Exudative Age-related Macular Degeneration Research Articles

INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?

Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment in the elderly. The current management of nAMD is limited and involves regular intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF). However, the effectiveness of these treatments is limited by overlapping and compensatory pathways leading to unresponsiveness to anti-VEGF treatments in a significant portion of nAMD patients. Therefore, a system view of pathways involved in pathophysiology of nAMD will have significant clinical value. The aim of this study was to identify proteins, miRNAs, long non-coding RNAs (lncRNAs), various metabolites, and single-nucleotide polymorphisms (SNPs) with a significant role in the pathogenesis of nAMD. To accomplish this goal, we conducted a multi-layer network analysis, which identified 30 key genes, six miRNAs, and four lncRNAs. We also found three key metabolites that are common with AMD, Alzheimer's disease (AD) and schizophrenia. Moreover, we identified nine key SNPs and their related genes that are common among AMD, AD, schizophrenia, multiple sclerosis (MS), and Parkinson's disease (PD). Thus, our findings suggest that there exists a connection between nAMD and the aforementioned neurodegenerative disorders. In addition, our study also demonstrates the effectiveness of using artificial intelligence, specifically the LSTM network, a fuzzy logic model, and genetic algorithms, to identify important metabolites in complex metabolic pathways to open new avenues for the design and/or repurposing of drugs for nAMD treatment.

Diagnosing Polypoidal Choroidal Vasculopathy using Color Fundus Photography, Optical Coherence Tomography and Optical Coherence Tomography Angiography.

To compare the diagnostic accuracy of differentiating polypoidal choroidal vasculopathy (PCV) from exudative age-related macular degeneration (AMD), using color fundus photography (CFP), optical coherence tomography (OCT), and swept-source optical coherence tomography angiography (SS-OCTA) without using fluorescein angiography/ indocyanine green angiography (FA/ICGA). Treatment-naïve eyes with exudative age-related macular degeneration (AMD) that underwent CFP, OCT, SS-OCTA, and FA/ICGA imaging before treatment were identified. Images of each patient were categorized into 2 sets (Set A: CFP+OCT; Set B: CFP+ SS-OCTA). In Set B, both the en face and cross-sectional B-scans were analyzed. Each set was reviewed by two graders, and it was determined whether the presumed diagnosis was PCV. Sensitivity, specificity, and area under the curve (AUC) for the diagnosis of PCV were assessed for each set by comparing diagnoses that included ICGA. The number of polypoidal lesions in each set was calculated and compared to ICGA. A total of 94 study eyes from 94 patients with AMD were included in the study, of which 66.0% were male, and the mean age was 71.8±9.0 years. The PCV diagnosis rate using ICGA was 45.7%. Sensitivity of sets A, B: 0.88, 0.93; specificity: 0.94, 0.96; positive predictive value: 0.93, 0.95; negative predictive value: 0.91, 0.94, AUC: 0.90 (95% confidence interval [CI]:0.83-0.97), 0.96 (95% CI:0.90-1.00). Set A detected polypoidal lesions 1.28±0.91, Set B detected polypoidal lesions 1.47±1.01, ICGA showed 1.51±0.86. In the interclass correlation coefficient analysis, the correlation between Set A and ICGA was ICC=0.76(95% CI:0.60-0.86, p<0.001), and the correlation between Set B and ICGA was ICC=0.84(95% CI:0.72-0.91, p<0.001). This study highlights that, without using ICGA, both CFP combined with OCT and CFP combined with SS-OCTA demonstrate high sensitivity, specificity, and AUC in diagnosing PCV. It is evident that SS-OCTA contributes to enhancing sensitivity, specificity, and AUC for PCV diagnosis.

Correlation of the OCT Double-Layer Sign with Type 1 Non-Exudative Neovascularization on OCT-A in Age-Related Macular Degeneration.

Background and Objectives: Early diagnosis of the exudative form of age-related macular degeneration (AMD) is very important for a timely first treatment, which is directly related to the preservation of functional visual acuity over a long period. The goal of this paper was to examine the correlation between the double-layer sign (DLS) and the presence of non-exudative macular neovascularization (MNV). Materials and Methods: Our research included 60 patients with AMD, exudative in one eye and non-exudative in the other eye. We analyzed only the non-exudative form using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). The patients were classified into three groups, depending on the duration of the disease (<2 years, 2 to 5 years, >5 years). The onset of the disease was deemed the moment of establishing a diagnosis of exudative AMD in one eye. We defined the presence or absence of a DLS using OCT and the presence of non-exudative MNV using OCT-A, both on 3 × 3 mm and 6 × 6 mm sections. DLS was used as a projection biomarker for non-exudative MNV, with the aim of establishing a rapid diagnosis and achieving early treatment of the disease. Results: We found that there was a statistically significant correlation between the DLS diagnosed using OCT and non-exudative MNV diagnosed by OCT-A for both 3 × 3 mm (p < 0.001) and 6 × 6 mm (p < 0.001) imaging. There was a statistically significant difference between the frequencies of both DLS and MNV in Groups I and III on both 3 × 3 and 6 × 6 mm imaging. A statistically significant difference was also noted in the frequencies of DLS and MNV on 6 × 6 mm imaging, but not on 3 × 3 mm imaging, between Groups I and II. No differences were found between the frequencies of DLS and MNV between Groups II and III. Conclusions: The DLS on OCT can be used as a projection biomarker to assess the presence of a non-exudative MNV.

Visual outcomes of early and late vitrectomy for breakthrough vitreous hemorrhage associated with exudative age-related macular degeneration and polypoidal choroidal vasculopathy.

To compare the visual outcomes of early and late vitrectomy for breakthrough vitreous hemorrhage (VH) associated with exudative age-related macular degeneration (exudative AMD) and polypoidal choroidal vasculopathy (PCV). A retrospective chart review was performed with data of all patients diagnosed with exudative AMD and PCV-related breakthrough VH who underwent early or late vitrectomy (within or after 3 months, respectively). Demographic data and best-corrected visual acuity (BCVA) at baseline, and 1, 3, 6, and 12 months postoperatively were recorded and analyzed. Overall, 105 eyes with breakthrough VH were examined and categorized in either the early or late vitrectomy group. In the early and late vitrectomy group, LogMAR BCVA improved from 2.15 ± 0.08 and 2.07 ± 0.14 at baseline to 1.26 ± 0.09 and 1.27 ± 0.14 at 12 months, respectively (P < .001). Between early and late vitrectomy, the PCV subgroup demonstrated improved LogMAR BCVA at 1 year, but there was no statistically significant (P = .754). Conversely, the LogMAR BCVA improvement at 1 year in the early vitrectomy group demonstrated statistically significant differences from the late vitrectomy group (P = .025) in the exudative AMD subgroup. Both, early and late vitrectomy can improve visual acuity in patients with breakthrough VH secondary to exudative AMD and PCV. However, early vitrectomy is more beneficial for breakthrough VH-associated exudative AMD.

Vitreous body in the treatment of exudative age-related macular degeneration : The medium is the message

Intravitreal anti-vascular endothelial growth factor (VEGF) is the standard treatment for exudative age-related macular degeneration (AMD). The constitution of the vitreomacular interface varies greatly in cases of attached (with or without traction) or detached vitreous body, which can impact the effectiveness of the anti-VEGF treatment. Based on the current literature this article displays the current state of the science on whether the constitution of the vitreous body has an effect on the anti-VEGF treatment. The published data extracted from current trials and post hoc analyses concerning this topic are presented and put into the clinical context. The presence of a vitreomacular adhesion reduces the efficacy of anti-VEGF treatment of exudative AMD. Posterior vitreous body detachment represents apositive prognostic factor concerning the efficacy of anti-VEGF treatment but not necessarily the prognosis for visual acuity. Patients with attached vitreous body need a more intensive treatment monitoring compared to patients with detached vitreous body. Therefore, in eyes with initial posterior vitreous body detachment receiving atreat and extend regimen, the interval between anti-VEGF injections can be extended to 4instead of 2weeks without endangering the success of treatment.

Automated detection of crystalline retinopathy via fundus photography using multistage generative adversarial networks

PurposeCrystalline retinopathy is characterized by reflective crystal deposits in the macula and is caused by various systemic conditions including hereditary, toxic, and embolic etiologies. Herein, we introduce a novel application of deep learning with a multistage generative adversarial network (GAN) to detect crystalline retinopathy using fundus photography. MethodsThe dataset comprised major classes (healthy retina, diabetic retinopathy, exudative age-related macular degeneration, and drusen) and a crystalline retinopathy class (minor set). To overcome the limited data on crystalline retinopathy, we proposed a novel multistage GAN framework. The GAN was retrained after CutMix combination by inputting the GAN-generated synthetic data as new inputs to the original training data. After the multistage CycleGAN augmented the data for crystalline retinopathy, we built a deep-learning classifier model for detection. ResultsUsing the multistage CycleGAN facilitated realistic fundus photography synthesis with the characteristic features of retinal crystalline deposits. The proposed method outperformed typical transfer learning, prototypical networks, and knowledge distillation for both multiclass and binary classifications. The final model achieved an area under the curve of the receiver operating characteristics of 0.962 for internal validation and 0.987 for external validation for the detection of crystalline retinopathy. ConclusionWe introduced a deep learning approach for detecting crystalline retinopathy, a potential biomarker of underlying systemic pathological conditions. Our approach enables realistic pathological image synthesis and more accurate prediction of crystalline retinopathy, an essential but minor retinal condition.

Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials

Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy. OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic atrophy secondary to age-related macular degeneration were enrolled at 110 clinical sites and 122 clinical sites worldwide, respectively. Patients were randomly assigned (2:2:1:1) by central web-based randomisation system to intravitreal 15 mg per 0·1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month using stratified permuted block randomisation (stratified by geographic atrophy lesion area at screening, history or presence of active choroidal neovascularisation in the eye not under assessment, and block size of six). Study site staff, patients, reading centre personnel, evaluating physicians, and the funder were masked to group assignment. Sham groups were pooled for the analyses. The primary endpoint was the change from baseline to month 12 in the total area of geographic atrophy lesions in the study eye based on fundus autofluorescence imaging, in the modified intention-to-treat population (ie, all patients who received one or more injections of pegcetacoplan or sham and had a baseline and at least one post-baseline value of lesion area). Key secondary endpoints (measured at 24 months) were change in monocular maximum reading speed of the study eye, change from baseline in mean functional reading independence index score, change from baseline in normal luminance best-corrected visual acuity score, and change from baseline in the mean threshold sensitivity of all points in the study eye by mesopic microperimetry (OAKS only). Safety analyses included patients who were randomly assigned and received at least one injection of pegcetacoplan or sham. The now completed studies are registered with ClinicalTrials.gov, NCT03525613 (OAKS) and NCT03525600 (DERBY). Between Aug 30, 2018, and July 3, 2020, 1258 patients were enrolled in OAKS and DERBY. The modified intention-to-treat populations comprised 614 (96%) of 637 patients in OAKS (202 receiving pegcetacoplan monthly, 205 pegcetacoplan every other month, and 207 sham) and 597 (96%) of 621 patients in DERBY (201 receiving pegcetacoplan monthly, 201 pegcetacoplan every other month, and 195 sham). In OAKS, pegcetacoplan monthly and pegcetacoplan every other month significantly slowed geographic atrophy lesion growth by 21% (absolute difference in least-squares mean -0·41 mm2, 95% CI -0·64 to -0·18; p=0·0004) and 16% (-0·32 mm2, -0·54 to -0·09; p=0·0055), respectively, compared with sham at 12 months. In DERBY, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth, although it did not reach significance, by 12% (-0·23 mm2, -0·47 to 0·01; p=0·062) and 11% (-0·21 mm2, -0·44 to 0·03; p=0·085), respectively, compared with sham at 12 months. At 24 months, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth by 22% (-0·90 mm2, -1·30 to -0·50; p<0·0001) and 18% (-0·74 mm2, -1·13 to -0·36; p=0·0002) in OAKS, and by 19% (-0·75 mm2, -1·15 to -0·34; p=0·0004) and 16% (-0·63 mm2, -1·05 to -0·22; p=0·0030) in DERBY, respectively, compared with sham. There were no differences in key secondary visual function endpoints at 24 months. Serious ocular treatment-emergent adverse events were reported in five (2%) of 213, four (2%) of 212, and one (<1%) of 211 patients in OAKS, and in four (2%) of 206, two (1%) of 208, and two (1%) of 206 patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. New-onset exudative age-related macular degeneration was reported in 24 (11%), 16 (8%), and four (2%) patients in OAKS, and in 27 (13%), 12 (6%), and nine (4%) patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. Pegcetacoplan, the first treatment approved by the US Food and Drug Administration for geographic atrophy, slowed geographic atrophy lesion growth with an acceptable safety profile. Apellis Pharmaceuticals.

Diurnal variation of optical coherence tomography–based macular fluid in exudative age-related macular degeneration

BackgroundSignificant 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.MethodsProspective 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.Results21 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.ConclusionsNo significant diurnal variation in OCT-based macular fluid or thickness was identified in patients with eAMD, either quantitatively or qualitatively.

Prognostic factors for visual acuity improvement after treatment of submacular hemorrhage secondary to exudative age-related macular degeneration.

To recognize prognostic factors for better final visual acuity (VA) in patients presenting with submacular hemorrhage (SMH) secondary to exudative age-related macular degeneration. This retrospective study included patients who presented to a tertiary ophthalmology department between 2012 and 2019 with SMH and were treated by pars plana vitrectomy (PPV) or injection of tissue plasminogen activator (tPA) with pneumatic displacement. Baseline characteristics included demographic data, VA and optical coherence tomography (OCT) characteristics of the SMH. Patients were divided into groups by improvement of at least 2 lines in BCVA (best corrected visual acuity), and by having a final BCVA better than 20/200. Forty-three eyes of 43 patients were included. Mean age was 86.72 ± 7.18. Prognostic factors for final VA better than 20/200 included better VA at presentation (1.25 vs 1.90 logMAR, p < 0.001), smaller area of SMH in the infra-red image (19.47 mm2 vs 38.45 mm2, p = 0.024), and lower height of SMH as measured by OCT (713.5 µm vs 962.5 µm, p = 0.03). Third of the patients improved in ≥2 lines from presentation, all in the group of the pneumatic and TPA displacement. Smaller SMHs with good VA at presentation have a better chance for improvement and result in a better final VA. These patients may benefit the most from pneumatic displacement of the SMH with intravitreal tPA and gas.

Vision-Related Quality of Life among Patients with Different Types of Age-Related Macular Degeneration.

This study aimed to assess the vision-related quality of life (VRQol) of patients with age-related macular degeneration (AMD) and to evaluate VRQol according to different types of AMD. In this small-scale, single-center, prospective investigation, patients with AMD and subjects without any signs of macular disease were asked to complete the NEI-VFQ-39. A total of 159 subjects were included and grouped according to the type of AMD as follows: 40 patients with dry AMD in both eyes (DD), 40 patients with exudative AMD in one eye (DE), 41 patients with exudative AMD in both eyes (EE), and 38 subjects without any signs of macular disease, as a control group (CG). The average age of the participants was 76 ± 7 years, and 44% were male. Most participants were retired (22.4%), and 75% of patients were initially diagnosed by their ophthalmologist. All the AMD groups had significantly worse overall VRQol than the CG. For general vision, near vision, mental health, and role difficulties, all the AMD groups had significantly lower scores than the CG. For distance vision, color vision, peripheral vision, driving difficulties, dependency, and social functioning, only patients in the EE and DE groups had significantly worse scores than the CG. The type of retinal fluid in patients with exudative AMD had no effect on overall VRQol; however, we found that the presence of pigment epithelial detachment could be associated with more role difficulties, such as completing work or working long hours. All types of AMD had a negative effect on vision-related quality of life. This effect was significantly more pronounced in patients with exudative AMD in at least one eye. However, the type of retinal fluid in patients with exudative AMD had no influence on their overall vision-related quality of life.

Retinal Hydration Assessment With Optical Coherence Tomography: Unraveling Its Significance in Retinal Fluid Dynamics, Macular Edema and Cell Viability.

The purpose of this study was to quantify retinal hydration (RH) levels with optical coherence tomography (OCT) and determine the extent of cellular damage resulting from intraretinal fluid alterations. We took 6.0 mm sections of the human sensory retina that were excised from 18 fresh (<24 hours) donor eyes. They were either exposed to various osmotic stresses between 90 and 305 mOsm or dehydrated under a laminar flow hood. Change in tissue weight was used to calculate the retinal water content (RWC). Image analyses were conducted on OCT between 0 and 180 minutes to assess retinal thickness (RT) and "optically empty areas" (OEAs) representing intraretinal fluid. Correlations were sought among RWC, OEA, RWC, and RT. The effect of RH on retinal cell viability (RCV) was assessed with the Live-Dead Assay. RH demonstrated a stronger correlation with the OEA than plain RT measurements (r = 0.99, P < 0.001). RH-RCV interaction fits well to a bell-shaped curve. A significant proportion of retinal cells (>80%) remained viable despite the change in RH ranging between 0.87 and 1.42 times. This "safe zone" was found to be associated with a 22% increase in OEA (r = 0.99, P < 0.01). OCT has been demonstrated as a valuable tool for assessing RH and can be used for intraretinal fluid content analysis. RH is a better indicator of RCV compared with RT. Computing RH may improve the determination of functional outcome of intravitreal pharmacotherapeutics used for diabetic macular edema and exudative age-related macular degeneration. We link basic research and clinical care by assessing retinal hydration's impact on retinal fluid dynamics, macular edema, and cell viability.

Assessing Change in Exudative Age-Related Macular Degeneration With Macular Thickness Maps as a Surrogate Strategy for Remote Patient Monitoring

To determine if macular thickness maps (MTMs) are sufficient to guide management of eyes with exudative age-related macular degeneration (eAMD), we compared the ability to detect change using MTMs with the ability to detect change using the entire optical coherence tomography (OCT) scan in patients undergoing therapy. Retrospective, comparative diagnostic analysis. Patients with eAMD were imaged using macula-centered 6×6-mm OCT scans (CIRRUS HD-OCT 5000; Zeiss). In each case, graders were asked to determine if there were changes that warranted a full clinical assessment after viewing 2 consecutive scans using one of 3 different imaging strategies: MTMs alone, individual foveal-centered B scans alone, or 5 macular B scans including the foveal-centered B scan. Graders were told the 2 scans were taken 2 weeks apart. The consensus ground truth was reached by the graders using a CIRRUS review station to evaluate all the information contained within the OCT scans. A total of 53 eyes were included in this study with 1385 imaging sessions. The Fleiss kappa was highest when graders were given MTMs alone compared with the ground truth. When the averages of all 5 graders were compared with the ground truth, the MTMs alone showed the highest level of agreement (90.05%, SD 0.78%) followed by the central B scans (87.87%, SD 1.59%) and the 5-B scan method (86.512%, SD 0.64%). MTMs alone provide sufficient information to easily identify recurrent exudation in patients with eAMD, and these maps may be all that is needed for remote monitoring.

Diabetes-Related Risk Factors for Exudative Age-Related Macular Degeneration: A Nationwide Cohort Study of a Diabetic Population.

The purpose of this study was to identify diabetes-related risk factors for exudative age-related macular degeneration (AMD). This was a nationwide population-based cohort study using authorized clinical data provided by the Korean National Health Insurance Service. A total of 1,768,018 participants with diabetes over 50 years of age participated in the Korean National Health Screening Program between 2009 and 2012. Data on covariates, including age, sex, income level, systemic comorbidities, behavioral factors, and diabetes-related parameters, including duration of diabetes, use of insulin for diabetes control, number of oral hypoglycemic agents used, and accompanying vision-threatening diabetic retinopathy, were collected from health screening results and claims data. Patients were followed up until December 2018. Incident cases of exudative AMD were identified using registered diagnostic codes from the claims data. The prospective association of diabetes-related parameters with incident exudative AMD was investigated using the multivariable-adjusted Cox proportional hazard model. During an average follow-up period of 5.93 years, 7331 patients were newly diagnosed with exudative AMD. Compared to those who had diabetes for less than 5 years, individuals with diabetes for 5 years or more had a greater risk of future exudative AMD development, with a hazard ratio (95% confidence interval) of 1.13 (1.07-1.18) in the fully adjusted model. Use of insulin for diabetes control and the presence of vision-threatening diabetic retinopathy were also associated with an increased risk of exudative AMD with a hazard ratio (95% confidence interval) of 1.16 (1.07-1.25) and 1.40 (1.23-1.61), respectively. A longer duration of diabetes, administration of insulin for diabetes control, and comorbid vision-threatening diabetic retinopathy were associated with an increased risk of developing exudative AMD.

Association of oral montelukast with reduced odds of developing exudative age-related macular degeneration.

This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development. This case-control study was conducted using Institutional Cohort Finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Sub-analysis among 1913 exAMD and 324 non-exudative AMD was also conducted. A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use prior to exAMD diagnosis, compared to 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted OR: 0.50, 95% CI: 0.31 - 0.80) as well as NSAID usage (adjusted OR: 0.69). Caucasian race, history of smoking, non-exudative macular degeneration in either eye were also found to have significant relationship with increased odds of exAMD. In the sub-analysis, montelukast usage showed significant association with reduced odds of developing exAMD from non-exudative AMD (adjusted OR: 0.53 95% CI: 0.29 - 0.97) as well as the presence of atopic disease (adjusted OR: 0.60). The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

Analysis of Aqueous Humor Cytokines in Exudative Age-related Macular Degeneration and Diabetic Macular Edema

Purpose: To investigate the cytokine concentrations of aqueous humor in patients with exudative age-related macular degeneration (AMD) and diabetic macular edema (DME).Methods: Fifty-seven subjects were included in the exudative AMD, DME and control groups, each group has 19 patients. Aqueous levels of cytokines epidermal growth factor (EGF), vascular endothelial growth factor-C (VEGF-C), monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), interleukin (IL)-3, IL-8, IL-6, IL-12p40, intercellular adhesion molecule 1 (ICAM-1) were investigated in each groups. Kruskal-Wallis test and Mann-Whitney U test were performed to compare cytokine concentrations.Results: Aqueous levels of EGF, VEGF-C, MCP-1, HGF, IL-3, IL-8 were significantly higher in exudative AMD group than control group (&lt;i&gt;p&lt;/i&gt; = &lt; 0.0001, &lt; 0.0001, 0.004, 0.015, &lt; 0.0001, 0.014) and EGF, VEGF-C, IL-3, IL-8 were significantly higher in DME group than control group (&lt;i&gt;p&lt;/i&gt; = &lt; 0.0001, &lt; 0.0001, &lt; 0.0001, 0.005). In the comparison between the exudative AMD and DME groups, EGF was significantly higher in the exudative AMD group (&lt;i&gt;p&lt;/i&gt; = 0.001).Conclusions: Various cytokines were increased in patients with exudative AMD and DME. In particular, EGF showed a higher level in exudative AMD than in DME.

Complement inhibitors for age-related macular degeneration.

Complement inhibitors for age-related macular degeneration.

Scale-adaptive model for detection and grading of age-related macular degeneration from color retinal fundus images

Age-related Macular Degeneration (AMD), a retinal disease that affects the macula, can be caused by aging abnormalities in number of different cells and tissues in the retina, retinal pigment epithelium, and choroid, leading to vision loss. An advanced form of AMD, called exudative or wet AMD, is characterized by the ingrowth of abnormal blood vessels beneath or into the macula itself. The diagnosis is confirmed by either fundus auto-fluorescence imaging or optical coherence tomography (OCT) supplemented by fluorescein angiography or OCT angiography without dye. Fluorescein angiography, the gold standard diagnostic procedure for AMD, involves invasive injections of fluorescent dye to highlight retinal vasculature. Meanwhile, patients can be exposed to life-threatening allergic reactions and other risks. This study proposes a scale-adaptive auto-encoder-based model integrated with a deep learning model that can detect AMD early by automatically analyzing the texture patterns in color fundus imaging and correlating them to the vasculature activity in the retina. Moreover, the proposed model can automatically distinguish between AMD grades assisting in early diagnosis and thus allowing for earlier treatment of the patient’s condition, slowing the disease and minimizing its severity. Our model features two main blocks, the first is an auto-encoder-based network for scale adaption, and the second is a convolutional neural network (CNN) classification network. Based on a conducted set of experiments, the proposed model achieves higher diagnostic accuracy compared to other models with accuracy, sensitivity, and specificity that reach 96.2%, 96.2%, and 99%, respectively.

The role of blood neutrophil lymphocyte ratio in predicting the initial response to anti-VEGF treatment in neovascular AMD patients.

Vascular endothelial growth factor (VEGF) has a critical role in age-related macular degeneration (AMD), and intravitreal injection of anti-VEGF drugs is the mainstay of neovascular AMD treatment. Blood neutrophil-to-lymphocyte ratio (NLR) is shown to be a biomarker of inflammation in AMD. We aimed to investigate the role of NLR in predicting favorable short-term anti-VEGF treatment results in neovascular AMD patients. A total of 112 patients diagnosed with exudative AMD and had taken 3 monthly intravitreal bevacizumab injections were analyzed retrospectively. Medical records were reached to obtain neutrophil and lymphocyte values to calculate NLR. Best-corrected visual acuity and central macular thickness (CMT) measurements were recorded at each visit. T test or Mann-Whitney U test was used to compare continuous variables, and chi-square test was used to compare categorical variables. Receiver operating characteristics curve (ROC) analysis was performed to determine cut-off, sensitivity, and specificity values. P value of ≤ 0.05 was considered statistically significant. The mean age was 68.1 ± 7.2years, and the mean NLR was 2.11 ± 0.81. The ROC analysis revealed a cut off value of 2.0 for NLR to predict at least 100μm CMT change (sensitivity 87.1%; specificity 87.8%) and a cut off value of 2.4 for NLR to predict at least 0.1 logMAR visual improvement (sensitivity 77.2%; specificity 64.8%) after 3 monthly IVT bevacizumab injections. NLR can provide additional prognostic information for the identification of patients with a good initial response to anti-VEGF therapy.

Impact du confinement français en 2020 sur la prise en charge des patients atteints de dégénérescence maculaire liée à l’âge exsudative

To assess the impact of the measures taken during the lockdown period from March 17to May 11, 2020on the management of patients with exudative age related macular degeneration treated by intravitreal anti-VEGF injections at the University Hospital of Tours. In this retrospective study, patients were included after analysis of the computerized medical records of patients with age related macular degeneration. Those who were treated for exudative age related macular degeneration who received at least 1 intravitreal injection in the 12 months prior and at least one consultation in the 6 months prior to the lockdown period, were included. The initial and final mean visual acuity were compared with a 5 letter non-inferiority margin. A subgroup analysis was performed according to outcomes. The visual acuities immediately after this period were also recorded. In all, 595 eyes of 493 patients were included. The mean initial visual acuity was 59.6 letters, vs. 58.5 for the final visual acuity, i.e. a difference of -1.13 letters with a lower limit of the confidence interval of less than 5. The visual acuity on release from lockdown was comparable to the other 2 measurements. Initial visual acuity and the number of missed treatments were the main factors associated with functional loss. Patients' visual acuity during the lockdown period was able to be maintained despite the restrictive measures and limitation of care access in France. The most common cause of substantial visual decline was missed intravitreal injections.