Nonexudative AMD Research Articles

Comparison between OCT B-scan and En Face Imaging for the Diagnosis of Early Macular Atrophy in Age-Related Macular Degeneration

The gradings of complete retinal pigment epithelium and outer retinal atrophy (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) on spectral domain optical coherence tomography (SD-OCT) B-scans were compared with the grading of persistent choroidal hypertransmission defects (hyperTDs) on swept-source OCT angiography (SS-OCTA) en face images. Comparative diagnostic analysis of prospective study data METHODS: Patients with late nonexudative AMD underwent same day 6 × 6 mm macular scans using both SD-OCT (Spectralis® Heidelberg, 512 × 97, ART:9) and SS-OCTA (PLEX® Elite 9000, Carl Zeiss Meditec, 500 × 500 angio pattern) instruments. SS-OCTA and SD-OCT en face images were generated from a sub-retinal pigment epithelium slab positioned 64-400 μm below Bruch's membrane. SD-OCT B-scan gradings, which included an inspection of neighboring B-scans for the diagnosis of cRORA and iRORA, were performed at the Moran Eye Center, while gradings of en face images to identify persistent choroidal hyperTDs were performed at the Bascom Palmer Eye Institute and Tel Aviv Medical Center. There was a high degree of agreement (99.6%) between the gradings of cRORA lesions and persistent hyperTDs. However, 27.4% of iRORA lesions were found to be contained within persistent hyperTDs. This discrepancy was due to the finding that 27.5% of iRORA lesions were diagnosed as having a greatest linear horizontal dimension of < 250 µm on B-scans, but on en face images, these B-scan defined iRORA lesions were found to have a greatest linear dimensions in the non-horizontal dimension that were ≥ 250 µm. This report demonstrates the benefits of using en face OCT imaging to identify cRORA lesions and highlights the need to acquire dense raster B-scans with the grading neighboring B-scans when identifying iRORA lesions to assess the full extent of the iRORA lesions in the non-horizontal dimension. Even though neighboring B-scans were inspected, 27.5% of iRORA lesions were actually part of larger cRORA lesions when graded using an en face strategy.

Cardiovascular risk in anti-VEGF treatment of neovascular age-related macular degeneration

ObjectiveAssess 5-year all-cause mortality (ACM), hemorrhagic stroke, ischemic stroke, and myocardial infarction (MI) risks in nAMD patients receiving anti-VEGF injections compared with controls. DesignPopulation-based retrospective cohort study using a U.S. federated health research network, containing de-identified data of 96 million patients from 1/1/2003 to 3/6/2023. ParticipantsnAMD Patients with anti-VEGF injections. Controls included nAMD patients without anti-VEGF injections, non-exudative AMD patients, and patients without AMD. MethodsPatients were identified using nAMD ICD-10 and anti-VEGF CPT codes and matched for age, sex, and comorbidities. Five-year relative risk of ACM (RR1), hemorrhagic stroke (RR2), ischemic stroke (RR3), and MI (RR4) in nAMD patients receiving anti-VEGF injections were calculated. ResultsA total of 27,609 nAMD patients (mean diagnosis age [SD], [78.2 (10.3)]) received anti-VEGF injections; 769 nAMD patients without injections (75.8 [12.2]), 27,599 non-exudative AMD patients (78.2 [10.3]), and 21,902 no-AMD patients (76.1 [10.5]) were identified. After matching, nAMD patients receiving injections did not show increased risk versus nAMD patients without injections (RR1, 0.66; 95% CI [0.53, 0.82]), (RR2, 1.00 [0.42, 2.38]), (RR3, 1.70 [0.92,3.13]), (RR4, 0.63 [0.33, 1.18]). No increased risk was found compared to non-exudative AMD patients (RR1, 0.99 [0.95, 1.03]), (RR2, 0.94 [0.83,1.07]), (RR3, 1.04 [0.96, 1.12]), (RR4, 0.99 [0.91, 1.08]). Increased risk for ACM was observed versus no-AMD patients (RR1, 1.21 [1.15, 1.27]), but no other differences were found (RR2, 0.81 [0.70, 0.93]), (RR3, 1.00 [0.92, 1.09]), (RR4, 0.986 [0.90, 1.09]). ConclusionAnti-VEGF injections were not associated with major cardiovascular events in nAMD patients over 5 years.

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.

Posterior Vitreous Detachment and Its Role in the Evolution of Dry to Wet Age Related Macular Degeneration.

To examine the state of the posterior vitreous in eyes with exudative age-related macular degeneration, AMD, non-exudative AMD and in normal eyes. This is a prospective, cross-sectional study. B-scan ultrasonography and Optical Coherence Tomography, OCT were performed in 165 patients older than 65 years with any AMD and in 22 patients older than 65 years with normal eyes in order to diagnose the eyes with complete posterior vitreous detachment, PVD and the eyes with persistent central vitreomacular adhesion, VMA. All patients were selected from the outpatient clinic of the Ophthalmology Department in the University Hospital of Patras. Fundus Fluoroangiography, FFA was used in order to determine the development of exudative AMD from non-exudative AMD. Follow up time was 48 months. 16/171 eyes with exudative AMD (9.36%) had complete PVD, and the rest 155/171 (90.64%) had central VMA. Eleven of 138 eyes with non-exudative AMD (7.97%) had complete PVD and the remaining 127 eyes (92.03%) had central VMA. During the 48 months of the study, 28 eyes, all with central VMA progressed to exudative AMD. Vitreomacular adhesion is associated with both exudative and non-exudative AMD. Progression of the non-exudative eyes to exudative AMD seems to be lower in eyes with complete PVD. On the other hand, the progression of normal eyes to exudative AMD appears to be independent of the posterior vitreous status. Larger and longer studies need to replicate these findings and support the potential of a protective role of complete posterior vitreous detachment in the evolution of the disease.

Subretinal Pigment Epithelium Illumination Combined With Focal Electroretinogram and Visual Acuity for Early Diagnosis and Prognosis of Non-Exudative Age-Related Macular Degeneration: New Insights for Personalized Medicine.

PurposeTo evaluate the correlation between functional visual acuity and focal electroretinograms (fERGs) and morphological abnormalities in the retinal pigment epithelium and outer retinal atrophy (RORA) assessed by subretinal illumination (SRI) parameter at optical coherence tomography (OCT) examinations as signs of early disease in early and intermediate non-exudative age-related macular degeneration (ne-AMD).MethodsOne hundred forty-one eyes of 74 patients were retrospectively evaluated. A subgroup of patients (34/74) had a follow-up of at least 1 year. The study included both cross-sectional and longitudinal analyses. All eyes were assessed by OCT to measure the macular outer nuclear layer thickness, extent of ellipsoid zone interruption, absence or presence of drusen/reticular pseudodrusen in the foveal and perifoveal fields, and the SRI area closest to the fovea. Additionally, fERGs were performed.ResultsIn the cross-sectional analysis, visual acuity and fERG amplitude were correlated (P < 0.01) with the SRI area. The fERG amplitude was correlated (P < 0.01) with the extent of ellipsoid zone interruption and tended to be lower in reticular pseudodrusen compared with drusen. In the longitudinal analysis, fERG amplitudes and outer retinal thickness tended to decrease on average by 15% and 18%, respectively, after 1 year of follow-up. The baseline RORA area, but not fERG amplitude or visual acuity, significantly predicted with 77% accuracy (P < 0.01) morphological deterioration, which was determined by an increase in the RORA area after 1 year.ConclusionsFunctional visual acuity and its morphological correlations can be assessed in early and intermediate ne-AMD eyes. SRI, as a result of RORA, is a potential predictor of ne-AMD progression in a short-term follow-up.Translational RelevanceSRI assessment, an objective method to measure RORA, is a potential biomarker for non-exudative AMD progression.

Thiol and Glutathione Homeostasis Parameters as Plasma Biomarkers of Oxidative Stress in Age-Related Macular Degeneration

Purpose: To determine extracellular thiol homeostasis and intracellular glutathione homeostasis as a plasma biomarker for oxidative stress and to compare these parameters in non-exudative/exudative AMD patients and healthy individuals. Method: 30 non-exudative AMD, 28 exudative AMD, and 36 age-matched healthy control subjects enrolled to the study. Extracellular total thiol, native thiol, disulphide amounts and intracellular oxidized/reduced glutathione levels of subjects were determined, and disulphide/thiol and oxidized/reduced glutathione percent ratios were calculated. Results: In comparison with the control group both non-exudative and exudative AMD patients had higher plasma disulfide levels (20.5(4.8) vs. 4(3.1), p<0.001 and 22.5(7.5) vs. 15.4(3.1), p<0.001; respectively) and higher disulphide/thiol (6.64(2.57) vs. 5.4(1.9), p=0,002 and 7.05(3.14) vs. 5.4(1.9), p<0.001; respectively), in addition to higher oxidized glutathione levels (64.6(40.8) vs. 27.3(21.9), p=0.015 and 73.9(44.1) vs. 27.3(21.9), p=0.002; respectively) and oxidized/reduced glutathione ratio(6.48(8.35) vs. 3.14(3.31), p=0,034 and 10.21(10.28) vs. 3.14(3.31), p=0,003; respectively). Although there was no significant difference between groups in term of total thiol (361.5(61.6), 355.1(87.7) and 340.9(72.4), respectively, p=0,585); native thiol (318.8(62.4), 307.1(73.7) and 299.3(79.2), respectively, p=0,382); total reduced glutathione (986.3(282.1), 871.5(271.6) and 881.8(290.9), respectively, p=0.344) and native reduced glutathione (873.4(367.6), 723.7(379.0) and 797.2(307.5), respectively, p=0,113). However, there was no significant difference between non-exudative and exudative AMD groups in terms of both extracellular thiol homeostasis and intracellular glutathione homeostasis. Conclusion: Greater extent of both extracellular disulphide and intracellular oxidized glutathione production occurred in AMD patients compared to age-matched healthy controls indicates the role of increased oxidative stress in AMD development. Further studies are needed to confirm the pathophysiologic role of homeostasis in these buffer systems in AMD.

Влияние мелатонина на продукцию провоспалительных цитокинов при хирургии катаракты у пациентов с неэкссудативной формой ВМД

Background. In recent years, the studies concerning the role of melatonin and cytokines in the development of various pathological processes have been conducted in various fields of medicine, including ophthalmology. Purpose. To study the effect of melatonin-containing therapy on the concentration of pro-inflammatory cytokines, melatonin in the lacrimal fluid and melatonin in the blood serum in patients with non-exudative AMD in the course of surgery for uncomplicated senile cataract. Material and methods. During the study, 2 groups have been formed: group 1 (main group) – 40 patients who took the drug «Melaxen» (3 mg at night) for 3 months before the surgery; group 2 (control group) – 40 patients who did not take melatonin before the surgery. Laboratory studies of blood samples and tear fluid for the hormone melatonin and cytokines (IL-1β and IL-8) were carried out using enzyme-linked immunosorbent assay. Results. When taking exogenous melatonin in patients of the main group, the concentration of melatonin in blood serum and lacrimal fluid was significantly higher during the entire observation period, compared with the control group patients. Also, melatonin-containing therapy contributed to a decrease in the concentration of pro-inflammatory IL-8 and IL-1β cytokines. A correlation analysis of the level of cytokines and the content of melatonin in lacrimal fluid of the examined groups patients revealed a significantly higher feedback before surgery and significantly weaker and direct after the surgery. Conclusion. An increase in the concentration of melatonin in the lacrimal fluid after surgery for senile cataract in both groups indicates a possible increase in its production in response to surgical treatment and is aimed at reducing the activity of the local inflammatory process. The obtained results allow us to conclude that melatonin has an antiinflammatory effect.

Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers

We propose a hybrid sequential prediction model called “Deep Sequence”, integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3 months) and long term (within 21 months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3 months (0.96 ± 0.02 AUCROC) and within 21 months (0.97 ± 0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.

Choriocapillaris Flow Deficits and Treatment-Naïve Macular Neovascularization Secondary to Age-Related Macular Degeneration.

PurposeTo evaluate choriocapillaris (CC) flow deficits (FD) in eyes with treatment-naïve macular neovascularization (MNV) and to compare CC FD around exudative versus nonexudative MNV.MethodsTreatment-naïve eyes with a diagnosis of either exudative or nonexudative AMD and type 1 MNV were included. Normal control eyes were age-matched to each AMD eye one to one. En face optical coherence tomography angiograms were analyzed for percentage of CC FD (FD%) in two concentric 500 µm rings, ring 1 and ring 2, surrounding the dark halo around MNV. The mean CC FD% in ring 1 and ring 2 was evaluated for each eye. A secondary analysis was similarly carried out to investigate the differences in CC FD% in exudative versus nonexudative treatment-naïve MNV.ResultsTwenty-three eyes with treatment-naïve MNV were age matched with 23 normal controls. The mean CC FD% was significantly greater in both rings in the MNV versus the normal control group (P < 0.05) and was significantly greater in the inner ring, closer to the lesion, than the outer ring. The mean FD% was also greater in both rings in the exudative versus the nonexudative MNV group, but this difference did not reach statistical significance.ConclusionsThe CC FD% was greater in the area surrounding MNV versus age-matched normal controls and in the ring closer to the MNV lesion. Further, CC FD was greater in eyes with exudative versus nonexudative MNV in both rings surrounding the associated dark halo, although this difference was not statistically significant.

Vascularized drusen: a cross-sectional study

BackgroundTo investigate whether neovascularization may arise and be detectable in drusen, as reported in histopathologic studies, by OCTA prior to developing exudation and to assess its prevalence in a cohort of patients with intermediate AMD.MethodsRetrospective cross-sectional study of 128 patients with intermediate AMD recruited as part of a separate ongoing clinical trial conducted at multiple large tertiary referral retina clinics. One hundred and twenty-eight consecutive patients with exudative AMD in one eye and intermediate non-exudative AMD in the fellow eye were enrolled and analyzed between September 2015 and March 2017.ResultsSD-OCTA identified vascularization within drusen in 7 of 128 eyes, for a prevalence of 5.5%. A total of 12 instances of vascularized drusen were noted. Out of the 12 vascularized drusen noted, 7 were located in the parafoveal region or subfoveal region and 5 was in the extrafoveal region. 9 of 12 instances of vascularized drusen exhibited a uniform sub-RPE hyperreflectivity, whilst 3 of 12 exhibited more heterogenous reflectivity. In all 12 instances, FA images failed to identify the neovascular nature of vascularized drusen.ConclusionsOur results demonstrate the utility of SD-OCTA for the diagnosis of vascularized drusen in patients with intermediate non-exudative AMD. Longitudinal studies are needed to delineate the evolution and conversion risk of these lesions over time, which can be of substantial clinical relevance.

Increased Nonexudative Age-Related Macular Degeneration Diagnosis Among Medicare Beneficiaries With Rheumatoid Arthritis.

PurposeAMD is the leading cause of blindness in the United States. The role of secondary inflammatory disease on AMD progression is largely unknown. Here we investigate the association between AMD and rheumatoid arthritis (RA), using MarketScan data for patients aged ≥65 years on Medicare.MethodsBaseline data were extracted for subjects with at least two International Classification, Ninth Revision (ICD-9) diagnosis codes of RA and control subjects (no RA) and were matched at baseline by propensity score. Matched cohort data were extracted post-baseline time and examined up to 4.5 years of follow-up for ICD-9 diagnosis code AMD records. Multivariable regression models compared risk of an AMD diagnosis post-baseline for RA subjects and matched controls. Days until first AMD diagnosis between RA patients and controls was examined using survival analysis.ResultsRisk of new AMD diagnosis was elevated in RA patients (odds ratio [OR] 2.08; 95% confidence interval [CI] 1.98–2.18), with an increase in nonexudative AMD patients (P < 0.0001). Risk was elevated in female (n = 27,548) (OR 1.11; 95% CI 1.05–1.17) compared with male (n = 9704; P < 0.001) patients. The time to first AMD diagnosis was shorter for RA subjects than controls (P < 0.0001).ConclusionsOur analysis provides support of association between RA diagnosis and increased nonexudative AMD diagnosis.

SYSTEMIC BETA-BLOCKERS AND RISK OF PROGRESSION TO NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To determine whether oral beta-blockers (BBs) are associated with the development of neovascular age-related macular degeneration (nAMD). Retrospective cohort study of patients from 2000 to 2014 using data from a large national U.S. insurer's administrative medical claims database. Patients with nonexudative AMD who initiated (index date) BB, a calcium channel blocker (CCB), an angiotensin-converting enzyme/angiotensin receptor blocker, or a diuretic. Patients were excluded for <2 years in the plan before the index date, any history of nAMD or diagnosis, or treatment for an ocular disease that could be confused with nAMD. Hazard of developing of nAMD was the main outcome measure. Primary analysis compared BB with CCB patients with BB versus the other classes as secondary analyses. In addition, a sensitivity analysis was performed between BB and CCB cohorts using 1:1 propensity score matching. Cox proportional hazard regression was performed to estimate the hazard ratio (HR) of developing nAMD at 90, 180, and 365 days for BB. Covariates of interest included demographic information, year of index date, number of antihypertensive medications, and other comorbid systemic conditions. Eighteen thousand seven hundred and fifty-four BB patients and 12,784 CCB patients met criteria for inclusion. After controlling for covariates, patients on BB had a lower hazard for nAMD at both 90 and 180 days than patients on CCB (HRs: 0.67-0.71; P < 0.01 for both) and diuretics (HRs: 0.55-0.62; P < 0.01). Patients on BB versus angiotensin-converting enzyme/angiotensin receptor blocker at all time points and BB versus CCB and diuretics at 365 days did not have a significantly lower association with nAMD (HR: 0.73-0.85; P > 0.06 for all comparisons). A sensitivity analysis using propensity score matching yielded similar results with patients on BB significantly less likely to develop nAMD at 90 and 180 days (HR: 0.70-0.76; P < 0.049 for both) but not at 365 days (HR: 0.88; P = 0.30) compared with patients on CCB. No evidence was found that BB usage increased the hazard for nAMD relative to other antihypertensive medications.

Patterns of Fundus Autofluorescence Lifetimes In Eyes of Individuals With Nonexudative Age-Related Macular Degeneration.

PurposeTo investigate fundus autofluorescence (FAF) lifetimes in patients with nonexudative AMD.MethodsA total of 150 eyes of 110 patients (mean age: 73.2 ± 10.7 years) with nonexudative AMD, as well as a healthy group of 57 eyes in 38 subjects (mean age: 66.5 ± 8.7 years), were included. Investigations were conducted at the University Eye Clinic in Jena, Germany, as well as the Moran Eye Center in Salt Lake City, Utah, USA, using the Heidelberg Engineering Spectralis-based fluorescence lifetime imaging ophthalmoscope (FLIO). A 30° retinal field centered at the fovea was investigated. FAF decays were detected in short (498–560 nm) and long (560–720 nm, LSC) spectral channels. The mean fluorescence lifetimes (τm) were calculated. Optical coherence tomography scans and fundus photographs were also recorded.ResultsIn patients with nonexudative AMD, FLIO shows a ring-shaped pattern of prolonged τm in the LSC. This pattern occurs in all patients with AMD (including very early stages) and in one-third of the healthy controls. FAF lifetimes were longer with more advanced stages. The presence of drusen is associated with prolonged τm when compared with the healthy fundus, but drusen identification is difficult with FLIO only.ConclusionsFLIO detects a clear pattern of changes within the fundus, which appears to be AMD-associated. These changes are already visible in early AMD stages and not masked by the presence of other coexisting retinal diseases. These findings may be useful for the early diagnosis of AMD and to distinguish AMD from other retinal diseases.

Beyond Retinal Layers: A Deep Voting Model for Automated Geographic Atrophy Segmentation in SD-OCT Images.

PurposeTo automatically and accurately segment geographic atrophy (GA) in spectral-domain optical coherence tomography (SD-OCT) images by constructing a voting system with deep neural networks without the use of retinal layer segmentation.MethodsAn automatic GA segmentation method for SD-OCT images based on the deep network was constructed. The structure of the deep network was composed of five layers, including one input layer, three hidden layers, and one output layer. During the training phase, the labeled A-scans with 1024 features were directly fed into the network as the input layer to obtain the deep representations. Then a soft-max classifier was trained to determine the label of each individual pixel. Finally, a voting decision strategy was used to refine the segmentation results among 10 trained models.ResultsTwo image data sets with GA were used to evaluate the model. For the first dataset, our algorithm obtained a mean overlap ratio (OR) 86.94% ± 8.75%, absolute area difference (AAD) 11.49% ± 11.50%, and correlation coefficients (CC) 0.9857; for the second dataset, the mean OR, AAD, and CC of the proposed method were 81.66% ± 10.93%, 8.30% ± 9.09%, and 0.9952, respectively. The proposed algorithm was capable of improving over 5% and 10% segmentation accuracy, respectively, when compared with several state-of-the-art algorithms on two data sets.ConclusionsWithout retinal layer segmentation, the proposed algorithm could produce higher segmentation accuracy and was more stable when compared with state-of-the-art methods that relied on retinal layer segmentation results. Our model may provide reliable GA segmentations from SD-OCT images and be useful in the clinical diagnosis of advanced nonexudative AMD.Translational RelevanceBased on the deep neural networks, this study presents an accurate GA segmentation method for SD-OCT images without using any retinal layer segmentation results, and may contribute to improved understanding of advanced nonexudative AMD.

Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging.

PurposeTo analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD.MethodsEyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study–like target centered on the fovea.ResultsTwenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 μm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD.ConclusionsOur fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD.

Peripapillary RNFL thickness in nonexudative versus chronically treated exudative age-related macular degeneration

ObjectiveTo compare the peripapillary retinal nerve fibre layer (RNFL) thickness in nonexudative versus exudative age-related macular degeneration (wet AMD) eyes treated chronically with intravitreal injections of anti–vascular endothelial growth factor (anti-VEGF). DesignCross-sectional study. ParticipantsTwenty-nine patients with unilateral wet AMD with at least 12 prior intravitreal anti-VEGF injections and 2 years of therapy were analyzed. The fellow eye with nonexudative (dry) AMD with no prior treatment served as the control group. MethodsAll patients were prospectively enrolled from a single academic subspecialist practice. Bilateral spectral-domain optical coherence tomography (Cirrus SD-OCT; Carl Zeiss Meditec, Dublin, Calif.) of the peripapillary RNFL was performed on all pairs of eyes. Optic nerve head (ONH) parameters were also computed. The primary outcome was mean difference in peripapillary RNFL thickness compared between the treated and the nontreated eyes. ResultsMean RNFL in the chronically treated eyes (95.0 [95% CI 89.8–100.2] μm) was significantly greater than the nontreated fellow eyes (89.9 [95% CI 85.5–94.3] μm) (p = 0.01). Quadrantic optic nerve analysis revealed the temporal RNFL to be greater in the treated group (p = 0.02), whereas all other locations were similar. No significant differences were found between the 2 groups in any ONH parameters. ConclusionsThis study demonstrated no deleterious optic nerve RNFL thinning in a series of wet AMD eyes with long-term repetitive exposure to intravitreal anti-VEGF injections. Furthermore, we observed that those with wet AMD have a relatively thickened temporal peripapillary RNFL layer, which is an important association for all observers of optic nerve disease.

Henle fiber layer phase retardation changes associated with age-related macular degeneration.

To quantify and compare phase retardation amplitude and regularity associated with the Henle fiber layer (HFL) between nonexudative AMD patients and age-matched controls using scanning laser polarimetry (SLP) imaging. A scanning laser polarimeter was used to collect 15 × 15° macular-centered images in 25 patients with nonexudative AMD and 25 age-matched controls. Raw image data were used to compute macular phase retardation maps associated with the HFL. Consecutive, annular regions of interest from 0.5 to 3.0° eccentricity, centered on the fovea, were used to generate intensity profiles from phase retardation data and analyzed with two complementary techniques: a normalized second harmonic frequency (2f) of the fast Fourier Transform (FFT) analysis and a curve fitting analysis using a 2f sine function. Paired t-tests were used to compare the normalized 2f FFT magnitude at each eccentricity between the two groups, the eccentricity that yielded the maximum normalized 2f FFT between paired individuals across the two groups, and curve fitting RMS error at each eccentricity between the two groups. Normalized 2f FFT components were lower in the AMD group at each eccentricity, with no difference between the two groups in the maximum normalized 2f FFT component eccentricity. The root-mean-square (RMS) error from curve fitting was significantly higher in the AMD group. Phase retardation changes in the central macula indicate loss and/or structural alterations to central cone photoreceptors in nonexudative AMD patients. Scanning laser polarimetry imaging is a noninvasive method for quantifying cone photoreceptor changes associated with central macular disease.

Correlation Between Subfoveal Choroidal Thickness and the Severity or Progression of Nonexudative Age-Related Macular Degeneration

To investigate the correlation between subfoveal choroidal thickness (SFChT) and the severity or progression of nonexudative AMD. One hundred seventy-six eyes of 114 patients with nonexudative AMD were included in this study. These eyes were divided into stages I through IV, based on the Age-Related Eye Disease Study (AREDS) classification of fundus findings. Using enhanced depth imaging from spectralis domain optical coherence tomography (SD-OCT), the central retinal thickness (CRT), SFChT, and parafoveal choroidal thickness (PFChT) were measured. The area of geographic atrophy (GA) was measured from fundus autofluorescence (FAF) images, and the progression of GA was calculated using RegionFinder software. The age-adjusted SFChT levels were lower at later stages of nonexudative AMD. These measurements were as follows: 266.68 ± 12.60 (stage I: 28 eyes), 263.34 ± 9.87 (stage II: 48 eyes), 200.55 ± 8.83 (stage III: 71 eyes), and 188.34 ± 13.72 (stage IV: 29 eyes) (P = 0.0028). The age-adjusted SFChT was also negatively correlated with the best corrected visual acuity (BCVA) (estimate, -0.001; P = 0.0006). Among 16 eyes with GA at baseline, SFChT showed a negative correlation with the baseline area of GA (r = 0.5521, P = 0.0133). In addition, GA progressed more rapidly during the mean follow up of 22.19 ± 9.08 months when the SFChT was lower at baseline (r = 0.5658, P = 0.0112). Subfoveal choroidal thickness is closely related to the BCVA, the severity of nonexudative AMD, as well as the rate of GA progression. Subfoveal choroidal thickness may be a predictor of disease progression in GA cases.

Aurintricarboxylic Acid Inhibits Complement Activation, Membrane Attack Complex, and Choroidal Neovascularization in a Model of Macular Degeneration

Immunocytochemical and genetic data implicate a significant role for the activation of complement in the pathology of AMD. Individuals homozygous for a Y402H polymorphism in Factor H have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and RPE relative to individuals homozygous for the wild-type allele. An R95X polymorphism in C9, a protein necessary for the final assembly of MAC, is partially protective against the formation of choroidal neovascularization (CNV) in AMD patients. Aurintricarboxylic Acid (ATA) is a small molecule inhibitor of MAC. Our hypothesis was that attenuation of the formation of MAC on ocular tissues by ATA may protect mice against laser-induced CNV. The ability of ATA to inhibit human complement-mediated cell lysis, inhibit formation of human MAC, and inhibit formation of tubes by endothelial cells was examined in vitro. Subsequently, the Bruch's membrane of adult mice was damaged using an argon laser, followed by intravitreal injection of ATA. One week later, choroidal flat mounts from these mice were stained for the presence of MAC, endothelial cells, and macrophages. ATA protects cells from human complement-mediated lysis, attenuates assembly of the MAC, and inhibits tube formation by endothelial cells in vitro. ATA also attenuates CNV, MAC deposition, and macrophage infiltration in a murine model of exudative AMD. ATA warrants further study as a potential drug for the treatment of exudative and nonexudative AMD.

Age-related macular degeneration: Effects of a short-term intervention with an oleaginous kale extract—a pilot study

ObjectiveAge-related macular degeneration (AMD) is a multifactorial degenerative disease of the retina, which accounts for slowly progressive visual impairment in the elderly. An increased dietary intake of xanthophylls is suggested to be inversely related to the risk of macular disease. MethodsThe present study was designed as a randomized, double-blind, placebo-controlled, parallel trial examining the influence of a short-term intervention with an oleaginous extract of Brassica oleracea var. sabellica L. (kale) on plasma xanthophyll concentrations and the optical density of the macular pigment xanthophylls (MPOD). Twenty patients with non-exudative AMD were recruited for a 10-wk study period (2-wk run-in, 4-wk intervention, 4-wk washout). All participants received 50 mL of a beverage containing either an oleaginous extract of kale (kale) or refined rapeseed oil (placebo). The verum product provides 10 mg lutein and 3 mg zeaxanthin per day. ResultsThe concentrations of the xanthophylls in plasma and the MPOD increased significantly in the kale group after 4 wk of intervention. The successive washout period resulted in a significant decline of the values in plasma and macula. The values at the end of the study were still significantly higher than the initial values. Nevertheless, the improvements did not persist over 4 wk of washout. ConclusionThe distribution of the xanthophylls in the macula seems to be more dynamic than originally assumed.