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Background: This study aimed to assess the neuronal and microvascular retinal and choroidal involvement in COVID-19 recovered patients using optical coherence tomography (OCT) and OCT angiography (OCTA)., Methods: This observational cross-sectional study recruited patients recovered from COVID-19 and a group of healthy controls for comparisons. OCT (peripapillary scan and macular map) and OCTA (macular map) were performed to obtain: the central subfield thickness (CST), the macular volume (MV), the peripapillary retinal nerve fibre layer (pRNFL) thickness, the vessel area density (VAD), vessel length fraction (VLF), vessel diameter index (VDI) and fractal dimension (FD) of the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), and the vessel density (VD), stromal density (SD) and vascular/stromal (V/S) ratio of the choriocapillaris (CC) and choroid (Ch). Data regarding disease severity, administered therapy and prior comorbidities were collected., Results: We recruited 676 eyes from 338 patients and 98 eyes from 49 healthy controls. VAD of all the three retinal plexuses, VLF and VDI of ICP and DCP and VD of CC were significantly reduced in patients versus controls. No differences were found in CST, MV and pRNFL. A multivariate analysis showed that oxygen therapy, previous cardio/cerebrovascular events and hypertension negatively influenced vascular parameters., Conclusion: A microvascular retinal and choriocapillaris damage may be identified secondary to SARS-CoV-2 infection, even after recovery. OCTA may represent a reproducible and non-invasive tool to assess microangiopathy in these patients, with particular regard to those with previous cardio/cerebrovascular events, hypertension and those who received oxygen therapy., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To analyze and classify neurofibromatosis Type 1 (NF1)-related retinal vascular abnormalities (RVAs), their natural history and correlation with disease severity, in a large cohort of patients., Methods: This was an observational longitudinal study with prospective enrollment. Four hundred and seventy-three patients affected by NF1 and 150 age-matched healthy subjects were consecutively enrolled. Retinal vascular abnormalities were detected by means of near-infrared reflectance and studied by optical coherence tomography angiography. The superficial vascular plexus and the deep vascular complex (DVC) were quantitatively and qualitatively analyzed., Results: We identified RVAs in 82 of 473 (17%) NF1 patients, but in none of the 150 healthy subjects. A comparison revealed that NF1 patients with RVAs showed a higher number of NF1 diagnostic criteria (4.3 ± 1.5 vs. 3.9 ±1.5, respectively; P = 0.02) than patients without RVAs. Three different RVA types were identified on optical coherence tomography angiography: macrovascular angiomatosis of the sole superficial vascular plexus; macrovascular angiomatosis of the superficial vascular plexus combined with microvascular angiomatosis of the deep vascular complex; and combined macrovascular angiomatosis of both superficial vascular plexus and deep vascular complex. The prospective analysis of optical coherence tomography angiography images showed no significant longitudinal evolution of RVAs (mean follow-up: 3.7 ± 2.8 years). A single patient developed a de novo single RVA, and two RVAs showed detectable changes during follow-up., Conclusion: In NF1 patients, RVAs are a characteristic sign that correlates with a more severe systemic disease expression, usually remaining stable during time. Optical coherence tomography angiography allows for the identification of different RVAs subtypes.

Optical coherence tomography (OCT) allows us to identify, into retinal layers, new morphological entities, which can be considered clinical biomarkers of retinal diseases. According to the literature, solitary, small (<30 µm), medium level hyperreflective (similar to retinal fiber layer) retinal foci (HRF) may represent aggregates of activated microglial cells and an in vivo biomarker of retinal inflammation. The identification and quantification of this imaging biomarker allows for estimating the level and possibly the amount of intraretinal inflammation in major degenerative retinal disorders, whose inflammatory component has already been demonstrated (diabetic retinopathy, age-related macular degeneration, radiation retinopathy). Currently, diabetic retinopathy (DR) probably represents the best clinical model to apply this analysis in the definition of this clinical biomarker. However, the main limitation to the clinical use of HRF is related to the technical difficulty of counting them: a time-consuming methodology, which also needs trained examiners. To contribute to solve this limitation, we developed and validated a new method for the semi-automatic detection of HRF in OCT scans. OCT scans of patients affected by DR, were analyzed. HRF were manually counted in High Resolution spectral domain OCT images. Then, the same OCT scans underwent semi-automatic HRF counting, using an ImageJ software with four different settings profiles. Statistical analysis showed an excellent intraclass correlation coefficient (ICC) between the manual count and each of the four semi-automated methods. The use of the second setting profile allows to obtain at the Bland-Altman graph a bias of -0.2 foci and a limit of agreement of ±16.3 foci. This validation approach opens the way not only to the reliable and daily clinical applicable quantification of HRF, but also to a better knowledge of the inflammatory component-including its progression and regression changes-of diabetic retinopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Midena, Torresin, Velotta, Pilotto, Parrozzani and Frizziero.)

Purpose: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population., Methods: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility., Results: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters., Conclusions: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography., Methods: Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry., Results: Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009)., Conclusion: The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.

Aims: To investigate, with optical coherence tomography angiography (OCTA), short-term changes of type 1 choroidal neovascularisation (CNV), secondary to exudative age-related macular degeneration, after anti-vascular endothelial growth factor (VEGF) treatment., Methods: Patients affected by type 1 CNV treated with intravitreal anti-VEGF were consecutively enrolled. All patients underwent OCTA examination before and 48 hours after anti-VEGF treatment. Quantitative and qualitative vascular and morphological macular changes were evaluated., Results: Sixteen eyes were included (11 treated with aflibercept and 5 with ranibizumab). Both CNV mean area and pigment epithelium detachment significantly reduced (p=0.0004 and p=0.0007, respectively) after treatment. Cystoid macular oedema (four eyes) decreased in all cases. Neuroretinal detachment (13 eyes) decreased in 85% of cases (11 eyes). Fine CNV vessels density decreased in 75% (12 eyes), whereas larger CNV vessels density remained stable in 66.7% (10 eyes), choroidal flow void signal (7 eyes at baseline) increased in 42.9% (3 eyes) of them and remained stable in 57.1% (4 eyes). Interoperator reproducibility for OCT examination was good for all measurements (intraclass correlation coefficient>0.65)., Conclusion: Early remodelling of type 1 CNV network after treatment may be non-invasively and reproducibly analysed by means of OCTA. Choroidal perfusion impairment, choroidal flow void signal, surrounding CNV may change during treatment., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To evaluate peripapillary retinal nerve fibre layer (RNFL) thickness, measured by spectral-domain optical coherence tomography (SD-OCT), as a surrogate of visual function in a population of paediatric patients affected by optic pathway glioma (OPG) associated with neurofibromatosis type 1 (NF1)., Methods: A total of 38 paediatric patients (66 eyes) affected by MRI-proven OPG were included. Each patient underwent complete ophthalmological examination, including age-appropriate visual acuity (VA) assessment and RNFL analysis by SD-OCT. Visual acuity was classified as normal or pathologic using age-based normative data. Visual acuity was correlated to mean RNFL thickness of the whole peripapillary area and of each single analyzed sector (nasal, superior, temporal, inferior)., Results: Visual acuity was normal in 43 (65%) and pathologic in 23 (35%) eyes. Mean parapapillary RNFL thickness of each analyzed sector was significantly lower in eyes with abnormal VA (p < 0.05). The best balanced cut-off value of global RNFL thickness allowing to discriminate between eyes with normal and pathologic VA was 76.25 μm (91%, 76%, 67% and 94% of sensitivity, specificity, positive and negative predicting value, respectively). Considering best balanced cut-off values of other analyzed RNFL sectors, the superior (p = 0.0029) and the inferior (p = 0.0024) sectors reached the higher sensitivity (87% and 87%, respectively) and specificity (81% and 79%, respectively)., Conclusion: Retinal nerve fibre layer thickness is directly related to VA in children affected by NF1-related OPG, and should be considered as a potential surrogate marker of VA. Retinal nerve fibre layer thickness cut-off values can be used in paediatric patients to discriminate false-positive results obtained by VA measurement., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: To investigate peripapillary vascular changes secondary to radiation optic neuropathy (RON) using optical coherence tomography angiography (OCT-A) and to propose a clinical grading of RON based on OCT-A findings., Methods: Thirty-four patients affected by RON were consecutively included. Each patient underwent best corrected visual acuity measurement (ETDRS score) and OCT-A (Nidek RS-3000 Advance device, Nidek, Gamagori, Japan). The radial peripapillary capillary plexus (RPCP) and the entire peripapillary capillary bed (EPCB) were analysed. Quantitative analysis of the OCT-A images was performed using open-source available ImageJ software (National Institutes of Health, Bethesda, Maryland, USA). Qualitative analysis based on the proposed clinical grading (Grades 0-4) was also performed by two masked graders., Results: RON clinical (qualitative) classification based on RPCP correlated with the quantitative RPCP perfusion analysis (P=0.0001). RON clinical classification based on RPCP statistically correlated with ETDRS score (P=0.001). RON clinical classification based on EPCB also correlated with the quantitative EPCB perfusion analysis and ETDRS score (P=0.02 and P=0.01, respectively). Compared with the clinical classification based on EPCB, the qualitative classification based on RPCP reached a higher intergrader agreement (0.96 and 0.86, respectively)., Conclusion: OCT-A can be used to detect RPCP abnormalities and to clinically classify RON with a high interexaminer agreement. The proposed clinical classification is supported by the quantitative analysis based on the use of specific images elaboration techniques and correlates with visual acuity of the examined eyes., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To compare the foveal avascular zone (FAZ) area measurements produced by different optical coherence tomography angiography (OCTA)., Methods: Healthy enrolled volunteers underwent OCTA using 2 different devices: Spectralis HRA+OCTA (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Advance (Nidek, Gamagori, Japan). Two graders measured FAZ in both superficial (SCP) and deep (DCP) retinal capillary plexuses. The SCP and DCP en face images were visualized automatically segmenting 2 separate slabs defined by the arbitrary segmentation lines created by the software of each OCT device. One grader repeated each measure twice., Results: Fifty-nine eyes were included. The mean FAZ was 0.33 ± 0.09 mm2 at the SCP and 0.57 ± 0.17 mm2 at the DCP measured with RS-3000 versus 0.30 ± 0.08 and 0.35 ± 0.08 mm2, respectively, measured with Spectralis. The measurements of the 2 devices were significantly different (p < 0.0001). The intraoperator agreement was excellent at the SCP (intraclass correlation coefficient, ICC: 0.97 with Spectralis and 0.96 with RS-3000). At the DCP, it was good with Spectralis and fair with RS-3000 (ICC: 0.85 and 0.64, respectively). The interoperator agreement was excellent for Spectralis and good for RS-3000 at the SCP (ICC: 0.97 and 0.93, respectively). It was good at the DCP with both devices (ICC: 0.74 with RS-3000 and 0.81 with Spectralis)., Conclusions: FAZ measurements obtained with different OCTA devices differ. These findings should be considered in follow-up studies of patients with retinal vascular diseases., (© 2018 S. Karger AG, Basel.)

Purpose: To better pathophysiologically characterize macular edema secondary to eye irradiation, analyzing the presence of optical coherence tomography (OCT) hyperreflective spots., Methods: Twenty-five consecutive eyes affected by radiation maculopathy, secondary to irradiation for a primary uveal melanoma, without macular involvement in the irradiation field, were consecutively enrolled. All subjects underwent full ophthalmologic examination, including fluorescein angiography, color fundus photography, and spectral domain OCT, even in en face modality. Optical coherence tomography central subfield thickness was stratified into the following 3 categories: <400 μm, 400 to 600 μm, and >600 μm. Spectral domain OCT images were analyzed to measure and localize hyperreflective spots by two independent masked graders., Results: Hyperreflective spots were documented in all eyes (100%). Hyperreflective spots significantly increased in number according to OCT central subfield thickness (<400 μm, 400-600 μm, >600 μm, P < 0.05). The intergrader agreement was at least substantial for all measurements (intraclass correlation coefficient: 0.80)., Conclusion: Spectral domain OCT documents discrete intraretinal reflectivity changes (hyperreflective spots) in all (studied) eyes affected by radiation maculopathy. Hyperreflective spots increase in number with increasing central subfield thickness and could be considered as a new clinical biomarker of intraretinal inflammation in patients affected by macular edema secondary to irradiation for uveal melanoma.