Search

Purpose: The purpose of this study was to evaluate Retromode (Nidek Co., Gamagori, Japan) as an adjunct diagnostic tool in vitreoretinal lymphoma (VRL). By integrating Retromode findings with multimodal imaging, we aimed to enhance lesion detection of VRL lesions in the retina., Methods: This monocentric retrospective pilot study was conducted at the Ocular Oncology unit of San Raffaele Scientific Institute, Milan. Six consecutive patients with biopsy-proven vitreoretinal lymphoma (VRL) were analyzed. Comprehensive retinal examinations and multimodal imaging, encompassing Retromode, pseudocolor fundus photography, fundus autofluorescence (FAF), and optical coherence tomography (OCT). The study specifically focused on the role of Retromode findings used in conjunction with traditional imaging modalities like FAF and OCT to enhance lesion detection associated with VRL. Imaging analysis was conducted using ImageJ software., Results: Retromode identified detailed structural abnormalities in the deep retinal layers and RPE, revealing additional or more widespread lesions compared to FAF imaging. Retromode pinpointed areas affected by VRL for further examination with OCT. However, in patients with vitritis-a common condition in VRL-Retromode did not yield quality images or meaningful information., Conclusion: Retromode imaging proved to be a valuable adjunct in the multimodal imaging approach to VRL. Its capacity to delineate subtle retinal changes facilitates a tailored diagnostic strategy, enhancing lesion detection and characterization in VRL., Competing Interests: Declarations. Ethics approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of San Raffaele Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was obtained from all individual participants included in the study. Patients signed informed consent regarding publishing their data and photographs. Competing interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the sensitivity and specificity of the "triple layer sign" (TLS) (retinal pigment epithelium (RPE), neovascular tissue, and Bruch's membrane) on structural optical coherence tomography (OCT) images for the diagnosis of treatment-naïve non-exudative type-1 macular neovascularization (NE-MNV) in age-related macular degeneration (AMD)., Design: Cross-sectional study., Methods: Two masked retinal experts evaluated the presence of the TLS in eyes with NE-MNV and controls with an RPE elevation without exudation due to other causes than NE-MNV in AMD [e.g., medium-large drusen, cuticular drusen, basal laminar deposits (BlamD)]., Results: 130 eyes of 98 consecutive patients met the study criteria; 40 eyes of 40 patients satisfied the criteria for being included in the NE-MNV secondary to AMD group (27 females, 13 males, with a mean age of 73.8 ± 8.0 years), and 90 eyes of 58 patients met the criteria to be included in the control group (31 eyes were included in the medium-to-large drusen sub-group, 32 eyes in the cuticular drusen sub-group, and 27 eyes in the BlamD group. The TLS was observed in 39/40 patients with NE-MNV and 8/90 controls. The sensitivity and specificity of the TLS for the diagnosis of NE-MNV were 97% and 91%, respectively., Conclusions: The TLS on OCT demonstrated high sensitivity and specificity values in detecting treatment-naive type 1 NE-MNV., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the (Federation France Macula, n°23/337) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent: Informed consent was obtained from all individual participants included in the study. Conflicts of interest: Vittorio Capuano, Enrico Borrelli, Francesca Amoroso, Eliana Costanzo, and Serena Fragiotta: No Conflicts of Interest. Alexandra Miere Sacconi is a consultant for Novartis (Basel, Switzerland). Riccardo Sacconi is a consultant for: Allergan Inc (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Zeiss (Dublin, USA). Mariacristina Parravano reports personal fees from La-Roche, Novartis, Bayer, Abbvie, Zeiss. Francesco Bandello is a consultant for: Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Shering-Pharma (Berlin, Germany), Bausch and Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA). Eric H Souied is a consultant for: Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Shering-Pharma (Berlin, Germany), Bausch and Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Heidelberg (Germany), Novartis (Basel, Switzerland). Giuseppe Querques is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Zeiss (Dublin, USA)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Geographic atrophy (GA) is an advanced, irreversible, and progressive form of age-related macular degeneration (AMD). Structural optical coherence tomography (OCT) and OCT angiography (OCTA) have been largely used to characterize this stage of AMD and, more importantly, to define biomarkers associated with the development and progression of GA in AMD., Methods: Articles pertaining to OCT and OCTA biomarkers related to the development and progression of GA with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility., Results: Previous reports have highlighted various OCT and OCTA biomarkers linked to the onset and advancement of GA. These biomarkers encompass characteristics such as the size, volume, and subtype of drusen, the presence of hyperreflective foci, basal laminar deposits, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), persistent choroidal hypertransmission defects, and the existence of subretinal drusenoid deposits (also referred to as reticular pseudodrusen). Moreover, biomarkers associated with the progression of GA include thinning of the outer retina, photoreceptor degradation, the distance between retinal pigment epithelium and Bruch's membrane, and choriocapillaris loss., Conclusion: The advent of novel treatment strategies for GA underscores the heightened need for prompt diagnosis and precise monitoring of individuals with this condition. The utilization of structural OCT and OCTA becomes essential for identifying distinct biomarkers associated with the initiation and progression of GA., Competing Interests: Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Conflict of interests: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (© 2024. The Author(s).)

KEY MESSAGES     : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the relationship of optical coherence tomography (OCT) findings and progression to foveal atrophy in a cohort of eyes with extrafoveal geographic atrophy (GA) and age-related macular degeneration (AMD) at inclusion., Methods: We retrospectively analyzed 45 participants (45 eyes) with extrafoveal GA at baseline and with 2 years of regular follow-ups. Several OCT qualitative features (i.e., presence of foveal flat pigment epithelium detachment with a thin double layer sign [DLS] and reticular pseudodrusen, GA focality) and quantitative measurements (outer retinal layer thickness, retinal pigment epithelium [RPE] to Bruch's membrane [BM] volume, minimum distance from the central foveal circle, and untransformed GA lesion size area) were assessed at baseline. Logistic regression analyses were carried out to identify independent significant predictors and compute odds ratios (ORs) for the risk of the development of atrophy., Results: At month 24, 26 eyes (57.8%) developed atrophy in the foveal central circle, while 11 eyes (24.4%) developed atrophy in the foveal central point. Significant independent predictive features for the development of atrophy in the foveal central circle included foveal outer retinal thickness (OR, 0.867; p = 0.015), minimum distance from the foveal central circle (OR, 0.992; p = 0.022), and foveal thin DLS (OR, 0.044; p = 0.036). The only independent predictive feature for the development of atrophy in the foveal central point was the presence of foveal thin DLS (OR, 0.138; p = 0.017)., Conclusions: We identified OCT risk factors for 2-year foveal atrophy in eyes with untreated extrafoveal GA at baseline., (© 2024. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) represent an optical coherence tomography (OCT) finding that has been characterized in different forms of pseudopapilledema. The aim of this study was to investigate the prevalence of PHOMS in patients affected by acute LHON using structural OCT, and to provide a detailed description of these findings., Methods: Patients with a clinical and molecularly confirmed diagnosis of acute LHON (visual loss having occurred less than 6 months) were enrolled from the neuro-ophthalmology clinic at San Raffaele Scientific Institute. Patients had a complete ophthalmologic evaluation, including imaging with structural OCT., Results: Our analysis included 16 patients (21 eyes-8 males and 8 females) with acute LHON. Structural OCT exhibited PHOMS in 12 eyes from 9 patients with a prevalence rate of 57.1%. In a subsequent topographical assessment in the peripapillary area, the most common location of PHOMS was the temporal region (12 out of 12 eyes), while the nasal region was affected in 2 eyes (16.7%). Considering the 12 eyes with PHOMS, mean ± SD temporal peripapillary RNFL thickness was 87.5 ± 28.4 microns. The temporal peripapillary RNFL thickness was significantly lower in eyes without PHOMS (63.7 ± 32.2 microns; P = 0.40). At the 12-month follow-up visit, PHOMS disappeared in 10 out of 12 eyes., Conclusions: Acute LHON eyes have PHOMS which are mainly confined to the temporal peripapillary sector. PHOMS may represent swelled retinal fibers that have herniated or are in stasis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 mm 2 vs 0.538 ± 0.391 mm 2 , 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., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To describe the functional and anatomical results of complicated retinal detachment (RD) treated with small-gauge pars plana vitrectomy (PPV) and combined perfluorodecalin and polydimethylsiloxane tamponade (double filling, DF)., Methods: Retrospective analysis of consecutive patients with complex RD (severe proliferative vitreoretinopathy, inferior/posterior/giant retinal tears, and traumatic detachments) treated with small-gauge PPV, membrane peeling, and DF at the Department of Ophthalmology at San Gerardo Hospital, Monza, Italy. Main outcome measures included best-corrected visual acuity (BCVA), rates of retinal reattachment, and complications., Results: This study included 15 patients with a median follow-up (FU) of 6 months (range 1-22). Three patients with early retinal redetachment under tamponade and FU shorter than 3 months were excluded from the final functional analysis, but they were considered anatomical failure. At the last examination, BCVA improved in 50% of patients and remained stable in 25% of patients and anatomical success was achieved in 73% of eyes, 64% of them without any endotamponade. Three eyes had retinal redetachment after perfluorodecalin/silicone oil exchange because of diffuse proliferative vitreoretinopathy (PVR) and required reoperation to achieve retinal attachment. In eyes with anatomical success, macular pucker was the most frequent long-term complication (27%)., Conclusion: In the management of complex RD, small-gauge pars plana vitrectomy, and double filling endotamponade using wide-angle viewing systems was a well-tolerated and effective technique to preserve visual acuity and achieve anatomical success., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Extended depth-of-focus (EDOF) is a promising intraocular lens (IOL) technology for cataract surgery. The aim of the study was to report the real-life experience related to the implant of EDOF AcrySof® IQ Vivity® (Alcon Inc., USA) IOL., Methods: The study was designed as a interventional, prospective, case series with 3 months of follow-up. Patients needing cataract surgery, without any other kind of ocular diseases, were recruited and implanted with AcrySof® IQ Vivity® IOL. We evaluated the refractive success of this IOL through complete ophthalmologic assessments and the administration of the Quality of Vision test. The main outcome measures were the refractive outcome; far, intermediate, and near vision; and Quality of Vision score., Results: We included 108 eyes (54 patients; age 62 ± 5 years). Intra-operative and post-operative complications were 0%. Thirty out of 100 eyes (28%) required toric IOL. Best-corrected visual acuity improved from 0.4 ± 0.3 LogMAR to 0.0 ± 0.0 LogMAR (p < 0.01). Refractive outcome was very good for far and intermediate visions, whereas a spherical addition of at least + 1.0D was required for near vision. The mean Quality of Vision score was of 15.5 ± 6.5. The most complained visual disturbances were haloes and glares, although resulting well-tolerated. Dynamic pupillometry findings well-correlated with the amount of complained post-operative visual discomforts., Conclusions: AcrySof® IQ Vivity® IOL is a well-tolerated choice to correct far and intermediate vision. Spectacles are needed to optimize near vision. Our data strongly suggest dynamic pupillometry as a useful investigation to optimize post-operative refractive success., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To analyze the functional impact of ectopic inner foveal layers (EIFL), along with other clinical and optical coherence tomography biomarkers, on patients with epiretinal membrane (ERM) and preserved foveal layers' segmentation undergoing ERM removal., Methods: Retrospective review of consecutive patients with ERM who underwent pars plana vitrectomy with ERM peeling from December 2018 to December 2019. Baseline factors including age, gender, lens status, phacoemulsification at the time of surgery, tamponade agent, dye used for ERM and internal limiting membrane (ILM) enhancement, ILM peeling, best-corrected visual acuity (BCVA) and central macular thickness (CMT), presence and thickness of EIFL, thickness of outer nuclear layer (ONL), presence of a cotton ball, subfoveal state of photoreceptors, and presence of cystoid macular edema were included in a multivariable model having the BCVA at 12 months as the main outcome. The changes in EIFL and ONL thickness over time were also analyzed., Results: Fifty-one patients (58 eyes, 23 eyes in the no EIFL group, and 35 eyes in the EIFL group) were enrolled. The BCVA significantly improved over 12 months after surgery, regardless of the presence of EIFL (p < 0.001). Eyes with no EIFL had better BCVA at month 3 (p = 0.04), but this difference was no longer detectable at 6 and 12 months. The presence of EIFL was not associated with the final BCVA (p = 0.9), while the CMT at 12 months correlated with EIFL thickness (r = 0.8, p = 0.008)., Conclusion: Patients with EIFL could reach optimal visual acuity in the absence of disorganization of the inner retinal layers but should be warned of potentially longer healing times. None of the morphologic signs included in this study precluded good visual recovery on long-term follow-up., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

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 (V 0 ), 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 V 0 ., Results: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V 0 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 V 0 visit as compared with the immediately preceding (V -1 ) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V 0 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 V 0 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 V 0 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.

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.

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.

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.

Purpose: To assess the functional and anatomical outcomes of concurrent administration of aflibercept injection and dexamethasone (DEX) implant in patients with macular edema (ME) secondary to retinal vein occlusion (RVO), refractory to each of the two drugs previously administered as monotherapy. Secondary outcomes included the number of retreatments required in a 12-month follow-up and safety., Methods: This is a prospective, interventional case series of consecutive patients with refractory ME secondary to RVO, followed over a year. One injection of aflibercept was followed by a DEX implant on the same day; retreatment was driven by the persistence of ME on SD-OCT at least 4 months after the previous combined therapy. Central retinal thickness (CRT), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were collected at 1 month and then every 2 months until the end of follow-up., Results: Thirty eyes of 30 Caucasian patients were enrolled; mean duration of RVO before the first combined treatment was 25 ± 5 months (range 11 ± 30). Baseline BCVA was 0.73 ± 0.5 LogMAR, with no significant changes at 12 months (0.77 ± 0.51 μm, p = 0.2). Baseline CRT was 578.3 ± 161 μm, reducing to 352.5 ± 81 μm at 12 months (p = 0.003). Thirteen eyes (43.3%) required a second treatment. Twenty eyes (66.6%) showed no ME at the end of follow-up. One patient (3.3%) required topical IOP-lowering therapy during the study., Conclusion: In eyes with ME secondary to RVO unresponsive to either aflibercept or DEX administered singularly, a combination therapy with simultaneous administration of aflibercept and DEX was effective in resolving ME, despite the absence of visual improvement. Earlier combined treatment in the course of the disease might lead to better functional outcomes.

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.

Purpose: The vitelliform stage is the typical phenotypic manifestation of Best vitelliform macular dystrophy (BVMD). As yet, no study has focused specifically on the clinical changes occurring in the vitelliform stage over the follow-up., Methods: The survey takes the form of a prospective observational study with a 5-year follow-up. Twenty-one eyes of 11 patients in the vitelliform stage were examined annually. The primary outcome was the identification of the changes in the vitelliform lesion over a 5-year follow-up. Secondary outcomes included changes in structural optical coherence tomography (OCT) parameters and the correlation with the BCVA variation over the follow-up., Results: Spectral domain OCT at baseline showed one subform characterized by solid vitelliform deposition, in 81% of eyes, and another subform characterized by a combination of solid deposition and subretinal fluid, in 19% of eyes. Overall, 62% of eyes showed an increase in the area of vitelliform deposition. Once the maximal area was reached, a progressive flattening of the vitelliform deposition took place, with subsequent flattening of the vitelliform lesion and formation of subretinal fluid. Hyperreflective foci (HF) increased in number as long as the vitelliform area continued to expand, with no variation in HF when the vitelliform lesion flattened or the subretinal fluid formed., Conclusions: The vitelliform stage reveals more subforms with clinical variations over the follow-up. Our data suggest that the substage before the flattening of the lesion, thus before the so-called subretinal fluid accumulates and when the visual acuity is still high, might offer the best opportunity for an optimal therapeutic approach.

Purpose: To describe the natural history of diabetic macular edema (DME) with respect to best-corrected visual acuity (BCVA) and central retinal thickness (CRT) outcomes and to identify baseline patient characteristics and systemic factors associated with improvement or worsening of outcomes in sham-treated patients., Methods: The study population was sham-treated patients (n = 350) in the 3-year MEAD registration study of dexamethasone intravitreal implant for treatment of DME. Patients had center-involved DME and received sham intravitreal injections in the study eye at ≥ 6-month intervals. Potential prognostic factors for outcomes were evaluated using multiple linear regression analysis., Results: Visual and anatomic outcomes were poorer in patients who left the study early (n = 198) than in study completers (n = 152). Mean change in BCVA from baseline at the last visit with available data was + 0.9 letters; 37.5% of patients had no change in BCVA, 23.2% had gained > 10 letters, and 16.0% had lost > 10 letters. Older age and baseline diabetic retinopathy score > 6 were associated with worse BCVA outcomes; thicker baseline CRT and larger number of hypertension medications used were associated with larger reductions in CRT during the study., Conclusions: BCVA and CRT outcomes were variable in this population of DME patients with generally good glycemic control. In DME patients without active treatment, older age and baseline diabetic retinopathy score > 6 were associated with less improvement in BCVA; thicker baseline CRT and a larger number of antihypertensive medications used predicted better improvement in CRT., Trial Registration: The MEAD study trials are registered at ClinicalTrials.gov with the identifiers NCT00168337 and NCT00168389.

Purpose: To evaluate the efficacy of intravitreal anti-VEGF injections in choroidal neovascularization (CNV) related to pattern dystrophy-like deposit in pseudoxanthoma elasticum (PXE)., Methods: One-year prospective, interventional study. Nine eyes were recruited in the ophthalmology departments of San Raffaele University and University of Barcelona. Each patient underwent best corrected visual acuity (BCVA) measurement on ETDRS chart, slit-lamp biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). The protocol included a first anti-VEGF injection, followed by monthly evaluations with re-treatments based on new funduscopic hemorrhages, fluid on OCT or leakage on FA and/or ICGA. Primary outcome measures were the mean BCVA changes. Secondary outcomes included central macular thickness (CMT) variations and the number of injections needed., Results: At month 12, mean BCVA significantly improved from 20/45 to 20/35 Snellen equivalent, with 3 eyes gaining at least 3 ETDRS lines. Mean CMT decreased from 297 ± 22 to 262 ± 13 μm, after 5.5 ± 4.0 injections. No leakage was observed at the end of follow-up., Conclusions: Intravitreal anti-VEGF injections represent an effective treatment for CNV related to pattern dystrophy-like deposit in PXE, with an improvement of BCVA and CMT. Mean injection number is in line with other studies performed in CNV secondary to angioid streaks.

Purpose: To describe the hyperreflective foci (HF) characteristics in eyes affected by Stargardt disease (STGD), correlating HF with the atrophy progression at 1-year follow-up., Methods: Prospective observational case series with 1-year follow-up. Twenty-eight eyes (14 patients) affected by STGD and 28 eyes (14 age- and sex-matched healthy patients) used as control group were recruited. All patients underwent a complete ophthalmologic examination including fundus autofluorescence and spectral-domain optical coherence tomography. The primary outcome was the identification of HF specific location in STGD and their modification over a 1-year follow-up. Secondary outcome included the correlation between the number and the location of HF and atrophic changes., Results: HF turned out to be more frequent in STGD patients compared with healthy controls (p < 0.001). In particular, mean number of HF in the pathological edge was significantly higher than in the healthy edge of the atrophy (p < 0.001) and in the foveal area (p < 0.001). A negative correlation was found between the total HF number in the pathological edge and the atrophic area at baseline. HF number in the outer retina of the pathological edge significantly decreased between the baseline and the final follow-up examination (p = 0.011). The enlargement of the atrophic area in eyes with more than five outer retinal HF in the pathological edge at baseline was significantly less than that found in the eyes with fewer than five HF (p = 0.010)., Conclusions: HF are most common at the pathological margin of the central atrophy, with outer retina foci being more frequently found in smaller atrophic lesions.

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.

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.

Purpose: To investigate, using the Dynamic Vessel Analyzer (DVA), the retinal vascular changes that may occur after vitrectomy for idiopathic epiretinal membrane (ERM)., Methods: Twenty-six eyes of 13 patients affected by unilateral idiopathic ERM were prospectively analyzed. 13 fellow eyes were used as control. The static (central retinal artery and vein equivalents) and dynamic (after flicker light stimulus) DVA analysis was performed at baseline (1 day before surgery) and 6 months after vitrectomy., Results: The static DVA analysis did not highlight any significant change between investigational eyes and controls at baseline and 6 months after surgery. The DVA dynamic analysis showed similar arterial flicker response between cases and controls at baseline (p = 0.3396), but disclosed a significant reduction of the arterial flicker response after surgery in the study eyes compared to fellow eyes (p = 0.0024). No significant changes were appreciated in the venous flicker response after surgery between cases and controls, both at baseline (p = 0.3450) and at the follow-up examination (p = 0.4214)., Conclusions: The physiological flicker-induced vasoconstriction is reduced after vitrectomy in arteries. The oxygen saturation change occurring after vitrectomy might have a role in the vascular tone modification.

Purpose: To analyze the inter-methods agreement in arteriovenous ratio (AVR) evaluation between spectral-domain optical coherence tomography (SD-OCT) and Dynamic Vessel Analyzer (DVA)., Methods: Healthy volunteers underwent DVA and SD-OCT examination. AVR was measured by SD-OCT using the four external lines of the optic nerve head-centered 7-line cube and by DVA using an automated AVR estimation. The mean AVR was calculated, twice, separately by two independent readers for each tool., Results: Twenty-two eyes of 11 healthy subjects (five women and six men, mean age 35) were included. AVR analysis by DVA showed high inter-observer agreement between reader 1 and 2, and high intra-observer agreement for both reader 1 and reader 2. With regard to AVR analysis on SD-OCT, we found high inter-observer agreement between reader 1 and 2, and low intra-observer agreement for reader 2 but high intra-observer agreement for reader 1. Overall, the mean AVR measured on SD-OCT turned out to be significantly higher than mean AVR measured through DVA (reader 1, 0.9023 ± 0.06 vs 0.8036 ± 0.08; p < 0.001, and reader 2, 0.9067 ± 0.06 vs 0.8083 ± 0.05; p= 0.003)., Conclusions: No inter-method agreement in AVR could be detected in the present study due to bias in measurements (shift between DVA and SD-OCT). We found significant difference in the two noninvasive methods for AVR measurement, with a tendency for SD-OCT to overestimate retinal vascular caliber in comparison to DVA. This may be useful for achieving greater accuracy in the evaluation of retinal vessel in ocular as well as systemic diseases.

Purpose: Inherited retinal dystrophies and cone dysfunction syndromes may show a sharp hyporeflective interruption in the outermost retinal layers on optical coherence tomography (OCT), known as foveal cavitation (FC). The aim of the study was to describe the morpho-functional features of FC in patients affected by retinal dystrophies by means of multimodal imaging., Methods: A consecutive series of patients affected by FC were prospectively recruited for the study. Patients underwent short-wavelength (SW) and near-infraRed (NIR) fundus autofluorescence (FAF), spectral domain OCT (SD-OCT), microperimetry (MP), and multifocal electroretinogram (mfERG). Mean size of FC on OCT was correlated with best-corrected visual acuity (BCVA)., Results: Overall, 15 patients (30 eyes) were enrolled. Mean age was 38.2 ± 14.5 years (range: 10-60), with nine females (60 %). Mean BCVA was 0.5 ± 0.4 LogMAR. SD-OCT revealed focal loss of outer retinal layers and disruption of inner segment ellipsoid zone. Vertical height of FC (mean 27.77 ± 18.77 μm) was indirectly related to BCVA; complete forms of FC, with total loss of outer OCT bands, showed a poorer visual outcome. The FC size on NIR-FAF turned out to be larger with respect to SD-OCT and SW-FAF., Conclusion: Our data indicate that the presence of FC worsens functional outcome in patients affected by retinal disorders; complete and higher lesions are associated with a worse morpho-functional prognosis in these eyes.

Purpose: To identify the fundus autofluorescence (FAF) patterns in Best vitelliform macular dystrophy (VMD)., Methods: Patients affected by VMD in vitelliform, pseudohypopyon, and vitelliruptive stages underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA), short-wavelength FAF (SW-FAF), near-infrared FAF (NIR-FAF) and microperimetry., Main Outcome Measures: the identification of the correlation between SW-FAF and NIR-FAF patterns of the foveal region with BCVA, and central retinal sensitivity in eyes affected by VMD. The secondary outcomes included the definition of the frequency of foveal patterns on SW-FAF and NIR-FAF., Results: Thirty-seven of 64 (58 %), 8 of 64 (12.5 %) and 19 of 64 (29.5 %) eyes showed vitelliform, pseudohypopyon, and vitelliruptive stages respectively. Three main FAF patterns were identified on both techniques: hyper-autofluorescent pattern, hypo-autofluorescent pattern, and patchy pattern. BCVA was significantly different in eyes with hypo-autofluorescent and patchy patterns with respect to eyes showing a hyper-autofluorescent pattern. Similar differences were registered in the FS according to SW-FAF classification. However, the FS differed in each subgroup in the NIR-FAF analysis. Subgroup analyses were performed on the patchy pattern, combining FAF and fundus abnormalities. Considering both FAF techniques, the BCVA differed between the vitelliform and pseudohypopyon stages, and between the vitelliform and vitelliruptive stages. In the NIR-FAF classification, there was a significant statistical difference in the FS between each subgroup; in the SW-FAF, there was a significant difference between the vitelliform and pseudohypopyon stages and the vitelliform and vitelliruptive stages., Conclusions: Three main FAF patterns can be identified in VMD. The patchy pattern is the most frequent, accounting for 70 % of eyes on SW-FAF and 80 % of eyes on NIR-FAF. A tighter correlation links the classification of NIR-FAF patterns and FS. Longitudinal investigations are warranted to evaluate the course of FAF patterns and their role in disease monitoring.

Purpose: To describe the morphological macular changes detected by spectral domain optical coherence tomography (SD-OCT) in eyes with retinitis pigmentosa (RP) and to analyze their correlation with the visual function., Methods: Twenty-two patients (44 eyes) patients affected by RP were recruited. The following structures were evaluated on SD-OCT: outer plexiform layer (OPL), outer nuclear layer (ONL), external limiting membrane (ELM), photoreceptor inner/outer segment (IS/OS) junction, photoreceptor outer segment/retinal pigmented epithelium (OS/RPE) junction, inner limiting membrane thickening (ILMT), ganglion cell complex (GCC), and cystoid macular edema (CME). The relation between each SD-OCT finding and BCVA was evaluated at uni- and multivariate analysis., Results: Mean age and mean best-corrected visual acuity (BCVA) were 51 ± 17.5 years and 0.4 ± 0.5 LogMAR, respectively. Univariate linear regression model revealed a correlation between BCVA and the absence of ELM, IS/OS, ONL, and OS/RPE layers (R (2) values were, respectively, 0.51, 0.57, 0.48, and 0.68, with p values all <0.0001). At multivariate regression analysis, the absence of OS/RPE and ELM layers remained the only variables independently associated with a decrease of BCVA (R (2) = 0.85, t = 3.49, p = 0.0014)., Conclusions: Data show that in patients afflicted with RP, ELM and OS/RPE layers are independently associated with BCVA on multivariate regression analysis. These results highlight the key-role of external retinal layers in determining the visual function impairment attributable to RP.

Purpose: To analyze major retinal vessels in eyes with high myopia by means of the Dynamic Vessel Analyzer (DVA) in order to gather insight on retinal vascular functionality and better understand why these eyes are resistant to diabetes-related changes., Methods: A total of 20 high-myopia eyes with pathologic myopia, 20 high-myopia eyes without pathologic myopia and 20 age- and sex-matched control subjects (without pathologic myopia) were included and compared., Results: Dynamic analysis showed mean arterial dilation of 2.44 ± 1.59 % in high-myopia eyes with pathologic myopia, 2.67 ± 1.17 in high-myopia without pathologic myopia eyes, and 3.28 ± 1.46 % in healthy eyes. Mean venous dilation was 3.45 ± 1.82 %, 3.57 ± 1.72, and 4.45 ± 2.72 % respectively. Static analysis in high myopia eyes with pathologic myopia showed a mean central retinal artery equivalent (CRAE) of 171.6 ± 24.3, a mean central retinal vein equivalent (CRVE) of 199.5 ± 27.73, and a mean arteriovenous ratio (AVR) of 0.86 ± 0.01. In patients with high myopia without pathologic myopia, we found a mean CRAE of 173 ± 21.6, a mean CRVE of 198.2 ± 18.8, and a mean AVR of 0.87 ± 0.1. In control subjects, mean CRAE was 190.3 ± 11.93, mean was CRVE 215.7 ± 13.30, and mean AVR was 0.88 ± 0.04., Conclusions: Static and dynamic tests revealed that in high-myopia eyes, the vessels at the retinal posterior pole have reduced diameter, but are functionally comparable to control subjects. This supports the hypothesis of reduced oxygen consumption in high-myopia eyes.

Purpose: To report on the safety and efficacy of Nd: YAG laser goniopuncture (LGP) for postsurgical intraocular pressure increase after deep sclerectomy (DS) in a consecutive cohort of open-angle glaucoma patients., Methods: This case series included 56 eyes from 49 consecutive patients who underwent LGP between November 2008 and March 2015. Prior to LGP, patients had undergone DS augmented with mitomycin C and injectable cross-linked hyaluronic acid implant between October 2008 and May 2014. Demographic variables, type of glaucoma, prior phacoemulsification, intraocular pressure (IOP), best-corrected visual acuity, execution of post-LGP maneuvres, and post-LGP complications were analyzed. The success rate of the procedure was analyzed using the Kaplan-Meier survival curve. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model in order to highlight variables associated with a failure to achieve surgical success., Results: Mean IOP was 23.0 mmHg prior to LGP, and 12.5, 11.8, and 10.5 mmHg at 6, 12, and 24 months after LGP respectively. Post-laser IOP was significantly lower than pre-laser IOP at every time point. For an IOP ≤ 15 mmHg, success rates were 85 % at 6 months, 76 % at 1 year, and 62 % at 2 years. Thirty-eight eyes underwent prophylactic iridotomy and iridoplasty prior to LGP. Iris prolapse into the trabeculo-descemetic window following LGP occurred in 6/18 eyes (33.3 %) of the non-pretreated and in 1/38 eyes (2.6 %) of the pretreated group. One case of choroidal detachment and one delayed suprachoroidal hemorrhage occurred after LGP execution in two non-pretreated eyes., Conclusions: LGP is a relatively safe and effective complementary adjunct to deep sclerectomy that makes it possible to further lower IOP and avoid additional filtering surgery. Prophylactic iridotomy and localized iridoplasty may permit the frequency of post-LGP complications to be reduced.

Purpose: To evaluate the correlation between fundus autofluorescence (FAF) and spectral-domain OCT (SD-OCT) morphological analysis in eyes with acute central serous chorioretinopathy (CSCR)., Methods: Thirty-one patients with a first episode of CSCR and symptom duration of less than 6 weeks were prospectively enrolled. FAF and SD-OCT examination were performed at baseline and at 2-month intervals. Main outcome measure was the correlation between FAF and SD-OCT retinal morphology., Results: At baseline, 30/31 and 29/31 eyes showed a macular hypo-AF, corresponding to the neurosensory retinal detachment (SRD), on shortwave-FAF (SW-FAF) and near-infrared-FAF (NIR-FAF), respectively. While the SRD resolved, both FAF techniques showed a granular hyper-AF in 31 eyes. At first examination, SD-OCT confirmed the SRD with a photoreceptor outer-segment (OS) elongation in all cases. During SRD resolution, the photoreceptor layer appeared thicker and fragmented. Multiple hyper-reflective precipitates were detected in the outer plexiform and nuclear layer and between the photoreceptors and appeared colocalized with the hyper-AF dots composing the granular hyper-AF. After SRD resolution, the hypo-AF area reverted to a normal pattern on SW-FAF in all eyes and in 25/31 on NIR-FAF. Examination at 12 months showed that the granular hyper-AF was still detectable in 54 % eyes, whereas 6/31 eyes showed hypo-AF dots on NIR-FAF. On SD-OCT, the junction IS/OS was identifiable in 11/31 eyes soon after the SRD resolution and appeared completely restored in all patients at the final visit., Conclusion: The simultaneous acquisition of FAF and SD-OCT provides detailed findings of retinal abnormalities of CSCR and may help to understand the evolving process linked to CSCR.

Purpose: To compare the effects of subthreshold grid laser treatment (SGLT) and intravitreal bevacizumab injection (IVBI) for the treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) recurring after conventional grid laser photocoagulation., Methods: Thirty-five eyes were considered in this prospective, randomised, interventional study and treated with micropulse diode laser (SGLT subgroup) or IVBI (IVBI subgroup). SGLT was administered once, whereas IVBI (1.25 mg) was given at baseline and then on a pro re nata regimen according to ME presence on optical coherence tomography (OCT), performed at monthly examinations over a 12-month follow-up. Primary outcome measures were the mean BCVA changes over the follow-up and the decrease in mean central foveal thickness (CFT) on optical coherence tomography (OCT). Secondary outcomes included the proportion of eyes that gained at least 15 letters (approximately three lines) at the 12-month examination., Results: Eighteen and 17 patients were assigned to SGLT and IVBI subgroups, respectively. At baseline, the subgroups were similar with regard to mean ME duration, BCVA, and CFT. At month 12, mean CFT significantly improved from 484 μm to 271 μm in the IVBI subgroup, whereas it was unchanged in the SGLT subgroup. Mean BCVA changed from 0.92 ± 0.3 (LogMAR) to 0.99 ± 0.2 in the SGLT subgroup; in the IVBI subgroup, mean BCVA showed a statistically significant improvement from 0.94 ± 0.3 to 0.72 ± 0.2. Ten patients in the IVBI subgroup (58 %) and no patient in the SGLT subgroup gained at least three lines., Conclusion: At the 1-year follow-up, IVBI provided a significant functional and anatomical improvement, whereas SGLT failed to demonstrate any beneficial effects. IVBI might be a useful approach in the treatment of recurrent ME secondary to BRVO already treated with conventional grid laser photocoagulation. UMIN registry, number UMIN000005014, URL: http://www.umin.ac.jp/ctr/index.htm.

Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.

Purpose: To investigate the Ganglion Cell Complex (GCC) thickness change and visual recovery correlation after surgery for an idiopathic epiretinal membrane (ERM)., Methods: In this prospective, observational, case control study 30 eyes underwent vitrectomy for idiopathic ERM. We analysed best-corrected visual acuity (BCVA), mean macular thickness and mean GCC thickness one day before surgery, seven days and six months after surgery. Internal segment/outer segment junction, external limiting membrane, cone outer segment tips defects and intraretinalfluid were also investigated throughout the follow-up., Results: Baseline GCC thickness was higher in patients with ERM (130 ± 13 μm) compared with healthy eyes (94 ± 5 μm; p < 0.0001). GCC thickness decreased after surgery to 89 ± 11 μm (p < 0.0001), reaching a value similar to controls (p = 0.12). Preoperative macular thickness was 318 ± 32 μm and decreased to 281 ± 18 μm (p < 0.0001), remaining significantly higher than controls (260 ± 8 μm; p < 0.0001). The GCC proportion of the whole macular thickness was also reduced six months after surgery (p < 0.0001). Post-operative BCVA gain showed direct correlation with GCC reduction (R = 0.67, p < 0.0001), but did not correlate with the mean macular thickness reduction (R < 0.01, p = 0.97)., Conclusions: Ganglion cell complex thickness is higher in eyes with idiopathic ERM, and after surgery turns back to similar values of healthy eyes. Post-operative GCC reduction is proportionally higher than thinning of the whole retina, and this reduction is correlated with visual restoration.

Purpose: To analyze the course of eyes with vitreomacular traction (VMT), and to find by optical coherence tomography (OCT) possible correlations between vitreomacular interface area changes and the chance of spontaneous VMT resolution., Methods: Retrospective analysis of all consecutive patients presenting with VMT over a 24-month period. We introduced a novel OCT evaluation model to assess the vitreomacular interface area. Central foveal thickness (CFT) and best-corrected visual acuity (BCVA) were also analyzed throughout follow-up., Results: Twenty-six eyes of 18 symptomatic patients were followed for 12.9 ± 4.8 months. Eyes were subdivided into groups according to their clinical course. Six eyes (23%) had a spontaneous resolution of the VMT (group A), and the interface area before its occurrence (39565 ± 26409 μm(2)) was smaller than at study entry (99434 ± 38819 μm(2); p = 0.03). The interface area did not significantly change throughout follow-up in the group that underwent surgery (group B, 11 eyes) and in the group that remained overall stable (group C, 9 eyes). At baseline, the interface area was smaller in group A compared to groups with non-resolved VMT (mean values of group B and C together) (785095 ± 920721 μm(2); p = 0.002). CFT and BCVA did not significantly change in any of the studied groups. Vitreomacular interface area of 101002 μm(2) was identified as the threshold value separating the spontaneous VMT resolution group from the group with non-resolved VMT (p < 0.001)., Conclusions: The more the vitreomacular interface area reduced over time, the higher was the chance of spontaneous VMT resolution. An area below 101002 μm(2) was the threshold value indicating a higher chance of spontaneous release of VMT.

Background: To analyze the morphological and functional characteristics of malattia leventinese., Methods: This was a chart review of patients with Malattia Leventinese. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Microperimetry and Preferential Hyperacuity Perimeter (PHP) were performed in a subset of patients., Results: Twelve eyes of six patients were included. BCVA ranged from 20/25 to 20/200. The largest drusen were round, not radially distributed, localized in the perimacular area and around the optic disc. The smallest drusen were not round, radially distributed, mostly localized temporally to the macula. FAF revealed an intense autofluorescence of large drusen. On both FA and ICGA, large round drusen turned to hyperfluorescent in the late phase, while small radial drusen progressively decreased their fluorescence. OCT showed the large round drusen as focal or diffuse deposition of hyperreflective material between the RPE and Bruch membrane within the macula, determining focal dome-shaped or diffuse RPE elevation respectively, and the small radial drusen, which ranged from irregular slight thickening of the RPE/Bruch membrane complex to sawtooth RPE elevation. In three patients (six eyes) that underwent microperimetry and PHP, there was a good correspondence between macular sensitivity and PHP score. Functional impairment correlated topographically to sub-RPE deposition of drusenoid material., Conclusions: In this series, large round drusen of Malattia Leventinese appeared similar to drusen in age-related macular degeneration, while small radial drusen of Malattia Leventinese shared similarities with early-onset cuticular drusen.

Background: To review vascularized-pigment epithelial detachment (V-PED) treatment visual outcome, and to assess acute retinal pigment epithelium (RPE) tear incidence., Methods: One hundred and thirty-two eyes of 125 consecutive patients with age-related macular degeneration and V-PED were included. Ninety-four eyes (71.2%) were associated with choroidal new vessels (CNV), 38 (28.8%) with retinal angiomatous proliferation (RAP). Patients, treated over a 10-year period with the time-current therapy, received: verteporfin photodynamic therapy (PDT) (group 1, 38 eyes), combined intravitreal triamcinolone acetonide (IVTA) and PDT (group 2, 44 eyes) or intravitreal anti-VEGF injection (bevacizumab or ranibizumab) (group 3, 50 eyes)., Results: Mean follow-up was 20.5 months. At month 12, all eyes treated with PDT or with IVTA and PDT showed a mean significant severe visual decrease. Eyes with CNV lost -0.67 and -0.37 logMAR (p < 0.01 and p < 0.01 respectively), and eyes with RAP -0.55 and -0.31 logMAR (p < 0.01 and p = 0.01 respectively). RPE tear occurred in 14 eyes (36.8%) and in six eyes (13.6%) in groups 1 and 2 respectively. Eyes treated with anti-VEGF therapy showed slight mean visual acuity decrease at month 12. Those with CNV had a mean baseline best-corrected visual acuity (BCVA) of 0.36 ± 0.24 logMAR, final of 0.44 ± 0.30 logMAR (-0.08 logMAR, n.s.). In eyes with RAP, mean baseline BCVA was 0.58 ± 0.39 logMAR, final was 0.78 ± 0.47 logMAR (-0.20 logMAR, n.s.). RPE tear occurred in 14 eyes (36.8%). Patients with either V-PED with CNV or a better baseline BCVA showed greater risk of acute RPE tear (p = 0.01 and p = 0.003 respectively)., Conclusions: Effective treatment for vascularized PED is still lacking. Until now, only stabilization of the disease has been achieved using anti-VEGF therapy, but the risk of RPE tear can further hamper our expectations. Baseline characteristics are helpful for prognosis, but patients must be informed of the uncertain response. New therapeutic strategies are needed.

Background: To investigate changes in indocyanine green angiography (ICGA) features of occult choroidal neovascularization (CNV) after intravitreal ranibizumab injections., Methods: We reviewed the charts of all consecutive patients with newly diagnosed occult CNV secondary to age-related macular degeneration (AMD) treated by intravitreal ranibizumab. In all patients, optical coherence tomography (OCT) and ICGA were performed at baseline, after 3 months and 12 months., Results: Fifty-one eyes of 44 patients (ten males, 34 females, mean age 77.8 ± 7.3 years) were included. Mean follow-up was 20.3 ± 6.2 months. During the first 12 months, patients received 5.5 ± 2.7 intravitreal ranibizumab injections. When compared with baseline, best-corrected visual acuity (BCVA) significantly improved at the 3-month follow-up visit (60.5 ±22.0 vs 50.9 ±20.7 letters, p = 0.04), and stabilized at 12-month visit (55.7 ±18.2 letters; p = 0.05). Central macular thickness (CMT) significantly improved during follow-up (229.0 ±54.7 μm vs 281.0 ±61.3 μm at baseline, p = 0.003). An overall stabilization was observed on ICGA in both the lesion area (5.27 ± 3.9 mm(2) at baseline vs 4.60 ± 3.5 mm(2) at month 12, p = 0.4), and greatest linear dimension (GLD 2.66 ± 1.2 mm at baseline vs 2.55 ± 1.0 mm at month 12, p = 0.3). Eight eyes (15.7%) showed CNV growth on ICGA (lesion area 3.98 ± 3.2 mm2 at baseline vs 4.3 ± 2.7 mm2 at month-12, p = 0.6; GLD 2.11 ± 1.0 mm at baseline vs 2.70 ± 0.8 mm at month-12, p = 0.05)., Conclusion: ICGA suggests that functional outcomes after intravitreal ranibizumab is related to CMT reduction rather than CNV regression.

Background: To correlate the three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) features of retinal-choroidal anastomosis (RCA) to conventional angiography., Methods: This is a retrospective chart review of consecutive patients diagnosed with RCA who underwent 3D SD-OCT between July 2007 and June 2010. Main outcome measures were the diagnostic capabilities of 3D SD-OCT, and the correlation between 3D findings and the features distinguished by conventional angiography., Results: Eighteen eyes of 18 patients [five males, 13 females, mean age 79.5 ± 19.4 years (range, 70-93 years)] were included in the analysis. In eyes (n = 3) showing a focal staining on angiography, 3D OCT revealed a slight convex prominence of the inner retinal surface in correspondence of a small dome-shaped retinal pigment epithelium (RPE) elevation (which represented the early RCA). In eyes (n = 7) showing a "hot spot" without pigment epithelium detachment (PED) on angiography, 3D OCT revealed a convex prominence of the inner retinal surface in correspondence with a well-demarcated prominence of RPE with steep margins (which represented the RCA). In eyes (n = 8) showing a "hot spot" with PED on angiography, 3D OCT revealed a convex prominence of the inner retinal surface in correspondence with a convex RPE prominence with a peak at the top., Conclusions: 3D SD-OCT provides a map of the retina and RPE, allowing a realistic visualization of the different pathological features in the disease development, and may be able to provide clinically relevant information to complement angiography in the diagnosis of RCA.

Background: The spectrum of ocular indications in which intravitreal injections of triamcinolone acetonide may be therapeutically useful has recently been expanding., Methods: Prospective clinical interventional case study in a young adult male with florid proliferative diabetic retinopathy (FPDR)., Results: A greater reduction of retinal thickening and fluorescein leakage from retinal new vessels was observed in the right eye after intravitreal injection of triamcinolone followed by scatter panretinal photocoagulation (PKP) than in the left eye treated only by laser., Conclusion: Intravitreal injection of triamcinolone acetonide may be a useful adjunct to scatter panretinal photocoagulation for FPDR.