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Purpose: To characterize relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization (MNV) and visual responses to ranibizumab in patients with neovascular age-related macular degeneration (nAMD)., Methods: This was a post hoc analysis of the phase 3 HARBOR trial of ranibizumab in nAMD. Analyses included ranibizumab-treated eyes with baseline multimodal imaging data; baseline MNV; subretinal and/or intraretinal fluid at screening, baseline, or week 1; and spectral-domain optical coherence tomography images through month 24 (n = 700). Mean best-corrected visual acuity (BCVA) over time and mean BCVA change at months 12 and 24 were compared between eyes with type 1, type 2/mixed type 1 and 2 (type 2/M), and any type 3 MNV at baseline., Results: At baseline, 263 (37.6%), 287 (41.0%), and 150 (21.4%) eyes had type 1, type 2/M, and any type 3 lesions, respectively. Type 1 eyes had the best mean BCVA at baseline (59.0 [95% CI: 57.7-60.3] letters) and month 24 (67.7 [65.8-69.6] letters), whereas type 2/M eyes had the worst (50.0 [48.6-51.4] letters and 60.8 [58.7-62.9] letters, respectively). Mean BCVA gains at month 24 were most pronounced for type 2/M eyes (10.8 [8.9-12.7] letters) and similar for type 1 (8.7 [6.9-10.5] letters) and any type 3 eyes (8.3 [6.3-10.3] letters)., Conclusion: Differences in BCVA outcomes between CONAN lesion type subgroups support the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD., Trial Registration: ClinicalTrials.gov identifier: NCT00891735. Date of registration: April 29, 2009., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch's membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD)., Methods: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity., Results: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size., Conclusion: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity., (© 2021. The Author(s).)

Purpose: To investigate the reliability and comparability of retinal measurements obtained with spectral-domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), confocal scanning laser ophthalmoscopy (cSLO) colour images, and fundus autofluorescence (FAF) between two multimodal imaging platforms in eyes with macular pathology and normal, healthy volunteers., Methods: This cross-sectional, multi-centre, instrument validation study recruited 94 consecutive subjects. All participants underwent a dilated examination and were scanned consecutively on the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Nidek Mirante (Nidek Co. Ltd., Gamagori, Japan) devices. Agreement between device images were evaluated from measures of the central retinal thickness (CRT), presence of segmentation and fixation imaging artefacts (IA), foveal avascular zone (FAZ) measurements; as well as sensitivity and specificity values from the detection of atrophy on fundus autofluorescence (FAF), drusen, subretinal drusenoid deposits, geographic atrophy, epiretinal membrane, fibrosis and haemorrhage on multicolour imaging, and agreement between devices and groups., Results: Compared with reference clinical examination, sensitivity values for the identification of retinal features using sole device images ranged from 100% for epiretinal membranes to 66.7% for subretinal drusenoid deposits (SSD). Mean absolute difference for CRT between OCT devices was 3.78 μm (95% confidence interval [CI]: - 21.39 to 28.95, P = 0.809). Differences in the superficial and deep capillary plexus FAZ area on OCTA between devices were not statistically significant (P = 0.881 and P = 0.595, respectively). IAs were significantly increased in the presence of macular pathology., Conclusion: Comparison of retinal measurements between the OCT devices did not differ significantly. Common ultrastructural biomarkers of multiple macular pathologies were identified with high sensitivities and specificities, with good agreement between graders, indicating that they can be identified with comparable confidence in retinal imaging between the two devices., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a group of eyes with Type 1 and/or 2 MNV versus healthy eyes., Methods: In this cross-sectional, retrospective, multicenter, observational study, consecutive patients with Type 3 MNV, Type 1 and/or 2 MNV, and age-matched controls were included. PLEX Elite optical coherence tomography angiography was performed with a 6 × 6 mm scan pattern centered on the fovea. The CC FD was computed in 4 peripheral 1 × 1 mm squares to allow comparison between equidistant regions unaffected by MNV., Results: Twenty Type 3, 20 Type 1 and/or 2 MNV [13 (65%) Type 1 MNV, 1 (5%) Type 2 MNV, and 6 (30%) mixed Type 1 and 2 MNV], and 20 age-matched controls were included. The mean impairment in the CC in the 4 peripheral squares was 16.07 ± 7.27% in Type 3 MNV eyes, 11.48 ± 5.59% in Type 1/2 MNV eyes, and 9.64 ± 3.59% in controls. Type 3 MNV displayed a statistically significantly higher CC FD compared with both Type 1/2 MNV (P = 0.031) and controls (P < 0.0001). No significant differences were observed between Type 1/2 MNV and controls (P = 0.223)., Conclusions: CC FD was significantly greater in the peripheral macular regions of eyes with Type 3 MNV compared to eyes with Type 1/2 MNV and normal control eyes. Pathogenic choroidal mechanisms may differ in eyes with different MNV subtypes. Whereas focal CC impairment may drive the development of Type 1/2 MNV, diffuse CC disruption may be more important in eyes with Type 3 MNV., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Comparing two different sutureless scleral fixation techniques., Methods: A retrospective study of patients who underwent sutureless scleral fixation IOL from October 2013 to May 2018 at "Luigi Sacco Hospital", University of Milan. Comparison between two groups: Group 1 implanted with a 3-piece ALCON-MA60AC and group 2 implanted with a newly developed single-piece foldable IOL SOLEKO FIL-SSF. Patients underwent a complete preoperative ophthalmic assessment and post-operative evaluation at 1, 3, and 6 months. Vitrectomy was performed in all cases. The two groups were compared for age, axial length, and lens status at baseline. Visual acuity, refractive results, surgical time, and post-operative complications were recorded., Results: Thirty-one eyes were included: group 1, 15 eyes of 15 patients, and group 2, 16 eyes of 14 patients. No difference was found in visual acuity. Mean refractive error was 1D in both groups (group 1 1.01D, group 2 1.09D), but spherical equivalent was more often moved toward negative values and induced astigmatism was greater in the 3-piece group (group 1 1.91D [SD ± 2.07], group 2 0.67D [SD ± 0.88] P = 0.04). Surgical procedure was faster in group 2 (mean time difference 21', P = 0.01*). New displacement occurred in 5 cases (33%) of group 1 and in no cases of group 2 (P = 0.01*). Post-operative bleeding was registered only in group 1 (20%), but the difference was not statistically significant., Conclusions: The group 2 IOL gives in our sample better results due to less post-operative astigmatism and reducing dislocation and bleeding during follow-up. Surgical technique appeared easier and faster: the specifically designed IOL seems to be a feasible solution for sutureless scleral fixation.

Purpose: To evaluate the ability of optical coherence tomography angiography (OCTA) to detect macular neovascularization (MNV) in eyes with atrophy compared with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT)., Methods: In this prospective study, eyes with MNV and atrophy (termed macular atrophy or MA) secondary to age-related macular degeneration (AMD), and AMD eyes with geographic atrophy (GA) without MNV underwent multimodal imaging with FA, ICGA, structural OCT, and OCTA. The presence of MNV was determined using all imaging modalities by senior retina specialists and was considered the gold standard reference. Each individual imaging modality was then evaluated independently by two expert readers for the presence of MNV in a masked fashion. Morphologic characteristics of the MNV were evaluated on the custom OCTA slab., Results: Twenty-one patients with MA+MNV and 21 with GA only were enrolled. Manual segmentation on OCTA allowed detection of the MNV in 95.2% of eyes with MA+MNV and in 4.7% of eyes with GA, showing high specificity (95.2%) and sensitivity (95.2%). FA, ICGA, and OCT detected MNV in 57.1%, 52.3%, and 66.7% of eyes with MA+MNV and in 14.2%, 9.5%, and 42.8% with GA. Sensitivity and specificity were 85.7% and 57.1% for FA, 90.5% and 52.4% for ICGA, and 66.7% and 57.1% for OCT., Conclusions: OCTA appears to be superior to other imaging modalities for identification of MNV in eyes with macular atrophy. OCTA should be considered as part of the multimodal imaging evaluation of eyes with atrophy, particularly in the context of clinical trials.

Purpose: To evaluate criteria driving retreatment with ranibizumab in Italian patients with myopic choroidal neovascularization (mCNV)., Methods: OLIMPIC was a 12-month, phase IIIb, open-label study. Patients with active mCNV were treated with ranibizumab 0.5 mg according to the European label. The study assessed local criteria in Italy driving retreatment decisions with ranibizumab; and the efficacy, safety, and tolerability of ranibizumab., Results: The mean (standard deviation [SD]) age of treated patients (N = 200) was 61.8 (12.7) years; range 22-85 years. The multivariate regression model indicated that presence of active leakage (odds ratio [OR] 95% confidence interval [CI]: 11.30 [1.03-124.14]), presence of intraretinal fluid (OR [95%CI]: 28.21 [1.55-513.73]), and an improvement in best-corrected visual acuity (BCVA) from baseline < 10 letters (OR [95%CI]: 17.60 [1.39-222.75]) were the factors with the greatest effect on retreatment with ranibizumab. The mean (SD) BCVA gain from baseline to month 12 was 8.4 (12.8) letters (P < 0.0001). The mean (SD) number of injections was 2.41 (1.53); range 1-9. Ocular and non-ocular adverse events were reported in 41 (20.5%) and 30 (15.0%) patients, respectively., Conclusions: Individualized treatment with ranibizumab was effective in improving BCVA in patients with mCNV over 12 months. Both anatomical and functional variables had significant effects on causing retreatment. There were no new safety findings., Trial Registration: www.ClinicalTrials.Gov (NCT No: NCT02034006).

Optical coherence tomography angiography (OCT-A) is a non-invasive, non-dye-based imaging modality that has the potential to enhance our understanding of retinal diseases. While this rapidly advancing imaging modality offers great potential, there is a need for community-wide understanding of the range of technologies and methods for interpreting the images, as well as a need to enhance understanding of images from disease-free eyes for reference when screening for retinal diseases. Importantly, clinical trials have been designed without OCT-A-based endpoints; therefore, caution is required when making treatment decisions based on OCT-A imaging alone. With this in mind, a full understanding of the advantages and limitations of OCT-A will be vital for effective development of the technique within the field of ophthalmology. On behalf of the Vision Academy Steering Committee (sponsored by Bayer), this publication summarizes the views of the authors on the current use of OCT-A imaging and explores its potential for future applications in research and clinical practice.

Purpose: To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc pit maculopathy., Methods: We retrospectively evaluated medical records and imaging studies of 11 consecutive patients with optic disc pit maculopathy who underwent vitrectomy at Sacco University Hospital, Milan, Italy, between October 2008 and December 2015. Induction of a posterior vitreous detachment (PVD) was the aim of our surgery. Intravitreal injection of ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) was performed before surgery in three eyes of very young patients. Gas tamponade (sulfur hexafluoride (SF6) 20%) was used only in the first five cases. Main outcome measures were anatomic results as determined by optical coherence tomography and postoperative best-corrected visual acuity (BCVA)., Results: Before surgery, a macular detachment was present in 10 eyes and a lamellar hole of the outer retina was detected in 9 eyes. Intraoperatively, two iatrogenic paramacular holes developed in two patients during posterior hyaloid dissection. Time to PVD induction appeared to be greatly reduced in the three patients injected with ocriplasmin before surgery. Patients were followed up for a mean of 38 months (range, 18-84) after surgery. Postoperatively, one patient (9%) developed a retinal detachment that was repaired with one additional vitrectomy. Complete resolution of fluid in and under the fovea was achieved in 8 of the remaining 10 eyes (80%) without additional treatment. Reduction of the inner retinal fluid always preceded the decrease of outer retinal fluid, which in turn anticipated the absorption of macular detachment. The macular detachment resolved in a mean of 14 months after surgery. Postoperative BCVA (mean, 0.63) improved significantly compared with preoperative BCVA (mean, 0.27) (P = 0.005). Nine eyes (82%) had a postoperative BCVA of 0.5 or better., Conclusion: Vitrectomy with induction of PVD is a safe and successful therapeutic option for the treatment of optic disc pit maculopathy. The adjunct of ocriplasmin might facilitate the induction of PVD and reduce the risk of iatrogenic retinal holes.

Purpose: To determine the best imaging procedure for the definition of tangential tractions generated by epiretinal membranes in lamellar macular holes., Methods: Inclusion criteria were a diagnosis of lamellar macular hole with tractional epiretinal membranes based upon fundus autofluorescence (FAF), and spectral-domain optical coherence tomography (SD-OCT) imaging (HRA + OCT Spectralis, Heidelberg Engineering, Heidelberg, Germany). Tangential tractions were evaluated with infrared reflectance (IR; 820 nm) and OCT en face (193 B-scans, 30 × 20°pattern size, 31 μm between two consecutive B-scans). Three different categories of tangential traction were previously defined: 1) unidirectional, 2) pluridirectional, and 3) concentric. Two independent masked physicians evaluated the images in order to categorize the type of tangential traction either with IR and OCT (en face) for every single patient. Cohen's kappa statistic was used to evaluate inter-observer and inter-instrument agreement., Results: Twenty eyes of 19 patients were included in the study. Inter-observer OCT test showed almost perfect agreement between examiners (κ = 0.86). Inter-observer IR test showed substantial agreement (κ = 0.7). Inter-instrument agreement was fair for both observers, respectively κ = 0.35 for observer 1 and κ = 0.22 for observer 2. Intra-observer agreement was almost perfect for OCT (κ = 0.93) and substantial for IR (κ = 0.78)., Conclusion: Tangential traction associated with epiretinal membranes in lamellar macular holes can be successfully evaluated by OCT en face and IR reflectance. Inter-observer concordance is high for both instruments. However, high inter-instrument discordance is present. Therefore, the gold standard imaging technique for differentiating the different types of contraction in epiretinal membranes has still to be determined.

Background: To evaluate macular changes in fellow eyes of patients diagnosed with lamellar macular hole (LMH) using spectral-domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (B-FAF)., Methods: Fellow eyes of patients diagnosed with a LMH were retrospectively evaluated on OCT. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were recorded. Corresponding B-FAF images, vitreo-macular relations, and type of epiretinal membranes (ERMs) were also examined., Results: Thirty-five patients were included. At baseline, six fellow eyes (17%) showed a normal foveal profile, 26 (74%) had a tractional ERM, and three cases (9%) revealed a bilateral LMH, one of them with a lamellar hole-associated epiretinal proliferation (LHEP). A posterior vitreous detachment (PVD) was present in 29 patients (83%), four (11%) had only a vitreo-papillary adhesion (VPA), and two (6%) had both vitreo-macular adhesion (VMA) and VPA. After a mean follow-up of 4.6 ± 1.9 years, one eye (3%) developed a vitreous detachment from the macula with persistent VPA, and one developed a PVD from a VPA with subsequent ERM formation. BCVA and mean CFT remained stable in 35 eyes (100%). Likewise, no B-FAF signal variations were detected. One patient developed a LMH during the 3rd year of follow-up., Conclusions: Our data suggest that the presence of a LMH in one eye does not increase significantly the risk of developing the same condition in the fellow eye after 4 years. Bilateral condition is uncommon, and an ERM is often detected in the fellow eye. LHEPs were not observed in fellow eyes with foveal integrity, and all LHEPs observed (in main and fellow eyes) were always associated with LMHs; this supports the hypothesis that LHEP is a consequence and not a causative factor for LMHs. The occurrence of a LMH in one fellow eye after 3 years follow-up may suggest that a higher incidence of bilateral disease could develop in a longer time span.

Purpose: We aimed to describe imaging findings in primary inflammatory choriocapillaropathies (PICCPs) after a photobleaching process., Methods: 2Images from six consecutive cases of patients affected by PICCPs (four with multiple evanescent white dot syndrome and two with multifocal choroiditis) were reviewed. Patients underwent fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT) by means of the Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany). FAF images were acquired at the beginning of the examination in partially dark-adapted conditions followed by light adapted conditions., Results: During the active phase of the diseases, all patients showed areas of increased FAF that became isoautofluorescent after photobleaching. Simultaneously with increased FAF, the ICGA showed typical hypofluorescent dark areas that were more evident in the late phase. SD-OCT showed disruptions in the hyper-reflective band at the ellipsoid zone., Conclusions: FAF and SD-OCT are complementary imaging techniques that show alterations in the outer retina of patients affected by PICCPs.

Background: To study the evolution of lamellar macular holes (LMHs) using spectral domain-optical coherence tomography (SD-OCT)., Methods: Thirty-four consecutive patients diagnosed with a LMH were followed prospectively at Sacco University Hospital from October 2008 to January 2011. Inclusion criteria were a foveal defect on SD-OCT with residual foveal tissue above the retinal pigment epithelium and corresponding hyperautofluorescence on fundus autofluorescence imaging. Epiretinal membranes (ERMs) were categorized by SD-OCT at baseline as two different types: normal and thicker than normal. Best corrected visual acuity (BCVA) and SD-OCT findings were collected and compared at baseline and every 6 months thereafter. Active eye tracking technology ensured that the same scanning location was identified on follow-up visits. Main outcome measures were visual acuity changes (Early Treatment Diabetic Retinopathy charts) and progression of the lamellar macular defect. The influence of ERM type on disease progression was also evaluated., Results: The patients included 15 males and 19 females with a mean age of 73 years and mean refraction of -0.25 diopters. The mean follow-up period was 18 months (range 6 to 24 months). BCVA at baseline (±standard deviation) was 63 ± 6 letters and did not change significantly during the follow-up period (P = 0.256). Foveal thickness at baseline, 180 ± 29 μm, was also stable (P = 0.592). All eyes had an ERM at baseline. Both thicker and normal ERMs showed similar functional and morphological evolution during follow-up with no significant changes. Two LMHs (5.8 %) developed a full thickness macular hole after 6 and 15 months follow-up respectively., Conclusions: Lamellar macular holes seem to be a stable macular condition. Vitrectomy should be considered only in the presence of progressive thinning of foveal thickness and/or decrease of visual acuity during the follow-up of the disease.

Purpose: To describe the spectral-domain optical coherence tomography (SD-OCT) findings in a patient with a premacular hemorrhage due to Valsalva retinopathy treated with Nd:YAG laser., Methods: Serial SD-OCT examinations were performed before and after Nd:YAG laser treatment to identify the cleavage plane of blood accumulation, as well as the exact location of the areas targeted by the laser spots and the different involvement of the affected retinal layers., Results: The SD-OCT scan above the level of settled blood showed that the cleavage plane was located under the internal limiting membrane (ILM). A raster box of 48 horizontal scans centered on the treatment area identified the two spots of ILM targeted by laser. The hyporeflective perforations appeared along an ILM still detached from the underlying retinal layers. Two months after treatment, the blood was completely reabsorbed. The ILM appeared reattached in the previously detached area. Only a mild thickening of the ILM remained visible at the laser-treated spots., Conclusions: SD-OCT evaluation of Nd:YAG laser treatment for Valsalva retinopathy confirmed the cleavage plane of the premacular hemorrhage. In addition, it revealed the exact location of the ILM disruptions caused by the laser spots, and the safety of the procedure, with no involvement of the underlying retinal layers.