Treatment Of Age-related Macular Degeneration Research Articles

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells.

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.

Associations with baseline visual acuity in 12,414 eyes starting treatment for neovascular AMD

AimsTo determine baseline visual acuity before the start of treatment for neovascular age-related macular degeneration (AMD), compare median and visual acuity states between treatment sites and investigate the association of socio-demographic and clinical characteristics with baseline acuity.MethodsAnonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation. Associations with baseline acuity were investigated using multivariate linear regression.ResultsAnalysis included 12,414 eyes of 9116 patients at 13 NHS Trusts. Median baseline acuity was LogMAR 0.46 (interquartile range = 0.26–0.80) and 34.5% of eyes had good acuity, defined as LogMAR ≤0.3. Baseline acuity was positively associated with second-treated eye status, younger age, lower socio-economic deprivation, independent living, and female sex. There was little evidence of association between baseline acuity and distance to the nearest treatment centre, systemic or ocular co-morbidity. Despite case-mix adjustments, there was evidence of significant variation of baseline visual acuity between sites.ConclusionsDespite access to publicly funded treatment within the NHS, variation in visual acuity at the start of neovascular AMD treatment persists. Identifying the characteristics associated with poor baseline acuity, targeted health awareness campaigns, professional education, and pathway re-design may help to improve baseline acuity, the first eye gap, and visual acuity outcomes.

Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review.

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

Downregulation of Inflammatory Response via Nrf2/Trx1/TXNIP Axis in Oxidative Stress-Induced ARPE-19 Cells and Mouse Model of AMD.

Aim Chronic inflammation is crucial for age-related macular degeneration (AMD) pathogenesis. However, the mechanism involved in activating inflammation remains unclear. This study is aimed at investigating whether nuclear factor erythrocyte-associated factor 2 (Nrf2) negatively regulated the Nod-like receptor protein 3 (NLRP3) inflammasomes through the thioredoxin 1 (Trx1)/thioredoxin interaction protein (TXNIP) complex. Methods We determined the optimal hydrogen peroxide (H2O2) concentration, time, and changes in reactive oxygen species (ROS) levels. We also constructed animal models using blue LED irradiation. Then, the expression of Nrf2, TXNIP, Trx1, NLRP3, and inflammation-related factors and proteins, along with the changes in retinal thickness and functional status, was analyzed. Results The oxidative stress model was established after 1 h intervention with 100 μM H2O2. Nrf2 reduced ROS production, protected the ultrastructure of mitochondria, increased the thickness of the ONL layer, and increased the amplitude of a- and b-wave amplitudes in ERG. Trx1 knockdown increased the production of ROS, damaged the ultrastructure of mitochondria, reduced the thickness of the other ONL layer, and reduced the amplitudes of a- and b-waves in the electroretinogram (ERG). Thus, TXNIP in the cytoplasm activated the inflammasomes. Conclusions Nrf2 showed antioxidant and anti-inflammatory activity in the H2O2-induced cell stress model and blue LED-induced retinal light damage model. TXNIP transferred from the nucleus to the cytoplasm, activated NLRP3, and aggravated the retinal injury in both the cell stress model and the animal blue LED model. In contrast, Trx1 knockout promoted this process. This study revealed the possible role of the thioredoxin system in developing AMD while also providing newer insights for the future treatment of AMD.

Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1 R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.

Targeting the Complement Cascade for Treatment of Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the elderly population. AMD is characterized in its late form by neovascularization (wet type) or geographic atrophy of the retinal pigment epithelium cell layer (dry type). Regarding the latter type, there is growing evidence supporting an association between the pathophysiology of dry AMD and key proteins in the complement cascade. The complement cascade works as a central part of the innate immune system by defending against foreign pathogens and modified self-tissues. Through three distinct pathways, a series of plasma and membrane-associated serum proteins are activated upon identification of a foreign entity. Several of these proteins have been implicated in the development and progression of dry AMD. Potential therapeutic targets include C1q, C3, C5, complement factors (B, D, H, I), membrane attack complex, and properdin. In this review, we provide an understanding of the role of the complement system in dry AMD and discuss the emerging therapies in early phase clinical trials. The tentative hope is that these drugs may offer the potential to intervene at earlier stages in dry AMD pathogenesis, thereby preventing progression to late disease.

Brolucizumab for the Treatment of Degenerative Macular Conditions: A Review of Clinical Studies.

Age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion represent some of the commonest degenerative conditions that lead to severe vision impairment in the developed countries. The gold standard treatment of complications associated with these conditions is the intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents. Brolucizumab is a newly developed, humanised, single-chain fragment of a monoclonal antibody binding all VEGF-A isoforms, which was recently approved for the treatment of neovascular AMD. Intravitreal brolucizumab promises to reduce treatment burden for nAMD patients by achieving comparable therapeutic outcomes with fewer clinic visits. Promising also appears its use for the treatment of more challenging maculopathies like diabetic macular oedema (DMO). The aim of this review is to describe the special pharmacological properties of brolucizumab and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of degenerative macular disorders.

Bioinformatical and Biochemical Analyses on the Protective Role of Traditional Chinese Medicine against Age-Related Macular Degeneration

Purpose Age-related macular degeneration (AMD) is the commonest cause of permanent vision loss in the elderly. Traditional Chinese medicine (TCM) has long been used to treat AMD, although the underlying functional mechanisms are not understood. This study aims to predict the active ingredients through screening the chemical ingredients of anti-AMD decoction and to elucidate the underlying mechanisms. Methods We collected the prescriptions for effective AMD treatment with traditional Chinese medicine and screened several Chinese medicines that were used most frequently in order to compose "anti-AMD decoction." The pharmacologically active ingredients and corresponding targets in this anti-AMD decoction were mined using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the AMD-related targets were identified through the GeneCards database. Network pharmacology was performed to construct the visual network of anti-AMD decoction-AMD protein-protein interaction (PPI). Further, the Autodock software was adopted for molecular docking on the core active ingredients and core targets. The function of core ingredients against oxidative stress and inflammation in retinal pigment epithelial cells was assessed using biochemical assays. Results We screened out 268 active ingredients in anti-AMD decoction corresponding to 258 ingredient targets, combined with 2160 disease targets in AMD, and obtained 129 drug-disease common targets. The key core proteins were predominantly involved in inflammation. Furthermore, molecular docking showed that four potential active ingredients (Quercetin, luteolin, naringenin and hederagenin) had good affinity with the core proteins, IL-6, TNF, VEGFA and MAPK3. Quercetin, luteolin and naringenin demonstrated capacities against oxidative stress and inflammation in human retinal pigment epithelial cells. Conclusions The data suggests that anti-AMD decoction has multiple functional components and targets in treating AMD, possibly mediated by suppression of oxidative stress and inflammation.

Efficacy and safety of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration: a randomized trial in Indian patients

BackgroundThe current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks.MethodsA prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed.ResultsBrolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (−0.13 ± 0.21 logMAR vs. −0.10 ± 0.15 logMAR) and reduction in CMT (−112.59 ± 81.23 µm vs. −86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group.ConclusionThe results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals.Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName =

Neovascularization-directed bionic eye drops for noninvasive renovation of age-related macular degeneration

The current treatment of wet age-related macular degeneration (wAMD) relies on monthly intravitreal or intravenously injection of vascular endothelial growth factor (VEGF) inhibitor or photodynamic (PDT) agents to inhibit choroidal neovascularization. However, traumatic local therapy and exogenous long-distance fundus drug delivery often lead to secondary eye damage, low treatment efficiency, and immunogenic inflammation. Herein, inspired by the natural neovascular targeting ability of endogenous low-density lipoproteins (LDL), a noninvasive bionic nano-eye-drop with enhanced ocular penetrability and lesion recognizability is developed for enabling the PDT treatment of wAMD. Verteporfin (VP) as a laser-induced PDT agent is protected inside the hydrophobic core of reconstituted LDL (rLDL) vectors. 5-carboxyfluorescein (FAM) conjugated ste-penetratin (PEN, a transmembrane peptide) is anchored on the surface of the rLDL carrier, which enabled the nanoparticles (PEN-rLDL-VP) to cross the blood-retina barrier to realizing visual therapy. Following instillation, PEN-rLDL-VP can effectively deliver VP into neovascular that overexpress LDL receptors, which can respond to laser-induced PDT. Only with a single dose of the eye-drop and laser-induced PDT, the VEGF and proinflammatory intercellular adhesion molecule-1 (ICAM-1) proteins are significantly down-regulated in vivo, which implicates the neovascular inhibition and inflammation alleviation. This study presents an attractive non-invasive strategy for the PDT of wAMD.

TheNeed for Treatment of Neovascular Age-Related Macular Degeneration: A Study Based on the Polish National Registry.

IntroductionThe Polish National AMD Therapeutic Program offered us a unique opportunity to determine the need for treatment of neovascular age-related macular degeneration (nAMD).MethodsA search, extraction, and analysis of data from the monitoring system of the Therapeutic Program of the National Health Fund was performed. Demographic data from the Central Statistical Office were also obtained and analyzed. All national data, and from the Silesian Voivodeship specifically, from patients who had received treatment prior to January 14, 2022 (57,876 eyes) were analyzed.ResultsApproximately 0.1% of the Polish population requires treatment for nAMD when the best-corrected visual acuity (BCVA) criteria exclude irreversible severe changes in the fovea (0.2–0.8 by Snellen). There were 30,771 eyes in the therapeutic program in January 2022, and 4898 (15.9%) of them were in Silesia, which contains 11.7% of the total population and 12.4% of the elderly population (65 years of age and older). However, as a result of the COVID-19 pandemic, the average number of monthly enrollments in the therapeutic program decreased from 717 in the first quarter of 2020 to 505 in the second quarter (with a low of 407 in April). Moreover, in 2020, a negative balance was recorded between included and excluded patients.ConclusionThe need for nAMD treatment in the elderly community (65 years of age and older) is estimated to be 0.55–0.66%.

Novel Treatments for Age-Related Macular Degeneration: A Review of Clinical Advances in Sustained Drug Delivery Systems.

In recent years, the number of patients with ocular diseases is increasing as a consequence of population aging. Among them, one of the most common is the age-related macular degeneration (AMD), a condition that leads to vision loss if it is not treated. AMD is a multifactorial disorder with two advanced forms, dry and neovascular AMD. Currently, although there is no approved therapy that significantly impacts dry AMD progression, several pharmacologic therapies exist for neovascular AMD. Notwithstanding, evidence suggests a suboptimal result in a high number of patients receiving these therapeutic options. Consequently, finding effective strategies is not only a still unmet medical need in dry AMD but also in neovascular AMD. This underlines the need for new drug delivery technologies that can improve the pharmacological action and drug concentration at the target sites. In this regard, sustained drug delivery systems are presented as the most promising therapeutic options in AMD patients. This review summarized the pathogenesis and the current treatment options for AMD, focusing on the emerging ocular sustained drug delivery approaches undergoing clinical trials.

The Role of Dysregulated miRNAs in the Pathogenesis, Diagnosis and Treatment of Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an eye disease causing damage to the macular region of the retina where most of the photoreceptors responsible for central visual acuity are located. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by silent post-transcriptional gene expressions. Previous studies have shown that changes in specific miRNAs are involved in the pathogenesis of eye diseases, including AMD. Altered expressions of miRNAs are related to disturbances of regulating oxidative stress, inflammation, angiogenesis, apoptosis and phagocytosis, which are known factors in the pathogenesis of AMD. Moreover, dysregulation of miRNA is involved in drusen formation. Thus, miRNAs may be used as potential molecular biomarkers for the disease and, furthermore, tailoring therapeutics to particular disturbances in miRNAs may, in the future, offer hope to prevent irreversible vision loss. In this review, we clarify the current state of knowledge about the influence of miRNA on the pathogenesis, diagnosis and treatment of AMD. Our study material consisted of publications, which were found in PubMed, Google Scholar and Embase databases using “Age-related macular degeneration”, “miRNA”, “AMD biomarkers”, “miRNA therapeutics” and “AMD pathogenesis” as keywords. Paper search was limited to articles published from 2011 to date. In the section “Retinal, circulating and vitreous body miRNAs found in human studies”, we limited the search to studies with patients published in 2016–2021.

Association between Polymorphisms in CFH, ARMS2, CFI, and C3 Genes and Response to Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. The gold standard of nAMD treatment is intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Genetic factors may influence the response to anti-VEGF therapy and result in a high degree of response variability. The aim of the study was to evaluate the association of the polymorphisms in genes related to the complement system (rs2285714-CFI, rs10490924-ARMS2, rs2230199-C3, rs800292-CFH, and rs6677604-CFH) with nAMD its clinical features and optical coherent tomography (OCT) biomarkers of treatment response to anti-VEGF therapy. Genotyping by allele-specific PCR was performed in 193 AMD patients and 147 age-matched controls. A prospective study of the dynamics of changes in OCT biomarkers during aflibercept treatment included 110 treatment-naive patients. Allele T rs10490924 was associated with the increased risk of nAMD. For both rs800292 and rs6677604, carriage of the A allele was protective and decreased the nAMD risk. Associations of rs2230199 with central retinal thickness (CRT) and intraretinal cysts were revealed. The height of pigment epithelium detachment and the height of neuroretinal detachment were significantly higher in carriers of the minor allele of rs2285714, both at baseline and during treatment. The reduction of CRT was associated with higher CRT at baseline and the presence of the T allele of rs2285714. By the end of one-year follow-up the patients homozygous for the minor allele rs2285714 had significantly higher odds of the presence of anastomoses and loops and active neovascular membrane. Furthermore, minor allele carriers had decreased levels of complement factor I level in aqueous humor but not in the plasma, which may be due to the influence of rs2285714 on tissue-specific splicing. Our results suggest that the severity of AMD macular lesions is associated with rs2285714 and rs2230199 polymorphisms, which could be explained by their high regulatory potential. Patients with the minor allele of rs2285714 respond worse to antiangiogenic therapy.

A detailed density functional theory investigation on physicochemical properties of ciclopirox derivatives: A potential candidate for prevention of age-related macular degeneration

Structural, electronic and spectral data such as intramolecular hydrogen bonding interaction, HOMO, LUMO energies, reactivity indices, molecular electrostatic potential maps, aromaticity indices, 1HNMR and 13CNMR of ciclopirox derivatives 1-7 as antifungal agents and efficient compounds for treatment and prevention of age-related macular degeneration were calculated using B3LYP/6-311+G(d, p) method and interpreted in detail. Their antioxidant properties were also investigated by three mechanisms. The results show that the antioxidant activity of ciclopirox derivatives 1-7 is higher than phenol as the reference molecule. Finally, the interaction of ciclopirox 3 with metals cations Mn+ was investigated by DFT calculations. The calculated cation affinity for 3 increases as Cu+<Fe2+< Cu2+<Fe3+. Cation affinity is strongly dependent on the charge-to-size ratio of the Mn+.

Brachytherapy for Central Serous Chorioretinopathy.

Brachytherapy is widely used for the treatment of choroidal melanoma and has recently been explored for the treatment of wet age-related macular degeneration. We propose the use of low dose radiation via episcleral brachytherapy in refractory cases of central serous chorioretinopathy (CSCR). The pathogenesis of CSCR involves dilatation and hyperpermeability of large choroidal vessels. Low dose radiation can induce intimal proliferation in large choroidal vessels and decrease their hyperpermeability. Concerns about the use of brachytherapy in CSCR include damage to the choriocapillaris or the retinal vessels. This can be addressed with the use of a specialized device through which a very precise and appropriate dose can be delivered. The dose of the radiation delivered decreases exponentially at a depth of approximately 0.5–1.5 mm from the devise–sclera interface. Considering an increased choroidal thickness in cases of CSCR, delivery of a safe dose can be assured.

The importance of monitoring wet age-related macular degeneration patients during Coronavirus disease 19 pandemic: A retrospective study of assessment of functional and structural outcomes

ObjectivesIntravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2).MethodsWet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of ≥ 5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit.Main resultsGroup 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P = 0.04, P < 0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P = 0.03 and P = 0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome.ConclusionsThe cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained.

New Prospects for Retinal Pigment Epithelium Transplantation.

Retinal pigment epithelium (RPE) transplants rescue photoreceptors in selected animal models of retinal degenerative disease. Early clinical studies of RPE transplants as treatment for age-related macular degeneration (AMD) included autologous and allogeneic transplants of RPE suspensions and RPE sheets for atrophic and neovascular complications of AMD. Subsequent studies explored autologous RPE-Bruch membrane-choroid transplants in patients with neovascular AMD with occasional marked visual benefit, which establishes a rationale for RPE transplants in late-stage AMD. More recent work has involved transplantation of autologous and allogeneic stem cell-derived RPE for patients with AMD and those with Stargardt disease. These early-stage clinical trials have employed RPE suspensions and RPE monolayers on biocompatible scaffolds. Safety has been well documented, but evidence of efficacy is variable. Current research involves development of better scaffolds, improved modulation of immune surveillance, and modification of the extracellular milieu to improve RPE survival and integration with host retina.

Phloretin inhibits glucose transport and reduces inflammation in human retinal pigment epithelial cells

During age-related macular degeneration (AMD), chronic inflammatory processes, possibly fueled by high glucose levels, cause a breakdown of the retinal pigment epithelium (RPE), leading to vision loss. Phloretin, a natural dihydroxychalcone found in apples, targets several anti-inflammatory signaling pathways and effectively inhibits transporter-mediated glucose uptake. It could potentially prevent inflammation and cell death of RPE cells through either direct regulation of inflammatory signaling pathways or through amelioration of high glucose levels. To test this hypothesis, ARPE-19 cells were incubated with or without phloretin for 1 h before exposure to lipopolysaccharide (LPS). Cell viability and the release of pro-inflammatory cytokines interleukin 6 (IL-6), IL-8 and vascular endothelial growth factor (VEGF) were measured. Glucose uptake was studied using isotope uptake studies. The nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were determined alongside the phosphorylation levels of mitogen-activated protein kinases. Phloretin pretreatment reduced the LPS-induced release of IL-6 and IL-8 as well as VEGF. Phloretin increased intracellular levels of reactive oxygen species and nuclear translocation of Nrf2. It also inhibited glucose uptake into ARPE-19 cells and the phosphorylation of Jun-activated kinase (JNK). Subsequent studies revealed that Nrf2, but not the inhibition of glucose uptake or JNK phosphorylation, was the main pathway of phloretin’s anti-inflammatory activities. Phloretin was robustly anti-inflammatory in RPE cells and reduced IL-8 secretion via activation of Nrf2 but the evaluation of its potential in the treatment or prevention of AMD requires further studies.

Survey of Intravitreal Injection Preferences for the Treatment of Age-Related Macular Degeneration and Macular Edema Among Members of the Turkish Ophthalmological Association

Objectives:To analyze the current preferences of ophthalmologists for the treatment of macular edema and age-related macular degeneration (AMD) and to evaluate off-label use of bevacizumab in Turkey.Materials and Methods:All members of the Turkish Ophthalmological Association were contacted by e-mail to complete an anonymous, 47-question internet-based survey. The second part of the survey (questions 36-47) was evaluated.Results:When current legal regulations were considered, ophthalmologists used bevacizumab as the first-line agent in patients with diabetic macular edema (DME), AMD, and retinal vein occlusion (RVO) (58.25%, 55.89%, and 52.29%, respectively). When economic and legal constraints were disregarded, the participants’ preference for bevacizumab in the treatment of DME, AMD, and RVO decreased (11.64%, 10.58%, and 10.93%, respectively). Approximately three-quarters (75.75%) of ophthalmologists stated that dispensing multiple syringes from a single bevacizumab bottle could increase the risk of endophthalmitis. Most participants (93.68%) did not feel legally safe from harm caused by off-label bevacizumab use. However, 66.43% of ophthalmologists stated that bevacizumab is as effective as other anti-vascular endothelial growth factor (anti-VEGF) drugs.Conclusion:Bevacizumab is widely used as a first-line treatment for all indications of anti-VEGF use in the current reimbursement conditions, which preclude the right of ophthalmologists to treat according to their own preferences.