PurposeTo compare macular and peripapillary vessel density values calculated on optical coherence tomography angiography (OCT-A) images with different algorithms, elaborate conversion formula, and compare the ability to discriminate healthy from affected eyes.MethodsCross-sectional study of healthy subjects, patients with diabetic retinopathy, and glaucoma patients (44 eyes in each group). Vessel density in the macular superficial capillary plexus (SCP), deep capillary plexus (DCP), and the peripapillary radial capillary plexus (RCP) were calculated with seven previously published algorithms. Systemic differences, diagnostic properties, reliability, and agreement of the methods were investigated.ResultsHealthy eyes exhibited higher vessel density values in all plexuses compared to diseased eyes regardless of the algorithm used (p<0.01). The estimated vessel densities were significantly different at all the plexuses (p<0.0001) as a function of method used. Inter-method reliability and agreement was mostly poor to moderate. A conversion formula was available for every method, except for the conversion between multilevel and fixed at the DCP. Substantial systemic, non-constant biases were evident between many algorithms. No algorithm outperformed the others for discrimination of patients from healthy subjects in all the retinal plexuses, but the best performing algorithm varied with the selected plexus.ConclusionsAbsolute vessel density values calculated with different algorithms are not directly interchangeable. Differences between healthy and affected eyes could be appreciated with all methods with different discriminatory abilities as a function of the plexus analyzed. Longitudinal monitoring of vessel density should be performed with the same algorithm. Studies adopting vessel density as an outcome measure should not rely on external normative databases.

AimTo analyse quantitative optical coherence tomography angiography (OCTA) parameters of choriocapillaris (CC) at the foveal, perifoveal and parafoveal regions in healthy subjects of different age.MethodsIn 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.ResultsSeventy-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).ConclusionsWe 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.

PURPOSE. To investigate the macular quantitative parameters interchangeability of three different optical coherence tomography angiography (OCT-A) angiocubes (i.e., 3 3 3, 6 3 6, and 12 3 12 mm) on healthy subjects and patients affected by diabetic retinopathy (DR) and to assess the interrater reliability of such indices across the different scan protocols. METHODS.Retrospective study involving 20 eyes of healthy subjects and 20 eyes with DR. All eyes underwent swept-source OCT-A with 3 3 3-, 6 3 6-, and 12 3 12-mm angiocubes centered on the fovea. Foveal avascular zone (FAZ) area and vessel density on 3 3 3-, 6 3 6-, and 12 3 12-mm macular scans were calculated by three independent operators at all retina, superficial, deep, and choriocapillary vascular layers. Interchangeability and interrater reliabilities were estimated using intraclass correlation coefficient (ICC).RESULTS. Interscan reproducibility of FAZ area was very strong (ICC > 0.85) at every plexus. On the contrary, vessel density values significantly varied across different scan sizes (ICC < 0.51). Intrascan interrater reliability was high for all retina and superficial FAZ areas, while it was satisfactory at deep capillary plexus only for 3 3 3-mm scan.CONCLUSIONS. FAZ area at all plexuses is a robust parameter even if calculated on angiocubes with different size. However, interrater reliability is higher when measured in smaller scans. Conversely, vessel density results depend on the size of angiocube, although their interrater reliability is extremely high. Studies involving OCT-A should take into consideration that scan size may influence macular perfusion parameters and interrater reliability.

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.

AimTo analyse the choriocapillaris (CC) flow status in the area that subsequently showed geographic atrophy (GA) expansion secondary to age-related macular degeneration (AMD) during 1-year follow-up, matching optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF).MethodsIn this prospective longitudinal observational study, 30 eyes of 20 consecutive patients with GA secondary to AMD (mean age 75.5±7.4 years) were included. All patients underwent OCT-A and FAF at baseline and 1-year follow-up. Main outcome measures included analysis of perfusion density (PD) in the ‘area surrounding GA margin’ (between the GA border and 500 µm distance) in comparison with the ‘control area’ (area outside the 500 µm line), and of the ‘expansion area’ (area that subsequently developed GA expansion during 1-year follow-up).ResultsDuring the 1-year follow-up, visual acuity significantly decreased from 0.34±0.38 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.39±0.40 LogMAR (p<0.001), and mean GA area increased from 6.82±5.47 mm2 to 8.76±6.28 mm2 (p<0.001). CC PD of the area surrounding the GA margin revealed a significant flow impairment compared with control area (PD 0.679±0.076 and 0.734±0.057, respectively (p<0.001)). Furthermore, the PD of the expansion area showed a greater CC flow impairment in comparison to the remaining area surrounding GA margin (p<0.001).ConclusionsWe reported a greater CC impairment in the area that subsequently developed GA expansion, suggesting that the CC flow impairment could predict the enlargement of GA lesion. The CC impairment could be considered as a new a risk factor for GA progression and a biomarker to be measured to determine efficacy of new interventions aiming to slow progression of GA.

The aim of this study was to explore the relative prevalence and clinical differences between age-related macular degeneration (AMD) and pachychoroid disease in patients older than 50 years with newly diagnosed exudative neovascular maculopathy, and also assess the rate of misdiagnosis between these two disorders. In this retrospective observational study, we reviewed data from patients 50 years of age and older with newly diagnosed treatment-naïve exudative macular neovascularization (MNV) secondary to AMD or pachychoroid disease. Of the 139 patients (139 eyes) who fulfilled the inclusion criteria, 35 patients were graded as being affected by pachychoroid disease complicated by exudative MNV and 104 subjects had neovascular AMD. Therefore, prevalence of pachychoroid disease complicated by exudative MNV was 25.2% (confidence interval—CI 18.2–33.2%). Mean ± SD age was 67.0 ± 8.8 years in the pachychoroid disease group and 80.6 ± 6.6 years in the neovascular AMD group (P < 0.0001). At baseline, BCVA was better in patients with pachychoroid disease complicated by exudative MNV (0.4 ± 0.3 LogMAR vs. 0.7 ± 0.5 LogMAR, P = 0.003). At the 1-year follow-up visit, BCVA was still better in patients with pachychoroid-associated MNV (0.34 ± 0.32 LogMAR vs. 0.59 ± 0.52 LogMAR; P = 0.005). In our study cohort, 19 patients were graded to be affected by pachychoroid disease complicated by exudative MNV even though a diagnosis of neovascular AMD was erroneously reported in their medical records at baseline. In conclusion, pachychoroid disease is a frequent cause of exudative MNV in aged patients with a high rate of misdiagnosis. A correct diagnosis may be important as these two disorders differ in terms of clinical characteristics and prognosis.

PurposeTo assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects.MethodsIn this cross-sectional study, macular structural OCT and OCT angiography (OCTA) images were acquired from healthy subjects. The main outcome measures were: (i) choriocapillaris (CC) flow deficits percentage (FD%), (ii) choroidal luminal (LA) and stromal (SA) areas and (iii) choroidal vascularity index (CVI), which was calculated as the LA divided by the total choroidal area. These measurements were generated using previously published algorithms and were separately computed in the foveal and extrafoveal regions.ResultsEighty-five eyes from 85 subjects (44 males, 41 females) were included in the analysis. Mean±SD age was 47.9±22.4 years (range: 19.0 to 85.0 years). Linear regression analysis displayed no significant associations between CC FD% and other parameters (LA, SA and CVI). Importantly, non-linear regression analysis showed that the relations of LA and SA to CC FD% were all best fitted by a quadratic function. Compared with the linear models, the use of the quadratic function allowed a relative increase in the R2 coefficients. No significant non-linear associations were found between CC FD% and CVI.ConclusionBased on our models, changes in the luminal and stromal areas in the choroid lead to an initial increase in CC perfusion. Subsequently, further increases in LA and SA amounts are accompanied by a progressive increment in CC FD%.

PurposeThis study aimed to describe the characteristics of microvascular retinal alterations in eyes with chronic central serous chorioretinopathy (CSC) employing optical coherence tomography angiography (OCTA) analysis.MethodsWe collected data from 472 eyes with chronic CSC from 336 patients who had OCTA obtained. Each OCTA image was graded by two readers to assess the presence of microvascular retinal alterations, including regions of vascular rarefaction/retinal hypoperfusion, enlargement of the foveal avascular zone (FAZ) and presence of telangiectasias or microaneurysms. Volume spectral domain optical coherence tomography (SD-OCT) scans were obtained through the macula and the OCT was correlated with the OCTA findings in eyes with retinal vascular alterations.ResultsOCTA displayed microvascular retinal alterations in 18 out of 474 eyes (3.6%) from 14 patients (13 male and 1 female; mean±SD age was 54.7±11.1 years). One eye displayed the presence of retinal telangiectasias, while 17 out of 18 eyes were graded as having areas of retinal vascular rarefactions, and 3 out of 17 eyes were also characterised by an enlargement of the FAZ. The parafoveal region was the location most involved by retinal vascular changes (66,7%), followed by foveal (22,2%) and perifoveal (11.1%) regions, respectively.ConclusionAlthough CSC is known to represent a choroidal disorder, retinal vascular alterations may be present in these eyes and OCTA may represent a useful tool to identify and describe them.