Ten-Year Follow-Up of Fellow Eyes in Patients with Unilateral Naïve Exudative AMD.

PURPOSE: To determine the 10-year morphological outcomes and identify potential risk factors for exudative AMD in the fellow eyes (FE) in patients with naïve exudative AMD. METHODS: Data from 100 patients were retrospectively reviewed. Baseline macular neovascularization (MNV) type in the exudative AMD eye and presence of drusen, intraretinal hyperreflective foci (iHRF), non-foveal incomplete atrophy (iRORA), central retinal thickness and subfoveal choroidal thickness in the FEs were analyzed as biomarkers for progression in the second eye. RESULTS: 54 patients developed exudative AMD in the FE at the end of the follow-up. Subjects with type 2 and 3 MNV in the exudative AMD eye had a higher risk of exudative AMD in the FE (HR=3.365; p=0.039 and HR=3.801; p=0.037). FEs with drusen (large HR=6.938, p=0.001; cuticular HR=6.937, p<0.0001; subretinal drusenoid deposits HR=13.678, p<0.0001) and iHRF (HR=1.853, p=0.041) were also at higher risk. Seven patients were legally blind by the end of the follow-up. CONCLUSIONS: The rate of exudative AMD in the FE was 54% 10 years after the diagnosis in the exudative eye. The FE of patients with type 2 and 3 MNV was at high risk for early progression. Drusen and iHRF were also significant risk factors for MNV development.

CORRELATION BETWEEN INFLAMMATORY FOCI REACTIVATION AND ATROPHY GROWTH IN EYES WITH IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To correlate the number of inflammatory reactivations in atrophic foci of multifocal choroiditis (MFC) with their growth rate over a 4-year span. METHODS: Comparative case series. Optical coherence tomography scans of patients affected by MFC were reviewed to identify reactivations within or at the margin of atrophic MFC foci. The area of selected lesions was semiautomatically delineated on fundus autofluorescence images and recorded at yearly intervals for a total follow-up of 4 years. The main outcome was the difference in annual square-root transformed area growth rate between lesions that reactivated and lesions that did not. RESULTS: Sixty-six foci of 30 eyes of 24 patients were included. All MFC foci enlarged over time, but the annual growth rate was more than double in lesions that reactivated compared with those that did not (mean [SD], 0.051 [0.035] vs. 0.021 [0.015] mm/year, P < 0.001), despite starting from comparable baseline areas. For each additional inflammatory reactivation, the annual growth rate increased by more than 20% (+0.009 mm/year, 95% CI [0.006, 0.012], P < 0.001). CONCLUSION: Increasing number of reactivations of atrophic foci led to proportional increments in their growth rate, highlighting the need for a tight control of inflammatory relapses in patients affected by MFC.

Haller's vessels patterns in non-neovascular age-related macular degeneration.

PURPOSE: To investigate the optical coherence tomography (OCT) en face reconstruction of the choroid in different phenotypes of non-neovascular age-related macular degeneration (AMD), to identify the relative distribution of the vascular patterns of the Haller's layer in each AMD category. METHODS: Retrospective study enrolling consecutive patients with non-neovascular AMD. Patients were divided into the following: (1) those with reticular pseudodrusen (RPD); (2) those with small (< 63 µm) or medium-large drusen (63-124 µm); (3) those with geographic atrophy (GA). Qualitative analysis of the en face images provided by CIRRUS HD-OCT 5000 (Carl Zeiss Meditech, Inc., Dublin, USA) was performed, identifying five arrangements of Haller's vessels: temporal herringbone, branched from below, laterally diagonal, double arcuate, and reticular. Choroidal thickness (CT) was measured from structural OCT. Healthy age-matched subjects were included as a control group. RESULTS: Fifty-eight eyes of 58 patients (20 eyes with RPD; 22 eyes with drusen; 16 eyes with GA) and 18 control eyes were enrolled. The laterally diagonal configuration was the most prevalent (40.0%) in the RPD group; the reticular pattern was the most frequent in the drusen group (50.0%); the double arcuate (62.5%) was the most recurrent pattern in patients with GA. In the control group, the temporal herringbone (38.9%) arrangement was the most represented. The CT associated with the temporal herringbone and reticular arrangement was significantly higher compared to the branched from below (p < 0.001), the laterally diagonal (p = 0.014), and the double arcuate pattern (p = 0.009). CONCLUSION: Different phenotypes of non-neovascular AMD present a specific distribution of vascular arrangement on en face OCT. The temporal herringbone and the reticular pattern (the ones more associated in a physiological setting) disclosed a thicker choroid compared to the arrangements more represented in non-neovascular AMD-correlated phenotypes.

RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN.

PURPOSE: To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer. METHODS: Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis. RESULTS: Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 ± 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 ± 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 ± 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10). CONCLUSION: Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.

In Vivo Correlation Between Macular Pigment Optical Volume and Retinal Layers Thickness.

Purpose: This study aims to investigate the potential in vivo relationship between macular pigment (MP) and retinal layers thickness in healthy subjects and dry, non-advanced age-related macular degeneration (AMD). Methods: An observational, cross-sectional study was conducted. Healthy subjects >40 years and patients with early or intermediate AMD were recruited. Structural OCT and macular pigment optical volume (MPOV) were collected for each subject. Retinal layers parameters were calculated based on the standard early treatment diabetic retinopathy study (ETDRS) map. Additionally, MPOV within 1°, 2°, and 9° of eccentricity was assessed and associated with retinal layers thickness and volume. Linear mixed-effects models were used to test the relationship between MP and structural OCT parameters, while adjusting for known possible confounding factors. Results: A total of 144 eyes of 91 subjects (60.4% females) were evaluated, comprising 43% normal eyes and 57% with early/intermediate AMD. Among the retinal layers, only the outer nuclear layer (ONL) thickness and volume appeared to be associated to higher MP levels. Specifically, the central ONL thickness was identified as a significant predictor of the MPOV 1°(P = 0.04), while the parafoveal ONL thickness (inner ETDRS subfield) was identified as a significant fixed effect on the MPOV 9° (P = 0.037). Age and the presence of drusen or subretinal drusenoid deposits were also tested without showing significant correlations. Conclusions: Among the retinal layers examined, only the ONL thickness demonstrated a significant association with MPOV. Consequently, ONL thickness might serve as a potential biomarker related to MP levels.

The retinal neurovascular coupling is impaired in men with vasculogenic erectile dysfunction.

The aim of this study was to study the retinal vessels in patients affected by vasculogenic erectile dysfunction (ED), using dynamic vessel analyzer (DVA). Patients with vasculogenic ED and control subjects were prospectively enrolled to undergo a complete urological and ophthalmologic evaluation, including DVA and structural optical coherence tomography (OCT). The main outcome measures were: (1) arterial dilation; (2) arterial constriction; (3) reaction amplitude (the difference between arterial dilation and constriction); and, (4) venous dilation. Thirty-five patients with ED and 30 male controls were included in the analysis. Mean ± SD age was 52.0 ± 10.8 years in the ED group and 48.1 ± 16.3 years in the control group (p = 0.317). In the dynamic analysis, the arterial dilation was lower in the ED group (1.88 ± 1.50%), as compared with the control group (3.70 ± 1.56%, p < 0.0001). Neither arterial constriction nor venous dilation differed between groups. The reaction amplitude was decreased in ED patients (2.40 ± 2.02%, p = 0.023), compared to controls (4.25 ± 2.20%). In the Pearson correlation analysis, the ED severity, was directly correlated with both reaction amplitude (R = .701, p = 0.004) and arterial dilation (R = .529, p = 0.042). In conclusion, subjects with vasculogenic ED are featured by a significant dysfunction of the retinal neurovascular coupling, which is inversely correlated with ED severity.

Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease.

There is a lack of studies evaluating the sub-clinical retinal changes in patients with long-term type 1 diabetes mellitus (T1DM) and without history of systemic/ocular complications. The aim of this cross-sectional study was to investigate sub-clinical structural and/or vascular retinal changes in patients with long-term (≥30 years) T1DM and without systemic/ocular complications ("happy few" patients) using structural optical coherence tomography (OCT), OCT-angiography and microperimetry. Twelve eyes of 12 consecutive T1DM patients (mean age 52 ± 12 years, mean duration of disease 35 ± 3 years, mean HbA1c level 7.3 ± 2.8%), without micro/macrovascular complications associated with long-standing T1DM, and twelve healthy subjects were consecutively included. No statistically significant differences were disclosed comparing patients and controls for age, sex, best-corrected visual acuity, central macular thickness, and choroidal thickness. Using OCT-angiography, we did not find any significant difference in foveal avascular zone area, perfusion density, vessel length density, and tortuosity. Moreover, no significant differences were disclosed in retinal nerve fiber layer and ganglion cell complex thickness using structural OCT. No differences were disclosed in retinal sensitivity by microperimetry. New diagnostic tools are able to confirm the presence of a particular population of patients with type 1 diabetes who have been completely spared from diabetic retinal complications. The finding of these "happy few" patients could help us to better understand and target future treatments for diabetes.

Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy.

The aim of this cross-sectional case-control study is to investigate the possible presence of vascular/neurodegenerative alterations in the retina of type 1 diabetes mellitus (T1DM) patients without diabetic retinopathy (DR). Thirty-four eyes of 34 consecutive T1DM without DR (mean age 21 ± 2 years) were included. Another cohort of 27 eyes (27 healthy control subjects matched with age and sex) was also recruited. All patients underwent multimodal imaging evaluation using structural optical coherence tomography (OCT), OCT-angiography (OCT-A), dynamic vessel analyzer (DVA) and microperimetry. No significant differences were disclosed comparing diabetics and controls for visual acuity, central macular thickness, and subfoveal choroidal thickness. On retinal nerve fiber layer and ganglion cell complex thickness, no significant differences were disclosed comparing each 3-mm-diameter macular and peripapillary subfield between two groups. Using OCT-A, deep capillary plexus perfusion density (PD) of diabetics was significantly lower compared to control group, whereas PD of other retinal/choriocapillaris plexuses and foveal avascular zone area did not show any significant difference. Using DVA, diabetic eyes revealed a significantly decreased vessel response to flicker light in comparison to controls. No differences were disclosed using microperimetry analysis. Taken together, these results suggest that vascular alterations could be the first detectable retinal change in the development of DR.

Quantitative changes in the ageing choriocapillaris as measured by swept source optical coherence tomography angiography.

AIM: To analyse quantitative optical coherence tomography angiography (OCTA) parameters of choriocapillaris (CC) at the foveal, perifoveal and parafoveal regions in healthy subjects of different age. METHODS: In this observational cross-sectional study, consecutive healthy subjects underwent swept source OCTA (PLEX Elite 9000, Carl Zeiss Meditec, USA). 3×3 mm and 6×6 mm scans centred on the fovea were acquired analysed and postprocessed with thresholding and binarisation processes. The main outcome measures included CC quantitative OCTA features (perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI)) at the foveal, perifoveal and parafoveal regions, and their relationship with age. RESULTS: Seventy-two eyes (72 patients, mean age 47.4±19.2 years, mean axial length 24.0±0.7 mm) were included. The mean PD was statistically lower in the foveal region compared with the parafoveal region in 3×3 mm scans (p=0.009). In subjects aged 70-80, PD of the foveal region was significantly reduced compared with the perifoveal region in 6×6 mm scans (p=0.008). A strong negative correlation was found between PD and ageing in the foveal, parafoveal and perifoveal regions (p<0.001 in all analyses). Furthermore, PD in the nasal-perifoveal region was significantly lower than the temporal-perifoveal region (p=0.005). No significant correlation was found between VLD and age in all regions, whereas VDI was strictly correlated with age (p<0.001). CONCLUSIONS: We reported in vivo a strong negative correlation between PD and ageing in the CC of healthy subjects. This reduction seems related to a reduced diameter, and not to a reduced number, of capillaries. The age-related changes were higher in the central area compared with the perifoveal area.