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Background To analyze the therapeutic response to faricimab 6 mg/0.05 ml in eyes with neovascular AMD (nAMD) with refractory intra- and/or subretinal fluid due to choroidal neovascularization (CNV), previously unresponsive to 4 mg monthly aflibercept and combination therapy with anti-VEGF and long-acting steroids. Methods A retrospective case series study of 22 eyes with unresponsive CNV, despite monthly intravitreal treatment (mean number of pre-faricimab injections: 35.52 ± 17.12). We evaluated therapeutic response in eyes with persistent intra/subretinal fluid (IRF/SRF) unresponsive to anti-VEGF double-dose (DD) monotherapy (4-mg aflibercept) and/or simultaneous DD anti-VEGF (4-mg aflibercept) with steroids (triamcinolone). Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and optical coherence tomography (OCT) measurements of central retinal thickness (CRT) were recorded for 7 follow-ups. Baseline and follow-up OCTs were examined by an AI-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland) to measure the volume of IRF, SRF, and pigment epithelium detachment (PED) in nanoliters (nL) and CRT in micrometers (μm). Paired t-test compared these parameters at baseline and after treatment. OCTA analysis of CNV before and after treatment with faricimab was conducted using Angio-Tool software. Results Anatomic outcomes included mean CRT reduction of -25.3 μm (p = 0.0118) at month-1, -16.15 μm (p = 0.0414) at month-4, and -26.36 μm (p = 0.0129) after the 7th follow-up. AI-assisted software analysis showed a significant reduction of IRF, SRF, and PED volume at multiple time points after initiating faricimab. There was a non-significant improvement in BCVA. Conclusions Switching to faricimab improved anatomy in highly treatment-resistant CNV eyes, indicating its potential when other therapeutic options have failed.

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

Age-related macular degeneration (AMD) was described for the first time in the 1840s and is currently the leading cause of blindness for patients over 65 years in Western Countries. This disease impacts the eye’s posterior segment and damages the macula, a retina section with high levels of photoreceptor cells and responsible for the central vision. Advanced AMD stages are divided into the atrophic (dry) form and the exudative (wet) form. Atrophic AMD consists in the progressive atrophy of the retinal pigment epithelium (RPE) and the outer retinal layers, while the exudative form results in the anarchic invasion by choroidal neo-vessels of RPE and the retina. This invasion is responsible for fluid accumulation in the intra/sub-retinal spaces and for a progressive dysfunction of the photoreceptor cells. To date, the few existing anti-AMD therapies may only delay or suspend its progression, without providing cure to patients. However, in the last decade, an outstanding number of research programs targeting its different aspects have been initiated by academics and industrials. This review aims to bring together the most recent advances and insights into the mechanisms underlying AMD pathogenicity and disease evolution, and to highlight the current hypotheses towards the development of new treatments, i.e., symptomatic vs. curative. The therapeutic options and drugs proposed to tackle these mechanisms are analyzed and critically compared. A particular emphasis has been given to the therapeutic agents currently tested in clinical trials, whose results have been carefully collected and discussed whenever possible.

Background Significant diurnal fluctuation of optical coherence tomography (OCT)-based macular fluid occurs in patients with several macular conditions including diabetic macular edema (DME) and cystoid macular edema due to retinal venous occlusion (RVO). OCT imaging and analysis of macular fluid status plays a central role in clinical management of exudative age-related macular degeneration (eAMD), however diurnal variation of eAMD OCT findings has not yet been formally studied. Herein, we investigate whether clinically meaningful fluctuation of OCT-based macular fluid occurs in patients with eAMD. Methods Prospective observational study. Patients with eAMD and intra- and/or sub-retinal fluid on early AM OCT were enrolled to receive two consecutive OCT scans at least four hours later. Retinal layers were manually segmented on all OCT rasters and AM-to-PM and PM-to-PM image pairs were analyzed for total retinal and neurosensory retinal volume changes within the central 1 and 3 mm ETDRS subfields. Finally, two masked retinal specialists analyzed all OCT image pairs for qualitative differences that may impact clinical management. Results 21 patients with eAMD and fluid on OCT were recruited between January 2020 and November 2021. There was no mean difference between AM and PM central 3 mm total retinal volume (p = 0.56), central 3 mm neurosensory retinal volume (p = 0.25), central 1 mm total retinal mean thickness (p = 0.96), or central 1 mm neurosensory retinal mean thickness (p = 0.63), nor were any differences identified in PM-to-PM control comparisons. Qualitative analysis by two masked experts identified no clinically significant differences between any AM-to-PM OCT image pairs. Conclusions No significant diurnal variation in OCT-based macular fluid or thickness was identified in patients with eAMD, either quantitatively or qualitatively.

Purpose: The aim of this study was to establish the prevalence and association of age-related macular degeneration (AMD) and obesity which was not studied extensively in Indian population over 60 years of age. Methods: This was a cross-sectional, population-based study. A total of 4791 patients with gradable fundus photography were included. All patients underwent detailed ophthalmic examination and AMD was graded with retinal photographs. Grading of AMD was done according to the International ARM Epidemiological Study Group and staged based on grading in worse eye. The association of AMD severity and obesity (based on body mass index, waist-hip ratio, waist circumference, isolated abdominal obesity, isolated generalized obesity, and combined obesity) was assessed. The main outcome variable was an association between the presence and severity of AMD with different grades of obesity. Results: No direct significant association was noted between the presence and severity of AMD and any obesity indices. Subgroup analyses based on lifestyle patterns and common systemic pathologies in AMD population were done. Late AMD was significantly associated with tobacco consumption in population with combined obesity (P = 0.033 and odds ratio = 2.998). Conclusion: No direct association was noted between the presence or severity of AMD and obesity in South Indian population. However, indirect associations between the severity of AMD and combined obesity were found.

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number.

IntroductionRanibizumab (Lucentis), a humanised antibody fragment that inhibits vascular endothelial growth factor (VEGF)-A, is widely used for the treatment of neovascular age-related macular degeneration (NV-AMD). The objective of this study was to compare the outcomes of two different treatment protocols: loading dose (LD) and pro re nata (PRN (as needed)) dosing schedule from baseline.MethodsThis retrospective chart review was conducted at King's College Hospital, London, UK. Consecutive patients were identified using the ‘Ranibizumab in NV-AMD’ database. These patients had treatment-naive choroidal neovascularisation (CNV) secondary to AMD, received ranibizumab therapy and had completed 12 months of follow-up. Baseline examination included visual acuity (Early Treatment Diabetic Retinopathy Study (ETDRS) letters), slit-lamp biomicroscopy, fluorescein angiography, and qualitative and quantitative assessment of central macular characteristics on optical coherent tomography (OCT). Intravitreal ranibizumab (0.5 mg/0.05 ml) was given to all patients at baseline. Patients on LD regimen received two further consecutive monthly intravitreal ranibizumab injections independent of clinical findings. Further injections were determined by the same re-treatment criteria as patients on PRN schedule from baseline. The main outcome variables in the two treatment groups were visual acuity and central macular thickness at different time points.ResultsThe LD group contained 47 patients and the PRN group contained 31 patients. There were no significant differences between groups in the mean changes in visual acuity or central macular thickness. Visual acuity was similar in both groups at 6 months. However, twice as many patients improved visual acuity by 15 or more letters in the LD group (29.8% in the LD group compared with 12.9% in the PRN group (p=0.01)).ConclusionThis study showed that standard protocols used for OCT-guided retreatment achieved smaller mean gains in vision than those obtained with monthly ranibizumab administration. Further, loading doses of ranibizumab resulted in more visual gains than the PRN protocol.

Purpose To identify preference of treatment regimen in patients with anti-VEGF therapy for neovascular age-related macular degeneration (AMD) in real life. Methods A cross-sectional study was conducted in 200 patients receiving ranibizumab therapy on a pro re nata regimen with monthly controls. One hundred and twenty-four patients were recruited in a tertiary health care clinic, and 76 patients were recruited in a private practice. Patients were asked to respond to a 14-item questionnaire covering items such as treatment burden and preference for treatment: either monthly injections or pro re nata. Results Mean time under anti-VEGF treatment was 33.7 months, and the mean number of intravitreal injections was 17.7. Despite a high treatment burden in 60.3 % of patients, there was an acceptance rate for monthly examinations or injections of 93 %. The proportion of patients who favoured a PRN regimen was 53.0 %, whereas 37.9 % of patients favoured continuous injections. Major concern was recurrent disease activity in 54.5 %. Conclusion We identified two groups of patients of considerable size who would prefer either monthly injections or as-required. Overall, there was a high acceptance rate despite a high treatment burden. Nevertheless, efforts should be undertaken to improve examination and injection procedures and to consider the patient’s preference for a treatment regimen.

To assess the 12-month outcomes of intravitreal faricimab (IVF) in treatment-resistant neovascular age-related macular degeneration (nAMD) subjects recalcitrant to intravitreal aflibercept (IVA). This study was conducted as a retrospective interventional case series of nAMD patients receiving treatment at a single private practice institution. All included patients at baseline had undergone six or more IVA injections over the previous 12 months, four or more IVA injections over the previous 6 months, had a central macular thickness (CMT) ≥320 µm on optical coherence tomography (OCT), and were observed to have intraretinal and/or subretinal fluid on OCT assessment. The baseline exam for the purpose of this study was considered the visit in which the patient was switched from IVA to IVF. Patients were managed with a real-world treat-and-extend protocol and followed over a 12-month study period. A total of 54 eyes of 54 subjects were analyzed. Overall, 31.5% (17/54) of subjects attained a treatment interval ≥8 weeks and had a fluid-free macula on OCT at 12 months. The CMT on OCT decreased from 395.4 (383.5-407.3) µm at baseline to 350.0 (335.1-364.8) µm at the end of the 12-month study interval ( <0.01). There were 16.7% (9/54) of subjects who gained three or more lines of Snellen visual acuity at the end of the study. Visual acuity improved from 0.72 (0.67-0.77) logMAR (Snellen 20/105) at baseline to 0.59 (0.55-0.64) logMAR (Snellen 20/78) at the end of the study ( <0.01). A clinically significant minority of aflibercept-resistant nAMD subjects may attain longer treatment intervals and improved outcomes at 12 months after switching to IVF when a treat-and-extend treatment protocol is utilized. IVF use may be considered whenever resistance to IVA is encountered in this patient population.