Reticular Pseudodrusen Research Articles

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

To examine spatial patterns of retinal sensitivity loss in the three key features of intermediate age-related macular degeneration (iAMD). 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. 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. 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. Defining the spatial patterns of retinal sensitivity loss in iAMD can facilitate a targeted visual field protocol for iAMD assessment.

Identification of retinal thickness and blood flow in age-related macular degeneration with reticular pseudodrusen.

To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen (RPD) as an early detection strategy for age-related macular degeneration (AMD). This retrospective study included 24 subjects (33 eyes) with RPD and 25 heathy control subjects (34 eyes). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) of the retinal posterior poles were investigated with optical coherence tomography angiography (OCTA). Retinal thicknesses and vessel densities were analyzed statistically. The general retinal thicknesses of RPD eyes were significantly decreased (95%CI -14.080, -0.655; P=0.032). The vessel densities of DCP in RPD eyes were significantly increased in the global (95%CI 1.067, 7.312; P=0.027), parafoveal (95%CI 0.417, 5.241; P=0.022), and perifoveal (95%CI 0.181, 6.842; P=0.039) quadrants. However, the vessel densities of the SCP were rarely increased in the eyes with RPD. The thinning of retinas in the RPD group suggests a reduction in the number of cells. Additionally, the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply, possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina. This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.

Subclinical Angioid Streaks with Pseudodrusen: A New Phenotype of Age-Related Macular Degeneration.

To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences. Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7years), 73 eyes of 46 patients (81 ± 7years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%. Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.

A semi-automated pipeline for quantifying drusen-like deposits in human induced pluripotent stem cell-derived retinal pigment epithelium cells

Age-Related Macular Degeneration (AMD) is a highly prevalent form of retinal disease amongst Western communities over 50 years of age. A hallmark of AMD pathogenesis is the accumulation of drusen underneath the retinal pigment epithelium (RPE), a biological process also observable in vitro. The accumulation of drusen has been shown to predict the progression to advanced AMD, making accurate characterisation of drusen in vitro models valuable in disease modelling and drug development. More recently, deposits above the RPE in the subretinal space, called reticular pseudodrusen (RPD) have been recognized as a sub-phenotype of AMD. While in vitro imaging techniques allow for the immunostaining of drusen-like deposits, quantification of these deposits often requires slow, low throughput manual counting of images. This further lends itself to issues including sampling biases, while ignoring critical data parameters including volume and precise localization. To overcome these issues, we developed a semi-automated pipeline for quantifying the presence of drusen-like deposits in vitro, using RPE cultures derived from patient-specific induced pluripotent stem cells (iPSCs). Using high-throughput confocal microscopy, together with three-dimensional reconstruction, we developed an imaging and analysis pipeline that quantifies the number of drusen-like deposits, and accurately and reproducibly provides the location and composition of these deposits. Extending its utility, this pipeline can determine whether the drusen-like deposits locate to the apical or basal surface of RPE cells. Here, we validate the utility of this pipeline in the quantification of drusen-like deposits in six iPSCs lines derived from patients with AMD, following their differentiation into RPE cells. This pipeline provides a valuable tool for the in vitro modelling of AMD and other retinal disease, and is amenable to mid and high throughput screenings.

Investigation of the choroidal structure in non-neovascular age-related macular degeneration patients with reticular pseudodrusen

BackgroundThis study aimed to compare choroidal thickness, total choroidal area (TCA), luminal area (LA), stromal area (SA) and choroidal vascularity index (CVI) in patients with reticular pseudodrusen (RPD) and drusen. MethodsA total of 100 eyes of 100 patients with non-neovascular age related macular degeneration (AMD) with five or more medium drusen (63–125 µm) and RPD in two or more quadrants were recruited to the study. 48 eyes of 48 patients with RPD were assigned as Group 1 and 52 eyes of 52 patients with drusen were assigned as Group 2. 40 right eyes of 40 healthy subjects were included as controls. Patients with neovascular AMD or advanced non-neovascular AMD were excluded from the study. After a detailed ophthalmic examination, infrared reflectance images and OCT with enhanced depth imaging mode was obtained from all patients. TCA, SA, LA and CVI were calculated using the Image J program. The data were analyzed for statistics using SPSS software. ResultsThe female/male ratio was 56/44 in the patient groups and 20/20 in the control group. The mean age was 73.63±6.14 (61–91) years for Group 1 and 69.43± 6.97 (59–87) years for Group 2 (p=0.005). The mean age of Group 3 patients was 71.14±8.17 (60–79) years and was statistically similar to Groups 1 and 2 (p=0.09 and p=0.12, respectively). Choroidal thickness, TCA, SA and LA were significantly lower in Group 1 (p<0.001). CVI and foveal thicknesses were not significantly different between Group 1 and 2 (p=0.214 and p=0.384 respectively). CVI was significantly lower in Group 3 (p<0.01). RPD was most commonly seen in the superior quadrant followed by temporal, nasal, and inferior quadrants. ConclusionsTCA, SA and LA, which reflect choroidal vasculature, were decreased in patients with RPD. These parameters can help evaluate the pathophysiology of the disease.

LOW-DOSE SUPPLEMENTATION WITH RETINOL IMPROVES RETINAL FUNCTION IN EYES WITH AGE-RELATED MACULAR DEGENERATION BUT WITHOUT RETICULAR PSEUDODRUSEN.

The aim of this study was to determine the functional impact of oral vitamin A supplementation in patients with intermediate age-related macular degeneration with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation. Five patients with intermediate age-related macular degeneration and without RPD (AMD group; mean ± SD age 78.0 ± 4.7 years) and seven with RPD (RPD group; age 74.1 ± 11.2 years) were supplemented with 16,000 IU of vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8, and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities, and the low-luminance quality of life questionnaire. In the linear mixed model, rod intercept time improved significantly in the AMD group (mean [95% CI] change -1.1 minutes [-1.8; -0.5] after 4 weeks ( P < 0.001) and -2.2 min [-2.9 to -1.6] after 8 weeks of vitamin A supplementation ( P < 0.001). The dark adaptation cone plateau also significantly improved (i.e., more sensitive cone threshold) at 4 and 8 weeks ( P = 0.026 and P = 0.001). No other parameters improved in the AMD group, and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum vitamin A levels measurable in both groups after supplementation ( P = 0.024 and P = 0.013). Supplementation with 16,000 IU vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients and/or may reflect the higher variability observed in the functional parameters for this group.

Clinical Characteristics and Progression of Geographic Atrophy in a Japanese Population

To elucidate the clinical characteristics and progression rate of geographic atrophy (GA) associated with age-related macular degeneration (AMD) in a Japanese population. Retrospective, multicenter, observational study. A total of 173 eyes from 173 patients from six university hospitals in Japan were included. Of 173 study eyes, 101 eyes from 101 patients were included in the follow-up group. All patients were Japanese, aged ≥ 50 years, and had definite GA associated with AMD in at least one eye. The GA area was measured semi-automatically using fundus autofluorescence (FAF) images. In the follow-up group followed for more than six months with FAF images, the GA progression rate was calculated by two methods: mm2/year and mm/year using the square-root transformation (SQRT) strategy. Simple and multiple linear regression analyses were used to identify the baseline factors associated with the GA progression rate. Clinical characteristics of GA and the GA progression rate. The mean age was 76.8 ± 8.8 years and 109 (63.0%) were males. Sixty-two (35.8%) patients had bilateral GA. The mean GA area was 3.06 ± 4.00 mm2 (1.44 ± 1.00 mm [SQRT]). Thirty-eight eyes (22.0%) were classified as having pachychoroid GA. Drusen and reticular pseudodrusen were detected in 115 (66.5%) and 73 eyes (42.2%), respectively. The mean subfoveal choroidal thickness was 194.7 ± 105.5 μm. In the follow-up group (follow-up period: 46.2 ± 28.9 months), the mean GA progression rate was 1.01 ± 1.09 mm2/year (0.23 ± 0.18 mm/year [SQRT]). In the multivariable analysis, baseline GA area [SQRT] (P=0.002) and the presence of reticular pseudodrusen (P<0.001) were significantly associated with a greater GA progression rate [SQRT]. Certain clinical characteristics of GA in Asian populations may differ from those in Caucasians. Asian patients with GA showed male-dominance and relatively thicker choroid than Caucasian patients. There was a group with GA without drusen but with features of pachychoroid. The GA progression rate in this Asian population was relatively lower than that in Caucasians. Large GA and reticular pseudodrusen were associated with a greater GA progression rate.

Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration

PurposeTo determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.DesignInterreader agreement study.ParticipantsTwelve readers from 6 reading centers.MethodsAll readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.Main Outcome MeasuresInterreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1).ResultsWhen evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30).ConclusionsThere was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Interreader agreement study. Twelve readers from 6 reading centers. All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Interreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1). When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). There was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.

Role of sleep-disordered breathing in age-related macular degeneration

AimsTo examine the association between obstructive sleep apnoea (OSA) and age-related macular degeneration (AMD), and the subphenotype of AMD with reticular pseudodrusen (RPD).MethodsCase–control study with 351 participants (211 AMD and...

Decreased Macular Choriocapillaris Perfusion in Eyes With Macular Reticular Pseudodrusen Imaged With Swept-Source OCT Angiography.

To determine if macular reticular pseudodrusen (RPD) were associated with markers of impaired macular choroidal perfusion, we investigated measurements of macular choriocapillaris (CC) flow deficits (FDs), CC thickness, and mean choroidal thickness (MCT) in eyes with macular RPD compared with normal eyes and eyes with soft drusen. Eyes with intermediate age-related macular degeneration (iAMD) and normal eyes underwent 6 × 6 mm swept-source optical coherence tomography angiography (SS-OCTA) imaging to diagnose macular RPD, occupying over 25% of the fovea-centered 5 mm diameter circle, and measure outer retinal layer (ORL) thickness, CC FDs, CC thickness, MCT, and choroidal vascularity index (CVI) using previously published strategies within the same fovea-centered 5 mm circle. Ninety eyes were included; 30 normal eyes, 30 eyes with soft drusen, and 30 eyes with macular RPD. The RPD eyes showed higher macular CC FDs than normal eyes (P < 0.001) and soft drusen eyes (P = 0.019). Macular CC thickness was decreased in RPD eyes compared with normal eyes (P < 0.001) and soft drusen eyes (P = 0.016). Macular MCT in RPD eyes was thinner than normal eyes (P = 0.005) and soft drusen eyes (P < 0.001). No statistically and clinically significant differences were found in the ORL thickness and CVI measurements between RPD eyes and the other two groups (all P > 0.05). Eyes with macular RPD had decreased macular CC perfusion, decreased CC thickness, and decreased MCT measurements compared with normal and soft drusen eyes, suggesting that RPD may result from impaired choroidal perfusion.

Yellow Subthreshold Micropulse Laser in Retinal Diseases: An In-Depth Analysis and Review of the Literature.

Yellow subthreshold micropulse laser (YSML) is a retinal laser capable of inducing a biologic response without causing thermal damage to the targeted tissue. The 577-nm YSML is delivered to the retina abiding by different protocols in which wavelength, power, duration, spot size and number of spots can be properly set to achieve the most effective and safe treatment response in various chorioretinal disorders. The ultrashort trains of power modulate the activation of the retinal pigment epithelium cells and intraretinal cells, such as Müller cells, causing no visible retinal scars. Subthreshold energy delivered by YSML stimulates the production of the heat-shock proteins, highly conserved molecules that protect cells against any sort of stress by blocking apoptotic and inflammatory pathways that cause cell damage. YSML treatment allows resorption of the subretinal fluid in central serous chorioretinopathy and intraretinal fluid in various conditions including diabetic macular edema, postoperative cystoid macular edema and other miscellaneous conditions. YSML also seems to modulate the development and progression of reticular pseudodrusen in dry age-related macular degeneration. The aim of this review is to discuss and summarize the safety and efficacy of YSML treatment in retinal diseases.

Serum miRNA modulations indicate changes in retinal morphology.

Age-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression. Serum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated. Differential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients. In conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.

Nascent Geographic Atrophy as a Predictor of Type 3 Macular Neovascularization Development

To investigate the association of nascent geographic atrophy (GA) preceding the development of exudative type 3 macular neovascularization (MNV) in patients with age-related macular degeneration (AMD). Retrospective longitudinal study. AMD patients diagnosed with treatment-naïve exudative type 3 MNV in one or both eyes were evaluated. Inclusion criteria included serial tracked structural optical coherence tomography (OCT) examinations for ≥ 2 years prior to the detection of exudative type 3 MNV. Clinical characteristics and retinal imaging including structural OCT at baseline and at each follow-up examination were analyzed. Eyes showing the presence of nascent GA during the follow-up were selected for analysis of prevalence, and clinical characteristics at the site of subsequent type 3 MNV development. Description of prevalence and clinical characteristics of nascent GA at the site of subsequent type 3 MNV development. Ninety-seven eyes affected by type 3 MNV meeting inclusion criteria were analyzed. Of 97 eyes (71 patients), 22 eyes of 21 patients (mean age 82±9 years) showed nascent GA preceding exudative type 3 MNV. The observed prevalence of nascent GA preceding exudative type 3 MNV was 22.7% (95% CI: 14.4-31.0%). Exudative Type 3 MNV developed a mean of 9±6 months following detection of nascent GA. The presence of reticular pseudodrusen in the study eye did not significantly influence the timing of exudative type 3 MNV development after the observation of nascent GA (p>0.1 in all analyses). Reduced BCVA was recorded at the exudative type 3 stage in comparison to the nascent GA stage (p=0.003). As nascent GA may precede the development of exudative type 3 MNV, the detection of nascent GA in eyes with AMD may warrant closer surveillance in order to identify early exudative type 3 MNV warranting treatment.

PATTERN AND CHARACTERISTICS OF DRUSEN SUBTYPES IN CHINESE AND INDIAN POPULATIONS IN SINGAPORE

To report the pattern and characteristics of drusen subtypes in Asian populations and the association with choroidal thickness. This is the cross-sectional analysis of the population-based cohort study. Two thousand three hundred and fifty-three eyes of 1,336 Chinese and Indian participants aged older than 50 years, eyes with best-corrected visual acuity better than 20/60, and without other retinal diseases were recruited. Pachydrusen, reticular pseudodrusen, soft and hard drusen were graded on both color fundus photographs, and optical coherence tomography imaging with automated segmentation yielding and measurements of choroidal thickness. Nine hundred and fifty-five Chinese and 381 Indians were included in the final analysis. The pattern of pachydrusen, soft drusen, hard drusen, and reticular pseudodrusen was 14.0%, 3.7%, 12.5%, and 0.2%, respectively. Mean choroidal thickness was the thickest in eyes with pachydrusen (298.3 μm; 95% confidence interval: 290.5-306.1), then eyes with hard (298.1 μm; 95% confidence interval: 290.6-305.5) and soft drusen (293.7 μm; 95% confidence interval: 281.9-305.4) and thinnest in eyes without drusen (284.6 μm; 95% confidence interval: 280.5-288.7). Systemic associations of the various drusen subtypes also differed. Patterns, characterization and choroidal thickness of drusen subtypes, and their associations provide insights into the Asian phenotypic spectrum of age-related macular degeneration and the underlying pathogenesis.

Implementing Predictive Models in Artificial Intelligence through OCT Biomarkers for Age-Related Macular Degeneration

Artificial intelligence (AI) represents a growing and promising branch of computer science that is expanding the horizon of prediction, screening, and disease monitoring. The use of multimodal imaging in retinal diseases is particularly advantageous to valorize the integration of machine learning and deep learning for early diagnosis, prediction, and management of retinal disorders. In age-related macular degeneration (AMD) beyond its diagnosis and characterization, the prediction of AMD high-risk phenotypes evolving into late forms remains a critical point. The main multimodal imaging modalities adopted included color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT), which represents undoubtful advantages over other methods. OCT features identified as predictors of late AMD include the morphometric evaluation of retinal layers, drusen volume and topographic distribution, reticular pseudodrusen, and hyperreflective foci quantification. The present narrative review proposes to analyze the current evidence on AI models and biomarkers identified to predict disease progression with particular attention to OCT-based features and to highlight potential perspectives for future research.

Inner Retinal Thickness and Vasculature in Patients with Reticular Pseudodrusen

Introduction: The aim of this study was to investigate retinal layer thickness and vessel density differences between patients with reticular pseudodrusen (RPD) and intermediate dry age-related macular degeneration (iAMD). Methods: Participants included in the study were patients diagnosed by retinal specialists with RPD, iAMD, and both RPD and iAMD at our academic referral center, seen from May 2021 until February 2022. The central 3 mm retinal thickness was measured using spectral-domain optical coherence tomography (Heidelberg Spectralis HRA+OCT System; Heidelberg Engineering, Heidelberg, Germany). Individual retinal thickness measurements were obtained from the innermost layer (nerve fiber layer) until the outermost layer (retinal pigment epithelium [RPE]). Each thickness measurement was subdivided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For the vessel density, OCT angiography from the Heidelberg Spectralis System was measured using proprietary third-party software (AngioTool; National Institutes of Health, National Cancer Institute, Bethesda, MD). Clinical and demographic characteristics were compared across the three groups (iAMD, RPD, iAMD and RPD) and analyzed with necessary adjustments. Linear mixed-effects models with necessary corrections were employed to compare continuous eye-level measurements between our three groups as well as in pairwise fashion using the R statistical programming software (R version 4.2.1). Results: A total of 25 eyes of 17 patients with RPD, 20 eyes of 15 patients with iAMD, and 14 eyes of 9 patients with both iAMD and RPD were analyzed. Retinal thickness analysis identified that the superior inner (p = 0.028) and superior outer (p = 0.027) maculas of eyes with both iAMD and RPD were significantly thinner than those with iAMD alone. In eyes with RPD, the superior inner and superior outer RPE (p = 0.011 and p = 0.05, respectively), outer plexiform layer (p = 0.003 and p = 0.013, respectively), and inner nuclear layer (p = 0.034 and p = 0, respectively) were noted to be thinner compared to eyes with iAMD alone. In addition, the macular deep capillary plexus vessel density was significantly reduced in eyes with RPD compared to eyes with iAMD (p = 0.017). Conclusion: Patients with RPD had inner retinal structural as well as vascular changes compared to iAMD patients. Inner retinal vascular attenuation should be investigated further to see if there is a causal association with retinal thinning.

Longitudinal change of reticular pseudodrusen area in ultrawide-field imaging

This study aimed to investigate the longitudinal change in the reticular pseudodrusen (RPD) area in the fundus and its association with late age-related macular degeneration (AMD). 91 RPD eyes (55 patients; age 67.9 ± 7.3 years) with > 5 years’ follow-up (6.8 ± 0.9 years) from a single medical center were enrolled. Ultrawide-field photography images were analyzed using the concentric rings method, and the RPD area was semi-quantitatively classified according to the affected segment number into central, intermediate, and extensive types. Correlations of longitudinal changes in the RPD area and late AMD risk were investigated. RPD area increased significantly during the follow-up (p < 0.001). The increase rate correlated with age (r = 0.207; p = 0.048), RPD area at first visit (r = − 0.222; p = 0.035), and the decrease rate of subfoveal choroidal thickness (SFCT) (r = 0.217; p = 0.039). Many central (18/49, 36.7%) and intermediate (15/23, 65.2%) types switched to the more advanced type during the follow-up. Macular neovascularization and geographic atrophy developed in 12.3% and 18.7% of patients by 7 years. Late AMD incidence was significantly higher in eyes with large than in those with small RPD areas (p = 0.002). Larger RPD area at baseline, faster increase in RPD area, thinner SFCT, rapid decrease in SFCT, and the presence of late AMD on fellow eye were associated with late AMD. All RPD areas progressively increase over time. The regular assessment of RPD area may help to predict late AMD risk in RPD eyes.

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). European, multicenter cohort study. Overall, 301 eyes of 301 subjects with early (n= 34), intermediate (n= 168), and late AMD (n= 43), as well as eyes without any AMD features (n= 56). In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning-based algorithm. Prevalence and topographic distribution of structural iAMD features. A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92× 10-4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center. Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages. Proprietary or commercial disclosure may be found after the references.

The research progress of multimodal imaging for the diagnosis of reticular pseudodrusen

The emergence and development of multimodal imaging techniques, such as optical coherence tomography, fundus autofluorescence and adaptive optics, make it much easier to differentiate reticular pseudodrusen (RPD) from other fundus lesions. It is of great significance to understand the imaging characteristics of RPD observed with multimodal imaging techniques. This article reviews the formation mechanism and multimodal imaging characteristics of RPD, so as to provide help for better identification of RPD and assessment of the development and prognosis of the disease.

Reticular Pseudodrusen Status, ARMS2/HTRA1 Genotype, and Geographic Atrophy Enlargement: Age-Related Eye Disease Study 2 Report 32

To determine whether reticular pseudodrusen (RPD) status, ARMS2/HTRA1 genotype, or both are associated with altered geographic atrophy (GA) enlargement rate and to analyze potential mediation of genetic effects by RPD status. Post hoc analysis of an Age-Related Eye Disease Study 2 cohort. Eyes with GA: n = 771 from 563 participants. Geographic atrophy area was measured from fundus photographs at annual visits. Reticular pseudodrusen presence was graded from fundus autofluorescence images. Mixed-model regression of square root of GA area was performed by RPD status, ARMS2 genotype, or both. Change in square root of GA area. Geographic atrophy enlargement was significantly faster in eyes with RPD (P < 0.0001): 0.379 mm/year (95% confidence interval [CI], 0.329-0.430 mm/year) versus 0.273 mm/year (95% CI, 0.256-0.289 mm/year). Enlargement was also significantly faster in individuals carrying ARMS2 risk alleles (P < 0.0001): 0.224 mm/year (95% CI, 0.198-0.250 mm/year), 0.287 mm/year (95% CI, 0.263-0.310 mm/year), and 0.307 mm/year (95% CI, 0.273-0.341 mm/year) for 0, 1, and 2, respectively. In mediation analysis, the direct effect of ARMS2 genotype was 0.074 mm/year (95% CI, 0.009-0.139 mm/year), whereas the indirect effect of ARMS2 genotype via RPD status was 0.002 mm/year (95% CI, -0.006 to 0.009 mm/year). In eyes with incident GA, RPD presence was not associated with an altered likelihood of central involvement (P= 0.29) or multifocality (P= 0.16) at incidence. In eyes with incident noncentral GA, RPD presence was associated with faster GA progression to the central macula (P= 0.009): 157 μm/year (95% CI, 126-188 μm/year) versus 111 μm/year (95% CI, 97-125 μm/year). Similar findings were observed in the Age-Related Eye Disease Study. Geographic atrophy enlargement is faster in eyes with RPD and in individuals carrying ARMS2/HTRA1 risk alleles. However, RPD status does not mediate the association between ARMS2/HTRA1 genotype and faster enlargement. Reticular pseudodrusen presence and ARMS2/HTRA1 genotype are relatively independent risk factors, operating by distinct mechanisms. Reticular pseudodrusen presence does not predict central involvement or multifocality at GA incidence but is associated with faster progression toward the central macula. Reticular pseudodrusen status should be considered for improved predictions of enlargement rate. Proprietary or commercial disclosure may be found after the references.