Exudative Age-related Macular Degeneration Research Articles

Investigating the impact of tadalafil on progression of age-related macular degeneration: a health insurance claims database analysis

PurposeTo assess the effect of tadalafil use on progression of early/intermediate to advanced exudative or non-exudative age-related macular degeneration (AMD) in a real-world population. DesignRetrospective cohort study utilizing Optum's de-identified Clinformatics® Data Mart Database (CDM). MethodsPatients were included from January 2015 to December 2020 aged 55 and older with an index International Classification of Diseases, Tenth Revision (ICD-10) diagnosis of early or intermediate AMD who had a 2-year period of continuous enrollment prior to the index diagnosis date (lookback period), 5 years of continuous follow-up, and who did not meet any exclusion criteria (claims for a phosphodiesterase-5 (PDE-5) inhibitor other than tadalafil during the study, diagnosis of advanced non-exudative or exudative AMD, or claims for exudative AMD treatment during the lookback period). Treated patients with claims for tadalafil during the study period were matched 1:1 to untreated controls by age, sex, race, and smoking status. We assessed the effect of any tadalafil use, high (≥2700 mg) cumulative dose tadalafil vs. matched untreated controls, high (>2700 mg) vs. low (≤2700 mg) cumulative dose tadalafil, and the 2-year cumulative dose of tadalafil (per 100 mg) as a continuous variable on incidence of progression to exudative or advanced non-exudative AMD during the 2-year follow-up. ResultsThere was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD in the control vs treated groups (OR = 0.802, 95% CI (0.558–1.152), p = 0.233; OR = 1.326, 95% CI (0.757–2.323), p = 0.323). High (≥2700 mg) cumulative dose tadalafil was not associated with a significant difference in odds of progression to exudative AMD or advanced non-exudative AMD when compared to the matched controls (OR = 0.455, 95% CI (0.202–1.025), p = 0.057; OR = 1.000, 95% CI (0.318–3.142), p = 1.000). There was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD in the high (>2700 mg) vs. low (≤2700 mg) cumulative dose tadalafil (OR = 0.590, 95% CI (0.296–1.177), p = 0.134; OR = 1.039, 95% CI (0.440–2.460), p = 0.931). Lastly, there was no significant difference in odds of progression to exudative AMD or advanced non-exudative AMD when assessing the 2-year cumulative tadalafil dose (per 100 mg) as a continuous variable (OR = 1.000, 95% CI (1.000–1.000), p = 0.305; OR = 1.000, 95% CI (1.000–1.000), p = 0.878). ConclusionIn a retrospective cohort study of a large nationwide health insurance claims database, tadalafil use was not associated with progression of AMD.

Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD, also known as exudative or neovascular AMD, is less common but more severe than dry AMD and is responsible for 90% of the visual impairment caused by AMD and affects 20 million people worldwide. Current treatment options mainly involve biologics that inhibit the vascular endothelial growth factor or complement pathways. However, these treatments have limitations such as high cost, injection-related risks, and limited efficacy. Therefore, new therapeutic targets and strategies have been explored to improve the outcomes of patients with AMD. A promising approach is the use of small-molecule drugs that modulate different factors involved in AMD pathogenesis, such as tyrosine kinases and integrins. Small-molecule drugs offer advantages, such as oral administration, low cost, good penetration, and increased specificity for the treatment of wet and dry AMD. This review summarizes the current status and prospects of small-molecule drugs for the treatment of wet AMD. These advances are expected to support the development of effective and targeted treatments for patients with AMD.

Intraoperative OCT-Guided Volumetric Measurements of Subretinal Therapy Delivery in Humans.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm2 in Patient 1, 55 mm2 in Patient 2, and 106 mm2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.

Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.

P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting. This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD. There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients. We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.

Human versus Artificial Intelligence: Validation of a Deep Learning Model for Retinal Layer and Fluid Segmentation in Optical Coherence Tomography Images from Patients with Age-Related Macular Degeneration.

Artificial intelligence (AI) models have received considerable attention in recent years for their ability to identify optical coherence tomography (OCT) biomarkers with clinical diagnostic potential and predict disease progression. This study aims to externally validate a deep learning (DL) algorithm by comparing its segmentation of retinal layers and fluid with a gold-standard method for manually adjusting the automatic segmentation of the Heidelberg Spectralis HRA + OCT software Version 6.16.8.0. A total of sixty OCT images of healthy subjects and patients with intermediate and exudative age-related macular degeneration (AMD) were included. A quantitative analysis of the retinal thickness and fluid area was performed, and the discrepancy between these methods was investigated. The results showed a moderate-to-strong correlation between the metrics extracted by both software types, in all the groups, and an overall near-perfect area overlap was observed, except for in the inner segment ellipsoid (ISE) layer. The DL system detected a significant difference in the outer retinal thickness across disease stages and accurately identified fluid in exudative cases. In more diseased eyes, there was significantly more disagreement between these methods. This DL system appears to be a reliable method for accessing important OCT biomarkers in AMD. However, further accuracy testing should be conducted to confirm its validity in real-world settings to ultimately aid ophthalmologists in OCT imaging management and guide timely treatment approaches.

Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.

The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown. In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.

Effects of slit lamp-delivered retinal laser photobiomodulation in a rat model of choroidal neovascularization

Neovascular age-related macular degeneration, also known as exudative or wet age-related macular degeneration, is the leading cause of blindness in the developed world. Photobiomodulation has the potential to target the up-stream hypoxic and pro-inflammatory drivers of choroidal neovascularization. This study investigated whether photobiomodulation attenuates characteristic pathological features of choroidal neovascularization in a rodent model.Experimental choroidal neovascularization was induced in Brown Norway rats with laser photocoagulation. A custom-designed, slit-lamp-mounted, 670 nm laser was used to administer retinal photobiomodulation every 3 days, beginning 6 days prior to choroidal neovascularization induction and continuing until the animals were killed 14 days later. The effect of photobiomodulation on the size of choroidal neovascular membranes was determined using isolectin-B4 immunohistochemistry and spectral domain-optical coherence tomography. Vascular leakage was determined with fluorescein angiography. The effect of treatment on levels of vascular endothelial growth factor expression was quantified with enzyme-linked immunosorbent assay.Treatment with photobiomodulation was associated with choroidal neovascular membranes that were smaller, had less fluorescein leakage, and a diminished presence of inflammatory cells as compared to sham eyes. These effects were not associated with a statistically significant difference in the level of vascular endothelial growth factor when compared to sham eyes.The data shown herein indicate that photobiomodulation attenuates pathological features of choroidal neovascularization in a rodent model by mechanisms that may be independent of vascular endothelial growth factor.

Sphingosine-1-phosphate receptor 1/5 selective agonist alleviates ocular vascular pathologies

Ocular abnormal angiogenesis and edema are featured in several ocular diseases. S1P signaling via S1P1 likely is part of the negative feedback mechanism necessary to maintain vascular health. In this study, we conducted pharmacological experiments to determine whether ASP4058, a sphingosine 1-phosphate receptor 1/5 (S1P1/5) agonist, is useful in abnormal vascular pathology in the eye. First, human retinal microvascular endothelial cells (HRMECs) were examined using vascular endothelial growth factor (VEGF)-induced cell proliferation and hyperpermeability. ASP4058 showed high affinity and inhibited VEGF-induced proliferation and hyperpermeability of HRMECs. Furthermore, S1P1 expression and localization changes were examined in the murine laser-induced choroidal neovascularization (CNV) model, a mouse model of exudative age-related macular degeneration, and the efficacy of ASP4058 was verified. In the CNV model mice, S1P1 tended to decrease in expression immediately after laser irradiation and colocalized with endothelial cells and Müller glial cells. Oral administration of ASP4058 also suppressed vascular hyperpermeability and CNV, and the effect was comparable to that of the intravitreal administration of aflibercept, an anti-VEGF drug. Next, efficacy was also examined in a retinal vein occlusion (RVO) model in which retinal vascular permeability was increased. ASP4058 dose-dependently suppressed the intraretinal edema. In addition, it suppressed the expansion of the perfusion area observed in the RVO model. ASP4058 also suppressed the production of VEGF in the eye. Collectively, ASP4058 can be a potential therapeutic agent that normalizes abnormal vascular pathology, such as age-related macular degeneration and RVO, through its direct action on endothelial cells.

CFH (rs1061170, rs1410996), KDR (rs2071559, rs1870377) and KDR and CFH Serum Levels in AMD Development and Treatment Efficacy.

Age-related macular degeneration (AMD) is a major global health problem as it is the leading cause of irreversible loss of central vision in the aging population. Av-vascular endothelial growth factor (anti-VEGF) therapies have been shown to be effective, but they do not respond optimally to all patients. This study investigates the genetic factors associated with susceptibility to AMD and response to treatment, focusing on key polymorphisms in the CFH (rs1061170, rs1410996) and KDR (rs2071559, rs1870377) genes and the association of CFH and KDR serum levels in patients with AMD. A cohort of 255 patients with early AMD, 252 patients with exudative AMD, and 349 healthy controls underwent genotyping analysis, which revealed significant associations between CFH polymorphisms and the risk of exudative AMD. The CFH rs1061170 CC genotype was associated with an increased risk of early AMD (p = 0.046). For exudative AMD, the CFH rs1061170 TC + CC genotype increased odds (p < 0.001), while the rs1410996 GA + AA genotype decreased odds (p < 0.001). Haplotypes of CFH SNPs were associated with decreased odds of AMD. In terms of response to treatment, none of the SNPs were associated with the response to anti-VEGF treatment. We also found that both early and exudative AMD patients had lower CFH serum levels compared to the control group (p = 0.038 and p = 0.006, respectively). Exudative AMD patients with the CT genotype of CFH rs1061170 had lower CFH serum levels compared to the control group (p = 0.035). Exudative AMD patients with the GG genotype of CFH rs1410996 also had lower CFH serum levels compared to the control group (p = 0.021). CFH polymorphisms influence susceptibility to AMD but do not correlate with a response to anti-VEGF therapy. Further research is imperative to fully evaluate the developmental significance, treatment efficacy, and predictive role in influencing susceptibility to anti-VEGF therapy for KDR and CFH.

Subretinal transient hyporeflectivity in neovascular age-related macular degeneration and its response to a loading phase of aflibercept: PRECISE report 4.

To describe the prevalence of subretinal transient hyporeflectivity (STHR) in exudative neovascular age-related macular degeneration (nAMD) and its response to a loading phase of aflibercept. Optical coherence tomography (OCT) scans of treatment-naïve nAMD patients captured at baseline and after a loading phase of aflibercept were graded for presence of STHR, defined as a small, well-defined, round, subretinal, hyporeflective area, delimited between the ellipsoid zone (EZ) and the retinal pigmented epithelium/Bruch membrane complex. OCT parameters recorded were macular neovascularisation (MNV) subtypes, location of retinal fluids (subretinal fluid, SRF and intraretinal fluid, IRF), central retinal and choroidal thickness. Response was defined as absence of IRF and SRF. Factors associated with completely resolved STHR versus persistent STHR post-loading phase were compared. 2039 eyes of 1901 patients were analysed. STHR was observed in 79 eyes of 78 patients, with an estimated prevalence of 3.87% (95% CI 3.08-4.81%). STHR were seen in 44 type 1 MNV (56%), 27 with type 2 (34%), and 8 with type 3 (10%). At baseline, a total of 303 STHR were present, ranging between 1-22 per eye. The total number of STHR reduced significantly after the loading phase to 173 (p = 0.002). Complete disappearance of STHR was seen in 44 eyes (56%) and persistent STHR in the rest (44%). STHR may represent a marker of low-grade exudation in nAMD eyes with good response to a loading phase of aflibercept. However, its potential role as an independent nAMD activity biomarker is limited as most resolve after the loading phase.

Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.

Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

Rediscovering Age-Related Macular Degeneration with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture

Swept-source OCT angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross sectional and en face imaging strategies. Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30,2022. Patients with AMD. Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. Swept-source OCT angiography imaging of AMD at different stages of disease progression. Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Giant retinal pigment epithelium tears with membranous nephropathy: a case report and literature review

BackgroundKidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy and light-chain deposition disease. However, pigment epithelium tears associated with membranous nephropathy have not been reported or systematically analysed.Case presentationA 68-year-old man presented with decreased right eye visual acuity. Optical coherence tomography (OCT) revealed cystic macular edema, localized serous detachment of the retina and loss of the outer retinal structure in the right eye and retinal pigment epithelium detachment (PED) combined with serous detachment of the retina in the left eye. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) revealed giant RPE tears in the right eye and exudative age-related macular degeneration in the left eye. The patient also suffered from severe membranous nephropathy-autoimmune glomerulonephritis. Renal biopsy immunofluorescence revealed a roughly granular pattern, with immunoglobulin G (IgA), immunoglobulin G (IgG), IgM, complement C3(Components 3), λ light chain and κ light chain subepithelial staining.ConclusionsIt is hypothesized that severe membranous nephropathy caused immune complex deposition on the surface of Bruch membrane, resulting in weakened adhesion between the RPE and Bruch membrane and impaired RPE pump function, combined with age-related macular degeneration, leading to giant RPE tears in the right eye. Close attention should be given to the ocular condition of patients with membranous nephropathy to facilitate timely treatment and avoid serious consequences.

The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.

The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8years). After 24months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p < 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51μM; p < 0.001) with 21% of eyes showing signs of exudation. Over the 24months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5weeks; p < 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9; p = 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1weeks; p < 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6; p = 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes. The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article. Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).

A Clinically Explainable AI-Based Grading System for Age-Related Macular Degeneration Using Optical Coherence Tomography.

We propose an automated, explainable artificial intelligence (xAI) system for age-related macular degeneration (AMD) diagnosis. Mimicking the physician's perceptions, the proposed xAI system is capable of deriving clinically meaningful features from optical coherence tomography (OCT) B-scan images to differentiate between a normal retina, different grades of AMD (early, intermediate, geographic atrophy (GA), inactive wet or active neovascular disease [exudative or wet AMD]), and non-AMD diseases. Particularly, we extract retinal OCT-based clinical imaging markers that are correlated with the progression of AMD, which include: (i) subretinal tissue, sub-retinal pigment epithelial tissue, intraretinal fluid, subretinal fluid, and choroidal hypertransmission detection using a DeepLabV3+ network; (ii) detection of merged retina layers using a novel convolutional neural network model; (iii) drusen detection based on 2D curvature analysis; (iv) estimation of retinal layers' thickness, and first-order and higher-order reflectivity features. Those clinical features are used to grade a retinal OCT in a hierarchical decision tree process. The first step looks for severe disruption of retinal layers' indicative of advanced AMD. These cases are analyzed further to diagnose GA, inactive wet AMD, active wet AMD, and non-AMD diseases. Less severe cases are analyzed using a different pipeline to identify OCT with AMD-specific pathology, which is graded as intermediate-stage or early-stage AMD. The remainder is classified as either being a normal retina or having other non-AMD pathology. The proposed system in the multi-way classification task, evaluated on 1285 OCT images, achieved 90.82% accuracy. These promising results demonstrated the capability to automatically distinguish between normal eyes and all AMD grades in addition to non-AMD diseases.

The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.

Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Objective or PurposeA) To characterize the incidence of kidney failure associated with intravitreal anti-vascular endothelial growth factor (VEGF) exposure, and B) compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DesignRetrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. Subjects, Participants, and/or ControlsSubjects aged ≥18 years with ≥3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). Methods, Intervention, or TestingA) The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. B) For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random-effects meta-analysis was performed to combine each database’s hazard ratio (HR) estimate into a single network-wide estimate. Main Outcome MeasuresIncidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. ResultsOf the 6.1 million patients with blinding diseases, 37,189 who received ranibizumab, 39,447 aflibercept, and 163,611 bevacizumab were included; the total treatment exposure time was 161,724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100,000 persons (range 0 to 2389), and incidence rate 743 per 100,000 person-years (0 to 2661). The meta-analysis HR of kidney failure comparing aflibercept to ranibizumab was 1.01 (95% confidence interval (CI) 0.70, 1.47, p=0.45), ranibizumab to bevacizumab 0.95 (95% CI 0.68, 1.32, p=0.62), and aflibercept to bevacizumab 0.95 (95% CI 0.65, 1.39, p=0.60). ConclusionsThere was no substantially different relative risk for kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk for kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.

Long-term Follow-Up and Regeneration of Retinal Pigment Epithelium (RPE) after Tears of the Epithelium in Exudative Age-Related Macular Degeneration (AMD).

The goals of this study are to evaluate potential long-term visual deterioration associated with retinal pigment epithelial (RPE) tears in patients with neovascular age-related macular degeneration (nAMD) and to find treatment-related and morphological factors that might influence the outcomes. This retrospective study enrolled 21 eyes of 21 patients from the database of Vista Eye Clinic Binningen, Switzerland, diagnosed with RPE tears, as confirmed by spectral domain optical coherence tomography (SD-OCT), with a minimum follow-up period of 12 months. Treatment history before and after RPE rupture with anti-VEGF therapy, visual acuity, and imaging (SD-OCT) were analyzed and statistically evaluated for possible correlations. Mean patient age was 80.5 ± 6.2 years. The mean length of total follow-up was 39.7 ± 13.9 months. The mean pigment epithelial detachment (PED) height increased by 363.8 ± 355.5 µm from the first consultation to 562.8 ± 251.5 µm at the last consultation prior to rupture. Therefore, a higher risk of RPE rupture is implied as a result of an increase in PED height (p = 0.004, n = 14). The mean visual acuity before rupture was 66.2 ± 16.0 letters. Mean visual acuity deteriorated to 60.8 ± 18.6 letters at the first consultation after rupture (p = 0.052, n = 21). A statistically nonsignificant decrease in vision was noted in the follow-up period. After 2 years, the mean BCVA decreased by 10.5 ± 23.7 ETDRS letters (p = 0.23, n = 19). PED characteristics before rupture and amount of anti-VEGF injections after rupture did not affect the visual outcome. None of the 21 patients included in our study showed a visual improvement in the long-term follow-up. RPE atrophy increased significantly from 3.35 ± 2.94 mm2 (baseline) to 6.81 ± 6.25 mm2 over the course of 2 years (p = 0.000 013, n = 20). The overall mean vision decrease after rupture was without statistical significance. There was no significant change in BCVA at the 2-year follow-up, independent of the amount of anti-VEGF injections provided. In this study, there was a significant increase in RPE defect over a follow-up of 2 years, implying progression of contraction of RPE and/or macular atrophy.

Relative yield of retinal imaging versus clinical exam in following neovascular exudative age related macular degeneration.

To compare therapeutic decisions between 3 diagnostic protocols and to assess the need for in-person physical doctor-patient encounter in follow up and treatment of neovascular exudative age-related macular degeneration (AMD). Analysis of 88 eyes of 88 unique patients with neovascular AMD who were routinely followed at our medical retina clinic. A retinal specialist reviewed all images in advance and wrote his decisions. He later attended an in-person encounters with all patients and documented his decisions. Masking was done by not exposing any identifying information to the specialist and by randomizing patient's images order before the in-person encounter. Therapeutic decisions regarding intravitreal injections intervals and agent selection were made based on three protocols: (1) optic coherence tomography (OCT); (2) OCT/Ultra-widefield (UWF) color image; (3) OCT/UWF/full clinical exam. Visual acuity (VA) was incorporated into all protocols. We found an agreement of 93% between those protocols regarding the intervals of injections, and of 100% regarding injection agent selection. When comparing OCT, OCT/UWF and OCT/UWF/clinical exam guided decision making, there were no discrepancies between OCT and OCT/UWF. There were 6 out of 88 discrepancies (7%) between OCT/UWF and OCT/UWF/clinical exam. Of those 6 discrepancies, all were regarding intervals (Bland-Altman bias = - 0.2386). All discrepancies between OCT/UWF and OCT/UWF/Clinical exam were due to patients' preferences, socioeconomic issues and fellow eye considerations, addressed during the face-to-face encounter with patients. Physical examination itself did not affect decision making. Neovascular exudative AMD follow up and treatment decisions can be guided by VA and OCT, with UWF adding important information regarding macula and peripheral retina, but rarely affecting decision making. However, decision making may also be driven by patients' preferences and other considerations that are being made only during the face-to-face visit and discussion. Thus, every approach supporting imaging only decision making, must take these factors into account.

Brolucizumab effectiveness in pigment epithelium detachment due to exudative AMD in naïve treatment or non-responder patients.

To investigate outcomes after Brolucizumab injection in naïve treatment or non-responder patients with exudative age-related macular degeneration (AMD). It is a retrospective, comparative, cohort study conducted at the tertiary referral center of the University Hospital Polyclinic of Bari, for 5 years, from November 2017 until May 2022. 41 eyes with wet-AMD (w-AMD) were included, undergoing anti-vascular endothelial growth factor (VEGF) intravitreal injections. The sample was divided into two groups, the Bro-Switch group, and the Bro-Naïve group. The Bro-Switch group previously received a slot of other anti-VEGF intravitreal drugs. The Bro-Naïve group received Brolucizumab (Bro) as the first treatment. The pigment epithelium detachment (PED) and the best-corrected visual acuity (BCVA) outcomes before and after Bro-injection were evaluated. A significant reduction in PED measurement was registered in all eyes treated with Bro-injection (p = 0.35). The Bro-Naïve group improved better in PED measurement (mean difference: 297.92 ± 72,32) as compared to the Bro-Switch group (mean difference: 185.06 ± 11.07). On the contrary, no significant reduction in BCVA in the two groups was recorded (p = 0.66). We suggest Bro-injection for w-AMD as effective anatomical outcomes in PED flattening, but not similar in visual results. Although this study evaluated short-term outcomes, the hopeful results can lead to interesting medium-long time effects.