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Purpose: To analyze the progression of structural and functional retinal impairment in type 1 diabetes mellitus (T1DM) patients with no clinical signs of diabetic retinopathy (DR) during a 3-year follow-up. Methods: This was an observational longitudinal study. Post-pediatric T1DM patients without clinical signs of DR, and sex- and age-matched healthy subjects were recruited at San Raffaele Hospital (Milan, Italy). Each patient underwent a comprehensive ophthalmological evaluation, including optical coherence tomography (OCT), OCT-angiography (OCT-A), retinal static and dynamic vessel analysis (DVA), and microperimetry. Results: 21 eyes of 21 T1DM patients (10 females; 24 ± 2 years old), and 21 age and sex-matched healthy subjects were enrolled. At baseline, T1DM eyes revealed a significantly decreased vessel length density using OCT-A (p < 0.001 and p = 0.046 in 3 × 3 and 6 × 6 mm images) and a significantly increased vessel density index (p = 0.013 and p = 0.087 in 3 × 3 and 6 × 6 mm images) of deep capillary plexus. DVA detected a significantly decreased vessel response to flicker light (p = 0.002). A significantly increased thickness of ganglion cellular layer 6-mm-diameter subfields in inferior and superior quadrants was found in diabetic patients (p < 0.001 in both subfields). At 3-years-follow-up no significant longitudinal changes were disclosed in all analyses. Conclusions: Concomitant subclinical microvascular and neurodegenerative damages could be early signs of DR onset that precede functional alterations and clinical signs of DR development. These alterations demonstrated a stable trend over time. [ABSTRACT FROM AUTHOR]

To investigate the variability in subthreshold laser treatment plans for patients with diabetic macular edema or central serous chorioretinopathy. Diagnostic images from 20 patients were utilized, and 25 retina specialists generated subthreshold treatment plans along with a self-rated experience level. Evaluation comprised of i) Area Variability (AV): quantifies the consensus regarding the covered area and is the difference between the areas planned by 75% and 25% of the participants ii) mean Centroid Distance (CD): level of agreement on the localization of a treatment. Subgroup analysis investigated the impact of participants’ experience levels, utilizing the Mann-Whitney-Wilcoxon test. The predominant plan style is a targeted treatment approach (92%) and avoidance of subfoveal region (89%). Mean CD is 71.0 ± 37.5 pixels (≈half disc diameter) and mean AV is 9.8%±8.9%. A slight difference is observed between the 50-75% areas, but a notable distinction exists between the 25-50% areas. Subgroup analysis revealed CD and AV value of 75.9 pixels and 24% in the lower experience level group as opposed to 55.9 pixels and 8.6% in the higher experience level group. There is significant variability in treatment planning which reduces with increased experience of retina specialists. While consensus is observed around focal points, differences in the surrounding extents persist. [ABSTRACT FROM AUTHOR]

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way. [ABSTRACT FROM AUTHOR]

Geographic atrophy is an eye disease that greatly interferes with the daily lives of patients and their families, posing a serious threat to the aging European demographic. Over the past 30 months, this initiative has assembled leading experts in the field of ophthalmology to share insights on the necessary policy steps that need to be taken to overcome this challenge on an EU-wide scale. Through analyzing best practices in Germany, Italy, France, and Spain, this consensus paper sets out a series of policy recommendations, which, if implemented, could greatly benefit all individuals affected by geographic atrophy. Amongst other features, these countries have provided valuable examples of awareness campaigns and an overall commitment to inclusive and comprehensive policies. The policy recommendations emerging from this paper include the adoption of comprehensive screening programs, retinal disease screening in the EU Driving License Directive, the development of a white paper at the European Commission, and the creation of Council recommendations on eye health screening. Given the significant improvements made at the national level throughout the EU, countries will require unitary support at the European level to further develop their policies and successfully address the burden of geographic atrophy. [ABSTRACT FROM AUTHOR]

This article discusses the impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities (IRMAs) in proliferative diabetic retinopathy (PDR). The study used optical coherence tomography angiography (OCTA) to analyze the characteristics of IRMAs in PDR eyes before and after anti-VEGF treatment. The results showed that most IRMAs experienced tuft regression after treatment, which was associated with a reduction in intraretinal flow. This regression of IRMAs may decrease the risk of retinal neovascularization and progression to PDR. However, the study had limitations, such as a small sample size and lack of association analysis with systemic parameters. [Extracted from the article]

Purpose: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR). Methods: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed. Results: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = −5.637, p = 0.026) were independently associated with the CNV activity at 3 years. Conclusion: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: 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). Methods: 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. Results: 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%. Conclusions: OCTA has an elevated diagnostic accuracy in identifying CSC-associated CNV, though a combination of ICGA and structural OCT has a comparable diagnostic efficiency. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate differences in acquisition time, peripheral extension, and chromaticity between 3 different commercialized ultra-wide-field (UWF) fundus cameras. Methods: Patients were prospectively enrolled from 07/2021 to 11/2021. Patients underwent fundus photography with the following scanning protocols: (1) single shot with Silverstone (Optos, California), two-shot montage with Clarus 500 (Carl Zeiss, Dublin, CA), and three-shot montage with iCare EIDON FA with UWF module (CenterVue Spa, a company of iCare Finland Oy; Vantaa, Finland). Acquisition time was calculated as the interval between the beginning and the end of the acquisition. Peripheral extension was quantified as the average ratio between the total retinal pixel area and the optic nerve head (ONH) pixel area. The average chromaticity of all pixels in the red–green–blue (RGB) space was calculated. Results: Twenty-three eyes of 13 prospectively enrolled healthy controls were included in the study. Optos Silverstone had a higher total retina area/ONH area ratio (509.1 [480.9;559.3]) compared to Zeiss Clarus (442.0 [431.9;510.5], p = 0.02) and iCare EIDON (369.7 [345.3;387.8], p < 0.0001). Silverstone demonstrated the shortest acquisition time (median [interquartile range]: 32 [20;58.5] s) compared to Zeiss Clarus (42 [28.5;53.5] s, p = 0.6733) and iCare EIDON (72 [68.5;78] s, p = 0.0003). iCare EIDON demonstrated the lowest variability of acquisition time (9.5 s), compared to Zeiss Clarus (25 s) and Optos Silverstone (38.5 s). A statistically significant difference was found in the RGB distribution between each of the 3 devices (p < 0.001). iCare EIDON demonstrated an average barycenter position (RGB = [0.412, 0.314, 0.275]) that represented the best color balance of the image. Zeiss Clarus had a noticeable red shift at the expense of the blue and green channels (RGB = [0.515, 0.294, 0.191]). Optos Silverstone showed an absence of the blue channel (RGB = [0.621, 0.372, 0.007]) which results in a distortion of the color of the image. Conclusion: Optos Silverstone and Zeiss Clarus required less time than iCare EIDON to acquire a comparable size image and captured larger areas of the retina than iCare EIDON. iCare EIDON provided more color-balanced retinal images with greater richness of color content than the other two devices. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the relationship of clinical characteristics to the rate of retinal thinning in eyes with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (VEGF) therapy. We analyzed subjects with a long-term follow-up (≥ 3 years) and evidence of resolved DME after the initiation of anti-VEGF therapy (baseline visit). To measure the long-term rate of retinal thinning during treatment, a second visit (first visit with evidence of resolved DME after 3 years) was also considered. A longitudinal quantitative topographical assessment of the inner and outer retinal thicknesses was provided. Clinical characteristics were associated with the rate of longitudinal retinal thinning. We included 56 eyes (50 patients) in the analysis. A significant longitudinal thinning in the inner and outer retina was detected in all the analyzed regions (p values between 0.027 and < 0.0001). In the multivariable analysis, type of diabetes (type 2 vs. type 1) was associated with increased foveal inner retinal thinning (p = 0.019). A higher number of subfoveal neuroretinal detachment during follow-up (p = 0.006) was associated with faster rates of foveal outer retinal thinning. Type of diabetes (p < 0.0001), higher age (p = 0.033) and cystoid macular edema phenotype (p = 0.040) were associated with increased parafoveal inner retinal thinning. Gender (p = 0.003) and diabetic retinopathy stage (p = 0.013) were associated with faster rates of perifoveal inner retinal thinning, while diabetic retinopathy stage (p = 0.036) was associated with increased perifoveal outer retinal thinning. In conclusion, clinical factors, including DME phenotypes, were associated with the rates of retinal thinning in patients undergoing anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

To describe a novel optical coherence tomography (OCT) signature resembling sub-retinal pigment epithelium (RPE) tubules (SRT) in non-neovascular age-related macular degeneration (AMD). Patients suffering from non-neovascular AMD with complete medical records and multimodal imaging were retrospectively revised in three different tertiary care centers. Multimodal imaging included color fundus photograph, spectral-domain OCT (Spectralis, Heidelberg Engineering, Germany), fundus autofluorescence, OCT angiography (RTVue XR Avanti, Optovue, Inc., Fremont, CA). A total of 7 eyes of 7 patients with drusenoid pigment epithelium detachment (PED) were consecutively analyzed. The sub-RPE tubules appeared as ovoidal structures with a hyperreflective contour and hyporeflective interior appreciable in the sub-RPE-basal lamina (BL) space on OCT B-scan. The anatomical location of the sub-RPE formations was lying above the Bruch's membrane in 5/7 cases (71.4%) or floating in the sub-RPE-BL space in 2/7 cases (28.6%). En-face OCTA revealed a curvilinear tubulation-like structure corresponding to SRT without flow signal. Sub-RPE tubules represent a newly identified OCT signature observed in eyes with drusenoid PED. The presumed origin may include a variant of calcified structure or alternatively activated RPE cells with some residual BL or basal laminar deposits attracted to BrM for craving oxygen. [ABSTRACT FROM AUTHOR]

Initial stages of Best vitelliform macular dystrophy (BVMD) and adult vitelliform macular dystrophy (AVMD) harbor similar blue autofluorescence (BAF) and optical coherence tomography (OCT) features. Nevertheless, BVMD is characterized by a worse final stage visual acuity (VA) and an earlier onset of critical VA loss. Currently, differential diagnosis requires an invasive and time-consuming process including genetic testing, electrooculography (EOG), full field electroretinogram (ERG), and visual field testing. The aim of our study was to automatically classify OCT and BAF images from stage II BVMD and AVMD eyes using a deep learning algorithm and to identify an image processing method to facilitate human-based clinical diagnosis based on non-invasive tests like BAF and OCT without the use of machine-learning technology. After the application of a customized image processing method, OCT images were characterized by a dark appearance of the vitelliform deposit in the case of BVMD and a lighter inhomogeneous appearance in the case of AVMD. By contrast, a customized method for processing of BAF images revealed that BVMD and AVMD were characterized respectively by the presence or absence of a hypo-autofluorescent region of retina encircling the central hyperautofluorescent foveal lesion. The human-based evaluation of both BAF and OCT images showed significantly higher correspondence to ground truth reference when performed on processed images. The deep learning classifiers based on BAF and OCT images showed around 90% accuracy of classification with both processed and unprocessed images, which was significantly higher than human performance on both processed and unprocessed images. The ability to differentiate between the two entities without recurring to invasive and expensive tests may offer a valuable clinical tool in the management of the two diseases. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: A literature review of histology and imaging features in neovascular AMD was conducted. Results: 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. Conclusions: New imaging technologies offer a remarkable chance to build a bridge between histology and clinical findings in neovascular AMD. [ABSTRACT FROM AUTHOR]

Aim: Since its relevance on diagnosis and prognosis of diabetic retinopathy (DR), this review will examine a multimodal imaging approach to detect diabetic macular ischemia (DMI). Methods: A PubMed engine search was carried out using the term "macular ischemia" paired with "diabetes," and "diabetic macular ischemia" paired to "fluorescein angiography," "ultra-wide field fluorescein angiography," "optical coherence tomography angiography," "octa," "2D octa," "ultra-wide field octa," "3D octa," "visual acuity." All studies published in English up to October 2021 irrespective of their publication status were reviewed, and relevant publications were included in this review. Results: Recently, new technologies have been proposed as an alternative to fluorescein angiography (FA), which is an actual diagnostic gold standard technique. Nowadays, optical coherence tomography angiography (OCTA) has emerged as the most promising and reliable procedure able to provide a qualitative and quantitative description of DMI. Newer three-dimensional (3D) OCTA approach will be discussed too. Moreover, we will discuss how OCTA might identify preclinical alterations before the onset of DR and allow prediction about the progression of disease. Conclusion: OCTA has significantly expanded our knowledge on diabetic macular ischemia. [ABSTRACT FROM AUTHOR]

Purpose: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). Methods: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 μm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. Results: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 μm vs 353 ± 105 μm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. Conclusion: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response. [ABSTRACT FROM AUTHOR]

Purpose: Validation of a recently described central serous chorioretinopathy (CSCR) classification system and assessment of levels of agreement among 10 retina physicians. Methods: This was a cross-sectional (inter-reader agreement) study. Ten retina physicians (assigned a role of masked grader) were provided with a comprehensive dataset of 61 eyes of 34 patients of presumed CSCR. Relevant clinical details and multimodal imaging (fundus autofluorescence, fluorescein and indocyanine green angiography, optical coherence tomography) of both involved and fellow eye were electronically shared. Later, only the fellow eye images were resent to understand the influence of affected eye on the grading of the fellow eye. Multiple inter-grader agreement using Fleiss Kappa was performed to determine the level of agreement among the 10 graders. p value of ≤ 0.05 was considered statistically significant. Results: Sixty-one eyes of 34 patients were evaluated. There was moderate agreement for major criteria with Fleiss Kappa value of 0.50 (p < 0.0001) with a single outlier observer. After excluding that observer, the Fleiss Kappa value increased to 0.57 (p < 0.0001) with statistically significant p values among all categories, i.e., simple CSC (κ = 0.575), complex CSC (κ = 0.621), and no CSC (κ = 0.452). Overall, moderate to substantial agreement was noted among the subtypes (primary, recurrent, and resolved). The influence of the affected eye on fellow eye grading was studied. The global Fleiss Kappa coefficient (κ = 0.642, p < 0.0001) showed substantial agreement when observers were aware of the affected eye grading. However, without prior available information on the affected eye, the inter-grader agreement was significantly lower (global κ = 0.255, p < 0.0001). Conclusion: A fair-moderate inter-grader agreement among the masked graders suggests a need for further refinement of this novel classification system. Disease grading should include both eyes as lack of information on affected eye has a bearing on fellow eye grading and inter-grader agreement as shown by a significant difference in global κ values. [ABSTRACT FROM AUTHOR]

To develop a novel scoring system aiming at guiding the differential diagnosis between macular neovascularization secondary to pachychoroid disease (pMNV) and neovascular age-related macular degeneration (AMD) in patients aged 50 years and older. In this retrospective study performed at University Vita-Salute San Raffaele (Milan, Italy) and Créteil University Eye Clinic (Créteil, France), we enrolled patients 50 years of age and older, visited between January 2017 and January 2019, who were diagnosed with either treatment-naïve pMNV or neovascular AMD. At the time of diagnosis, all patients underwent a comprehensive ophthalmologic evaluation, spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography. Univariate comparison between pMNV and neovascular AMD groups was performed to identify the main clinical predictors for pMNV. The selected predictors were taken into a binomial logistic regression and eventually served as the basis for the development of InCASEOf scoring system. Receiver operating characteristic (ROC) curves were used to study the model performance. Forty-eight right eyes from 48 patients with pMNV and 39 right eyes from 39 patients with neovascular AMD were considered in this study. Age (+ 2 points), sex (+ 2 points), choroidal thickness (+ 2 points), early pachyvessels (+ 2 points), and evidence of MNV at OCTA (+ 3 points) turned out to be predictors for pMNV. Four additional factors significant at univariate analysis were considered: type 2 and type 3 MNVs and presence of intraretinal fluid (− 0.5 points each), and presence of subretinal fluid (+ 0.5 points). InCASEOf scoring system was built with a high score of 11.5 points. The cutoff value of 6.5 showed good accuracy in separating pMNVs from neovascular AMDs. InCASEOf is a straightforward clinical scoring system, accessible to comprehensive ophthalmologists, with the purpose of enabling easy distinction and expert-like diagnosis of pMNV and neovascular AMD in patients aged 50 years or older. [ABSTRACT FROM AUTHOR]

The effects of anti-vascular endothelial growth factor (anti-VEGF) agents on the native ocular vasculature are poorly understood. This pilot study aimed to assess short-term changes in retinal and choroidal perfusion after anti-VEGF treatment for neovascular exudative age-related macular degeneration (nAMD) using the relative flow volume (RFV) parameter derived from laser speckle flowgraphy. Ten treatment-naïve nAMD patients underwent measurements of mean, maximum, minimum, and differential RFV within a retinal arteriolar segment and a choroidal vessel segment outside the neovascular area. Measurement of retinal RFV (rRFV), choroidal RFV (cRFV), and subfoveal choroidal thickness (SCT) was repeated 9 and 35 days after a single anti-VEGF injection. The treatment caused a statistically significant decrease in the mean rRFV, mean cRFV, and SCT during the follow-up (p < 0.05). At the intermediate visit, the mean cRFV and SCT were − 17.6% and − 6.4% compared to baseline, respectively. However, at the final measurement, the mean cRFV was not different from the baseline value, which indicated waning of the anti-VEGF effect. In conclusion, a single anti-VEGF injection in treatment-naïve nAMD resulted in a decrease in retinal arteriolar and choroidal perfusion, according to the RFV parameter, which is a promising tool to simultaneously assess retinal and choroidal perfusion changes in response to anti-VEGF therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.001). In detail, in the treated area, we observed a significant increase in the number of Stage 1 RPD during the follow-up (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. [ABSTRACT FROM AUTHOR]

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 ± 37.5 days within V0 and V−1 and 80.8 ± 39.7 days 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. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the shrinking in outpatient and intravitreal injections' volumes in a tertiary referral retina unit secondary to virus causing coronavirus disease 2019 (COVID-19). Methods: In this retrospective cross-sectional study, we reviewed the charts of all patients who had a visit at a medical retina referral center during the Italian quarantine (from 9th of March 2020 to 3rd of May 2020). Number and characteristics of these data were compared with data from the same period in 2019 (from 9th of March 2019 to 3rd of May 2019). Results: In the 2019 study period, there were 303 patients attending clinic (150 males, 153 females). In the 2020 study period, patients decreased to 75 (48 males, 27 females; P = 0.022 comparing gender prevalence between the two periods) with an overall reduction of 75.2%. Mean ± SD age was 71.4 ± 14.3 years (range 25–93 years) in the 2019 study period and 66.7 ± 13.1 years (range 32–91 years) in the 2020 study period (P = 0.005). The largest drop in outpatient volume was recorded in AMD patients (− 79.9%). Regarding the intravitreal treatments, there were 1252 injections in the 2019 period and 583 injections in the 2020 period (− 53.6% in injections). The drop in intravitreal treatments was larger in patients with posterior uveitis, retinal vein occlusion, and diabetes (− 85.7%, − 61.9%, and − 59.6%, respectively). Conclusion: The volume of outpatient visits and intravitreal injections declined during the COVID-19 quarantine. The short- and long-term impacts are that routine in-person visits and intravitreal injections are expected to increase after the quarantine and, even more, after the pandemic. [ABSTRACT FROM AUTHOR]

Aims: To compare the long-term functional and anatomical outcomes of cataract surgery with combined versus 1-month deferred intravitreal dexamethasone implant (DEX) in eyes with pre-existing diabetic macular edema (DME). Methods: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were retrospectively evaluated in both groups before treatments, then 1, 4, 12 and 24 months after DEX. Results: Forty eyes were analyzed, 20 in each group. BCVA disclosed comparable trends, increasing from similar starting values (p = 0.9913) to akin scores 1 month after DEX (p = 0.4229). After 4 months, it similarly reduced without significant variations within each group throughout the whole observation period. CRT was similar at the time of surgery (p = 0.6134) and was reduced by DEX injection in both samples, with a superior beneficial effect in the combined group after 1 month (p = 0.0010). At 4 months, CRT further elevated and remained overall stable in the long term without differences. By 12 months, 19 (95%) eyes received further injections: 1 (5%) fluocinolone, 3 (15%) received other DEX and fluocinolone, 13 (65%) ≥ 1 DEX only and 2 (10%) anti-VEGFs. During the second year, 6 additional eyes (from the 13 receiving DEX) switched to fluocinolone, reaching a total of 10 (50%). Similar results were observed in the deferred group. Conclusions: DEX implant performed at the time of surgery achieved the same long-term functional and anatomical outcomes compared to a 1-month injection deferral in treating eyes with pre-existing DME that should undergo cataract extraction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ± 11.6 years [range 31–80 years]. 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. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) treatment represents a challenge for the ophthalmologists, and several aspects of real treatment expectancy are still being discussed and not yet fully elucidated. A univocal definition of responsiveness to treatment has not been reached. How the clinicians can evaluate the therapeutic success? The evaluation of systemic and ocular factors should help in this complex management. The age influences the long-term outcomes, and the role of glycemic control is confounded by contrasting correlations between hemoglobin glycated A1c and DME. Long-term treatment success is influenced by baseline best-corrected visual acuity (BCVA), central macular thickness (CMT) and early BCVA response. Also baseline diabetic retinopathy severity scale score is useful to evaluate the chances of improvement before and during treatments. The time-switching was influenced by early BCVA response, however considering a delayed response in a percentage of patients. Several structural optical coherence tomography (OCT) findings could predict long-term success, as the presence of serous retinal detachment, hyperreflective retinal spots, the disruption of external limiting membrane and ellipsoid zone, the disorganization of inner retinal layers and continued increase in CMT were considered predictors of poor response to treatment. Foveal avascular zone enlargement, high number of microaneurysms (Mas), lower vessel density (VD) in deep capillary plexus and lower parafoveal VD in superficial capillary plexus were considered as OCT angiography biomarkers of poor responsiveness. The aim of this review is to report the factors that could influence the response to treatment of DME patients. [ABSTRACT FROM AUTHOR]

Background: To describe the "dimple," a previously unreported structural optical coherence tomography (OCT) finding in vascularized serous pigment epithelial detachment (PED) secondary to neovascular age-related macular degeneration (AMD). Methods: Retrospective, longitudinal, case series study. Clinical charts and multimodal imaging including OCT (structural and angiography) and dye-based angiography (fluorescein and indocyanine green) examinations of patients with dimple—defined as a localized invagination of the vascularized serous PED—were analyzed in 2 high-volume referral centers. Results: Nineteen eyes of 18 patients were included. Mean follow-up was at 64.1 ± 35.8 months. The greater basal and height diameters of the vascularized serous PED were respectively 3425.8 ± 1049.6 μm and 667.1 ± 279.9 μm at baseline and 3076.2 ± 1649.9 μm (p = 0.8) and 368.3 ± 295.1 at last follow-up (p = 0.0006). OCT analysis identified 2 phenotypes of dimple: type 1 or ("top denting") (9 eyes) and type 2 (or "side denting") (10 eyes). Both phenotypes are associated with hyper-reflective holding sub-retinal pigment epithelium (RPE) band encompassing the posterior face of the RPE and extending to the Bruch's membrane. Hyper-reflective holding band is not correlated with angiographic signs of neovascular tissue in all cases. During follow-up, no case of RPE tear was observed. Conclusions: We describe the characteristics of the dimple and its association with hyper-reflective holding sub-RPE bands in the context of large vascularized serous PED in neovascular AMD. The presence of a dimple does not seem to be an additional risk factor for the development of RPE tearing in high-risk PED secondary to neovascular AMD. [ABSTRACT FROM AUTHOR]

Aim: To investigate late changes in peripheral ischemia in patients affected by diabetic macular edema (DME) and treated with repeated dexamethasone (DEX) intravitreal implants over a 1-year period. Methods: In this retrospective cohort study, patients older than 18 years of age and with type 2 non-proliferative treatment-naïve diabetic retinopathy (DR) and DME at baseline were included. All patients were treated with two intravitreal DEX implants within 1 year of follow-up. A minimum of two annual ultra-widefield fluorescein angiography (UWF FA) were required to ensure that all cases had a baseline UWF FA (< 2 weeks before first treatment with dexamethasone) and a UWF FA performed at 12 months of follow-up. On baseline and 1-year UWFA images, peripheral retinal ischemia was quantified using the ischemic index (ISI). Results: Six eyes of five patients (two males, three females) met the inclusion criteria and were enrolled in this study. Best-corrected visual acuity was 0.34 ± 0.22 LogMAR at baseline and improved to 0.21 ± 0.14 logMAR at the 1-year follow-up visit (P = 0.050). Mean ± SD central macular thickness was 467.6 ± 63.0 μm at baseline and 272.0 ± 14.7 μm at the 1-year follow-up visit (P = 0.043). Mean ± SD ISI was 26.7 ± 14.1% at baseline and reduced to 12.2 ± 5.0% at the 1-year follow-up visit (P = 0.012). Conclusions: Improvement in retinal perfusion is still maintained 1 year after starting treatment with DEX implants. This improvement in retinal perfusion might be related to DEX implant-related positive effects on leukostasis. [ABSTRACT FROM AUTHOR]

Purpose: To provide an integrate multimodal imaging characterization of peripheral drusen in the eyes with and without macular signs of age-related macular degeneration (AMD) and to analyze their association with macular findings. Methods: In this retrospective, cross-sectional study, subjects with peripheral drusen were imaged with the Optos (Optos PLC, Dunfermline, Scotland, UK) and Spectralis devices to obtain referenced spectral domain optical coherence tomography (SD-OCT) images. Two experienced graders independently graded the ultra-widefield (UWF) pseudocolor and fundus autofluorescence (FAF) images for the presence of peripheral drusen and analyzed peripheral druse features using OCT. Main outcome measures included quantitative and qualitative assessment of peripheral drusen. Results: Fifty-seven eyes (30 subjects) were included in the analysis. Mean ± SD age was 77.6 ± 9.2 years (range 54–97 years). On pseudocolor images, graders identified the presence of drusen in all the enrolled eyes (Cohen's kappa was 1.0). On FAF images, Cohen's kappa was 0.71. In the topographical assessment, peripheral drusen were detected in 23 cases in the temporal region, in 40 cases in the nasal region, in 40 cases in the inferior region, and in 42 cases in the superior region. On SD-OCT images, peripheral drusen had a high reflective core in 97.1% of cases, while remaining drusen were characterized by a low reflective core. The macula was affected by early/intermediate AMD in 23 eyes (43.5%) and late AMD in 6 eyes (10.5%). Conclusions: We provided an integrate multimodal imaging assessment of peripheral drusen in the eyes with and without AMD. Peripheral drusen were characterized by distinguished features that may suggest that these lesions constitute a distinct disease, rather than representing an expansion of AMD. [ABSTRACT FROM AUTHOR]

Aims: To analyze the visual outcome after early switch to dexamethasone (DEX) in eyes with diabetic macular edema previously treated with ranibizumab (RNB), based on structural spectral-domain optical coherence tomography (SD-OCT) features. Methods: Retrospective study of data from 28 eyes which underwent a loading dose of three monthly RNB injections and were then shifted to DEX implant injection. SD-OCT analysis was performed before switch to DEX (week 12, 12W) according to the presence of integrity of ellipsoid zone (EZ) and external limiting membrane (ELM), disorganization of retinal inner layers (DRIL), and quantity of hyper-reflective spots (HRS). Best-corrected visual acuity (BCVA) changes at different time points after DEX (month 1, 1M; 4 months, 4M; and 12 months, 12M) were compared among groups. Results: Significantly better BCVA was achieved at 1M in eyes with intact EZ (84.2 ± 12.3 letters; p = 0.04), with intact ELM (83.2 ± 11.5 letters; p < 0.01), and with fewer HRS (84.6 ± 12.5 letters; p = 0.03). However, the greatest percentage visual increase was achieved in eyes with disrupted EZ (+ 11.4%; p < 0.01), with disrupted ELM (+ 17.2%; p < 0.01), without DRIL (+ 12.5%; p < 0.01), and with more HRS (+ 14.3%; p = 0.04). After 12 months, a significant BCVA gain was observed only in eyes with intact retinal inner layers (+ 14.2%; p = 0.03). Conclusions: Greater percentage BCVA improvement at 1M after switch to DEX was associated with EZ disruption, ELM disruption, intact retinal inner layers, and higher quantity of HRS. A switch to DEX therapy would be useful in patients with these SD-OCT features. [ABSTRACT FROM AUTHOR]

Purpose: To describe the characteristics and potential differences between focal and diffuse phenotypes of untreated chronic central serous chorioretinopathy (cCSC). Methods: For this study, patients were divided in two groups. Focal leakage was defined as 1 "hot spot" of leakage, whereas diffuse leakage was defined as either > 1 hot spot or a larger area of widespread leakage on FA. Clinical characteristics were assessed at presentation. After Bonferroni correction, P values < 0.00125 were deemed statistically significant. Results: The focal leakage group included 68 eyes (53 males), and the diffuse leakage group included 105 eyes (88 males). Mean best-corrected visual acuity (BCVA) was 77.1 ± 8.1 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters in the focal group and 76.0 ± 9.6 ETDRS letters in the diffuse group (p = 0.440). In the focal group, mean age was 46.9 ± 8.8 years, whereas this was 49.7 ± 8.3 years in the diffuse group (p = 0.033). Mean central foveal thickness was 107.1 ± 21.3 μm in the focal group and 106.2 ± 27.3 μm in the diffuse group (p = 0.818). Mean choroidal thickness was 407.5 ± 114.8 μm in the focal group and 419.1 ± 113.9 μm in the diffuse group (p = 0.578). In the focal group, subretinal fluid was present in the fellow eye in 16% of the patients, as compared to 29% in the diffuse group (p = 0.067). Conclusions: In untreated cCSC patients with focal or diffuse leakage on FA, no marked differences in clinical characteristics were found. Extensive choroidal abnormalities may be present in both groups, which are presumed to lie at the basis of the development of cCSC. [ABSTRACT FROM AUTHOR]

Purpose: To give an updated review of laser approaches to non-exudative age-related macular degeneration (AMD). Methods: PubMed and Medline database searches were carried out using the terms 'laser' and 'photocoagulation' associated with 'age-related macular degeneration', and latest publications up to May 2017 have been reviewed. Moreover, the design of an ongoing single-center, non-randomized, phase I-II, pilot study, the PASCAL-GA trial, coordinated by F. Bandello, MD and G. Querques, MD from the IRCCS Ospedale San Raffaele, is described. Results: Either standard or subthreshold laser strategies have been tried to induce regression of distinct phenotypes of AMD, as reticular pseudodrusen (RPD), nascent geographic atrophy (nGA), and drusen-associated geographic atrophy (DAGA), with heterogeneous results. The aim of the PASCAL-GA protocol is to assess if subthreshold laser can restore the retinal pigment epithelium function in eyes with RPD and nGA offering a protective effect against extensive GA. Conclusions: New-generation medical and surgical approaches, including subthreshold laser photocoagulation, may have some success in downstaging AMD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of our study was to describe ultra-widefield (UWF) imaging and optical coherence tomography angiography (OCT-A) findings in affected and fellow eyes of patients with Coats' disease. Methods: Consecutive patients affected by Coats' disease were prospectively recruited at the Department of Ophthalmology, San Raffaele Hospital, Milan, Italy in this cross-sectional, observational study. Patients underwent UWF color fundus photographs, UWF green autofluorescence, UWF fluorescein angiography (FA), optical coherence tomography (OCT), with 3 × 3 mm and 6 × 6 mm OCT-A scans of the macula. Images were qualitatively evaluated by two independent operators for the presence of pathology. Results: Eleven patients affected by Coats' disease (eight males, mean age 17.1 ± 6.7 years). Nine and two patients had a clinical diagnosis of unilateral and bilateral disease, respectively. Five eyes had macular fibrosis. All clinically affected eyes exhibited retinal pathology at UWF imaging with the temporal sector most involved followed by the inferior, nasal, superior and macula. In all eyes with macular fibrosis, OCT-A revealed replacement of the foveal avascular zone with coarse vessels suggestive of vascularized fibrosis and flow void area in the choriocapillaris due to a masking effect; type 3 neovascularization was seen in 75% of cases. Seven out of nine clinically unaffected fellow eyes showed retinal pathology at UWF FA with the temporal quadrant most involved. Conclusion: We demonstrated that Coats' disease is a highly asymmetric bilateral disease and that UWF imaging is able to identify more retinal pathology than standard fundus imaging, thus guiding proper retinal photocoagulation. OCT-A allowed easy identification of type 3 neovascularization in a proportion of patients with macular fibrosis. [ABSTRACT FROM AUTHOR]