Age-related Macular Degeneration Eyes Research Articles

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Defining the structure–function relationship of specific lesions in early and advanced age-related macular degeneration

The objective of this study is to define structure–function relationships of pathological lesions related to age-related macular degeneration (AMD) using microperimetry and multimodal retinal imaging. We conducted a cross-sectional study of 87 patients with AMD (30 eyes with early and intermediate AMD and 110 eyes with advanced AMD), compared to 33 normal controls (66 eyes) recruited from a single tertiary center. All participants had enface and cross-sectional optical coherence tomography (Heidelberg HRA-2), OCT angiography, color and infra-red (IR) fundus and microperimetry (MP) (Nidek MP-3) performed. Multimodal images were graded for specific AMD pathological lesions. A custom marking tool was used to demarcate lesion boundaries on corresponding enface IR images, and subsequently superimposed onto MP color fundus photographs with retinal sensitivity points (RSP). The resulting overlay was used to correlate pathological structural changes to zonal functional changes. Mean age of patients with early/intermediate AMD, advanced AMD and controls were 73(SD = 8.2), 70.8(SD = 8), and 65.4(SD = 7.7) years respectively. Mean retinal sensitivity (MRS) of both early/intermediate (23.1 dB; SD = 5.5) and advanced AMD (18.1 dB; SD = 7.8) eyes were significantly worse than controls (27.8 dB, SD = 4.3) (p < 0.01). Advanced AMD eyes had significantly more unstable fixation (70%; SD = 63.6), larger mean fixation area (3.9 mm2; SD = 3.0), and focal fixation point further away from the fovea (0.7 mm; SD = 0.8), than controls (29%; SD = 43.9; 2.6 mm2; SD = 1.9; 0.4 mm; SD = 0.3) (p ≤ 0.01). Notably, 22 fellow eyes of AMD eyes (25.7 dB; SD = 3.0), with no AMD lesions, still had lower MRS than controls (p = 0.04). For specific AMD-related lesions, end-stage changes such as fibrosis (5.5 dB, SD = 5.4 dB) and atrophy (6.2 dB, SD = 7.0 dB) had the lowest MRS; while drusen and pigment epithelial detachment (17.7 dB, SD = 8.0 dB) had the highest MRS. Peri-lesional areas (20.2 dB, SD = 7.6 dB) and surrounding structurally normal areas (22.2 dB, SD = 6.9 dB) of the retina with no AMD lesions still had lower MRS compared to controls (27.8 dB, SD = 4.3 dB) (p < 0.01). Our detailed topographic structure–function correlation identified specific AMD pathological changes associated with a poorer visual function. This can provide an added value to the assessment of visual function to optimize treatment outcomes to existing and potentially future novel therapies.

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: an AMISH Eye Study Analysis

To compare the Ganglion Cell Complex (GCC) thickness in eyes with age-related macular degeneration (AMD) versus healthy controls in an elderly Amish population DESIGN: Cross-sectional study METHODS: This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each compromising 512 A-scans) over a 6 mm x 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the GCL and the IPL layer. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of six sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of twelve hundred and ninety-four subjects had all required imaging studies of sufficient quality and were included in the final analysis, and of these 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (p<0.001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). Independent t test showed that, early (75.03 ± 12.45 µm), and late AMD (61.64 ± 21.18 µm) groups (among which GA eyes had the lowest thickness of 58.10 ± 20.27 microns) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant difference in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. The GCC thickness in AMD eyes is reduced compared to normal eyes, but the relationship is complex with the greatest reduction in late AMD eyes (particularly GA eyes) but no difference between early and intermediate AMD eyes.

Predictive Factors Influencing the Evolution of Acquired Vitelliform Lesions in Intermediate Age-Related Macular Degeneration Eyes

PurposeIn this study, we identify risk factors that predict the progression of AVL lesions over time. DesignRetrospective cohort study Subjects163 eyes of 132 patients with a diagnosis of iAMD with AVL MethodsThis retrospective study evaluated consecutive eyes with AMD from a retina clinic population and included 1181 patients and 2362 eyes. After excluding cases with associated geographic atrophy, macular neovascularization (MNV), vitreomacular traction, and those with less than two years of follow-up data, the final analysis cohort consisted of 163 eyes (132 patients) with at least one AVL lesion. The first available visit in which an AVL lesion was evident was considered the baseline visit, and follow-up data was collected from a visit 2years (+/- 3 months) later. Progression outcomes at the follow visit were classified into six categories: Resorbed, Collapsed, MNV, Stable, Increasing, and Decreasing. Subsequently, we analyzed the baseline characteristics for each category and calculated odds ratios to predict these various outcomes. Main Outcome MeasuresThe study focused on identifying predictive factors influencing the evolution of AVL in iAMD eyes. ResultsIn total, 163 eyes with AVL had follow-up data at 2 years. The collapsed group demonstrated a significantly greater baseline AVL height and width compared to other groups (P < 0.001). With regards to qualitative parameters, subretinal drusenoid deposits (SDD) and intra-retinal hyper-reflective foci (IHRF) at the eye level, AVL located over drusen, and IHRF and ELM disruption over AVL were significantly more prevalent in the collapsed group compared to other groups (P< 0.05 for all comparisons). Odds Ratio for progressing to atrophy after 2 years of follow-up, compared to the resorbed group, were significant for SDD (OR = 2.82, P = 0.048) and AVL height (OR = 1.016, P = 0.006). ConclusionsThe presence of SDD and greater AVL height significantly increases the risk of developing atrophy at the location of AVL after 2 years of follow-up. These findings may be of value in risk prognostication and defining patient populations for inclusion in future early intervention trials aimed at preventing progression to atrophy.

Retinal vessel diameters in intermediate age-related macular degeneration using en face optical coherence tomography

ABSTRACT Clinical relevance Clinical assessment of age-related macular degeneration (AMD) relies on biomarkers that do not necessarily reflect the contributions of vascular dysfunction. Validation of clinically accessible methods of measuring retinal vascular integrity could provide a more holistic understanding of AMD-related changes to facilitate appropriate care. Background There is conflicting evidence if retinal vessel calibre is significantly altered in the early stages of AMD. This study examined the outer and inner diameters of first order retinal vessels in intermediate AMD eyes using en face optical coherence tomography (OCT). Methods Retinal en face (6 × 6 mm) OCT images were examined in a single eye of participants with intermediate AMD (n = 46) versus normal macula (n = 43) for arterioles (all identifiable) and venules (40/46 and 39/43 identifiable). All participants were aged ≥50 years without diabetes mellitus, hypertension, or other systemic vascular disease. Results Intra- and inter-grader agreement was good-to-excellent for all en face OCT measurements of arteriole and venule diameters (intraclass correlation coefficient = 0.87 to 0.99). Arteriolar outer diameters (82.3 ± 19.8 µm vs 73.8 ± 16.1 µm; p < 0.05) and inner diameters (35.1 ± 8.4 µm vs 31.5 ± 8.1 µm; p < 0.05) were significantly greater in AMD eyes compared to normal eyes. Venular inner diameter was significantly greater (43.1 ± 9.5 µm vs 39.2 ± 10.1 µm; p < 0.05), but outer diameter remained unchanged (p = 0.17) in AMD eyes compared to normal eyes. Conclusion Arteriolar dilation and altered venular inner diameter were observed in intermediate AMD eyes. These results support further investigation of vascular contributions to AMD in the early stages of disease, possibly using the en face OCT imaging modality.

Knowledge about age-related eye diseases in the general population in Germany

BackgroundWith a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions.MethodsKnowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations.ResultsReplies were correct for a median of 9 out of 16 (range 2 – 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011).ConclusionsKnowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:xx-xx.].

Potential Structural Biomarkers in 3D Images Validated by the First Functional Biomarker for Early Age-Related Macular Degeneration - ALSTAR2 Baseline.

Lack of valid end points impedes developing therapeutic strategies for early age-related macular degeneration (AMD). Delayed rod-mediated dark adaptation (RMDA) is the first functional biomarker for incident early AMD. The relationship between RMDA and the status of outer retinal bands on optical coherence tomography (OCT) have not been well defined. This study aims to characterize these relationships in early and intermediate AMD. Baseline data from 476 participants was assessed including eyes with early AMD (n=138), intermediate AMD (n=101), and normal aging (n=237). Participants underwent volume OCT imaging of the macula and rod intercept time (RIT) was measured. The ellipsoid zone (EZ) and interdigitation zone (IZ) on all OCT B-scans of the volumes were segmented. The area of detectable EZ and IZ, and mean thickness of IZ within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid were computed and associations with RIT were assessed by Spearman's correlation coefficient and age adjusted. Delayed RMDA (longer RIT) was most strongly associated with less preserved IZ area (r=-0.591; P<0.001), followed by decreased IZ thickness (r=-0.434; P<0.001), and EZ area (r=-0.334; P<0.001). This correlation between RIT and IZ integrity was not apparent when considering normal eyes alone within 1.5 mm of the fovea. RMDA is correlated with the status of outer retinal bands in early and intermediate AMD eyes, particularly, the status of the IZ. This correlation is consistent with a previous analysis of only foveal B-scans and is biologically plausible given that retinoid availability, involving transfer at the interface attributed to the IZ, is rate-limiting for RMDA.

Relationship of Topographic Distribution of Macular Atrophy Secondary to Neovascular AMD and Reading Performance.

The purpose of this study was to provide a topographical assessment of macular atrophy in successfully treated neovascular age-related macular degeneration (AMD) eyes to investigate determinants of monocular reading performance. A total of 60 participants (60 eyes) with previously treated neovascular AMD and absence of optical coherence tomography (OCT) signs of exudation were enrolled. Reading performance was assessed monocularly using Radner charts. The following variables were obtained: (i) the reading acuity was defined as the logarithm of the reading acuity determination (LogRAD), at the smallest sentence, a patient is able to read in less than 30 seconds; (ii) the maximum reading speed was defined as the fastest time achieved and is calculated in words per minute (wpm). OCT images were reviewed for the presence of macular atrophy within the central, 4 inner and 4 outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid subfields. Contributory factors affecting reading performance were examined using univariable and multivariable linear mixed model considering reading acuity and reading speed as dependent variables. Median (interquartile range [IQR]) values were 0.53 (IQR = 0.17) LogRAD for reading acuity, and 144 (60) wpm for maximum reading speed. Thirty-five out of 60 (58.3%) eyes were characterized by the presence of macular atrophy. In multiple regression analysis, reading acuity was significantly associated with presence of macular atrophy in the foveal central circle (P = 0.024). Conversely, the maximum reading speed was associated with presence of macular atrophy in the inner-right ETDRS subfield (P = 0.005). We showed a significant relationship between presence and location of macular atrophy and reading performance in neovascular AMD.

Spectral Analysis of Human Retinal Pigment Epithelium Cells in Healthy and AMD Eyes.

Retinal pigment epithelium (RPE) cells show strong autofluorescence (AF). Here, we characterize the AF spectra of individual RPE cells in healthy eyes and those affected by age-related macular degeneration (AMD) and investigate associations between AF spectral response and the number of intracellular AF granules per cell. RPE-Bruch's membrane flatmounts of 22 human donor eyes, including seven AMD-affected eyes (early AMD, three; geographic atrophy, one; neovascular, three) and 15 unaffected macula (<51years, eight; >80years, seven), were imaged at the fovea, perifovea, and near-periphery using confocal AF microscopy (excitation 488nm), and emission spectra were recorded (500-710nm). RPE cells were manually segmented with computer assistance and stratified by disease status, and emission spectra were analyzed using cubic spline transforms. Intracellular granules were manually counted and classified. Linear mixed models were used to investigate associations between spectra and the number of intracellular granules. Spectra of 5549 RPE cells were recorded. The spectra of RPE cells in healthy eyes showed similar emission curves that peaked at 580nm for fovea and perifovea and at 575 and 580nm for near-periphery. RPE spectral curves in AMD eyes differed significantly, being blue shifted by 10nm toward shorter wavelengths. No significant association coefficients were found between wavelengths and granule counts. This large series of RPE cell emission spectra at precisely predefined retinal locations showed a hypsochromic spectral shift in AMD. Combining different microscopy techniques, our work has identified cellular RPE spectral AF and subcellular granule properties that will inform future in vivo investigations using single-cell imaging.

Glaucoma Tube Outcomes with and without Anti-VEGF in Patients with Age-related Macular Degeneration

PurposeTo compare glaucoma tube outcomes of wet age-related macular degeneration (AMD) eyes receiving anti-vascular endothelial growth factors (VEGF) injections versus dry AMD eyes and no anti-VEGF. DesignRetrospective clinical cohort study. ParticipantsPatients with wet AMD and a history of anti-VEGF within a year prior or after stand-alone glaucoma tube surgery and eyes with dry AMD and no history of anti-VEGF with at least 6 months of follow-up. Eyes with neovascular glaucoma or anti-VEGF for reason other than wet AMD were excluded. MethodsA Kaplan-Meier analysis compared survival for wet versus dry AMD eyes. Failure was defined as intraocular pressure (IOP) >21 mmHg or <20% IOP reduction from baseline or IOP ≤5 mm Hg for two consecutive post-operative visits starting at month three, additional glaucoma surgery, or no light perception. Complete success was defined as no failure or medications at final follow-up. Hypertensive phase was defined for valved tubes as IOP >21 mmHg within three months of surgery after a reduction to <22 mmHg during the first post-operative week. Intraocular pressure, percent reduction in IOP, number of glaucoma medications, and early (<1 year) and late (>1 year) complications were compared through five years. Main Outcome MeasuresSurvival analysis, IOP, number of medications ResultsBaseline IOP, number of medications, or tube type were not significantly different between wet (n=24) and dry AMD eyes (n=54). No wet AMD eyes failed versus 10 (18%) dry AMD eyes (P=0.03). Five-year survival was estimated as 100% for wet AMD and 72% for dry AMD (P=0.04). Wet AMD eyes had lower IOP (10.6 vs 12.7 mmHg, P=0.05), greater IOP reduction (60% vs 49%, P=0.04), fewer medications (1.2 vs 2.1, P=0.02), and more complete success (50% vs 15%, P=0.001) at final follow-up (32 versus 36 months, P=0.42). Fewer wet than dry AMD eyes experienced hypertensive phase (0/10 (0%) versus 4/10 (40%), P=0.04). There were no significant differences in early or late complications. ConclusionsExposure to anti-VEGF may influence post-operative wound healing and capsule formation which may improve glaucoma tube surgical outcomes. Prospective data is needed to consider perioperative administration of anti-VEGF for glaucoma tube surgery.

PREVALENCE AND PERSISTENCE OF HYPERTRANSMISSION DEFECTS OF VARIOUS SIZES IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

To determine the prevalence and rate of persistence over 2 years of various-sized hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration. Retrospective analysis of optical coherence tomography data from consecutive intermediate age-related macular degeneration patients. Choroidal en face optical coherence tomography images were evaluated for the presence and number of hyperTDs of three different sizes based on greatest linear dimension (small, 63-124 µ m; medium, 125-249 µ m; large, ≥250 µ m) at baseline and at the 2-year follow-up. Interreader agreement was determined by Gwet's agreement coefficient. Disagreements between graders were resolved by the senior investigator to yield a single consensus for all cases. From 273 intermediate age-related macular degeneration eyes (247 patients), 72 and 76 hyperTD lesions were independently identified by two graders at baseline and overall agreement coefficient was 0.89 (95% CI, 0.86-0.93). After adjudication by the senior grader, the final consensus yielded 78 hyperTD lesions from 46 eyes (16.8%) of 42 patients (17.0%) in this study cohort. Among eyes with follow-up optical coherence tomography, 32 of 45 hyperTD lesions (71.1%) persisted. The rates of persistence were 100.0%, 72.7%, and 53.3% in large, medium, and small hyperTD sizes, respectively. HyperTDs were present in a significant proportion of intermediate age-related macular degeneration eyes. Acceptable interreader agreement was demonstrated in identifying hyperTD. Larger hyperTD lesions were more likely to persist over 2 years.

Retrospective analysis of the progression of early dry age-related macular degeneration in patients receiving versus not receiving a multi-component nutraceutical for four years

Purpose: To retrospectively analyze the optical coherence tomography (OCT) changes in retinal morphology and progression in these changes in patients with early dry age-related macular degeneration (AMD) receiving versus not receiving a multi-component nutraceutical daily for four years. Material and Methods: We retrospectively analyzed disease progression in 52 patients (98 eyes) with early dry AMD who had been regularly followed up for four years. Group 1 was comprised of 24 patients (98 eyes) who had been receiving vitamin and mineral tablets containing the AREDS2 formulation plus resveratrol and vitamin D daily for four years. Group 2 was comprised of 28 patients (53 eyes) who had not been receiving any nutritional supplement. Retinal morphology was assessed by OCT and OCT angiography. Results: In group 1, best-corrected visual acuity (BCVA) did not change after completion of the 4-year observation period compared to baseline (0.6 ± 02, p = 0.72). In group 2, BCVA was 0.6 ± 0.2 at baseline and decreased to 0.2 ± 0.2 in four years (p ≤ 0.001). In patients with a low to moderate risk of progression in groups 1 and 2, the four-year progression rate was 15.4% and 45.4%, respectively, which corresponds to an annual progression rate of 3.8% and 11.3%, respectively. In patients with a high risk of progression in groups 1 and 2, the four-year progression rate was 26.3% and 80%, respectively, which corresponds to an annual progression rate of 6.5% and 20%, respectively. Patients who had early dry AMD eyes with a low to moderate risk of progression (and a high risk of progression) at baseline and were not taking the nutritional supplement, had 4.58 greater odds (95% CI, 1.291 – 16.267; р = 0.018) [and 11.2 greater odds (95% CI, 2.505 – 50.081; р = 0.0016)] of having AMD progression than those receiving the nutritional supplement daily for four years. Conclusion: A regular intake of tablets containing the AREDS2 formulation plus resveratrol and vitamin D slows the progression of early dry AMD, especially in eyes with a high risk of disease progression, and contributes to the preservation of visual function.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

PolySialic acid-nanoparticles inhibit macrophage mediated inflammation through Siglec agonism: a potential treatment for age related macular degeneration.

Age-related macular degeneration (AMD) is a chronic, progressive retinal disease characterized by an inflammatory response mediated by activated macrophages and microglia infiltrating the inner layer of the retina. In this study, we demonstrate that inhibition of macrophages through Siglec binding in the AMD eye can generate therapeutically useful effects. We show that Siglecs-7, -9 and -11 are upregulated in AMD associated M0 and M1 macrophages, and that these can be selectively targeted using polysialic acid (PolySia)-nanoparticles (NPs) to control dampen AMD-associated inflammation. In vitro studies showed that PolySia-NPs bind to macrophages through human Siglecs-7, -9, -11 as well as murine ortholog Siglec-E. Following treatment with PolySia-NPs, we observed that the PolySia-NPs bound and agonized the macrophage Siglecs resulting in a significant decrease in the secretion of IL-6, IL-1β, TNF-α and VEGF, and an increased secretion of IL-10. In vivo intravitreal (IVT) injection of PolySia-NPs was found to be well-tolerated and safe making it effective in preventing thinning of the retinal outer nuclear layer (ONL), inhibiting macrophage infiltration, and restoring electrophysiological retinal function in a model of bright light-induced retinal degeneration. In a clinically validated, laser-induced choroidal neovascularization (CNV) model of exudative AMD, PolySia-NPs reduced the size of neovascular lesions with associated reduction in macrophages. The PolySia-NPs described herein are therefore a promising therapeutic strategy for repolarizing pro-inflammatory macrophages to a more anti-inflammatory, non-angiogenic phenotype, which play a key role in the pathophysiology of non-exudative AMD.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration

PurposeTo evaluate the influence of macular neovascularization (MNV) lesion type on 12 months clinical outcomes in treatment-naïve eyes with age-related macular degeneration (nAMD) eyes treated with anti-vascular endothelial growth factor (VEGF) drugs nationwide. DesignMulticenter national nAMD database observational study. SubjectsOne thousand six-hundred six treatment-naïve nAMD eyes (1330 patients) undergoing Anti-VEGF therapy for 12 months nationwide. MethodsDemographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters, number of injections and visits data was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n=711), type 2 (T2, n=505), type 3 (T3, n=315) and aneurysmal type 1 (A-T1, n=75), according to the new proposed consensus classification. Main outcome measuresMean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. ResultsA total of 1606 treatment-naïve nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (±standard deviation) baseline VA was significantly lower for T2 (49.4±23.5 letters) compared to T1 (57.8±20.8) and T3 (58.2 ±19.4)(both p<0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared to T3 (+3.1 letters, p<0.05). T3 lesions had fewer active visits (24.9%) than the other lesion types (T1 30.5%, T2 32.6%, A-T1 27.5%, all p<0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%) and T3 (47.6%) lesions. ConclusionsThis study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support a personalized clinical decision making in these patients.

Through the Smoke: An In-Depth Review on Cigarette Smoking and Its Impact on Ocular Health.

Smoking is a widespread and pervasive habit, impacting health across various care settings, including acute care, subacute care, home-based care, and long-term care. Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. Cigarette smoke contains a complex mixture of harmful constituents, including nicotine and toxic chemicals, which permeate the bloodstream, affecting ocular tissues. The oxidative stress and inflammation induced by smoking are central to its detrimental effects on ocular health. Age-related macular degeneration (AMD), a leading cause of vision loss, exhibits a strong association with smoking. Research consistently demonstrates that smokers face a heightened risk of both early and advanced AMD. Cataracts, another prevalent ocular condition, develop earlier and progress more rapidly in smokers. The oxidative stress on the lens and reduced antioxidants among smokers contribute to the increased severity of cataracts. Moreover, thehealth of the eyes may be compromised by smoking-related chemicals that reduce blood flow and/or hasten thrombus formation in ocular capillaries thus increasing the chance of acquiringglaucoma, cataracts, AMD, and Graves' eye disease. Beyond individual health concerns, the societal implications of smoking on ocular health are substantial, including increased healthcare costs and diminished quality of life for affected individuals. Understanding the underlying mechanisms can provide insights into potential therapeutic interventions for preventing and managing smoking-related ocular damage. Given the global prevalence of smoking, raising awareness about the ocular risks associated with smoking is crucial for promoting eye health. The review underscores the urgent need for comprehensive anti-smoking initiatives and smoking cessation programs to alleviate the burden of ocular diseases associated with smoking.

Vision protection therapy for prevention of neovascular age-related macular degeneration

To access the effect of vision protection therapy on neovascular conversion in age-related macular degeneration (AMD). Patient unidentified data aggregated by Vestrum Health, LLC (VH) from over 320 US retina specialists was analyzed to compare the conversion rate from dry to neovascular (wet) AMD in a practice employing VPT (VPT group) compared to those employing standard care alone (SCA group) between January 2017 through July 2023. 500,00 eyes were filtered then matched for neovascular conversion risk factors by propensity scoring and compared in a 10/1 ratio of 7370 SCA and 737 VPT treated eyes. SCA eyes had significantly fewer clinical encounters and shorter follow up than the VPT group. Despite this, the risk of neovascular conversion by PS was significantly lower in the VPT group compared to SCA (HR 5.73, p < 0.0001). Analysis matching the encounter frequency of both groups as a post-randomization variable produced a similar HR (HR 5.98, p < 0.0001). Because 9% of eyes in the VPT group were not treated with VPT due to bilateral early (low-risk) AMD, analysis comparing the SCA group to VPT-treated eyes was done that also showed significantly lower conversion rates in the VPT-treated eyes, with or without encounter frequency matching (HR 5.84, 5.65, p < 0.0001). Visual acuity was consistently better in VPT eyes compared to SCA eyes throughout the study time window. The advantage of VPT over SCA increased with increased SCA encounter frequency and higher conversion risk factors, including age and ICD10 coded dry AMD severity. Neovascular (wet) AMD is the main cause of irreversible visual loss worldwide. Consistent with two prior studies, the current study finds Vision Protection Therapy markedly more effective at both recognizing and preventing neovascular AMD than the current standard of care, benefiting the highest risk dry AMD eyes the most.

Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.

Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables invivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging. Prospective cross-sectional study. A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects. Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band. Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (μm). In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls. Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times. Proprietary or commercial disclosure may be found after the references.

Clinical Characteristics of Eyes with Neovascular Age-Related Macular Degeneration and Retinal Pigment Epithelium Tears.

Although anti-vascular endothelial growth factor (anti-VEGF) therapy is the first choice of treatment for eyes with neovascular age-related macular degeneration (AMD), it sometimes results in retinal pigment epithelium (RPE) tears. This study presents the detailed clinical characteristics of RPE tears to help predict their occurrence before anti-VEGF therapy initiation. This study retrospectively analyzed neovascular age-related macular degeneration (nAMD) patients who visited the Kyushu University Hospital and started anti-VEGF therapy between April 2013 and June 2020. Using medical records, we collected the clinical data of patients with RPE tears, including age, sex, best-corrected visual acuity (BCVA), number of anti-VEGF drug injections and the type and size of pigment epithelial detachment (PED). RPE tears occurred in 16 (1.50%) eyes of 16 patients in all 1068 nAMD eyes of 987 patients. The mean age of these patients with RPE tear was 81.7 ± 8.7 years. Fifteen eyes had typical AMD and one eye had polypoidal choroidal vasculopathy. The mean number of anti-VEGF drug injections before RPE tears was 5.0 ± 5.1. All patients experienced PED before the RPE tear (hemorrhagic, 4 eyes; serous vascular, 2 eyes; fibrovascular, 10 eyes). The average PED height and area were 615.7 ± 175.3 μm and 21.0 ± 7.2 mm2, respectively. The sub-RPE cleft was observed in 10 eyes. The logMAR BCVA immediately after the RPE tear (0.73 ± 0.40) at 6 months (0.86 ± 0.51) and 12 months (0.84 ± 0.43) after the RPE tear were significantly worse than that before the RPE tear (0.58 ± 0.31; p < 0.05). The BCVA of patients with RPE tears that spread to the fovea was poorer than that of patients without RPE tears. In patients with nAMD, RPE tears tended to occur in typical AMD eyes with high or large PEDs, and sub-RPE clefts. The visual prognosis depended on whether the RPE tear included the fovea.