Non-neovascular Age-related Macular Degeneration Research Articles

Emerging Therapies in Neovascular Age-Related Macular Degeneration in 2020.

Age-related macular degeneration (AMD) is one of the most common causes of vision loss. Advanced forms of AMD are seen in primarily 2 types—neovascular AMD (nAMD) with the presence of choroid neovascularization and nonneovascular AMD (nnAMD) with geographic atrophy. Although there are 4 anti-vascular endothelial growth factor drugs either widely used or approved for the former, there are no current treatments for the latter. This review will highlight upcoming treatments for AMD currently in clinical trials. For nAMD: Abicipar pegol, an intravitreal anti-vascular endothelial growth factor based on designed ankyrin repeat proteins (DARP) in protein, is currently pending approval. Conbercept and Faricimab, 2 intravitreal anti-growth factors, are currently in phase 3. Nine other upcoming agents have at least produced results in the 2A phase including intravitreal injections (KSI-301, OPT-302, RGX-314, ICON-1, and DE-122), depot (GB-102), drug reservoir (PDS), topical drops (PAN-90806), and oral formulations (AKST4290). We summarize all the newer molecules.

Release of extracellular vesicle miR-494-3p by ARPE-19 cells with impaired mitochondria

BackgroundMitochondrial function in retinal pigmented epithelial (RPE) cells and extracellular vesicle (EV) formation/release are related through the lysosomal and exocytotic pathways that process and eliminate intracellular material, including mitochondrial fragments. We propose that RPE cells with impaired mitochondria will release EVs containing mitochondrial miRNAs that reflect the diminished capacity of mitochondria within these cells. MethodsWe screened ARPE-19 cells for miRNAs that localize to the mitochondria, exhibit biological activity, and are present in EVs released by both untreated cells and cells treated with rotenone to induce mitochondrial injury. EVs were characterized by vesicle size, size distribution, presence of EV biomarkers: CD81, CD63, and syntenin-1, miRNA cargo, and number concentration of EVs released per cell. ResultsWe found that miR-494-3p was enriched in ARPE-19 mitochondria. Knockdown of miR-494-3p in ARPE-19 cells decreased ATP production and mitochondrial membrane potential in a dose-dependent manner, and decreased basal oxygen consumption rate and maximal respiratory capacity. Increased number of EVs released per cell and elevated levels of miR-494-3p in EVs released from ARPE-19 cells treated with rotenone were also measured. ConclusionsARPE-19 mitochondrial function is regulated by miR-494-3p. Elevated levels of miR-494-3p in EVs released by ARPE-19 cells indicate diminished capacity of the mitochondria within these cells. General significanceEV miR-494-3p is a potential biomarker for RPE mitochondrial dysfunction, which plays a central role in non-neovascular age-related macular degeneration, and may be a diagnostic biomarker for monitoring the spread of degeneration to neighboring RPE cells in the retina.

Correction of perceived visual distortions using a software application and correlation to age-related macular degeneration.

Purpose:To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration.Methods:A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed.Results:Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption.Conclusion:Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

Linear and planar reflection artifacts on swept-source and spectral-domain optical coherence tomography due to hyperreflective crystalline deposits.

To describe novel spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) linear and planar reflection artifacts produced by hyperreflective crystalline deposits (HCD). Imaging from 10 eyes with HCD producing linear and planar artifacts on OCT was retrospectively analyzed. All eyes had SD-OCT (Spectralis HRA + OCT, Heidelberg Engineering, Germany) and SS-OCT angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc., Dublin, CA) acquired on the same day. The horizontal extent of planar artifacts and the corresponding HCD on B-scans was measured using a digital caliper. Artifact features from HCD in eyes with non-neovascular age-related macular degeneration (AMD) were analyzed and compared to those seen in two eyes with the "onion sign," an OCT signature previously shown to represent cholesterol crystals (CC) in the sub-retinal pigment epithelium-basal laminar space of eyes with neovascular AMD. A third eye with the "onion sign" was imaged with dense B-scan (DB)-OCTA. Ten eyes of ten patients (77.4 ± 8.7years) with HCD were analyzed. On SS-OCTA, HCD produced linear artifacts of high signal intensity passing through the HCD and spanning the entire scan depth. On SD-OCT, HCD produced planar artifacts located anterior to both the retina and a hyporeflective space representing normal vitreous signal. The horizontal extent of the artifact did not differ significantly from the corresponding HCD on OCT B-scans (P = 0.62). The OCT artifacts produced by the "onion sign" appeared similar to those of HCD. The additional eye with neovascular AMD imaged with DB-OCTA was characterized by a single, vertical, linear false-flow signal crossing retinal layers. To the authors' knowledge, this is the first description of SD- and SS-OCT/OCTA artifacts corresponding to both HCD and the "onion sign." These artifacts are likely due to highly reflective CC previously shown on histology to correspond to both of these OCT signatures.

Quantitative analysis of the optic nerve head parameters in patients with age-related macular degeneration

Background/aimTo evaluate the topographic parameters of the optic disc of patients with age-related macular degeneration (AMD) by performing confocal scanning laser ophthalmoscopy.Materials and methodsThis prospective study included 41 eyes of 41 patients with neovascular AMD, 56 eyes of 56 patients with nonneovascular AMD, and 48 eyes of 48 healthy control subjects. Images of the optic nerve head of all of the participants were obtained using Heidelberg retinal tomography III software 3.1. The following stereometric parameters were measured for each participant: disc area, cup area, rim area, cup volume, rim volume, cup-to-disc ratio, mean cup depth, maximum cup depth, cup shape, and mean retinal nerve fiber layer thickness.ResultsThe cup shape values ​​of the patients with neovascular and nonneovascular AMD were significantly different from those of the control subjects (P = 0.002 and P < 0.001, respectively). The cup-to-disc ratio was significantly higher in the patients with nonneovascular AMD when compared with the control subjects (P = 0.013), but no difference was found between the patients with neovascular AMD and the control subjects (P > 0.05). No significant differences were observed among the 3 groups with respect to the other optic disc parameters (P > 0.05).ConclusionThese data showed that the deterioration of the cup shape was an important finding in patients with AMD. Because AMD manifests with progressive ocular damage, including the optic nerve head, examination of the cup shape may be important during the follow-up of these patients.

CHOROIDAL VASCULARITY INDEX AND CHOROIDAL THICKNESS IN EYES WITH RETICULAR PSEUDODRUSEN.

To evaluate choroidal vascularity index (CVI), choroidal thickness, choroidal volume, and choroidal intensity in subjects with nonneovascular age-related macular degeneration (NNVAMD) with and without reticular pseudodrusen (RPD). We included 60 eyes of 35 subjects with NNVAMD (including 30 eyes of 18 subjects with RPD) and 30 eyes of 17 age-matched healthy individuals from the ongoing Amish Eye study. The choroid was segmented from dense volume spectral domain optical coherence tomography scans and choroidal thickness (microns), choroidal intensity (log units), and choroidal volume (mm) from the entire macula (6 × 6 mm) were computed. A central horizontal B-scan was binarized and the luminal and stromal portions of the choroid were segmented. Choroidal vascularity index (%) was calculated as the ratio of luminal area to total choroid area. Choroidal parameters were compared between the groups by pairwise comparisons using the Student's t-test. The CVI was significantly lower in healthy eyes compared to those with RPD (53.43 ± 8.51 vs. 54.76 ± 4.83, P < 0.001). The CVI was also significantly lower in NNVAMD eyes without RPD compared to those with RPD (50.09 ± 7.51 vs. 54.76 ± 4.83, P = 0.006). There was no difference in CVI between healthy eyes and NNVAMD eyes without RPD (P = 0.84). Choroidal thickness and choroidal volume were significantly higher in NNVAMD without RPD (P < 0.05); and significantly lower in NNVAMD with RPD (P < 0.05) when compared with normal eyes. Choroidal intensity was significantly higher in NNVAMD with RPD when compared with normal eyes (P = 0.02) and NNVAMD eyes without RPD (P = 0.001). Multiple choroidal parameters reflecting the status of the choroidal vasculature and stroma seem to be altered in eyes with RPD compared with both normal eyes and NNVAMD eyes without RPD. These findings may provide insights into the pathophysiology of RPD.

Surgical Method for Implantation of a Biosynthetic Retinal Pigment Epithelium Monolayer for Geographic Atrophy: Experience from a Phase 1/2a Study

To report the intraoperative methods and anatomic results for subretinal implantation of an investigational human embryonic stem cell-derived retinal pigment epithelium (RPE) monolayer seeded on a synthetic substrate (California Project to Cure Blindness Retinal Pigment Epithelium 1 [CPCB-RPE1]) in geographic atrophy (GA). Single-arm, open label, prospective, nonrandomized, Phase 1/2a study. Advanced non-neovascular age-related macular degeneration (NNAMD). The worse-seeing eye (≤20/200) of each subject underwent subretinal implantation of a single 3.5×6.25 mm CPCB-RPE1 implant with a preplanned primary end point of safety and efficacy at 365 days. Commercially available 23-gauge vitrectomy equipment, custom surgical forceps, and operating microscope with or without intraoperative OCT (iOCT) were used. Exact Wilcoxon rank-sum tests and Spearman rank correlation coefficients were used to assess the association of the percentage of the GA area covered by the implant with patient and surgery characteristics. The partial Spearman correlation coefficient was calculated for the correlation between duration of surgery and baseline GA size after adjustment for surgeon experience. Intraoperative exploratory measures are reported, including area of GA covered by implant, subretinal position of implant, duration of surgery, and incidence of adverse events. Operative recordings and reports were used to determine exploratory outcome measures. Sixteen subjects were enrolled with a median age of 78 years (range, 69-85 years). Median duration of the surgery for all subjects was 160 minutes (range, 121-466 minutes). Intraoperative OCT was used to guide subretinal placement in 9 cases. Intraoperative OCT was potentially useful in identifying pathology not evident with standard intraoperative visualization. Median GA area at baseline was 13.8 mm2 (range, 6.0-46.4 mm2), and median GA area left uncovered by the implant was 1.7 mm2 (range, 0-20.4 mm2). On average, 86.9% of the baseline GA area was covered by the implant. In 5 subjects, >90% of the GA area was covered. Baseline GA size was inversely correlated with percentage of GA area covered by the implant (rs=-0.72; P= 0.002). No unanticipated serious adverse events related to the implant or surgery were reported. Surgical implantation of CPCB-RPE1 targeted to the area of GA in subjects with advanced NNAMD is feasible in an outpatient setting. Intraoperative OCT is not necessary but potentially useful in identifying subretinal pathology and confirming implant location.

Detecting and measuring areas of choriocapillaris low perfusion in intermediate, non-neovascular age-related macular degeneration

.Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in the outer retina and rely primarily on the trophic support of the underlying choriocapillaris, imaging of flow or lack thereof in choriocapillaris by optical coherence tomography angiography (OCTA) has great clinical potential in AMD assessment. We introduce a metric using OCTA, named “focal perfusion loss” (FPL) to describe the effects of age and non-neovascular AMD on choriocapillaris flow. Because OCTA imaging of choriocapillaris is vulnerable to artifacts—namely motion, projections, segmentation errors, and shadows—they are removed by postprocessing software. The shadow detection software is a machine learning algorithm recently developed for the evaluation of the retinal circulation and here adapted for choriocapillaris analysis. It aims to exclude areas with unreliable flow signal due to blocking of the OCT beam by objects anterior to the choriocapillaris (e.g., drusen, retinal vessels, vitreous floaters, and iris). We found that both the FPL and the capillary density were able to detect changes in the choriocapillaris of AMD and healthy age-matched subjects with respect to young controls. The dominant cause of shadowing in AMD is drusen, and the shadow exclusion algorithm helps determine which areas under drusen retain sufficient signal for perfusion evaluation and which areas must be excluded. Such analysis allowed us to determine unambiguously that choriocapillaris density under drusen is indeed reduced.

Outer Retinal Thickness and Fundus Autofluorescence in Geographic Atrophy

Most studies of fundus autofluorescence (FAF) in geographic atrophy (GA) have been nonquantitative, with inadequate registration of image modalities. Furthermore, as pointed out in the recent Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT, it is unclear whether decreased FAF would be correlated exclusively with a single category of OCT-defined atrophy. We sought to determine how FAF intensity in eyes with GA correlates with structural changes of the outer retina and choroid as seen on co-registered spectral domain OCT (SD-OCT) images. Retrospective cross-sectional. Twenty eyes of 11 patients with GA secondary to non-neovascular age-related macular degeneration (AMD). Spectral domain OCT and FAF images for each eye were co-registered using MATLAB (MathWorks Inc, Natick, MA). On B-scans, the choroid, retinal pigment epithelium (RPE), photoreceptor (PR) layer, and outer nuclear layer (ONL) were segmented. Regions of interest (ROIs) including all atrophic and border regions were selected manually on the FAF scans. Regions of interest were subdivided into quartiles of FAF level to correlate with retinal thickness measurements taken along the B-scans. Mean choroid, RPE, PR, and ONL thicknesses were compared across quartiles using an analysis of variance factorial design testing for interaction effects, adjusted for repeated measures (on both eyes) with a within-subjects factor. Seventeen eyes of 10 patients were selected for analysis. The mean choroidal thicknesses were not significantly different across FAF quartiles, but the overall differences in mean RPE, PR layer, and ONL thicknesses across quartiles were statistically significant (analysis of variance, P < 0.001, P < 0.001, and P=0.015, respectively). Post hoc analysis demonstrated significant differences in thickness among quartiles 1, 2, and 3 for the RPE and PR layers (Tukey, P < 0.01 in each case). The FAF quartiles within GA did not correlate exclusively with single categories of Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration-defined atrophy. Not only RPE but also PR layer thickness on SD-OCT varies significantly with FAF levels in GA. This suggests that although the RPE cells are losing thickness and function, evidenced by decreased FAF from fluorophores, delicate PR cells also succumb early in the disease process. These relationships should be pursued as a possibly better-detailed mechanism in GA.

Pharmacotherapy of Non-neovascular AMD

Non-neovascular age-related macular degeneration (AMD) is not yet treatable. This article summarises current clinical research approaches. The reasons for the current lack of success are analysed. Literature and databank search. The number of therapeutic approaches and mechanisms is limited. Only reduction in lipofuscin containing deposits is specific for AMD. Further approaches include modulation of inflammation and neuroprotection. Confirmatory studies have failed to demonstrate efficacy in AMD, i.e. slowing or stopping AMD progression. To increase the probability of success for future developments, the pharmacological target space needs to be broadened. This may be achieved by application of molecular network analyses. As visual acuity is commonly not primarily affected by non-neovascular AMD, research on patient perspective is required to define reasonable target profiles for future therapies.

The Fate and Prognostic Implications of Hyperreflective Crystalline Deposits in Nonneovascular Age-Related Macular Degeneration.

To explore patterns of disease progression in nonneovascular age-related macular degeneration (AMD) associated with hyperreflective crystalline deposits (HCDs) in the sub-retinal pigment epithelium-basal laminar space. Retrospective review of medical records, multimodal imaging, and longitudinal eye-tracked near-infrared reflectance (NIR) and optical coherence tomography (OCT) spanning ≥2 years. NIR/OCT images were analyzed with ImageJ software to identify HCD morphology and location. Associated macular complications were reviewed from the time of HCD detection to the most recent follow-up, using NIR/OCT. Thirty-three eyes with HCDs from 33 patients (mean age: 72 ± 7.5 years) had 46.7 months (95% confidence limits: 33.7, 59.6) of serial eye-tracked NIR/OCT follow-up. Baseline best-corrected visual acuity (BCVA) was 0.44 logMAR (Snellen equivalent 20/55). At a mean of 11.3 months (3.1, 19.6) after HCD detection, 31/33 (93.9%) eyes had developed macular complications including de novo areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in 21/33 (64%) eyes, enlargement of preexisting cRORA in 4/33 (12%) eyes, and incident macular neovascularization in 3/33 (9%) eyes. Movement and clearance of HCDs in 9/33 (27%) eyes was associated with enlargement of preexisting cRORA (r = 0.44, P = 0.02). BCVA at the last follow-up visit had decreased to 0.72 logMAR (20/105). Eyes with nonneovascular AMD demonstrating HCDs are at risk for vision loss due to macular complications, particularly when movement and clearance of these structures appear on multimodal imaging. HCD reflectivity and dynamism may be amenable to automated recognition and analysis to assess cellular activity related to drusen end-stages.

Measuring dynamic levels of self-perceived anxiety and concern during simulated mobility tasks in people with non-neovascular age-related macular degeneration

Background/aimsTo assess response to real-world mobility scenarios in people with dry age-related macular degeneration (AMD) using a computer-based test.MethodsParticipants were shown 18 point-of-view computer-based movies simulating walking through real-world scenarios,...

Картина глазного дна при возрастной макулярной дегенераци и без неоваскуляризации

Картина глазного дна при возрастной макулярной дегенераци и без неоваскуляризации

'You've got dry macular degeneration, end of story': a qualitative study into the experience of living with non-neovascular age-related macular degeneration.

To investigate the impact of non-neovascular (dry) age-related macular degeneration (AMD) on the person with respect to diagnosis, vision loss and coping strategies. Volunteers with dry AMD with a range of disease severity were given an eye examination and asked to describe aspects of their experience with dry AMD in a semi-structured interview. Interviews were audio-recorded, transcribed, and subjected to Framework analysis. Overarching themes were pre-defined, whilst subthemes were derived from the data. Twenty-seven participants (81% female), with early (n = 3), intermediate (n = 16) and advanced dry AMD (GA; n = 8) were interviewed. Median (interquartile range) age (years), logMAR binocular visual acuity and Pelli-Robson contrast sensitivity were 76 (71, 80), 0.2 (0.18, 0.40) and 1.65 (1.35, 1.93), respectively. Overarching themes (and subthemes) were: diagnosis (relationship with healthcare professional, psychological impact of diagnosis, and knowledge of AMD, both pre- and post-diagnosis), impact of visual loss (functional and psychological) and coping strategies (help from others and personal strategies). Many participants reported feelings of distress at the time of diagnosis and, particularly noteworthy, several reported a constant fear of their condition worsening. Dry AMD, for which there is currently no treatment, can have a significant impact on individuals, even in its early stages, before significant functional vision loss is manifest, as well as in its intermediate and advanced stages. Results from this study offer important insight into the experience of living with dry AMD not previously explored. Moreover, the results have the potential to serve as an educational resource for eyecare professionals.

Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration

Risk factors associated with the development of neovascular age-related macular degeneration (AMD) have been identified. However, population size and methods to integrate imaging, genetic, and demographic factors associated with conversion to neovascular AMD are limited, specifically when treatment is administered in 1 eye. To determine the imaging, genetic, and demographic factors associated with conversion from nonneovascular to neovascular AMD in fellow eyes. This post hoc secondary analysis of the 24-month phase 3 multicenter, double-masked, active treatment-controlled HARBOR trial included 686 fellow eyes with nonneovascular AMD at baseline. Imaging features describing the presence, number, extent, density, and relative reflectivity of drusen were automatically extracted from spectral-domain optical coherence tomography scans. Genetic analysis included 34 single-nucleotide polymorphisms. Least absolute shrinkage and selection operator regression was performed to narrow imaging features. Survival analysis and Cox proportional hazards regression were performed to determine the association of the selected imaging features and genetic and demographic factors with conversion to neovascular AMD. Data were collected from November 2016 through October 2017 and analyzed from October 2017 through October 2018. Nonneovascular AMD in the fellow eye. Features associated with conversion to neovascular AMD. Hazard ratios (HRs) and their 95% CIs were calculated. Among the 686 fellow eyes included in the analysis (406 [59.2%] women; mean [SD] age, 78.12 [8.28] years), 154 (22.4%) converted to neovascular AMD. Female sex was significantly associated with conversion to neovascular AMD (HR, 1.57; 95% CI, 1.11-2.20; P = .009). After controlling for demographic and treatment effects, drusen area within 3 mm of the fovea (HR, 1.45; 95% CI, 1.24-1.69; HR for 1-SD increase, 1.36 [95% CI, 1.20-1.54]) and mean drusen reflectivity (HR, 3.97; 95% CI, 1.11-14.18; HR for 1-SD increase, 1.32 [95% CI, 1.02-1.71]) were significantly associated with conversion to neovascular AMD. In addition, 1 genetic variant (rs61941274) was found to be associated with conversion to neovascular AMD. Two imaging features (total en face area of drusen restricted to a circular area 3 mm from the fovea and mean drusen reflectivity) and 1 genetic variant (ACAD10 locus) were associated with conversion to neovascular AMD. Drusen characteristics may be associated with conversion to neovascular AMD despite treatment in 1 eye. ClinicalTrials.gov identifier: NCT00891735.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN GEOGRAPHIC ATROPHY

To analyze choriocapillaris (CC) vessel density (VD) around geographic atrophy (GA) secondary to non-neovascular dry age-related macular degeneration using optical coherence tomography angiography. We compared CC VD surrounding GA margin (500 μm radius) with control CC (outside GA margin) in a consecutive series of GA patients presenting between August 2016 and February 2017 at the Medical Retina and Imaging Unit of University Vita-Salute, IRCCS Ospedale San Raffaele in Milan. Images were obtained through thresholding and binarization. We also compared the CC VD in a sample area of 500 μm × 500 μm surrounding GA margin rated as hyperautofluorescent on fundus autofluorescence to a similar area rated as isoautofluorescent. Fifty eyes of 29 patients (19 women and 10 men; mean age 77 ± 6 years) with mean GA area of 9.43 ± 5.08 mm and mean subfoveal choroidal thickness of 164 ± 73 μm were included. Choriocapillaris VD surrounding GA margin as detected by optical coherence tomography angiography revealed a significant impairment compared with control CC outside GA margin (0.317 ± 0.083 vs. 0.461 ± 0.054, P < 0.001), which was even greater in patients with foveal involvement (P = 0.013). Furthermore, mean VD in hyperautofluorescent areas was significantly lower compared with isoautofluorescent areas (0.242 ± 0.112 vs. 0.327 ± 0.130, P = 0.001). A positive correlation was disclosed between VD surrounding GA margin and subfoveal choroidal thickness (r = 0.332, P = 0.019). Optical coherence tomography angiography discloses CC impairment surrounding GA margin. Such CC impairment at GA margin seems to precede retinal pigment epithelium alterations at fundus autofluorescence. Optical coherence tomography angiography could be a new valuable tool for detecting CC alterations and to evaluate potential therapeutic responses in clinical studies.

Possible Undiagnosed Glaucoma Detected by MultiColor Imaging of Retinal Diseases

To evaluate for the presence of visible retinal nerve fiber layer (RNFL) defects consistent with undiagnosed glaucoma in MultiColor images (Heidelberg Engineering, Heidelberg, Germany) obtained at clinicians' discretion for the diagnosis and management of retinal diseases. Retrospective chart review of MultiColor images obtained as part of routine clinical care between December 25, 2013 and June 24, 2014. Images were reviewed by 2 fellowship-trained glaucoma specialists (S.H.V.T., S.G.A.) for the presence of RNFL defects in the superotemporal or inferotemporal quadrants. No attention was given to the optic nerve head when identifying candidate images. Retinal nerve fiber layer defects were not considered glaucomatous if they traced to regions of retinal atrophy. A total of 157 retina clinic patients aged 18 years or older who carried at least 1 retinal diagnosis; patients were subsequently excluded if medical records review revealed a history of glaucoma or glaucoma suspect diagnoses at the time of imaging. MultiColor confocal scanning laser ophthalmoscopy images were obtained using the Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). The primary end point was the presence of at least 1 RNFL defect tracking toward the optic nerve. Among 157 reviewed charts, 134 eyes of 80 patients met inclusion criteria, of whom 13 eyes of 10 patients had visible RNFL defects consistent with possible undiagnosed glaucoma. The average age of patients with presumed glaucomatous eyes was 67 years (range, 35-88 years; standard deviation, 15.7 years). The retinal diagnoses in the glaucomatous eyes included branch retinal vein occlusion (3 eyes and 1 fellow eye), neovascular age-related macular degeneration (2 eyes), non-neovascular age-related macular degeneration (both eyes of 1 patient), proliferative diabetic retinopathy (2 eyes), nonproliferative diabetic retinopathy (both eyes of 1 patient), and epiretinal membrane (1 eye). Retinal nerve fiber layer defects consistent with glaucoma may be visible on MultiColor images obtained for the diagnosis and management of retinal diseases and may represent an underused opportunity to prevent additional visual dysfunction in patients already undergoing retinal disease management.

In vivo near-infrared autofluorescence imaging of retinal pigment epithelial cells with 757 nm excitation.

We demonstrate near-infrared autofluorescence (NIRAF) imaging of retinal pigment epithelial (RPE) cells in vivo in healthy volunteers and patients using a 757 nm excitation source in adaptive optics scanning laser ophthalmoscopy (AOSLO). NIRAF excited at 757 nm and collected in an emission band from 778 to 810 nm produced a robust NIRAF signal, presumably arising from melanin, and revealed the typical hexagonal mosaic of RPE cells at most eccentricities imaged within the macula of normal eyes. Several patterns of altered NIRAF structure were seen in patients, including disruption of the NIRAF over a drusen, diffuse hyper NIRAF signal with loss of individual cell delineation in a case of non-neovascular age-related macular degeneration (AMD), and increased visibility of the RPE mosaic under an area showing loss of photoreceptors. In some participants, a superposed cone mosaic was clearly visible in the fluorescence channel at eccentricities between 2 and 6° from the fovea. This was reproducible in these participants and existed despite the use of emission filters with an optical attenuation density of 12 at the excitation wavelength, minimizing the possibility that this was due to bleed through of the excitation light. This cone signal may be a consequence of cone waveguiding on either the ingoing excitation light and/or the outgoing NIRAF emitted by fluorophores within the RPE and/or choroid and warrants further investigation. NIRAF imaging at 757 nm offers efficient signal excitation and detection, revealing structural alterations in retinal disease with good contrast and shows promise as a tool for monitoring future therapies at the level of single RPE cells.

Quantitative Fundus Autofluorescence in Non-Neovascular Age-Related Macular Degeneration.

To use quantitative fundus autofluorescence (qAF) to analyze different stages of non-neovascular age-related macular degeneration (AMD). In this cohort study, 38 pseudophakic patients and 36 age-matched controls participated. We performed near-infrared, spectral-domain optical coherence tomography and qAF imaging on 31 pseudophakic eyes and controls of participants older than 60 years with non-neovascular AMD phenotypes using the Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). The patients included in this study had a mean age of 83.9 years, and 35.7% patients were men. Mean qAF was higher in control participants than in all patients with AMD (P < .001). According to non-neovascular AMD phenotype, mean qAF levels were significantly lower in eyes with subretinal drusenoid deposits than in control eyes (P < .05). The lowest mean qAF was in patients with geographic atrophy. Quantitative fundus autofluorescence of non-neovascular AMD decreases from normal to early to late AMD, suggesting that loss of lipofuscin fluorophores, not increase, signifies AMD progression. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:S34-S42.].

REDUCED CHORIOCAPILLARIS FLOW IN EYES WITH TYPE 3 NEOVASCULARIZATION AND AGE-RELATED MACULAR DEGENERATION.

To study choriocapillaris (CC) flow in eyes with Type 3 neovascularization (NV) and age-related macular degeneration, using optical coherence tomography angiography analysis. In this multicenter, retrospective, observational study, we collected data from 21 patients with unilateral Type 3 NV and age-related macular degeneration, based on clinical examination, structural optical coherence tomography, and fluorescein angiography when available. An additional group of 20 nonneovascular age-related macular degeneration eyes with unilateral Type 1 or Type 2 NV due to age-related macular degeneration was included for comparison. En face optical coherence tomography angiography imaging (3 × 3 mm scans) with quantitative microvascular analysis of the CC was performed. Main outcome measures were: 1) the percent nonperfused choriocapillaris area; and 2) the average CC signal void size. We included 21 patients with unilateral Type 3 NV (15 female, 71.5%) and 20 patients with unilateral Type 1 or 2 NV (9 female, 45.0% P = 0.118). Mean ± SD age was 82.1 ± 7.4 years in the unilateral Type 3 patients and 78.3 ± 8.1 in unilateral Type 1/2 NV subjects (P = 0.392). The percent nonperfused choriocapillaris area was 56.3 ± 8.1% in eyes with Type 3 NV and 51.9 ± 4.3% in the fellow eyes (P = 0.016). The average signal void size was also increased in those eyes with Type 3 NV (939.9 ± 680.9 μm), compared with the fellow eyes (616.3 ± 304.2 μm, P = 0.039). The number of signal voids was reduced in the Type 3 NV eyes (604.5 ± 282.9 vs. 747.3 ± 195.8, P = 0.046). The subfoveal choroidal thickness was 135.9 ± 54.2 μm in eyes with Type 3 NV and 167.2 ± 65.4 μm in the fellow eyes (P = 0.003). In addition, the fellow eyes of patients with unilateral Type 3 NV displayed more significant CC flow abnormalities versus the fellow eyes with unilateral Type 1/2 NV (percent nonperfused choriocapillaris area = 51.9 ± 4.3% vs. 46.0 ± 2.1%, respectively, P < 0.0001; and average signal void size 616.3 ± 304.2 μm versus 351.4 ± 65.5 μm, respectively, P < 0.0001; and number of signal voids 747.3 ± 195.8 vs. 998.5 ± 147.3, respectively, P < 0.0001). Eyes with unilateral Type 3 NV illustrated increased CC nonperfusion versus fellow nonneovascular eyes. These results suggest that choroidal ischemia may play an important role in the development of Type 3 NV.