Age-related Macular Degeneration Eyes Research Articles

A Novel Smartphone-Based Color Test for Detection of Color Vision Defects in Age Related Macular Degeneration.

Purpose To evaluate the efficacy of the smartphone-based K-color test to detect color defects in patients with Age-related Macular Degeneration (AMD). Methods 88 patients (n = 135 eyes) with AMD and 28 controls (n = 53 eyes) underwent color testing with the Hardy–Rand–Rittler (H-R-R), the K-color test, and the Ishihara test. The K-color test presents randomized colored shapes in decreasing steps of intensity, providing also a record system for result tele-transmission. Sensitivity, specificity, and reliability were examined to investigate the validity of the novel test. 26 participants with AMD also completed a questionnaire regarding the feasibility of the test. Results Linear mixed-effects models indicated a significant difference (p < 0.001) between AMD and normal eyes. The areas under the curve (AUC) were estimated to be 0.897 [95% CI: 0.841–0.952], 0.943 [95% CI: 0.901–0.984], and 0.931 [95% CI: 0.886–0.977] for the red, green, and blue color, respectively. Based on the H-R-R, the sensitivity of the test was 0.79, 0.90, and 0.95 for the red, green, and blue colors, respectively, and specificity was 0.88 for all colors. The new test recognized more abnormal cases than the Ishihara (sensitivity of 0.98 and 1.0 and specificity of 0.48 and 0.38 for red and green colors, respectively). Test-retest reliability was found to be high for the red [ICC = 0.996 (0.990–0.999)], green [ICC = 0.974 (0.929–0.990)], and blue [ICC = 0.992 (0.981–0.997)] colors. The majority of the asked participants stated that they could easily perform the test. Conclusion The K-color test was found to be sensitive and specific in detecting color defects in AMD patients. The K-color test may serve as a useful tool both for patients and their physicians.

Long-term outcomes of drusenoid pigment epithelium detachment in intermediate AMD treated with 577 nm subthreshold micropulse laser: a preliminary clinical study.

To evaluate the long-term anatomical and visual outcomes of drusenoid pigment epithelial detachment (D-PED) in intermediate age-related macular degeneration (AMD) eyes treated with 577 nm yellow subthreshold micropulse laser (SML). In this retrospective study, 21 eyes of 16 patients with D-PED in intermediate AMD were consecutively included and assessed. All the eyes were treated with 577 nm SML in several sessions according to D-PED growth status. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were assessed at the initial visit and after treatment. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate the D-PED lifecycle by volumetric calculations. Regression analysis was used to determine the breakpoint, growth, and collapse rate of the D-PED lesions. The progression to advanced AMD was also documented. All the eyes were treated with SML for 2.9±1.0 sessions. The mean follow-up period was 25.3±12.6mo. The BCVA was stable from the baseline to final visit. All the eyes were categorized into two groups according to the anatomical changes of the D-PED lesion: the collapse group (n=6, 28.6%) and non-collapse group (n=15, 71.4%). The change in logMAR BCVA did not differ significantly between the collapse group 0.00 (-0.31, 0.85) and non-collapse group 0.00 (0.00, 0.00; P=1). Regression analysis showed that the growth rate was significantly higher in the collapse group (0.090±0.095 mm3/mo) than in the non-collapse group (0.025±0.035 mm3/mo; P<0.001). One eye (4.8%) developed macular neovascularization at 11mo after SML treatment in the non-collapse group. Three eyes (14.3%) developed geographic atrophy (GA) in the collapse group. Compared to the natural course of D-PED reported by previous studies, our results preliminarily show that SML can alleviate visual loss and possibility of progression to advanced AMD in eyes with D-PED in intermediate AMD. A controlled clinical trial needs to further verify the benefit of the intervention.

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment

To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1–3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan–Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

Outcomes after switching eyes that were stable on aflibercept to ranibizumab versus continuing aflibercept in neovascular age-related macular degeneration.

To describe outcomes of neovascular age-related macular degeneration (nAMD) eyes that were stable on aflibercept but switched to ranibizumab compared to eyes maintained on aflibercept over the same period. In this retrospective cohort study, eyes switched from aflibercept to ranibizumab due to intraocular inflammation (IOI) concerns with aflibercept were identified. Data was gathered from 3 visits pre-switch, switch visit (Sw), and 3 visits post-switch (P1, P2, P3). Similar data was gathered on eyes eligible to switch but continued on aflibercept with the middle visit considered the "presumed switch." Outcome measures included visual acuity (VA) and central foveal thickness (CFT). A total of 142 eyes were analyzed with 71 in each of the switch and aflibercept groups. In the switch group, mean CFT increased from 165.7µm at Sw to 184.7µm at P1 (p = 0.009), 180.9µm at P2 (p = 0.007), and 183.3µm at P3 (p = 0.004). VA changed from logMAR 0.43 (20/54) at Sw to 0.49 (20/61) at P1 (p = 0.02), 0.54 (20/69) at P2 (p = 0.008), and 0.53 (20/68) at P3 (p = 0.04). In the aflibercept group, no significant change in CFT was found over the same period. VA changed from logMAR 0.56 (20/72) at the "presumed switch" to 0.58 (20/76) at P1 (p = 0.085), 0.62 (20/83) at P2 (p = 0.001), and 0.59 (20/77) at P3 (p = 0.14). nAMD eyes that were stable or improving on aflibercept but were switched to ranibizumab worsened, while those in a comparable group maintained on aflibercept remained fairly stable, suggesting a potential efficacy difference between the two drugs.

Progression of age-related macular degeneration in eyes with abnormal fundus autofluorescence in a Japanese population: JFAM study report 3.

PurposeTo evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD.MethodsSixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters.ResultsOf the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86).ConclusionThe fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

A histological study of atherosclerotic characteristics in age-related macular degeneration

This study investigated the pathogenesis of age-related macular degeneration (AMD) using histological methods that are commonly used for atherosclerotic vascular disease (ASVD). 1 normal, 3 early dry AMD, and 1 late dry AMD eyes were obtained from the Lions Eye Bank of Oregon and systematically dissected. They were stained with hematoxylin and eosin, Oil red O, Masson, Elastica van Gieson, Alizarin red, and Prussian blue. Additionally, the normal and late dry AMD eyes were immunostained for a-smooth muscle actin, CD45, and CD68 with Nile red and DAPI. Correlations were found between severity of AMD and lipid accumulation in the deep sclera (+), numbers of drusen between the Bruch's membrane and retinal pigment epithelium (RPE) (+), amount of collagen in the deep sclera (+), and amount of elastin in the deep sclera (-) (P < 0.1). Geographic atrophy, RPE detachment, and abnormal capillary shape and distribution in the choriocapillaris were observed in the fovea of late AMD. There were no stenosis, plaque, hemorrhage, and calcification. Additionally, late AMD tended to have higher smooth muscle thicknesses of the choroidal vascular walls, lower numbers of T lymphocytes in the choroid, and higher numbers of macrophages near the RPE and in the choroid relative to normal (P < 0.1). Macrophages-derived foam cells were detected near the Bruch's membrane in late AMD. Therefore, the present study showed many histological characteristics of ASVD in AMD, which suggests an association between them; however, there were also some histological characteristics of ASVD that were not found in AMD, which indicates that there exist pathogenic differences between them. The results generally support the vascular model of AMD, but some details still need clarification.

Computer-aided diagnosis of retinopathy based on vision transformer

Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are two common retinal diseases for elder people that may ultimately cause irreversible blindness. Timely and accurate diagnosis is essential for the treatment of these diseases. In recent years, computer-aided diagnosis (CAD) has been deeply investigated and effectively used for rapid and early diagnosis. In this paper, we proposed a method of CAD using vision transformer to analyze optical coherence tomography (OCT) images and to automatically discriminate AMD, DME, and normal eyes. A classification accuracy of 99.69% was achieved. After the model pruning, the recognition time reached 0.010 s and the classification accuracy did not drop. Compared with the Convolutional Neural Network (CNN) image classification models (VGG16, Resnet50, Densenet121, and EfficientNet), vision transformer after pruning exhibited better recognition ability. Results show that vision transformer is an improved alternative to diagnose retinal diseases more accurately.

A mutation in transmembrane protein 135 impairs lipid metabolism in mouse eyecups

Aging is a significant factor in the development of age-related diseases but how aging disrupts cellular homeostasis to cause age-related retinal disease is unknown. Here, we further our studies on transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wild-type, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlate with visual function deficits. Further analysis revealed that expression of many genes involved in lipid metabolism are changed due to the Tmem135 mutation. Consistent with these changes, we found increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with transcriptomic datasets of human AMD donor eyes. We found similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD.

OCULAR SURFACE TEMPERATURE DIFFERENCES IN RETINAL VASCULAR DISEASES.

To define the effect of age-related macular degeneration (AMD) and diabetic retinopathy (DR) on the ocular thermographic profile. This retrospective cross-sectional study included subjects diagnosed with DR or AMD between January and April 2019. Individuals without ocular disease served as controls. A thermal imaging camera was used for ocular surface temperature (OST) acquisition. The mean temperatures of the medial cantus, lateral cantus, and cornea were calculated. Thermographic images were obtained from 133 subjects (260 eyes, 97 DR and 163 AMD) and 48 controls (55 eyes). Ocular surface temperature was higher among patients with AMD and lowest among patients with DR (P < 0.001). A subgroup analysis revealed that eyes with diabetic macular edema had significantly higher OSTs than DR eyes without diabetic macular edema. Moreover, the OST in eyes with diabetic macular edema was similar to the measurements of the AMD group. There were no differences in OSTs between neovascular and nonneovascular AMD eyes. Although AMD and DR are considered posterior segment conditions, their effect on OST implies that the entire globe is involved. Although both conditions result from similar multifactorial pathophysiologic changes, the differences in OST between DR and AMD might be due to dissimilarity in the balance of pathologic processes involved in each condition. Further research is required to better understand the pathophysiology of these diseases and their effect on OST as well as to determine the effect of vasculature, circulation, and tissue metabolism on ocular temperature.

Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients

BackgroundTo identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings.MethodsAqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes.ResultsThe samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1β, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 macular neovascularization (MNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1β, but not VEGF (p = 0.083). However, type 2 MNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040).ConclusionInflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 MNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1β should be modulated. And the presence of SRF in MNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines.

BACILLARY LAYER DETACHMENT: MULTIMODAL IMAGING AND HISTOLOGIC EVIDENCE OF A NOVEL OPTICAL COHERENCE TOMOGRAPHY TERMINOLOGY: Literature Review and Proposed Theory.

To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging. The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions. A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. This review serves to strengthen the OCT nomenclature "bacillary layer detachment," based on specific reflectance information obtained by OCT and previously published histologic observations.

Clinical and Functional Characteristics of Secondary Geographic Atrophy Against the Background of Exudative Age-Related Macular Degeneration

Background.Studies demonstrate the need for long-term follow-up of patients with wet age-related macular degeneration (AMD) treated with inhibitors of angiogenesis to monitor long-term vision outcomes and assess the safety of antiangiogenic therapy in relation to the risk of secondary geographic atrophy.&#x0D; Aims to determine the characteristic clinical and functional signs of secondary GA that developed against the background of wet AMD.&#x0D; Methods.In 22 patients (25 eyes) with wet AMD and 18 healthy subjects comparable in age and sex standard ophthalmological and instrumental studies were performed and photopic electroretinograms (ERGs) were recorded according to ISCEV standards, flicker-ERGs, multifocal ERGs and electrooculogram.&#x0D; Results.The appearance of the area of secondary atrophy against the background of wet AMD in eyes treated with inhibitors of angiogenesis is clinically indistinguishable from areas of geographic atrophy that developed as an outcome of dry AMD. The ERG-signs of secondary atrophy are described, which are similar to the biomarkers of primary atrophy and specifically differ from them. Secondary atrophy is characterized by the dependence of the increase in the b/a ratio on the atrophic area, reducing of the 8.3 Hz-flicker-ERG amplitude in the absence of 24 Hz-flicker ERG changes. In eyes with secondary atrophy, a significant decrease in the density of the multifocal ERG P1-peak was shown not only in the first hexagon but also in the parafoveal zone. The electrooculography results showed a sharper dark troughs decrease in with an increase in Ardens ratio in patients with secondary atrophya on the background of wet AMD, in contrast to the previously described changes in primary geographic atrophy.&#x0D; Conclusion.Comparison of the change in the b/a ratio with secondary atrophy area in patients with wet AMD may have clinical implications for assessing retinal dysfunction and predicting visual function. Secondary atrophy is associated with a pronounced inhibition of photoreceptor activity with better preservation of cone bipolar cells. The ERG and electrooculography data taking together indicate a more significant dysfunction of the retinal pigment epithelium in GA against the background of wet AMD and the associated deterioration of photoreceptor function than the changes characterizing primary geographic atrophy.

Targeting nanocomposites with anti-oxidative/inflammatory/angiogenic activities for synergistically alleviating macular degeneration

Treatment of age-related macular degeneration (AMD) is a challenge due to frequent intravitreal injection of drugs, low retention time, risk of infection, need for drugs with multiple therapeutic efficacies, such as anti-inflammatory, anti-oxidant, and anti-angiogenesis. Herein, we demonstrate the synthesis and application of metformin-loaded gold-poly(catechin) core-shell nanoparticles (MF/Au@pCH NPs) as a potential nanocomposite for the treatment of AMD, via sustained drug release to the lesion site. To achieve targeted drug delivery to macula of the AMD eye, we immobilized the complement component protein C3 to form C3-MF/Au@pCH NPs. With this targeted nanocomposite, we aim to utilize the anti-oxidative and anti-inflammatory properties of phenol-rich poly(catechin) and the anti-angiogenic activity of metformin for the synergistic recovery from macular degeneration. The pharmacological efficacy of a single intravitreal dose of C3-MF/Au@pCH NPs is superior to Au@pCH NPs and MF/Au@pCH NPs. In addition, C3-MF/Au@pCH NPs exhibited good in vitro and in vivo biocompatibility. Our study suggests the potential of this multifunctional modality for translation into a clinical intervention for AMD therapy, due to the sustained release of drugs and targeted drug delivery. The findings of this work reveals that Au@pCH NPs could be extended to the treatment of various other diseases with the loading of relative drugs.

The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

Disturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β = + 0.18, p = 0.0007, β = + 0.18, p = 0.0008, respectively) and to dry AMD (β = + 0.17, p = 0.00003 for both ATC and AVC and β = − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs = − 0.13, p < 0.05; Rs = − 0.12; p < 0.05, Rs = − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs = − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

The Spectrum of Central Choriocapillaris Abnormalities on Swept-Source Optical Coherence Tomography Angiography in the Fellow Eye of Unilateral Exudative Age-Related Macular Degeneration Patients: From Flow Deficits to Subclinical Non-Exudative Neovascularization.

We evaluated the spectrum of choriocapillaris (CC) abnormalities in the fellow eyes of unilateral exudative age-related macular degeneration (AMD) patients using swept-source optical coherence tomography angiography (SS-OCTA). Fellow eyes of unilateral exudative AMD patients were prospectively included between May 2018 and October 2018. Patients underwent a multimodal imaging including a SS-OCTA. Demographics and clinical findings were analyzed. The estimated prevalence of macular neovascularization (MNV) was computed. Number and size of flow deficits (FDs) and percentage of flow deficits (FD%) were computed on the compensated CC flow images with the Fiji software. We included 97 eyes of 97 patients (mean age was 80 ± 7.66 years, 39 males, 58 females). The prevalence of MNV in the studied eyes was 8.25% (8/97 eyes). In the 89 non-neovascular eyes, FD% averaged 45.84% ± 11.63%, with a corresponding total area of FDs of 4.19 ± 1.12 mm2. There was a higher prevalence of drusenoid pigment epithelial detachment in eyes with subclinical neovascularization (p = 0.021). Fellow eyes with unilateral exudative AMD encompassed a series of CC abnormalities, from FDs of the aging CC to subclinical non-exudative MNV.

Assessment of Subfoveal Choroidal Thickness with SD-OCT in Eyes with Different Stages of Age-Related Macular Degeneration (AMD)

Purpose: The aim of the study was to compare the subfoveal choroidal thickness (SFCT) with the use of Spectral-Domain OCT in eyes with AMD of different stages.&#x0D; Methods: The participants comprised of 30 age-matched normal eyes as controls (Group 1), 19 with early-AMD eyes (Group 2), 14 with intermediate-AMD eyes (Group 3) and 29 with advanced (neovascular) AMD eyes (Group 4). All subjects underwent routine ophthalmologic examination. The choroid images, which included the subfoveal choroidal thickness images, obtained using Spectral-Domain Optical Coherence Tomography (and the technique of Enhanced Depth Imaging-EDI). All of the participants volunteered in this study and remained anonymous due to the protection of their personal data.&#x0D; Results: 92 eyes with age greater than 65 years old were included. The mean subfoveal choroidal thickness was 260.93 ± 46.54 μm in age-matched normal eyes, 255.10 ± 44.85 μm in early AMD eyes, 230.92 ± 45.70 μm in intermediate AMD eyes and 206.82 ± 44.43 μm in advanced (neovascular) AMD eyes. There were statistically significant differences in the measurement results between the 4th Group with the 1st Group (P&lt;0.0001) and 2nd Group (P=0.0006) respectively, meaning that SFCT was greater in normal and early AMD eyes.&#x0D; Conclusion: Decreasing subfoveal choroidal thickness was demonstrated in the progression of AMD, especially in the advanced AMD eyes compared to normal or early AMD eyes.

Differentiating Exudative Macular Degeneration and Polypoidal Choroidal Vasculopathy Using OCT B-Scan

Although polypoidal choroidal vasculopathy (PCV) is best diagnosed with indocyanine green angiography (ICGA), ICGA is often unavailable or not ordered. OCT is widely available, and OCT B-scan can visualize polypoidal lesions diagnostic of PCV as inverted U-shaped elevations of the retinal pigment epithelium (RPE) with heterogeneous reflectivity and sometimes ring-shaped lesions within the polypoidal lesion. This study aims to differentiate findings between eyes diagnosed with PCV or typical exudative age-related macular degeneration (AMD) using ICGA and then compares findings noted on the OCT B-scan line scan in each group. Retrospective, chart review. Clinical features of eyes with PCV and typical exudative AMD were compared by using ICGA. Eyes with PCV were evaluated for inverted U-shaped polypoidal lesions, which are the main differentiating finding of PCV from typical exudative AMD. Data collected included presence of subretinal fluid (SRF), macular edema or intraretinal edema, subretinal hyperreflective material (SHRM), and retinal pigment epithelial detachment (RPED). These findings were evaluated in 2 parts: baseline and after 6 to 9 months of antiangiogenic therapy. Additionally, analysis was performed for the presence of polypoidal lesions before and after treatment. Presence of inverted U-shaped lesions on OCT B-scan following treatment. A total of 112 eyes of 106 patients were included. A total of 69 eyes were diagnosed with PCV, and 43 eyes were diagnosed with typical exudative AMD. Compared with AMD eyes, PCV eyes had an increased prevalence of SRF at baseline and after 6 to 9 months of treatment, but the prevalence of macular edema, SHRM, and RPED was similar at baseline and at 6 to 9 months after treatment. In PCV eyes, the presence of visible polypoidal lesions decreased from 56.5% to 24.6% after treatment. If PCV is suspected in an anti-vascular endothelial growth factor (VEGF)-resistant case of exudative AMD, in the absence of ICGA availability, it is important to look at the baseline OCT B-scan before therapy for evidence of polypoidal lesions. The characteristic inverted U-shaped elevation was present in more than half of PCV eyes on OCT B-scan at baseline but disappeared after antiangiogenic therapy in 56.4% of cases in which this was initially identified. Subretinal fluid was more prevalent in PCV eyes than non-PCV AMD eyes.

Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration

To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

Association of Macular Thickness With Age and Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), An Ancillary Study of the Women's Health Initiative.

PurposeTo evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2.MethodsTotal retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69–78, 78–83, and 83–101 years) and AMD outcomes.ResultsMean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity.ConclusionsIn this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity.Translational RelevanceThe study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.

Topographic Distribution and Progression of Soft Drusen Volume in Age-Related Macular Degeneration Implicate Neurobiology of Fovea

PurposeTo refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes.MethodsIn a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas.ResultsSixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold.ConclusionsNormalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.