Advanced age-related macular degeneration and risk factors in eyes with pachydrusen.

The risk of progression to advanced age-related macular degeneration (AMD) varies depending on the type of drusen. This retrospective longitudinal study included 248 eyes of 156 patients with pachydrusen without advanced AMD at baseline. Macular neovascularization (MNV) and geographic atrophy (GA) were evaluated. Risk factors for progression to advanced AMD were determined using multivariate Cox regression analysis. The mean age at baseline was 65.4 ± 9.1 years, and the mean follow-up duration was 6.40 ± 3.58 years. The mean total number of pachydrusen and macular pachydrusen were 4.10 ± 2.85 and 2.27 ± 1.81 per eye, respectively. Pachydrusen was accompanied by other types of drusen in 4.8% (12 eyes) of eyes at baseline. During follow-up, MNVs occurred in 2.8% (seven eyes), including polypoidal choroidal vasculopathy (PCV six eyes); however, no GA occurred. Regarding risk factors for progression to neovascular AMD, age (p = 0.023) and macular pigmentary changes (p = 0.014) were significantly associated with MNV development. The cumulative incidence of MNV was significantly higher in the group with macular pigmentary changes (17.39% vs. 0.57% at 10 years; p = 0.0005). The number of macular pachydrusen and the presence of MNV in the fellow eye did not show a statistically significant relationship with MNV development. Age and macular pigmentary changes are risk factors for MNV development in the eyes with pachydrusen. Eyes with pachydrusen appear to have a risk profile for advanced AMD that is different from that of AMD eyes with drusen or drusenoid deposits other than pachydrusen.

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration.

PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. RESULTS: The mean EZ thickness differences between the SDD+D and drusen-only groups were (in µm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. CONCLUSION: Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.

Spatial Analysis Reveals Vascular Changes in Retinal and Choroidal Vessel Perfusion in Intermediate AMD With Reticular Pseudodrusen.

Purpose: To examine the effect of reticular pseudodrusen (RPD) on retinal and choroidal vessel perfusion (VP) topography in intermediate age-related macular degeneration (iAMD) using refined spatial analyses. Methods: This was a retrospective cross-sectional study of 120 individuals with 30 iAMDRPD, 60 iAMDno_RPD, and 30 normal eyes, propensity-score matched by age, sex, and presence of cardiovascular-related disease. VP of the superficial and deep retinal and choriocapillaris vascular slabs was assessed from 6 × 6-mm optical coherence tomography angiography (OCTA) scans divided into 126 × 126 grids, with adjustment for various person- and eye-level factors. Grid-wise VP differences (%) among the groups were spatially assessed according to analyses based on the Early Treatment for Diabetic Retinopathy Study (ETDRS), eccentricity (µm), and degree (°). Results: VP was significantly decreased between iAMDRPD and iAMDno_RPD, across all vascular slabs in various ETDRS sectors (up to -2.16%; 95% confidence interval, -2.99 to -1.34; P < 0.05). Eccentricity analyses revealed more complex patterns: a bisegmented relationship where VP in iAMDRPD eyes decreased linearly toward 1000 µm then returned toward similar values as iAMDno_RPD, plateauing around 2000 µm in the superficial and 3000 µm in the deep retina (R2 = 0.57-0.9; P < 0.001). Degree-based analysis further showed that the greatest VP differences in iAMDRPD eyes were commonly located superiorly and nasally across all vascular slabs (P < 0.05). Conclusions: RPD appears to compound the vascular impact of iAMD, displaying complex spatial patterns beyond the ETDRS sectors. This highlights the importance of considering spatial delineations for future work regarding the role of RPD and vascular dysfunction.

En Face Optical Coherence Tomography Illustrates the Trizonal Distribution of Drusen and Subretinal Drusenoid Deposits in the Macula.

PURPOSE: To analyze the topographic distribution of macular drusen and subretinal drusenoid deposits (SDDs) using single-capture en face spectral domain optical coherence tomography (SD-OCT) imaging. DESIGN: Retrospective case series. METHODS: Analysis of 33 eyes of 20 patients with evidence of SDDs. Structural en face OCT images were reconstructed using a 40-µm-thick slab positioned from 48 to 88 µm above the Bruch membrane. The Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and a rod/cone density map were overlaid on the en face OCT images, and the distribution of different subtypes of SDDs and macular drusen were assessed. RESULTS: A total of 31 eyes (94%) showed a trizonal distribution pattern of drusen and SDDs. Whereas small to large drusen tended to aggregate in the central circle, dot SDDs predominated in the inner ring and the inner portion of the outer ring of the ETDRS grid and ribbon SDDs localized to the outer ring and outside the ETDRS grid. Of note, drusen colocalized to the region of greatest cone density, whereas ribbon SDDs colocalized to the area of greatest rod density. The dot SDDs mapped to the intermediate region with mixed rod and cone representation. CONCLUSION: Dot and ribbon subtypes of SDDs and macular drusen show a characteristic trizonal distribution. The locations of these lesions colocalize according to the different densities of the cones and rods in the retina and may reflect varying pathophysiological activities of these photoreceptor subtypes.

Subretinal drusenoid deposits, age-related macular degeneration, and cardiovascular disease.

Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.

Optical coherence tomography biomarkers in early and intermediate age-related macular degeneration: A clinical guide.

Advanced forms of age-related macular degeneration (AMD), characterised by atrophic and neovascular changes, are a leading cause of vision loss in the elderly population worldwide. Prior to the development of advanced AMD, a myriad of risk factors from the early and intermediate stages of AMD have been published in the scientific literature over the last years. The ability to precisely recognise structural and anatomical changes in the ageing macula, altogether with the understanding of the individual risk implications of each one of them is key for an accurate and personalised diagnostic assessment. The present review aims to summarise updated evidence of the relative risk conferred by diverse macular signs, commonly seen on optical coherence tomography, in terms of progression to geographic atrophy or macular neovascularization. This information may also serve as a basis for tailored follow-up monitoring visits.

Calpain-specific breakdown fragment in human drusen.

PURPOSE: With aging and age-related macular dystrophy (AMD), proteolytic fragments are deposited in extracellular drusen located between the RPE and Bruch's membrane. Localized hypoxia may be a risk factor for AMD. Our hypothesis is that following hypoxia, activation of proteolytic enzymes called calpains may cause proteolysis/degeneration of retinal cells and RPE. No direct evidence has yet demonstrated activation of calpains in AMD. The purpose of the present study was to identify calpain-cleaved proteins in drusen. METHODS: Seventy-six (76) drusen were analyzed in human eye sections from six normal and twelve AMD human donor eyes. The sections were subjected to immunofluorescence for the calpain-specific 150 kDa breakdown product from α-spectrin, SBDP150 - a marker for calpain activation, and for recoverin - a marker for photoreceptor cells. RESULTS: Among 29 nodular drusen, 80% from normal eyes and 90% from AMD eyes stained positive for SBDP150. Among 47 soft drusen, mostly from AMD eyes, 72% stained positive for SBDP150. Thus, the majority of both soft and nodular drusen from AMD donors contained SBDP150. CONCLUSIONS: SBDP150 was detected for the first time in soft and nodular drusen from human donors. Our results suggest that calpain-induced proteolysis participates in the degeneration of photoreceptors and/or RPE cells during aging and AMD. Calpain inhibitors may ameliorate AMD progression.

RETINAL OPTICAL COHERENCE TOMOGRAPHY IMAGING BIOMARKERS: A Review of the Literature.

PURPOSE: The aim of this literature review was to summarize novel optical coherence tomography (OCT) imaging biomarkers that have recently been described in the literature and are frequently encountered clinically. METHODS: The literature was reviewed to identify novel OCT biomarkers reported to date. A descriptive summary of all terms and representative illustrations were provided to highlight the most relevant features. RESULTS: Thirty-seven OCT terminologies were identified. The vitreomacular interface disorder group included the four stages of epiretinal membrane, macular pseudohole, tractional lamellar hole (LH), degenerative LH, cotton ball sign, and foveal crack sign. The age-related macular degeneration group included outer retinal tubulation, multilayered pigment epithelial detachment, prechoroidal cleft, onion sign, double-layer sign, complete outer retinal atrophy, complete retinal pigment epithelium and outer retinal atrophy, and reticular pseudodrusen. The uveitic disorder group consisted of bacillary layer detachment, syphilis placoid, rain-cloud sign, and pitchfork sign. The disorders relating to the toxicity group included flying saucer sign and mitogen-activated protein kinase (MEK) inhibitor-associated retinopathy. The disorders associated with the systemic condition group included choroidal nodules and needle sign. The pachychoroid spectrum group included pachychoroid and brush border pattern. The vascular disorder group included pearl necklace sign, diffuse retinal thickening, disorganization of retinal inner layers, inner nuclear layer microcysts, hyperreflective retinal spots, paracentral acute middle maculopathy, and acute macular neuroretinopathy. The miscellaneous group included omega sign (ω), macular telangiectasia (type 2), and omega sign (Ω). CONCLUSIONS: Thirty-seven OCT terminologies were summarized, and detailed illustrations consolidating the features of each biomarker were included. A nuanced understanding of OCT biomarkers and their clinical significance is essential because of their predictive and prognostic value.

Prevalence and determinants of subretinal drusenoid deposits in patients' first-degree relatives.

PURPOSE: Subretinal drusenoid deposits (SDDs) are distinct extracellular alteration anterior to the retinal pigment epithelium (RPE). Given their commonly uniform phenotype, a hereditary predisposition seems likely. Hence, we aim to investigate prevalence and determinants in patients' first-degree relatives. METHODS: We recruited SDD outpatients at their visits to our clinic and invited their relatives. We performed a full ophthalmic examination including spectral domain-optical coherence tomography (SD-OCT) and graded presence, disease stage of SDD as well as percentage of infrared (IR) en face area affected by SDD. Moreover, we performed genetic sequencing and calculated a polygenic risk score (PRS) for AMD. We conducted multivariable regression models to assess potential determinants of SDD and associations of SDD with PRS. RESULTS: We included 195 participants, 123 patients (mean age 81.4 ± 7.2 years) and 72 relatives (mean age 52.2 ± 14.2 years), of which 7 presented SDD, resulting in a prevalence of 9.7%. We found older age to be associated with SDD presence and area in the total cohort and a borderline association of higher body mass index (BMI) with SDD presence in the relatives. Individuals with SDD tended to have a higher PRS, which, however, was not statistically significant in the multivariable regression. CONCLUSION: Our study indicates a potential hereditary aspect of SDD and confirms the strong association with age. Based on our results, relatives of SDD patients ought to be closely monitored for retinal alterations, particularly at an older age. Further longitudinal studies with larger sample size and older relatives are needed to confirm or refute our findings.

Fundus autofluorescence of retinal atrophy progression between fundus flavimaculatus and extensive macular atrophy with pseudo-drusen.

OBJECTIVE: To analyze the progression of macular atrophy in Fundus Flavimaculatus (FFM) versus Extensive Macular Atrophy with Pseudo-drusen (EMAP), using Spectralis® RegionFinder™ tool. METHODS: Retrospective review of patients diagnosed with FFM and EMAP. Ophthalmic imaging features were reviewed by retina specialists for each patient in both eyes. The atrophic zones were measured on fundus autofluorescence acquisitions using the RegionFinder™ tool. RESULTS: FFM group included 16 eyes of 8 patients, whose mean age was 61.42 ± 10.76 years, with a mean 4.54 ± 2.73 years of follow-up. EMAP group contained 16 eyes of 8 patients, whose mean age was 67.81 ± 3.03 years (p = 0.12), with a mean 3.62 ± 2.49 years of follow-up (P = 0.63). The atrophy progression rates were 3.73 ± 6.75 and 0.70 ± 0.98 mm2/year, for EMAP and FFM respectively. The yearly rate of progression of the atrophic areas in EMAP was 5.3 times higher than in FFM (mm2/year) (p = 0.03). CONCLUSION: The progression of the atrophy in eyes with Extensive Macular Atrophy with Pseudo-drusen (EMAP) is significantly more rapid than in eyes with Fundus Flavimaculatus (FFM).

Central macular choriocapillaris impairment as a manifestation of microvascular disease in eyes with subretinal drusenoid deposits.

BACKGROUND/OBJECTIVES: Microvascular alterations and choroidal impairment are emerging as a pathologic pathway in age-related macular degeneration (AMD). This study aimed to evaluate the central macular choriocapillaris (CC) in eyes with subretinal drusenoid deposits (SDD) and the retinal microvasculature in patients with early AMD phenotypes. SUBJECTS/METHODS: This was an institutional, multicentric observational cross-sectional study. Ninety-nine eyes of 99 subjects; 33 eyes with SDD only, 33 eyes with conventional drusen (CD) only, and 33 eyes of healthy age-matched subjects were included. Comprehensive ophthalmologic examination and optical coherence tomography angiography (OCTA) was performed. The central macular flow area of the CC was analysed in the SDD group and the vessel density of the retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) was analysed in the SDD and CD groups using automated OCTA output parameters. RESULTS: The flow area of the CC in the SDD group was significantly reduced (p ≤ 0.001) with respect to the healthy control group. There was a trend of reduction of vessel density of the SCP and the DCP in the SDD and CD group with respect to controls, although this did not reach statistical significance. CONCLUSIONS: OCTA data in the present report corroborate the role of vascular damage in early AMD with CC impairment in the central macular area in eyes with SDD.

Application of artificial intelligence system for screening multiple fundus diseases in Chinese primary healthcare settings: a real-world, multicentre and cross-sectional study of 4795 cases.

BACKGROUND/AIMS: This study evaluates the performance of the Airdoc retinal artificial intelligence system (ARAS) for detecting multiple fundus diseases in real-world scenarios in primary healthcare settings and investigates the fundus disease spectrum based on ARAS. METHODS: This real-world, multicentre, cross-sectional study was conducted in Shanghai and Xinjiang, China. Six primary healthcare settings were included in this study. Colour fundus photographs were taken and graded by ARAS and retinal specialists. The performance of ARAS is described by its accuracy, sensitivity, specificity and positive and negative predictive values. The spectrum of fundus diseases in primary healthcare settings has also been investigated. RESULTS: A total of 4795 participants were included. The median age was 57.0 (IQR 39.0-66.0) years, and 3175 (66.2%) participants were female. The accuracy, specificity and negative predictive value of ARAS for detecting normal fundus and 14 retinal abnormalities were high, whereas the sensitivity and positive predictive value varied in detecting different abnormalities. The proportion of retinal drusen, pathological myopia and glaucomatous optic neuropathy was significantly higher in Shanghai than in Xinjiang. Moreover, the percentages of referable diabetic retinopathy, retinal vein occlusion and macular oedema in middle-aged and elderly people in Xinjiang were significantly higher than in Shanghai. CONCLUSION: This study demonstrated the dependability of ARAS for detecting multiple retinal diseases in primary healthcare settings. Implementing the AI-assisted fundus disease screening system in primary healthcare settings might be beneficial in reducing regional disparities in medical resources. However, the ARAS algorithm must be improved to achieve better performance. TRIAL REGISTRATION NUMBER: NCT04592068.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

HYPERREFLECTIVE FOCI NOT SEEN AS HYPERPIGMENTARY ABNORMALITIES ON COLOR FUNDUS PHOTOGRAPHS IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the prognostic value of quantifying optical coherence tomography (OCT)-defined hyperreflective foci (HRF) that do not correspond to hyperpigmentary abnormalities (HPAs) on color fundus photographs (CFPs)-HRF (OCT+/CFP-) -when considered in addition to HPA extent, for predicting late age-related macular degeneration development. This study sought to understand the impact of HRF (OCT+/CFP-) extent on visual sensitivity. METHODS: Two hundred eighty eyes from 140 participants with bilateral large drusen underwent imaging and microperimetry at baseline, and then 6-monthly for 3-years. The extent of HPAs on CFPs and HRF (OCT+/CFP-) on OCT was quantified at baseline. Predictive models for progression to late age-related macular degeneration, accounting for drusen volume and age, were developed using HPA extent, with and without HRF (OCT+/CFP-) extent. The association between HPA and HRF (OCT+/CFP-) extent with sector-based visual sensitivity was also evaluated. RESULTS: Incorporating HRF (OCT+/CFP-) extent did not improve the predictive performance for late age-related macular degeneration development ( P ≥ 0.32). Increasing HPA and HRF (OCT+/CFP-) extent in each sector were independently and significantly associated with reduced sector-based visual sensitivity ( P ≤ 0.004). CONCLUSION: The addition of HRF (OCT+/CFP-) extent to HPA extent did not improve the prediction of late age-related macular degeneration development. HRF (OCT+/CFP-) extent was also independently associated with local reductions in visual sensitivity, after accounting for HPAs.

Drusen and Other Retinal Findings in People With IgA Glomerulonephritis.

PURPOSE: Retinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy and compared their location and composition with those for drusen in age-related macular degeneration. DESIGN: Immunohistological case series of eyes of patients with IgA nephropathy, and a comparison eye with age-related macular degeneration. METHODS: Donor eyes from 4 individuals (3 male, 1 female, aged 40-80 years) with biopsy-proven IgA nephropathy and kidney failure were examined for the presence of drusen, and location and composition using antibodies for vitronectin, IgA, IgM, IgG, C3, and C1q. Results were compared with those for drusen in macular degeneration without IgA nephropathy. RESULTS: All 4 donors had sparse, subretinal pigment epithelium drusen of 55-65 mm diameter that stained for vitronectin but not for IgA or complement. All donors had retinal capillaries and choriocapillaris staining for IgA. The youngest donor (female, 40) had rare deposits in the outer nuclear layer that stained for IgA, but not for vitronectin. The oldest donor (male, 82) had large cystlike spaces in the inner nuclear and plexiform layers, and smaller cysts in the outer nuclear layer, with no staining for IgA or complement. CONCLUSIONS: Retinal drusen are uncommon in IgA nephropathy, even with kidney failure. Drusen in IgA nephropathy resemble drusen found in age-related macular degeneration. IgA-staining deposits in the outer nuclear layer were likely due to systemic deposition of IgA and complement activation. The nature of cystic spaces is unknown. Further analysis of the retinas of people with glomerulonephritis is recommended.

Epidemiology of geographic atrophy and its precursor features of intermediate age-related macular degeneration.

Globally age-related macular degeneration (AMD) is a leading cause of blindness with a significant impact on quality of life. Geographic atrophy (GA) is the atrophic late form of AMD and its prevalence increases markedly with age with around 1 in 5 persons aged 85 and above having GA in at least one eye. Bilateral GA leads to severe visual impairment thus posing a significant burden on patients, careers and health providers. The incidence and prevalence of GA varies across different geographic regions, with the highest rates in those of European ancestry. Although heterogeneity in definitions of GA and reporting strategy can explain some of the discrepancies, the data overall are consistent in showing a lower prevalence in other ethnicities such as those of Asian heritage. This is at present unexplained but thought to be due to the existence of protective factors such as differences in eye pigmentation, diet, environmental exposures and genetic variability. This review covers key aspects of the prevalence and incidence of the ocular precursor features of GA (large drusen, pigmentary abnormalities and reticular pseudo-drusen), the late stage of GA and factors that have been known to be associated with modifying risk including systemic, demographic, environment, genetic and ocular. Understanding the global epidemiology scenario is crucial for the prevention of and management of patients with GA.

Prevalence of peripheral retinal findings in retinal patients using ultra-widefield pseudocolor fundus imaging.

Ultra-widefield retinal imaging is increasingly used in ophthalmology and optometry practices to image patients identifying peripheral abnormalities. However, the clinical relevance of these peripheral retinal abnormalities is unclear. This cross-sectional study aims to firstly validate a new grading system, secondly, assess the prevalence of peripheral retinal abnormalities in retinal patients, and finally understand how peripheral findings may associate with retinal disease. Ultra-widefield pseudocolor fundus images were taken from the eyes of clinic patients. Demographic data and clinical diagnosis for each patient was noted. The grading system was validated using masked retinal specialists. Logistic regression identified associations between retinal disease and peripheral retinal findings. Using the grading system, inter-observer agreement was 76.1% with Cohen's Kappa coefficient 0.542 (p < 0.0001) and the test-retest agreement was 95.1% with Kappa 0.677(p < 0.0001). 971 images were included, with 625 eyes (64.4%) having peripheral abnormalities. Peripheral drusen was the most common abnormality (n = 221, 22.76%) and correlated with age-related macular degeneration (p < 0.001). Novel correlations were also identified between diabetic retinopathy and retinal pigmentation as well as pigmentary degeneration. This study provides a validated system for identifying peripheral abnormalities and adds to literature highlighting peripheral retinal associations with retinal disease which would benefit from further study.

Multimodal Imaging of Reticular Pseudodrusen in Turkish Patients.

Objectives: To investigate the presence and prevalence of reticular pseudodrusen (RPD) in patients with age-related macular degeneration using multiple imaging modalities and to compare the sensitivity and specificity of these modalities in the detection of RPD. Materials and Methods: Images from a total of 198 consecutive patients were analyzed prospectively. Color fundus photography, red-free imaging, spectral domain optical coherence tomography (SD-OCT), infrared and blue reflectance (BR) imaging, fundus autofluorescence (FAF), enhanced-depth imaging OCT (EDI-OCT), fundus fluorescein angiography (FFA) and indocyanine green angiography were performed. RPD was diagnosed in the presence of relevant findings in at least two of the imaging methods used. Results: RPD were detected in 149 eyes (37.6%). In the detection of RPD, color fundus photography, red-free photography, SD-OCT, infrared, FAF, BR, and FFA imaging had sensitivity values of 50%, 57.7%, 91.6%, 95%, 74.6%, 65.7%, and 28.2% and specificity values of 99.6%, 100%, 98.4%, 94.6%, 100%, 99.6%, and 69.8%, respectively. Conclusion: Infrared imaging had the highest sensitivity. SD-OCT combined with infrared imaging was the most sensitive imaging technique for detecting RPD. The high specificity of FAF, red-free, and BR imaging may be useful to confirm a diagnosis of RPD.

INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.

BACKGROUND: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration. METHODS: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes. RESULTS: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells. CONCLUSION: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

Spatial Cluster Patterns of Retinal Sensitivity Loss in Intermediate Age-Related Macular Degeneration Features.

Purpose: To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD). Methods: One-hundred individuals (53 iAMD, 47 normal) underwent 10-2 mesopic microperimetry testing in one eye. Pointwise sensitivities (dB) were corrected for age, sex, iAMD status, and co-presence of co-localized key iAMD features: drusen load, pigmentary abnormalities, and reticular pseudodrusen (RPD). Clusters (labeled by ranks of magnitude C-2, C-1, C0) were derived from pointwise sensitivities and then assessed by quadrants and eccentricity/rings. Results: Two clusters of decreased sensitivities were evident in iAMD versus normal: C-2, -1.67 dB (95% CI (confidence intervals), -2.36 to -0.98; P < 0.0001); C-1, -0.93 dB (95% CI, -1.5 to -0.36; P < 0.01). One cluster of decreased sensitivity was independently associated each with increased drusen load (13.57 µm increase per -1 dB; P < 0.0001), pigmentary abnormalities (C-1: -2.23 dB; 95% CI, -3.36 to -1.1; P < 0.01), and RPD (C-1: -1.07 dB; 95% CI, -2 to -0.14; P < 0.01). Sensitivity loss in iAMD was biased toward the superior and central macula (P = 0.16 to <0.0001), aligning with structural distributions of features. However, sensitivity loss associated with drusen load also extended to the peripheral macula (P < 0.0001) with paracentral sparing, which was discordant with the central distribution of drusen. Conclusions: Drusen load, pigmentary abnormalities, and RPD are associated with patterns of retinal sensitivity loss commonly demonstrating superior and central bias. Results highlighted that a clinical focus on these three key iAMD features using structural measures alone does not capture the complex, spatial extent of vision-related functional impairment in iAMD. Translational Relevance: Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.