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Age-related macular degeneration (AMD) is a major cause of central visual loss in the developed world. Although the pathogenesis is not fully understood, vascular endothelial growth factor (VEGF) is considered the most important growth factor involved in angiogenesis and exudation in neovascular AMD eyes. Advances in anti-VEGF agents have changed the treatment approach for wet AMD, allowing better outcomes in visual acuity and retinal anatomy.The present review describes the main pharmacological and clinical characteristics of anti-VEGF drugs, focusing firstly on the molecules commonly in use and then on the new candidate therapies. We performed a comprehensive literature search using the PubMed database from 1 January 1993 to 1 June 2022, with search terms including anti-VEGF, biosimilar, neovascular macular degeneration, AMD, and safety.The management of AMD is still onerous for both the physician and patient due to the great number of required injections. Current research is underway to resolve not only the economic burden but also the discomfort of patients, aiming to develop a drug with a different or a multiple target, increasing the potency whilst maintaining a good safety profile. Furthermore, clinical research is currently investigating different forms of drug administration.

To identify baseline OCT predictors of the 3-year visual outcome for type 3 (T3) macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) treated by anti-vascular endothelial growth factor (VEGF) therapy.Retrospective longitudinal study.Forty eyes of 30 patients affected by exudative treatment-naive T3 MNV were enrolled.Baseline best-corrected visual acuity (BCVA) and several baseline OCT features were assessed and included in the analysis. Univariate and multivariate analyses served to identify risk factors associated with the 3-year BCVA.Baseline OCT features that are associated with bad or good visual outcomes of T3 MNV treated by anti-VEGF injections.Mean baseline BCVA was 0.34 ± 0.28 logarithm of the minimum angle of resolution (LogMAR), which significantly decreased to 0.52 ± 0.37 LogMAR at the end of the 3-year follow-up (P = 0.002). In the univariate analysis, the following baseline features were associated with the 3-year BCVA outcome: baseline BCVA (P = 0.004), foveal involvement of exudation (P = 0.004), and presence of subretinal fluid (SRF; P = 0.004). In the multivariate model, baseline BCVA (P = 0.032), central macular thickness (P = 0.036), number of active T3 lesions (P = 0.034), and presence of SRF (P = 0.008) were associated with the 3-year BCVA outcome. Interestingly, 3-year BCVA was significantly lower in 19 eyes with SRF at the baseline (0.69 ± 0.42 LogMAR) than 21 eyes without SRF (0.37 ± 0.24 LogMAR; P = 0.004).We identified structural OCT features associated with BCVA outcome after 3-year treatment with anti-VEGF injections. In contrast to previous studies on neovascular AMD, in our series, the presence of SRF at baseline was the most significant independent negative predictor of functional outcomes. Current findings may be employed to identify less favorable T3 patterns potentially deserving a more intensive treatment.

To investigate the correlation between choroidal vascularity index and the enlargement of geographic atrophy (GA) lesion secondary to age-related macular degeneration during the 2-year follow-up.In this longitudinal observational study, 26 eyes (26 patients, mean age 75.7 ± 8.8 years) affected by GA were included. Choroidal vascularity index was calculated in the subfoveal 3000-µm area. The main outcome measure included correlation analysis between baseline choroidal vascularity index and the rate of GA enlargement.During the 2-year follow-up, the mean GA area increased from 6.99 ± 5.28 mm2 to 10.69 ± 6.61 mm2(P0.001), accounting for a growth rate of 0.35 ± 0.20 and 0.31 ± 0.17 mm/year after the square root transformation in the first and second year of follow-up, respectively. Stromal choroidal area significantly decreased during the 2-year follow-up (P = 0.002). Interestingly, there was a significant correlation between the baseline choroidal vascularity index and the rate of GA enlargement (r=-0.432, P = 0.027) and between stromal choroidal area and the rate of GA enlargement (r = 0.422, P = 0.032). No other significant relationship was disclosed among choroidal parameters with the rate of GA enlargement.Choroidal vascularity index impairment is strictly related to the rate of GA enlargement during the 1-year and 2-year follow-up in patients affected by GA. For this reason, choroidal vascularity index could be considered a predictor of GA progression in the clinical setting, and it could be considered as a new potential biomarker in the efficacy evaluation of new GA interventions.

The aim of this study was to investigate changes in macular perfusion in patients affected by diabetic macular edema (DME) and treated with ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg using optical coherence tomography angiography (OCTA).This was a retrospective cohort study that included patients aged18 years with type 2 non-proliferative diabetic retinopathy (DR) and DME at baseline. All patients were treated with the ILUVIEN® implant. A minimum of two 6 × 6-mm OCTA scans were required to ensure that all cases had a baseline OCTA and an OCTA performed at 4 months of follow-up. Qualitative and quantitative comparisons were performed.Ten eyes from ten subjects were included in the analysis. Mean (± standard deviation) age of the study cohort was 57.1 ± 8.3 years. Mean parafoveal perfusion density (PD) at baseline was 64.1 ± 1.8% at baseline, increasing to 66.1 ± 2.9% (p = 0.013) at the 4-month follow-up visit. Mean parafoveal PD at baseline was 64.4 ± 2.1%, increasing to 65.2 ± 2.6% (p = 0.024) after 4 months. In the qualitative assessment, 60 regions (10 areas for each subject) were graded to assess changes in retinal perfusion between the baseline and follow-up visits. This assessment revealed that 24 regions (40.0%) were characterized by a qualitative increase in perfusion after treatment, while 22 (36.7%) and 14 (23.3%) regions were featured by a stability and reduction in retinal perfusion, respectively.OCTA analysis detects improvements in macular perfusion after treatment with ILUVIEN®. This improvement in macular perfusion may be associated with corticosteroid-related beneficial effects on leukostasis.

PURPOSE: To assess the impact of histogram adjustments and binarization thresholding selection on quantitative measurements of diabetic macular ischemia using optical coherence tomography angiography (OCTA). METHODS: Patients with diabetic retinopathy (DR) who had swept-source OCTA imaging obtained were enrolled. An additional group of 15 healthy control subjects was included for comparison. Previously used brightness/contrast changes and binarization thresholds were applied to original OCTA images to obtain and compare different binarized images. Qualitative and quantitative comparisons were performed. RESULTS: Thirty patients with DR (30 eyes) were included in the analysis. Fifteen eyes displayed the presence of diabetic macular edema. Qualitative grading revealed that binarized images obtained using a global threshold had better quality compared with local or multistep thresholds. The "median" filter was most frequently graded as the histogram adjustment resulting in binarized images with best quality. In the quantitative analysis, local thresholds tended to generate higher values of measured metrics. Differences in OCTA metrics between global and local thresholds were associated with presence of diabetic macular edema and signal strength index value. In the comparison between healthy and DR eyes, differences in OCTA metrics were significantly affected by binarization threshold selection. CONCLUSION: Quantitative OCTA parameters may be significantly influenced by strategies to quantify macular perfusion. Image quality and presence of macular edema can significantly impact OCTA-derived quantitative vascular measurements and differences between global and local binarization thresholds. These findings highlight the importance of consistent strategies to reliably generate quantitative OCTA metrics in patients with DR.

Objective To describe the effects of no-dose full fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC). Methods This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with half-dose full-fluence PDT (HDFF PDT) a minimum of 3- months before and were considered as control group. We described the changes of best-corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF) and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT. Results Fifteen eyes of 11 patients (10 males, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 males, mean age 53 ± 12 years) received also HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at the baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses). Conclusion BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise thermal elevation triggers and enhances photochemical activities by endogenous fluorophores that activates a biochemical cascade response that rescues / replaces sick, dysfunctional RPE cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable.

To assess the diagnostic accuracy of individual and combined imaging modalities compared with multimodal imaging for the detection of choroidal neovascularization (CNV) in central serous chorioretinopathy (CSC).We analyzed patients with CSC with and without CNV who had indocyanine green angiography (ICGA), structural optical coherence tomography (OCT), and OCT angiography (OCTA) obtained on the same day. The presence of CNV was determined using multimodal imaging by a senior retina specialist (i.e., diagnostic reference). Individual and combined (i.e., ICGA + structural OCT) imaging modalities were then graded by two expert readers for the presence of CNV. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were computed for individual and combined imaging modalities relative to the diagnostic reference.CNV was detected in 17 eyes in 17 out of 33 CSC patients according to the reference standard. Using ICGA, the identification of CNV had a sensitivity of 66.7%, specificity of 66.7%, PPV of 70.6%, and NPV of 62.5%. Structural OCT had the following diagnostic accuracy values: 83.3% of sensitivity, 53.3% of specificity, 68.1% of PPV, and 72.7% of NPV. Using OCTA, CNV was graded to be present with a sensitivity of 77.8%, specificity of 86.7%, PPV of 87.5%, and NPV of 76.5%. The combination of ICGA and structural OCT granted the identification of CNV with a sensitivity of 83.3%, specificity of 86.7%, PPV of 88.2%, and NPV of 81.3%.OCTA has an elevated diagnostic accuracy in identifying CSC-associated CNV, though a combination of ICGA and structural OCT has a comparable diagnostic efficiency.

PURPOSE: Two-dimensional (2D) optical coherence tomography angiography (OCTA) is known to be prone to segmentation errors, especially in pathologic eyes. Therefore, our aim was to systematically compare intrasession repeatability between repeated scans for 2D and three-dimensional (3D) OCTA metrics in quantifying retinal perfusion in eyes with diabetic macular edema. METHODS: Diabetic patients with diabetic retinopathy and diabetic macular edema who had two consecutive OCTA imaging scans obtained during the same visit were retrospectively included. A previously validated algorithm was applied to OCTA volume data to measure the 3D vascular volume and perfusion density. Optical coherence tomography angiography en face images were also processed to obtain 2D perfusion density metrics. RESULTS: Twenty patients (20 eyes) with diabetic retinopathy and diabetic macular edema were included. The intraclass correlation coefficient ranged from 0.591 to 0.824 for 2D OCTA metrics and from 0.935 to 0.967 for 3D OCTA metrics. Therefore, compared with the 2D OCTA analysis, the intraclass correlation coefficients of the 3D OCTA analysis were higher (without overlapping of the 95% confidential intervals). Similarly, the coefficient of variation (ranging from 2.2 to 4.2 for 2D OCTA metrics and from 1.9 to 2.0 for 3D OCTA metrics) indicated that the 3D OCTA-based quantifications had the highest interscan intrasession agreements. Differences in interscan 2D OCTA metrics' values were associated with average macular volume. CONCLUSION: Three-dimensional OCTA metrics have higher values of intrasession repeatability, as compared with 2D OCTA metrics. The latter finding seems to be related to the high rate of segmentation errors occurring in diabetic macular edema eyes.

To quantitatively evaluate the inner and outer choroidal changes in the fellow eyes of patients with unilateral central serous chorioretinopathy (CSC).We analyzed data from patients with a diagnosis of unilateral CSC who had structural optical coherence tomography (OCT) and swept-source OCT angiography obtained. An additional group of age-matched healthy patients was included for comparison. The main outcome measures were: (1) choriocapillaris flow deficits' quantitative metrics; (2) choroidal luminal (LCA) and stromal (SCA) areas; and (3) choroidal vascularity index.Fellow unaffected eyes from 60 patients with unilateral CSC and 30 healthy subjects were included in the analysis. Mean ± SD age was 47.5 ± 9.9 years in the unilateral CSC group and 50.7 ± 10.8 years in the control group (P = 0.410). In the structural OCT assessment, both the LCA and SCA were increased in the unilateral CSC group (0.33 ± 0.11 and 0.29 ± 0.10 mm2) compared with healthy controls (0.28 ± 0.08 and 0.27 ± 0.05 mm2), although only differences in LCA reached a statistical significance (P = 0.041 and P = 0.286 for LCA and SCA, respectively). The choroidal vascularity index was higher in CSC patients (53.7 ± 3.6 and 50.9 ± 5.5%, P = 0.045). In the OCT angiography evaluation, the choriocapillaris flow deficits' percentage and number were increased in those patients affected by unilateral CSC. In multiple regressions, the strongest association with choriocapillaris percentage of flow deficits was with the presence of pachychoroid pigment epitheliopathy signs in the study eye (P0.0001).Our results corroborate the hypothesis that inner and outer choroidal changes affect both eyes of patients with unilateral disease.

Purpose To assess the relationship between demographics, clinical characteristics, and structural optical coherence tomography (OCT) findings and the development of sight-threatening macular complications (choroidal neovascularization [CNV], large areas of retinal pigment epithelium [RPE] atrophy, and cystoid macular degeneration [CMD]) in a cohort of eyes with “resolved” chronic central serous chorioretinopathy (CSC) at study baseline. Design Retrospective cohort study. Methods In this study, a total of 71 eyes with “resolved” (absence of subretinal fluid) chronic CSC at baseline and 36 months of regular follow-up examinations were retrospectively enrolled. Structural OCT scans were reviewed. Baseline OCT qualitative features reflecting distress of the neuroretina, RPE, or choroid were assessed and included ellipsoid zone discontinuity, outer nuclear layer (ONL) thinning; presence of hyper-reflective intraretinal foci; dome-shaped pigment epithelium detachment (PED); hyper-reflective flat, irregular PED; hyporeflective flat, irregular PED; and inner choroidal attenuation. OCT images obtained at follow-up visits were also reviewed for development of macular complications (CNV, large areas of RPE atrophy [at least 250 μm in diameter], and CMD). Main outcome measurements included incidence of macular complications and hazard ratio (HR) for demographics, clinical characteristics, and OCT risk factors. Results At month 36, 20 eyes (28.2%) developed macular complications. Nine eyes (12.7%) displayed CNV, 9 eyes (12.7%) had large areas of RPE atrophy, and 2 eyes (2.8%) developed cystoid macular degeneration. The following factors were associated with an increased risk of development of CNV: intraretinal hyper-reflective foci had an HR of 11.58 (95% confidence interval [CI]: 1.10-37.24; P = .040); inner choroidal attenuation had an HR of 9.66 (95% CI: 1.07-22.34; P = .043); and the presence of macular complications in the fellow eye had an HR of 20.17 (95% CI: 1.34-39.41; P = .030). Factors associated with the development of RPE atrophy were also identified: ONL thinning had an HR of 13.47 (95% CI: 1.10-39.86; P = .042); dome-shaped PED had an HR of 21.40 (95% CI: 1.50-41.10; P = .031); and inner choroidal attenuation had an HR of 13.20 (95% CI: 1.07-39.32; P = .044). Conclusions OCT risk factors were identified for the development of macular complications in eyes with chronic CSC. Findings may help in the identification of high-risk patients.

Purpose: To analyze different clinical and anatomical features in treatment-naïve non-exudative macular neovascularizations (MNVs) secondary to age-related macular disease (AMD). Methods: In this retrospective longitudinal study with a minimum follow-up of 1 year, 31 eyes of 28 consecutive AMD patients (mean age 75 ± 9 years) with treatment-naïve non-exudative MNV were enrolled. Patients were divided in: short-term activated MNV group (exudation before 6-month) and quiescent MNV group (per definition no exudation during a minimum 6-month follow-up) showing no or late activation during follow-up (persistently quiescent and long-term activated MNV group, respectively). Results: During the follow-up (mean duration: 22 ± 9 months) four eyes (13%) showed exudation before 6-month follow-up (short-term activated MNV group), whereas 21 eyes (68%) did not develop signs of exudation (persistently quiescent group), and six eyes (19%) developed exudation after the minimum 6-month follow-up (long-term activated MNV group). Monthly MNV growth rate was significantly higher in the short-term activated MNV group (growth rate of 13.30%/month), vs persistently quiescent MNV group (0.64%/month, p Conclusion: We reported two different patterns for subclinical MNVs: subclinical MNVs characterized by short-term activation which could represent simply a pre-exudative stage in the development of an ordinary type 1 MNV, and quiescent MNVs characterized by low rate of growth and possible long-term activation. Analysis of OCT-A features may predict short-term activation for subclinical MNV but no features could predict the long-term activation.

In the last months, a rapidly increasing number of people have been infected with severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease 2019 (COVID-19). Due to the risk of cross-infections, the number of visits and injections was dramatically reduced in the last months, and the time between visits has been rescheduled from every 15 to 45 min, significantly impairing the total number of available visits. Although continuity of care has been allowed, a series of measures to diminish the risk of contamination need to be adopted until the end of this pandemic outbreak, which may persist until the development of an effective vaccine. For these reasons, we have introduced a new treatment regimen that is aimed at reducing the number of in-person visits and achieving continuity of treatment. This regimen is named “Triple and Plan” (TriPla). The main advantage of the TriPla regimen is to reduce the number of visits of patients in comparison to the pro re nata and treat and extend regimen. Using the TriPla regimen, the risk of contamination would be reduced. Furthermore, by reducing the number of scheduled visits, physicians could guarantee an adequate number of examinations for each patient, lengthening the interval between visits, and reducing the risk of cross-infections.

Purpose To assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects. Methods In 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. Results Eighty-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. Conclusion Based 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%.

Purpose To analyze the subclinical intraocular involvement using multimodal imaging approach in patients affected by Erdheim-Chester disease (ECD) without ocular symptoms. Patients and methods In this prospective cross-sectional study, 18 eyes of 9 consecutive patients with ECD were enrolled. Each patient underwent comprehensive ocular examination and extensive multimodal chorioretinal imaging. Results None of the patients presented any evidence of chorioretinal localization of disease using multimodal imaging. One patient exhibited a choroidal nevus complicated by active polypoidal choroidal neovascularization. Subretinal hyperreflective material was seen in three eyes, mainly resembling acquired vitelliform lesion. One patient had an isolated intraretinal hemorrhage. Most patients exhibited peripheral vascular abnormalities (ie, microaneurysms, peripheral vascular leakage). Fundus autofluorescence showed faint hyperautofluorescence in eleven eyes. Conclusion Intraocular involvement is an extremely rare event of an extremely rare disease. In patients affected by ECD without ocular symptoms, advance multimodal imaging examinations did not show signs of subclinical chorioretinal involvement related to the disease.

To provide a review of the salient histological and imaging features in neovascular age-related macular degeneration (AMD) that will be integrated in order to have a better comprehension of the pathogenesis and clinical aspects of this disease.A literature review of histology and imaging features in neovascular AMD was conducted.Histology has granted a detailed characterization of neovascular AMD ex vivo. In details, histological features in these eyes have offered important insights into the pathogenesis of neovascular AMD. In addition, histology donated a detailed characterization of the different types of macular neovascularization (MNV) that may complicate AMD. The introduction of optical coherence tomography angiography (OCTA) has enormously amplified our knowledge of neovascular AMD through in vivo assessment of the anatomical and pathological characteristics of this disease. New insights elucidating the morphological features of the choriocapillaris confirmed that this vascular structure plays a crucial role in the pathogenesis of neovascular AMD. OCTA also offered a detailed visualization of MNV complicating neovascular AMD.New imaging technologies offer a remarkable chance to build a bridge between histology and clinical findings in neovascular AMD.

Purpose The purpose of this study was to investigate the choroidal luminal and interstitial stromal alterations using choroidal vascularity index (CVI) among different cohorts of dry age-related macular degeneration (dAMD) compared to healthy subjects. Methods Four distinct cohorts were collected: three different cohorts of patients with dAMD (i.e. drusen, reticular pseudodrusen [RPD], and geographic atrophy [GA]) and an age-matched cohort of healthy subjects (controls). CVI (the ratio between the luminal choroidal area [LCA] and the total choroidal area [TCA]) was calculated in the subfoveal 1000 µm area. Results One hundred twenty eyes (from 120 patients) were included (30 eyes in each cohort). The mean age was 76.6 ± 7.1 years. No statistical differences were disclosed in terms of age, axial length, and central macular thickness among study groups. TCA showed a different distribution among the four cohorts (P = 0.003), mainly due to the LCA changes (P = 0.001). Interestingly, CVI showed a different distribution among the four cohorts (P < 0.001). RPD showed a lower CVI in comparison to controls (P = 0.040), whereas GA showed a lower CVI in comparison to drusen, RPD, and controls (P = 0.001, P = 0.046, and P < 0.001, respectively). Conclusions Different cohorts of dAMD are characterized by different impairments of the choroidal vascular and stromal components, reflecting different degrees of AMD severity. Translational Relevance CVI provides insights for better understanding the pathogenesis of AMD.

Purpose: To investigate the progression of diabetic microaneurysms (MAs) according to the spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) characteristics and to evaluate their influence on the retinal extracellular fluid accumulation at 1 year follow-up in patients with nonproliferative diabetic retinopathy (NPDR). Design: Prospective, observational case series. Methods: Fourteen patients with NPDR underwent SD-OCT and OCTA at the baseline and at 1 year follow-up. For all the selected MAs the visibility, the changes of internal reflectivity, graded as hyporeflective, moderate, or hyperreflective, and the extracellular fluid accumulation surrounding each MA on SD-OCT at 1 year were evaluated. The changes in terms of visualization at the level either of superficial (SCP) or deep (DCP) capillary plexus and the presence of flow on the corresponding OCTA scan at 1 year were evaluated. Results: Of 127 MAs selected at the baseline, 89 (70%) were still visible on SD-OCT at 1 year. The reflectivity pattern at baseline was strongly associated with extracellular fluid accumulation at 1 year, with 18% of hyporeflective vs 66% of hyperreflective MAs developing extracellular fluid (P =.004). Among OCTA findings, the presence of flow (P =.001), the visibility (P

To investigate the evolution of treatment-naive type 3 macular neovascularization (MNV) undergoing anti-vascular endothelial growth factor (VEGF) treatment through volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA).Retrospective observational study.Patients with type 3 MNV and age-related macular degeneration (AMD).Included subjects had three loading injections of an anti-VEGF agent. The OCTA volume data at baseline and follow-up were processed with a previously published algorithm in order to obtain a volume-rendered representation of type 3 MNV. Progressive changes in type 3 lesions were analyzed via 3D OCTA volume rendering.A total of 14 treatment-naive eyes with type 3 MNV from 11 AMD patients (7 females) were included. At both baseline and follow-up visits, a type 3 MNV complex was identifiable. Each complex was composed of a mean number of 2.5 ± 0.7 vascular branches at baseline and 1.4 ± 0.6 at the follow-up visit (p0.0001). The mean changes in central macular thickness and visual acuity were significantly correlated with modifications in the number of type 3 MNV branches (ρ = -0.533, p = 0.049, and ρ = -0.581, and p = 0.040, respectively).This study demonstrated that type 3 lesions do not disappear completely after loading treatment, as indicated previously by histopathologic studies. Importantly, quantitative volume changes in type 3 lesions are directly associated with treatment response.

There is a lack of treatment aimed at the regression of reticular pseudodrusen (RPD) secondary to age-related macular degeneration (AMD). The aim of this prospective, pilot study is to evaluate the safety and short-term efficacy of subthreshold laser treatment (SLT) in patients affected by RPD secondary to dry AMD (dAMD). Twenty eyes of 20 patients (mean age 78.4 ± 6.8 years) with RPD secondary to dAMD were prospectively enrolled. All patients were treated in an extrafoveal area of 1.27 mm2 using end-point management yellow subthreshold laser and followed for 3 months. Best-corrected visual acuity was 0.140 ± 0.09 LogMAR at the baseline and no changes were observed during the follow-up (p = 0.232). No significant worsening was disclosed before and after the treatment analyzing the macular sensitivity of the treated area (p = 0.152). No topical and/or systemic side effects were disclosed during the 3-month follow-up. The distribution among the RPD stages changed after the treatment (p p = 0.002), associated with a significant decrease of Stage 3 RPD (p = 0.020). Outer nuclear layer (ONL) thickness analysis showed a significant increase after the treatment associated with RPD regression (p = 0.001). End-point management SLT appears a safe treatment for RPD secondary to dAMD, showing short-term safety outcomes. Our results suggest that SLT could be effective in inducing a RPD regression in terms of RPD stage and ONL thickening.

PurposeTo assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to disease recurrence in a cohort of patients with newly diagnosed myopic choroidal neovascularisation (CNV)MethodsIn this retrospective, longitudinal study, a total of 64 participants (64 eyes) with successfully treated myopic CNV had obtained resolution of exudation after treatment (study baseline) and with 3 years of regular follow-ups. Several baseline OCT qualitative features and quantitative measurements were assessed at baseline and included in the analysis. Main outcome measures included incidence of disease recurrence and HR for demographics, clinical characteristics and OCT risk factors.ResultsAt month 36, 40 eyes (62.5%) developed disease recurrence (active CNV). Multivariate linear regression analysis revealed that final visual acuity (dependent variable) was associated with visual acuity at the first visit after complete resolution of exudation (pConclusionWe identified OCT risk factors for the disease recurrence in eyes with successfully treated myopic CNV. Assuming that disease recurrence is a sight-threatening event, our findings may help in the identification of high-risk patients and eventually ameliorate their outcome.

The aim of this study was to measure macular perfusion in patients with type 1 diabetes and no signs of diabetic retinopathy (DR) using volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). We collected data from 35 patients with diabetes and no DR who had OCTA obtained. An additional control group of 35 eyes from 35 healthy subjects was included for comparison. OCTA volume data were processed with a previously presented algorithm in order to obtain the 3D vascular volume and 3D perfusion density. In order to weigh the contribution of different plexuses’ impairment to volume rendered vascular perfusion, OCTA en face images were binarized in order to obtain two-dimensional (2D) perfusion density metrics. Mean ± SD age was 27.2 ± 10.2 years [range 19–64 years] in the diabetic group and 31.0 ± 11.4 years [range 19–61 years] in the control group (p = 0.145). The 3D vascular volume was 0.27 ± 0.05 mm3 in the diabetic group and 0.29 ± 0.04 mm3 in the control group (p = 0.020). The 3D perfusion density was 9.3 ± 1.6% and 10.3 ± 1.6% in diabetic patients and controls, respectively (p = 0.005). Using a 2D visualization, the perfusion density was lower in diabetic patients, but only at the deep vascular complex (DVC) level (38.9 ± 3.7% in diabetes and 41.0 ± 3.1% in controls, p = 0.001), while no differences were detected at the superficial capillary plexus (SCP) level (34.4 ± 3.1% and 34.3 ± 3.8% in the diabetic and healthy subjects, respectively, p = 0.899). In conclusion, eyes without signs of DR of patients with diabetes have a reduced volume rendered macular perfusion compared to control healthy eyes.

Purpose: To investigate whether the coronavirus disease 2019 (COVID-19) pandemic-associated postponement in care had effects on the baseline clinical presentation of patients with newly diagnosed treatment-naïve exudative neovascular age-related macular degeneration (AMD). Methods: We included the first 50 consecutive patients referred within the COVID-19 pandemic with a diagnosis of treatment-naïve exudative neovascular AMD. Two groups of fifty consecutive patients with newly diagnosed neovascular exudative AMD presenting in 2018 and 2019 (control periods) were also included for comparisons. Results: Baseline visual acuity was statistically worse in patients referred during the COVID-19 pandemic period (0.87 ± 0.51 logarithm of the minimum angle of resolution (LogMAR)) as compared with both the “2019” (0.67 ± 0.48 LogMAR, p = 0.001) and “2018” (0.69 ± 0.54 LogMAR, p = 0.012) control periods. Data on the visual function after a loading dose of anti-vascular endothelial growth factor (VEGF) was available in a subset of patients (43 subjects in 2020, 45 in 2019 and 46 in 2018, respectively). Mean ± SD best corrected visual acuity (BCVA) at the 1-month follow-up visit after the third anti-VEGF injection was still worse in patients referred during the COVID-19 pandemic (0.82 ± 0.66 LogMAR) as compared with both the “2019” (0.60 ± 0.45 LogMAR, p = 0.021) and “2018” (0.55 ± 0.53 LogMAR, p = 0.001) control periods. On structural optical coherence tomography (OCT), the maximum subretinal hyperreflective material (SHRM) height and width were significantly greater in the COVID-19 pandemic patients. Conclusions: We demonstrated that patients with newly diagnosed treatment-naïve exudative neovascular AMD referred during the COVID-19 pandemic had worse clinical characteristics at presentation and short-term visual outcomes.

Purpose: To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD). Methods: Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V0), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V−1 and V−2) were compared with data at V0. Results: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5days within V0 and V−1 and 80.8 ± 39.7days within V−1 and V−2, respectively (P< 0.0001). BCVA was statistically worse at the V0 visit as compared with the immediately preceding (V−1) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V0 and V−1 visits, respectively; P= 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V−1 visit (P= 0.022). No differences in terms of BCVA and OCT findings were detected between the V−1 and V−2 visits. In multiple regression analysis, the difference in BCVA between V0 and V−1 visits was significantly associated with the interval time within these two visits (P= 0.026). Conclusion: The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients. [Figure not available: see fulltext.]

We applied three-dimensional (3D) analysis to optical coherence tomography angiography (OCTA) to measure macular ischemia in eyes affected by non-proliferative diabetic retinopathy (DR). A previously validated algorithm was applied to OCTA data in order to obtain 3D visualization of the retinal vasculature. Successively, a global thresholding algorithm was applied and two novel quantitative metrics were introduced: 3D vascular volume and 3D perfusion density. Two-dimensional (2D) OCTA metrics were also obtained with different binarization thresholds for comparison. Of the 30 patients included, 15 were diagnosed with DR and 15 were controls. The 3D vascular volume and 3D perfusion density were reduced in DR eyes (P < .0001). The 2D variables also significantly differ between groups. The 3D perfusion density had the highest area under the receiver operating characteristic curve (0.964) among tested variables. Assessing quantitative perfusion using 3D analysis is reliable and promising, and with an elevated diagnostic efficacy in identifying DR eyes.

The aim of this study was to report normal measurements of green-emitting fluorophores in the macula of healthy young individuals and to assess the repeatability of these quantitative metrics. To do so, healthy young volunteers were imaged twice (7 &plusmn, 3 days apart) using a confocal blue-light fundus autofluorescence (FAF) device with a shorter excitation wavelength (peak at 450 nm) and the capability for separately detecting the red and green components of the emission spectrum. The main outcome measure was the percentage of area occupied by green-emitting fluorophores in the macula. In addition, this measure was performed in separate regions providing a topographical assessment in the foveal, parafoveal and perifoveal regions. Furthermore, the level of agreement between repeated measurements was evaluated. Thirty eyes from 30 healthy volunteers were included in this analysis. Mean age was 26.2 &plusmn, 2.8 years (median: 25.0 years, range: 23.0&ndash, 32.0 years). Median (interquartile range&mdash, IQR) area occupied by green-emitting fluorophores was 3.6% (1.9&ndash, 4.7%) in the macular region. In the topographical analysis, this percentage was higher in the foveal area (median = 33.3%, IQR = 21.9&ndash, 41.2%), as compared with both the parafoveal (median = 5.3%, IQR = 2.4&ndash, 8.1%, p &lt, 0.0001) and perifoveal (median = 0.5%, IQR = 0.2&ndash, 0.8%, 0.0001) regions. The coefficient of variation (CV, ranging from 1.1% to 1.7% in the analyzed regions) and the intraclass correlation coefficient (ICC, ranging from 0.93 to 0.97) indicated high levels of repeatability. In conclusion, the assessment of green-emitting fluorophores is repeatable. The distribution of these fluorophores is highest in the foveal region. Assuming that flavin adenine dinucleotide (FAD) emits in the green autofluorescence spectrum, this variability could be secondary to an increased quantity of mitochondria in the foveal region.

PURPOSE To quantitatively evaluate the photoreceptor structural changes in the fellow unaffected eyes of patients with unilateral central serous chorioretinopathy (CSC). METHODS This is a retrospective cross-sectional study. We analyzed data from patients with diagnosis of unilateral CSC, as based on clinical examination and multimodal imaging, who had structural optical coherence tomography obtained. An additional group of age-matched healthy patients was included for comparison. Main outcome measures were as follows: (1) the foveal photoreceptor outer segment lateral surface and (2) the foveal choroidal thickness. RESULTS One hundred and sixty fellow unaffected eyes of 160 unilateral CSC patients and 50 age-matched controls (50 eyes) were included. The mean ± SD age was 51.6 ± 11.1 years (range 28-80 years) in the unilateral CSC group and 52.8 ± 10.8 years (range 31-74 years) in the control group (P = 0.511). The foveal photoreceptor outer segment lateral surface was significantly increased in the unaffected eyes with CSC in the fellow eye (0.068 ± 0.007 mm2) as compared with control eyes (0.060 ± 0.005 mm2, P < 0.0001). The mean ± SD foveal choroidal thickness was 368.0 ± 105.7 µm in the unilateral CSC group and 302.9 ± 92.2 µm in control patients (P < 0.0001). In the Pearson correlation test, the photoreceptor outer segment lateral surface correlated with the choroidal thickness in the CSC group (R = 0.166, P = 0.016) but not in the control group (R = -0.025, P = 0.864). CONCLUSION Our results corroborate the hypothesis that retinal and choroidal changes affect both eyes of patients with acute/history of unilateral disease. These structural changes could be intended as an imaging evidence of reduced photoreceptor outer segment turnover secondary to retinal pigment epithelium and choroid dysfunction.

Purpose Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are novel and not well characterized findings occurring in several disorders of the optic nerve. The aim of this study is to present two cases of tilted disc syndrome (TDS) and one case with optic disc drusen undergoing a multimodal imaging approach. Methods In this case series, a qualitative evaluation of the OCTA findings in regions with PHOMS was performed. Results Structural OCT revealed the presence of PHOMS. OCTA identified the presence of a vascular complex within this hyperreflective structure. Conclusions Assuming that PHOMS are thought to correspond to herniating nerve fibers or be secondary to axoplasmic stasis, this vascular complex may represent a displacement of the deeper vessels deputed at the irroration of the optic nerve into the retina or, alternatively, might be secondary to an increase in vascular endothelial growth factor (VEGF) levels and a subsequent development of neovessels.

Purpose To describe the pre-exudative stage of exudative perifoveal vascular anomalous complex (ePVAC), referred to as nonexudative PVAC (nePVAC). Design Retrospective noncomparative case series. Methods Patients diagnosed with nePVAC were identified at 4 retina referral centers worldwide. Multimodal retinal imaging, including structural optical coherence tomography (OCT) and OCT-angiography (OCT-A), were performed at baseline and follow-up visits. Results Six eyes (6 patients, mean 75 ± 10 years of age) were included. Unrelated chorioretinal diseases were diagnosed in the affected eyes in 5 of 6 cases. At baseline, nePVAC is characterized by microvascular abnormalities featuring an isolated, perifoveal, large intraretinal aneurysm surrounded by capillary rarefaction at OCT-A examination, without any sign of exudation with structural OCT, and without visual impairment. Four patients were followed for a mean of 21 ± 14 months. During the follow-up, 3 of 4 eyes (75%) developed signs of exudation after a mean of 15 ± 9 months, associated with metamorphopsia and visual decline at the time of exudation. Best-corrected visual acuity decreased from 20/25 to 20/40 Snellen equivalent (P = .035) and central macular thickness increased from 268 ± 27 μm to 339 ± 65 μm (P = .145). Three patients were treated with 2.3 ± 0.6 intravitreal injections of anti–vascular endothelial growth factor without significant improvement of best-corrected visual acuity or macular edema. Conclusions nePVAC may represent the subclinical pre-exudative stage of ePVAC, notable for an absence of exudation or visual impairment. nePVAC and ePVAC should be considered as part of the same spectrum, namely PVAC. Typically, nePVAC develops signs of exudation over time, causing metamorphopsia and visual decline and therefore these lesions warrant continued close monitoring with multimodal retinal imaging.

Purpose: To compare nonmydriatic montage widefield images with dilated fundus ophthalmoscopy for determining diabetic retinopathy (DR) severity. Materials and methods: In this prospective, observational, cross-sectional study, patients with a previous diagnosis of diabetes and without history of diabetes-associated ocular disease were screened for DR. Montage widefield imaging was obtained with a system that combines confocal technology with white-light emitting diode (LED) illumination (DRSplus, Centervue, Padua, Italy). Dilated fundus examination was performed by a retina specialist. Results: Thirty-seven eyes (20 patients, 8 females) were finally included in the analysis. Mean age of the patients enrolled was 58.0 ± 11.6years [range 31–80years]. The level of DR identified on montage widefield images agreed exactly with indirect ophthalmoscopy in 97.3% (36) of eyes and was within 1 step in 100% (37) of eyes. Cohen's kappa coefficient (κ) was 0.96, this suggesting an almost perfect agreement between the two modalities in DR screening. Nonmydriatic montage widefield imaging acquisition time was significantly shorter than that of dilated clinical examination (p = 0.010). Conclusion: Nonmydriatic montage widefield images were compared favorably with dilated fundus examination in defining DR severity; however, they are acquired more rapidly.

Perifoveal exudative vascular anomalous complex (PEVAC) is a peculiar and rare clinical entity that does not fit into any other previously described macular disease, defined by the presence of a unilateral, isolated perifoveal aneurysm in otherwise healthy patients. By definition, PEVAC occurs in subjects without any signs of arterial hypertension, diabetes, or any other systemic or local vasculopathy; however, eyes with PEVAC may manifest other macular diseases including age-related macular degeneration (AMD) (40% of cases) or pathological myopia (13% of cases). No other coincident retinal diseases have been detected. Age of diagnosis is variable; both young people, and more frequently, aged subjects could be affected (mean age at onset is 71 ± 13 years) (Sacconi et al. 2017).

PurposeTo investigate optical coherence tomography angiography (OCT-A) findings in recurrent type 3 macular neovascularisation (MNV).MethodsIn this retrospective cohort study, consecutive patients with type 3 MNV secondary to age-related macular degeneration underwent OCT-A at three different time points: baseline, after anti-vascular endothelial growth factor treatment with complete resolution of the exudative signs (ie, non-exudative stage) and at the recurrence of exudation (ie, recurrence stage). Demographics and clinical findings were analysed, including OCT-A features of type 3 MNV recurrence.ResultsTwelve eyes (12 patients, mean age 78±7 years) were included. Using OCT-A, at baseline all type 3 MNVs showed the presence of detectable flow downgrowing from the deep vascular complex (DVC) to the retinal pigment epithelium (RPE)/sub-RPE space. 6/12 eyes (50%) showed anomalous flow under the RPE, while the other 6 eyes showed flow reaching the RPE without anomalous flow in the sub-RPE space. At the non-exudative stage (after treatment), BCVA and CMT significantly improved (p=0.004 and p=0.036), and flow inside the retinal lesions reduced; interestingly the connection to the RPE/sub-RPE space regressed. At the time of recurrence, all type 3 MNVs showed the presence of intra/sub-retinal exudation with restoration of the flow deepening from the DVC to the RPE/sub-RPE space.ConclusionsDetectable flow deepening from the DVC to the RPE/sub-RPE space using OCT-A is mandatory to have a new exudation secondary to recurrent type 3 MNV. Early detection of type 3 MNV recurrence by OCT-A characterisation may prompt retreatment and potentially prevent progression to late stages of the disease.