. Potential dose-response associations were explored with the use of generalized least-squares trend estimation. 21 studies were included in the meta-analysis. Higher dietary intakes of omega-3 PUFA was significantly associated with 14% (relative risk [RR]: 0.86, 95% confidence interval [CI]: 0.77, 0.96) and 29% (RR: 0.71, 95% CI: 0.55, 0.91) lower risk of early and late AMD, respectively. The dose-response analysis showed a 6% and 22% decrease in the risk of early and late AMD for each additional 1g/d omega-3 PUFA intake. For individual omega-3 PUFA, the intake of eicosapentaenoic acid and docosahexaenoic acid was inversely associated with lower AMD risk, whereas no association was found for the alpha-linolenic acid. Consistent inverse associations were also found between fish intake and AMD. The pooled RRs comparing extreme categories of fish intake were 0.79 (95% CI: 0.70, 0.90) and 0.71 (95% CI: 0.60, 0.85) for early and late AMD risk, respectively. Every 15g/d of fish consumption was associated with 13% and 14% lower early and late AMD. In addition, fish intake was associated with a significantly reduced risk of AMD progression (RR: 0.73, 95% CI: 0.53, 1.00). A high intake of dietary omega-3 PUFA or fish was associated with a reduced risk of developing of AMD, which further supports that consumption of omega-3 PUFA-rich foods may be a new avenue nutritional approach to preventing AMD.

СПОСІБ ОЦІНЮВАННЯ ВПЛИВУ ХІРУРГІЧНОГО ЛІКУВАННЯ КАТАРАКТИ НА ПРОГРЕСУВАННЯ ВІКОВОЇ МАКУЛЯРНОЇ ДЕГЕНЕРАЦІЇ

У роботі наводяться результати дослідження впливу хірургічного лікування вікової катарак-ти на прогресування вікової макулярної дегенерації (ВМД).Мета роботи – розробити спосіб оцінки впливу хірургічного лікування катаракти на прогре-сування вікової макулярної дегенерації.У 82 хворих (93 ока) вивчено вплив параметрів факоемульсифікації (ФЕК), операційні тапісляопераційні ускладнення на прогресування ВМД. Встановлено, що факторами ризикупрогресування ВМД після хірургічного лікування є щільність ядра кришталика по Buratto,тривалість операції, обсяг іригаційної рідини, показник кумулятивної розсіяної енергії (се-редня потужність і експозиція лінійного ультразвуку та середня торсійна амплітуда і тор-сійний час), післяопераційне запалення. Розроблено шкалу бальної оцінки прогресуваннявікової макулярної дегенерації після хірургічного лікування катаракти.