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Purpose: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD)., Methods: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients., Results: The model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R 2 ) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10)., Conclusions: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians' assessments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intermediate and posterior manifestations of vitreoretinal lymphoma (VRL) are well characterised. However, there is limited information on anterior segment involvement in VRL. This study aimed to describe the anterior manifestations of VRL, and their association with molecular testing., Methods: Retrospective analysis of patients with biopsy-proven VRL. Study variables included anterior segment manifestations, findings from slit-lamp photos and in vivo confocal microscopy (IVCM) when available. MYD88 L265P mutation and cytology in the aqueous humour, retinal and systemic findings were also analysed., Results: The analysis included 108 eyes of 55 VRL patients. Anterior segment involvement was present in at least one visit in 55 eyes (51%) of 33 patients (60%); it included keratic precipitates (dendritiform with branching and irregular margins in 33 eyes, dust-like in 16 eyes and large granulomatous in 12 eyes), cells in the anterior chamber (51 eyes) and posterior synechiae (2 eyes). IVCM was available for 41 eyes and showed different morphologies of keratic precipitates, including floral, spikes and mulberry patterns (66%, 56% and 20%, respectively). MYD88 L265P mutation in the aqueous humour was detected in 10/21 (48%) eyes with no anterior segment involvement and 24/37 (65%) eyes with anterior segment involvement., Conclusions: Anterior segment manifestations are often present in VRL and include dendritiform and dust-like keratic precipitates. IVCM in VRL can identify different patterns associated with keratic precipitates. MYD88 L265P mutation in the aqueous humour of VRL patients can also be found in eyes without significant anterior segment involvement., Competing Interests: Competing interests: FB is consultant for Abbvie, Alimera, Bayer, Boehringer-Ingelheim, Fidia Sooft, Hofmann La, Roche, Novartis, Ntc Pharma, Oxurion Nv, SIFI. All other authors have no relevant competing interests to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/rationale: Artificial intelligence (AI)-based clinical decision support tools, being developed across multiple fields in medicine, need to be evaluated for their impact on the treatment and outcomes of patients as well as optimisation of the clinical workflow. The RAZORBILL study will investigate the impact of advanced AI segmentation algorithms on the disease activity assessment in patients with neovascular age-related macular degeneration (nAMD) by enriching three-dimensional (3D) retinal optical coherence tomography (OCT) scans with automated fluid and layer quantification measurements., Methods: RAZORBILL is an observational, multicentre, multinational, open-label study, comprising two phases: (a) clinical data collection (phase I): an observational study design, which enforces neither strict visit schedule nor mandated treatment regimen was chosen as an appropriate design to collect data in a real-world clinical setting to enable evaluation in phase II and (b) OCT enrichment analysis (phase II): de-identified 3D OCT scans will be evaluated for disease activity. Within this evaluation, investigators will review the scans once enriched with segmentation results (i.e., highlighted and quantified pathological fluid volumes) and once in its original (i.e., non-enriched) state. This review will be performed using an integrated crossover design, where investigators are used as their own controls allowing the analysis to account for differences in expertise and individual disease activity definitions., Conclusions: In order to apply novel AI tools to routine clinical care, their benefit as well as operational feasibility need to be carefully investigated. RAZORBILL will inform on the value of AI-based clinical decision support tools. It will clarify if these can be implemented in clinical treatment of patients with nAMD and whether it allows for optimisation of individualised treatment in routine clinical care., Competing Interests: Competing interests: FGH reports grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, Geuder, Heidelberg Engineering, IvericBio, Kanghong, Roche, and Zeiss; personal fees from Grayburg Vision, Oxurion, and Pixium; grants from Biogen, and Optos, outside the submitted work. RAG reports personal fees from Allergan, Bausch & Lomb, Nidek, and Novartis, outside the submitted work. FB reports personal fees from Allergan, Bayer, Boehringer-Ingelheim, Fidia Sooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, and Zeiss, outside the submitted work. RD reports grants and personal fees from Bayer, and personal fees from Novartis, outside the submitted work. LO reports grants from Novartis, and personal fees from Bayer, outside the submitted work. DP has nothing to disclose. GS reports grants and personal fees from Centervue, Nidek and Novartis; grants from Carl Zeiss Meditec, Heidelberg Engineering, Ocular Instruments, Optos, Optovue, Quantel Medical, and Topcon; personal fees from Apellis, Allergan, Astellas, Bayer, Boheringer, Genentech, Graybug, Iveric, Roche, Chengdu Kanghong Biotechnology, Kyoto Drug Discovery & Development, outside the submitted work. AW reports grants from Novartis, outside the submitted work. DL reports full-time employment of Novartis Pharma AG. AC reports full-time employment and shareholder of Novartis Pharma AG. BG reports full-time employment at Novartis Pharma GmbH and is a shareholder of Novartis Pharma AG., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To characterise macular neovascularisation (MNV) developing in eyes affected by geographic atrophy (GA)., Methods: In this multicentric longitudinal study involving three retina referral centres, patients previously affected by GA who developed an active MNV were included. Patients were investigated using structural optical coherence tomography (OCT), fundus autofluorescence, OCT-angiography and dye angiographies. Patients were treated with ProReNata antivascular endothelial growth factor (VEGF) injections and were revaluated after treatment., Results: Among 512 patients previously diagnosed with GA, 40 eyes of 40 patients (mean age 80.8±7.9 years, mean GA area 8.73±7.39 mm 2 ) presented with treatment-naïve exudative MNV (accounting for an estimated prevalence of 7.81%; 5.49 to 10.13, 95% CIs) and thus were included in the analysis. 67.5% of MNVs were classified as type 2 MNV, 25% as type 1, 2.5% as type 3 and 5% as mixed phenotype. In 92.5% of cases, active MNV in GA showed subretinal hyperreflective material with or without evidence of subretinal/intraretinal hyporeflective exudation. During a mean follow-up of 28±25 months, patients were treated with 6.6±6.3 anti-VEGF injections, with 2.9±1.4 injections in the first year of treatment. No patient developed GA enlargement in the area of MNV., Conclusions: MNVs in GA showed different features and therapeutic response in comparison to previously reported features of MNV in age-related macular degeneration (AMD) without GA. For these reasons, the combined phenotype (ie, GA with neovascular AMD) should be considered as a distinct entity in the research and clinical setting., Competing Interests: Competing interests: RS is a consultant for Carl Zeiss Meditec (Dublin, USA), Novartis (Basel, Switzerland). EB is a consultant for Centervue (Padova, Italy), Carl Zeiss Meditec (Dublin, USA), Novartis (Basel, Switzerland). MP is a consultant for Allergan (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Zeiss (Dublin, USA). EHS is a consultant for Allergan (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland). FB is a consultant for Alcon (Fort Worth,Texas,USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (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). GQ is a consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to disease recurrence in a cohort of patients with newly diagnosed myopic choroidal neovascularisation (CNV) METHODS: In this retrospective, longitudinal study, a total of 64 participants (64 eyes) with successfully treated myopic CNV had obtained resolution of exudation after treatment (study baseline) and with 3 years of regular follow-ups. Several baseline OCT qualitative features and quantitative measurements were assessed at baseline and included in the analysis. Main outcome measures included incidence of disease recurrence and HR for demographics, clinical characteristics and OCT risk factors., Results: At month 36, 40 eyes (62.5%) developed disease recurrence (active CNV). Multivariate linear regression analysis revealed that final visual acuity (dependent variable) was associated with visual acuity at the first visit after complete resolution of exudation (p<0.0001), baseline size of patchy atrophy (p=0.010), baseline subfoveal choroidal thickness (p=0.008), baseline maximum CNV height and width (p=0.011 and p=0.003) and recurrence of CNV exudation (p=0.007). The following factors were associated with an increased risk of disease recurrence: size of patchy atrophy had an HR of 1.14 (95% CI 1.01 to 1.29; p=0.036); maximum CNV width had an HR of 1.02 (95% CI 1.01 to 1.04; p<0.0001)., Conclusion: We identified OCT risk factors for the disease recurrence in eyes with successfully treated myopic CNV. Assuming that disease recurrence is a sight-threatening event, our findings may help in the identification of high-risk patients and eventually ameliorate their outcome., Competing Interests: Competing interests: FB 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). GQ is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Amgen (Thousand Oaks, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), KBH (Chengdu, China), LEH Pharma (London, UK), Lumithera (Poulsbo; USA), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Sooft-Fidea (Abano, Italy), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To analyse multimodal imaging alterations in the subclinical form of best vitelliform macular dystrophy (BVMD)., Methods: The study was designed as an observational, cross-sectional case series. Eleven eyes of 7 subclinical patients with BVMD and 12 age-matched and sex-matched controls were included. Multimodal imaging included fundus blue-light autofluorescence, near-infrared autofluorescence (NIR-AF), structural optical coherence tomography (OCT) and OCT angiography (OCTA). The quantitative analysis included the calculation of the following parameters: vessel density (VD), vessel tortuosity (VT), vessel dispersion (Vdisp), vessel rarefaction (VR), foveal avascular zone (FAZ) area, reflectivity of the outer retinal bands and choriocapillaris porosity (CCP)., Results: Mean best-corrected visual acuity was 0.0±0.0 LogMAR in both groups. The round central hypoautofluorescent alteration on NIR-AF corresponded to a significant reflectivity attenuation of the outer retinal bands on structural OCT (0.55±0.18 vs 0.75±0.08; p<0.001). VD, VT, VR and Vdisp were normal compared with controls (all p>0.05). The FAZ area turned out to be significantly restricted at the level of the deep capillary plexus in subclinical BVMD eyes (p<0.001). Furthermore, quantitative OCTA revealed a significant central increase of CCP, compared with controls (18.25±2.43 vs 4.58±1.36; p<0.001)., Conclusions: The subclinical stage of BVMD is characterised by significant alterations of the outer retinal bands and the choriocapillaris. Quantitative multimodal imaging assessment suggests that subclinical BVMD is affected by the functional impairment of the outer retinal structures, leading to an alteration in melanin and growth factor production., Competing Interests: Competing interests: FB consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (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), NovagaliPharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Placoid lesions of the retina may be secondary to a wide spectrum of acquired inflammatory conditions that have been reported as single entities with different presentation and clinical course. These conditions include acute posterior multifocal placoid pigment epitheliopathy, persistent placoid maculopathy, serpiginous choroiditis, serpiginous-like choroiditis, relentless placoid chorioretinitis and acute syphilitic posterior placoid chorioretinitis. In this article, we will group these conditions under the name of 'placoids'. The recognition of the specific condition may be challenging in clinical practice, often resulting in diagnostic and therapeutic delay. Given the complex nature of placoids and their similarities, a systematic approach including differentiating between infectious and non-infectious aetiologies increases the chance of reaching the correct diagnosis. Detailed history and comprehensive clinical examination are the first steps to formulate a diagnostic hypothesis that should be corroborated by multimodal imaging and appropriate investigations. The advent of multimodal imaging has made it possible to extensively study placoids and revealed a constellation of specific findings that may help clinicians in the diagnostic process. The treatment of the conditions other than syphilis is complex and sometimes challenging. Our article is aimed at giving an overview of the individual entities associated with placoids and discussing the differential diagnosis. A practical and systematic approach is then proposed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings., Methods: The study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone-retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC., Results: Mean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters., Conclusions: Our study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects., Methods: In this cross-sectional study, macular structural OCT and OCT angiography (OCTA) images were acquired from healthy subjects. The main outcome measures were: (i) choriocapillaris (CC) flow deficits percentage (FD%), (ii) choroidal luminal (LA) and stromal (SA) areas and (iii) choroidal vascularity index (CVI), which was calculated as the LA divided by the total choroidal area. These measurements were generated using previously published algorithms and were separately computed in the foveal and extrafoveal regions., Results: Eighty-five eyes from 85 subjects (44 males, 41 females) were included in the analysis. Mean±SD age was 47.9±22.4 years (range: 19.0 to 85.0 years). Linear regression analysis displayed no significant associations between CC FD% and other parameters (LA, SA and CVI). Importantly, non-linear regression analysis showed that the relations of LA and SA to CC FD% were all best fitted by a quadratic function. Compared with the linear models, the use of the quadratic function allowed a relative increase in the R 2 coefficients. No significant non-linear associations were found between CC FD% and CVI., Conclusion: Based on our models, changes in the luminal and stromal areas in the choroid lead to an initial increase in CC perfusion. Subsequently, further increases in LA and SA amounts are accompanied by a progressive increment in CC FD%., Competing Interests: Competing interests: FB 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). GQ is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Amgen (Thousand Oaks, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), KBH (Chengdu; China), LEH Pharma (London, UK), Lumithera (Poulsbo; USA), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Sooft-Fidea (Abano, Italy), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate optical coherence tomography angiography (OCT-A) findings in recurrent type 3 macular neovascularisation (MNV)., Methods: In this retrospective cohort study, consecutive patients with type 3 MNV secondary to age-related macular degeneration underwent OCT-A at three different time points: baseline, after anti-vascular endothelial growth factor treatment with complete resolution of the exudative signs (ie, non-exudative stage) and at the recurrence of exudation (ie, recurrence stage). Demographics and clinical findings were analysed, including OCT-A features of type 3 MNV recurrence., Results: Twelve eyes (12 patients, mean age 78±7 years) were included. Using OCT-A, at baseline all type 3 MNVs showed the presence of detectable flow downgrowing from the deep vascular complex (DVC) to the retinal pigment epithelium (RPE)/sub-RPE space. 6/12 eyes (50%) showed anomalous flow under the RPE, while the other 6 eyes showed flow reaching the RPE without anomalous flow in the sub-RPE space. At the non-exudative stage (after treatment), BCVA and CMT significantly improved (p=0.004 and p=0.036), and flow inside the retinal lesions reduced; interestingly the connection to the RPE/sub-RPE space regressed. At the time of recurrence, all type 3 MNVs showed the presence of intra/sub-retinal exudation with restoration of the flow deepening from the DVC to the RPE/sub-RPE space., Conclusions: Detectable flow deepening from the DVC to the RPE/sub-RPE space using OCT-A is mandatory to have a new exudation secondary to recurrent type 3 MNV. Early detection of type 3 MNV recurrence by OCT-A characterisation may prompt retreatment and potentially prevent progression to late stages of the disease., Competing Interests: Competing interests: RS, EB and VC are consultants for ZEISS (Dublin, USA). FB 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 + 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). EHS is a consultant for: Allergan Inc (Irvine, California, USA), Bausch + Lomb (Rochester, New York, USA), Bayer Shering-Pharma (Berlin, Germany), Novartis (Basel, Switzerland). GQ is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California, USA), Amgen (Thousand Oaks, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), KBH (Chengdu; China), LEH Pharma (London, UK), Lumithera (Poulsbo, USA), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Sooft-Fidea (Abano, Italy), ZEISS (Dublin, USA)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To analyse the choriocapillaris (CC) flow status in the area that subsequently showed geographic atrophy (GA) expansion secondary to age-related macular degeneration (AMD) during 1-year follow-up, matching optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF)., Methods: In this prospective longitudinal observational study, 30 eyes of 20 consecutive patients with GA secondary to AMD (mean age 75.5±7.4 years) were included. All patients underwent OCT-A and FAF at baseline and 1-year follow-up. Main outcome measures included analysis of perfusion density (PD) in the 'area surrounding GA margin' (between the GA border and 500 µm distance) in comparison with the 'control area' (area outside the 500 µm line), and of the 'expansion area' (area that subsequently developed GA expansion during 1-year follow-up)., Results: During the 1-year follow-up, visual acuity significantly decreased from 0.34±0.38 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.39±0.40 LogMAR (p<0.001), and mean GA area increased from 6.82±5.47 mm 2 to 8.76±6.28 mm 2 (p<0.001). CC PD of the area surrounding the GA margin revealed a significant flow impairment compared with control area (PD 0.679±0.076 and 0.734±0.057, respectively (p<0.001)). Furthermore, the PD of the expansion area showed a greater CC flow impairment in comparison to the remaining area surrounding GA margin (p<0.001)., Conclusions: We reported a greater CC impairment in the area that subsequently developed GA expansion, suggesting that the CC flow impairment could predict the enlargement of GA lesion. The CC impairment could be considered as a new a risk factor for GA progression and a biomarker to be measured to determine efficacy of new interventions aiming to slow progression of GA., Competing Interests: Competing interests: FB is a consultant for: Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (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). GQ is a consultant for: Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Amgen (Thousand Oaks, USA), Bayer Shering-Pharma (Berlin, Germany), Heidelberg (Germany), KBH (Chengdu; China), LEH Pharma (London, UK), Lumithera (Poulsbo; USA), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Sooft-Fidea (Abano, Italy), ZEISS (Dublin, USA)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to describe the characteristics of microvascular retinal alterations in eyes with chronic central serous chorioretinopathy (CSC) employing optical coherence tomography angiography (OCTA) analysis., Methods: We collected data from 472 eyes with chronic CSC from 336 patients who had OCTA obtained. Each OCTA image was graded by two readers to assess the presence of microvascular retinal alterations, including regions of vascular rarefaction/retinal hypoperfusion, enlargement of the foveal avascular zone (FAZ) and presence of telangiectasias or microaneurysms. Volume spectral domain optical coherence tomography (SD-OCT) scans were obtained through the macula and the OCT was correlated with the OCTA findings in eyes with retinal vascular alterations., Results: OCTA displayed microvascular retinal alterations in 18 out of 474 eyes (3.6%) from 14 patients (13 male and 1 female; mean±SD age was 54.7±11.1 years). One eye displayed the presence of retinal telangiectasias, while 17 out of 18 eyes were graded as having areas of retinal vascular rarefactions, and 3 out of 17 eyes were also characterised by an enlargement of the FAZ. The parafoveal region was the location most involved by retinal vascular changes (66,7%), followed by foveal (22,2%) and perifoveal (11.1%) regions, respectively., Conclusion: Although CSC is known to represent a choroidal disorder, retinal vascular alterations may be present in these eyes and OCTA may represent a useful tool to identify and describe them., Competing Interests: Competing interests: FB is a consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (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), NovagaliPharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA), outside the submitted work. GQ is a consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Heidelberg (Germany), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), Zeiss (Dublin, USA), outside the submitted work. MP reports personal fees from Allergan, personal fees from Bayer, personal fees from Novartis, outside the submitted work. Other authors: none. Other acknowledgements: The research for this paper was in part financially supported by the Italian Ministry of Health and Fondazione Roma. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The clinical phenotype of Stargardt disease (STGD) can be extremely heterogeneous, with variable macular and peripheral retinal involvement. The study aim was to correlate peripheral ultrawide field (UWF) involvement with macular alterations, as assessed by structural optical coherence tomography (OCT) and OCT angiography (OCTA), in order to identify potentially different phenotypes., Methods: The study involved patients with STGD and healthy controls. We performed a complete ophthalmologic assessment and multimodal imaging, including OCT, OCTA, fundus autofluorescence and UWF imaging. Patients with STGD were subdivided according to the peripheral involvement. OCT and OCTA quantitative parameters were analysed. The main outcome of the study was the classification of UWF subtypes and the correlation between UWF subtypes and macular involvement., Results: Seventy STGD eyes (19 male; mean age 41.3±13.2 years) and 70 healthy eyes (35 male; 50%; mean age 41.2±9.8 years) were included in the analyses. Mean best-corrected visual acuity was 0.60±0.45 LogMAR for the STGD group and 0.0±0.0 LogMAR for controls (p<0.01). All clinical and imaging findings proved to be statistically worse in patients with STGD than in the control subjects (p<0.01). UWF types were distributed as follows: type I (49%), type II (34%), type III (17%). Type III patients proved to be significantly worse in terms of visual function and OCT and OCTA imaging parameters., Conclusions: The UWF autofluorescence performed in the present study suggests that there exist three different STGD phenotypes. Each phenotype is associated with variable OCT and OCTA impairment. Further studies providing a better assessment of the peripheral retinal involvement in STGD are warranted., Competing Interests: Competing interests: Francesco Bandello consultant for Allergan (Irvine, California, USA), Bayer Shering-Pharma (Berlin, Germany), Hoffmann-La-Roche (Basel, Switzerland), NTC Pharma, Novartis (Basel, Switzerland), SIFI, SOOFT, Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To evaluate the effects of neurovascular damage in patients with the typical vitelliform lesion of Best vitelliform macular dystrophy (BVMD) in the attempt to identify different progression patterns., Methods: Prospective, observational case series. Patients in the vitelliform stage of BVMD and healthy controls underwent complete ophthalmological examination on a yearly basis, including best-corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT) and OCT angiography (OCT-A). 4.5×4.5 mm OCT-A slabs were imported into ImageJ software and their vessel density (VD) was calculated. Similarly, the ellipsoid zone (EZ) was manually outlined and the reflectivity was measured above the vitelliform lesion and in the 500 µm external to it. Retinal pigment epithelium-Bruch's membrane complex was taken as internal reference., Results: 34 eyes (24 patients) and 34 matched controls were included in the study. Mean follow-up was of 28.4±5.8 months, with 12 eyes showing signs of stage progression at the end follow-up. The EZ overlying the vitelliform lesion and in the peri-lesional area disclosed a significant reduction in reflectivity when compared with the foveal and para-foveal EZ of controls, respectively. VD resulted meaningfully decreased only at the deep capillary plexus. Of notice, more extensive EZ (reflectivity <0.7) and vascular alterations (VD <0.4) at baseline strongly correlated with worse BCVA and were associated with a more rapid progression at follow-up., Conclusions: Both EZ reflectivity and VD at deep capillary plexus may prove valuable biomarkers to assess BVMD severity and detect progression. In this view, 'rapid progressors' might benefit the most from timely genetic therapies in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This article aims to analyse the key regulatory guidelines across the globe concerning biosimilars., Materials and Methods: Review of the current literature., Results: Biosimilars are well regulated with the majority of regulators having enforced the guidelines for the development and approval, and new biosimilar drugs are appearing on the horizon to provide a therapeutic option to a wider population base because of its cost-effectiveness and proven safety. Due to their extensive analytical data, clinical data and pharmacovigilance studies, their development should not be considered similar to generic drugs., Conclusion: This review discusses the biosimilars, their regulation globally and their difference from generics from ophthalmic perspective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the anatomical changes and the macular function in neovascular age-related macular degeneration (AMD) eyes, according to the recognition of either fibrocellular or fibrovascular phenotype., Methods: We enrolled eyes with previously treated neovascular AMD in remission (no subretinal haemorrhage, sign of fluid in or under the retina and no treatment for at least 6 months). Subjects underwent multimodal imaging assessment and were tested for macular sensitivity using microperimetry. The study cohort was divided according to the presence of fibrosis on multicolour (MC) images, yielding two distinct phenotypic subgroups: (1) fibrocellular group and (2) fibrovascular group., Results: Nineteen eyes were classified as fibrocellular on MC images, while 22 eyes as fibrovascular. Mean±SD age was 73.9±11.0 years in the fibrocellular group and 75.9±7.1 years in the fibrovascular group (p=0.221). Best-corrected visual acuity was 0.7±0.5 logarithm of the minimum angle of resolution (LogMAR) in the fibrocellular group and 0.3±0.2 LogMAR in the fibrovascular group (p=0.003). On the optical coherence tomography and fundus autofluorescence evaluation, 17/19 eyes with the fibrocellular phenotype and 8/22 eyes with the fibrovascular phenotype displayed the presence of retinal pigment epithelium (RPE) atrophy (p=0.001). The perfusion density within the neovascular lesion was 28.9%±9.9% in the fibrocellular group and 44.2%±5.9 % in the fibrovascular group (p<0.0001)., Conclusion: Neovascular AMD eyes in remission and with evidence of fibrocellular scar are characterised by RPE atrophy and reduced perfusion, which are associated with a higher degree of functional impairment. These findings suggest that maturation of vessels in fibrosis might be a better target in neovascular AMD treatments rather than their abolishment., Competing Interests: Competing interests: GQ has the following disclosures: Allergan (S), Alimera (S), Amgen (S), Bayer (S), KHB (S), Novartis (S), Roche (S), Sandoz (S), Zeiss (S); Allergan (C), Alimera (C), Bausch and Lomb (C), Bayer (C), Heidelberg (C), Novartis (C), Zeiss (C). FB has the following disclosures: Allergan (S), Alimera (S), Bayer (S), Farmila-Thea (S), Schering Pharma (S), Sanofi Aventis (S), Novagali (S), Pharma (S), Hoffmann-La Roche (S), Genetech (S), Novartis (S). MP has the following disclosures: Allergan (S), Bayer (S) and Novartis (S)., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To evaluate the safety and tolerability of ranibizumab 0.5 mg in patients with uni/bilateral neovascular age-related macular degeneration (nAMD) and best-corrected visual acuity (BCVA)<2/10 and/or second eye affected, regardless of BCVA., Methods: In this 12-month, prospective, multicentre, open-label, single arm, pragmatic interventional study, patients (N=941) aged ≥ 50 years were to receive ranibizumab as per approved label, monthly until maximum stable visual acuity (VA) was achieved (initially, three or more injections may be required). Thereafter, patients were to be monitored monthly for VA and treatment was to be resumed if VA was reduced due to disease activity., Results: Of the 936 patients treated with ranibizumab at least once during the study, 823/113 were unilaterally/bilaterally (not simultaneously) treated . The mean (SD) number of ranibizumab injections during the study was 5.4 (2.9)/10.6 (5.0) injections in uni/bilaterally treated patients. Three systemic drug-related adverse events (AEs) (all serious, all in unilaterally treated patients) and 18 systemic AE of special interest (AESIs) (11 serious, 16/2 in unilaterally/bilaterally treated patients) occurred during the study. The annual incidence rate (AIR) (events/1000 person-years) for systemic drug-related AEs, considering a 15-day/30-day risk period, 11.0/8.5 for unilaterally treated patients. Considering the same risk period, the AIR (events/1000 person-years) for systemic AESIs for unilaterally treated patients was 22.1/19.9. Considering a 30-day risk period, the AIR (events/1000 treated eye-years) of ocular drug-related AEs was 23 and AESIs was 11.5., Conclusions: The low incidence of AEs and AESIs demonstrated the good safety and tolerability of ranibizumab in unilaterally/bilaterally treated patients with nAMD in this real-world setting., Competing Interests: Competing interests: FB: Consultant—Acucela (Seattle, Washington), Alcon (Fort Worth, Texas), Bayer (Leverkusen, Germany), Boehringer-Ingelheim (Ingelheim, Germany), Genentech (South San Francisco, California), Heidelberg Engineering (Heidelberg, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland) and Zeiss (Oberkochen, Germany); Financial support—Bayer (Leverkusen, Germany), Genentech (South San Francisco, California), Heidelberg Engineering (Heidelberg, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland) and Zeiss (Oberkochen, Germany). GS: Consultant—Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), Allergan (Dublin, Ireland), Genentech (South San Francisco, California), Roche (Basel, Switzerland), Heidelberg Engineering (Heidelberg, Germany) and Alcon (Fort Worth, Texas); Financial support—Bayer HealthCare (Leverkusen, Germany), Centervue (Padova, Italy), Heidelberg Engineering (Heidelberg, Germany) and Novartis (Basel, Switzerland); Lecturer—Zeiss (Oberkochen, Germany); Patent holder—in conjunction with Ocular Instruments, Inc. (Bellevue, Washington); Payment for development of educational presentations—Roche (Basel, Switzerland). FR: Alcon (Fort Worth, Texas), Bayer (Leverkusen, Germany), Novartis (Basel, Switzerland), Roche (Basel, Switzerland), Allergan (Dublin, Ireland), SIFI (Catania, Italy). FV: Consultant—Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), Financial support—Allergan (Dublin, Ireland), Novartis (Basel, Switzerland), Bayer HealthCare (Leverkusen, Germany), SIFI (Catania, Italy). TLS: Employee—Novartis Farma S.p.A (Origgio, Italy) at the time of development of the manuscript and submission. EP, SB: Employees—Novartis Farma S.p.A (Origgio, Italy). LC: Employee—Novartis Farma S.p.A (Origgio, Italy) at the time of development of the manuscript and submission., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Peculiar retinal signs of vitreoretinal lymphoma (VRL) have been identified. However, limited information on the vitreous features of VRL is available. This study aims to characterise the vitreous involvement in VRL with the help of multimodal imaging., Methods: In this retrospective, observational study, we reviewed charts and imaging of all patients with biopsy-proven VRL seen from January 2016 to April 2018 at a single referral centre. These included ultrawide-field imaging, ophthalmic ultrasonography and slit-lamp photography. The main outcome measures were patterns of vitreous haze of VRL, as observed by combining clinical and multimodal imaging information., Results: Twenty-six eyes of 13 patients were included. At presentation, vitreous haze was present in 24 eyes (92%) and was the only sign of VRL in 4 eyes (15%). Three patterns of vitreous haze were identified in VRL. An aurora borealis pattern was present in 12 eyes and showed linear opacities with a myriad of cells aligned along the vitreous fibrils. A string of pearls pattern was present in two eyes at baseline and developed in other four eyes after vitrectomy, showing fine fibrils connecting bunches of inflammatory material. A non-specific pattern was observed in 10 eyes. Ophthalmic ultrasound showed corpuscular material correlating with the grading of vitreous haze., Conclusion: VRL shows different patterns of vitreous haze. Multimodal imaging, including ultrawide-field imaging and slit-lamp photography, helps in recognising these patterns, raising suspicion for VRL., Competing Interests: Competing interests: AM, EM, CG, MVC and GM have no financial disclosures. GQ has the following disclosures: Allergan (S), Alimera (S), Amgen (S), Bayer (S), KHB (S), Novartis (S), Roche (S), Sandoz (S), Zeiss (S); Allergan (C), Alimera (C), Bausch and Lomb (C), Bayer (C), Heidelberg (C), Novartis (C), Zeiss (C). FB has the following disclosures: Allergan (S), Alimera (S), Bayer (S), Farmila-Thea (S), Schering Pharma (S), Sanofi-Aventis (S), Novagali (S), Pharma (S), Hoffmann-La Roche (S), Genentech (S), Novartis (S)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To analyse quantitative optical coherence tomography angiography (OCTA) parameters of choriocapillaris (CC) at the foveal, perifoveal and parafoveal regions in healthy subjects of different age., Methods: In this observational cross-sectional study, consecutive healthy subjects underwent swept source OCTA (PLEX Elite 9000, Carl Zeiss Meditec, USA). 3×3 mm and 6×6 mm scans centred on the fovea were acquired analysed and postprocessed with thresholding and binarisation processes. The main outcome measures included CC quantitative OCTA features (perfusion density (PD), vessel length density (VLD) and vessel diameter index (VDI)) at the foveal, perifoveal and parafoveal regions, and their relationship with age., Results: Seventy-two eyes (72 patients, mean age 47.4±19.2 years, mean axial length 24.0±0.7 mm) were included. The mean PD was statistically lower in the foveal region compared with the parafoveal region in 3×3 mm scans (p=0.009). In subjects aged 70-80, PD of the foveal region was significantly reduced compared with the perifoveal region in 6×6 mm scans (p=0.008). A strong negative correlation was found between PD and ageing in the foveal, parafoveal and perifoveal regions (p<0.001 in all analyses). Furthermore, PD in the nasal-perifoveal region was significantly lower than the temporal-perifoveal region (p=0.005). No significant correlation was found between VLD and age in all regions, whereas VDI was strictly correlated with age (p<0.001)., Conclusions: We reported in vivo a strong negative correlation between PD and ageing in the CC of healthy subjects. This reduction seems related to a reduced diameter, and not to a reduced number, of capillaries. The age-related changes were higher in the central area compared with the perifoveal area., Competing Interests: Competing interests: FB is a consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Farmila-Thea (Clermont-Ferrand, France), Bayer Schering 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) and Zeiss (Dublin, USA). GQ is a consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Bayer Schering Pharma (Berlin, Germany), Heidelberg (Germany), Novartis (Basel, Switzerland), Sandoz (Berlin, Germany) and Zeiss (Dublin, USA)., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To investigate the clinical spectrum of choroidal neovascularisation (CNV) in patients with dome-shaped macula with the aid of multimodal imaging., Methods: In this cross-sectional, retrospective, observational study, we reviewed charts and imaging studies of 144 eyes of 79 consecutive patients with dome-shaped macula evaluated at a tertiary referral centre, including optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Three masked graders evaluated the prevalence and type of CNV. Primary outcome measures were the diagnostic agreement between OCTA and FA±ICGA, the multimodal imaging characteristics and prevalence of CNV associated with dome-shaped macula., Results: We identified 30 eyes with dome-shaped macula complicated by CNV with an estimated prevalence of 20.8% (95% CI 14.2 to 27.4). Twenty-two eyes (73%) showed a type 2 CNV while eight eyes (27%) showed a type 1 CNV. Serous macular detachment was present in 39 eyes (27%) and harboured a CNV in five cases (13%). The overall diagnostic agreement between OCTA and FA±ICGA was excellent (k=0.894, p<0.001), but only the use of both techniques allowed the identification of the whole pool of CNVs., Conclusion: Eyes with dome-shaped macula may either develop typical myopic CNV (ie, type 2 CNV) or pachychoroid-associated CNV (ie, type 1 CNV), similar to those observed in central serous chorioretinopathy. Accordingly, in case of serous macular detachment complicating dome-shaped macula, the presence of an associated CNV should be considered. When suspecting a CNV associated with dome-shaped macula, the application of both OCTA and FA±ICGA is superior to the use of one technique alone., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To describe the optical coherence tomography angiography (OCT-A) features of patients affected by acute macular neuroretinopathy (AMN)., Methods: This is a prospective, observational, cross-sectional study. Multimodal imaging, including spectral domain OCT (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) and 6×6 mm swept source OCT-A (ZEISS PLEX Elite 9000; ZEISS, Dublin, California), was performed on all patients. The primary outcome measure was assessment of the vascular alterations of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris (CC). A segmentation of the AMN lesions using enface OCT images of photoreceptors-retinal pigment epithelium complex was used to discriminate intralesional and extralesional regions on the OCT-A enface slabs of the DCP and CC reconstructions. Each OCT-A slab was imported into ImageJ V.1.50 and digitally binarised for quantitative analyses., Results: Overall, seven patients (mean age 19.4±3.2 years, six women) affected by AMN were included. The mean best-corrected visual acuity was 0.00±0.00 logarithm of the minimum angle of resolution. Twelve healthy age-matched subjects (mean age 22±3.4 years, 10 women) represented the control group. The quantitative analysis of global vessel densities showed that the CC vessel density was significantly lower in patients with AMN (0.495±0.03) compared with the age-matched controls (0.545±0.02) (corrected p=0.0003). The intralesional vessel density of the DCP was 0.349±0.04 in AMN and vs 0.497±0.02 in the controls (corrected p=0.0002)., Conclusions: Our study confirmed inner choroidal vascular flow void as a possible pathogenetic mechanism of AMN. We also found a focal impairment of the DCP within the AMN lesions. Future studies are needed to clarify which is the primary location of the vascular insult in this condition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To describe optical coherence tomography angiography (OCT-A) abnormalities of patients with pseudophakic cystoid macular oedema (PCMO) before and after pharmacological resolution, compared with diabetic macular oedema (DMO) and normal eyes., Methods: In this retrospective, observational study, 44 eyes (30 patients) were included: 15 eyes (15 patients) affected by PCMO; 14 healthy fellow eyes used as negative control group; 15 eyes (15 age-matched and sex-matched patients) with DMO used as positive control group. All patients underwent a complete ophthalmological examination at baseline, including OCT-A scans of the macula through AngioPlex CIRRUS-5000 (Carl Zeiss Meditec, Dublin, USA). Patients with PCMO and DMO were re-evaluated after the pharmacological resolution of cystoid macular oedema (CMO)., Results: Disruption of parafoveal capillary arcade and cystoid spaces in deep capillary plexus (DCP) were frequent in patients with PCMO and DMO (73% and 100%, 87% and 100%). Capillary abnormalities and non-perfusion greyish areas in DCP were more frequent in DMO (P<0.001 and P=0.014). Patients with PCMO showed a larger foveal avascular zone area in DCP at baseline (P<0.001), which significantly reduced after treatment (P=0.001). Vessel density of full-thickness retina and DCP was reduced in patients with PCMO (P=0.022 and P=0.001), and no changes were observed after treatment. Interestingly, DCP appeared less represented in patients with DMO than PCMO subjects (P=0.001)., Conclusions: Patients with PCMO have an impairment of mainly DCP, partially reversible after treatment. Furthermore, we disclosed that different alterations of the retinal vasculature characterise CMO derived from two different diseases, namely PCMO and DMO, and this could be due to their distinct pathophysiology., Competing Interests: Competing interests: RS, EC, AC, SM, LQ, AR: none declared. GM is the consultant for: Alcon (Fort Worth, Texas, USA), Allergan Inc (Irvine, California, USA), Bausch and Lomb (Rochester, New York, USA), Santen (Osaka, Japan). FB is the 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), NovagaliPharma (Évry, France), Novartis (Basel, Switzerland), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss (Dublin, USA) Giuseppe Querques 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)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To investigate the intraretinal structural and vascular alterations in patients featuring reticular pseudodrusen (RPD), RPD with outer retinal atrophy (ORA), and drusen., Design: Observational cross-sectional study., Methods: Clinical practice study including 68 eyes of 57 patients (22 eyes of 17 patients with RPD; 24 eyes of 21 patients with RPD+ORA; 22 eyes of 19 patients with drusen). Each patient underwent spectral-domain optical coherence tomography (OCT) and OCT angiography (OCT-A). Measurement of retinal layers' thickness was obtained by the automated segmentation protocol of the Spectralis OCT (Heidelberg Eye Explorer V.1.9.10.0). The superficial capillary plexus (SCP) and the deep capillary plexus (DCP) vessel density, as well as the size of the foveal avascular zone were calculated on 3×3 OCT-A. Main outcome was to compare vessel density at the SCP and DCP among the groups and controls., Results: At the SCP, the vessel density was lower in RPD and RPD+ORA patients with respect to controls (P=0.02 and P=0.003, respectively). At the DCP, meaningful disparity was found between the study groups and the healthy subjects in the vessel density (P<0.001, P=0.04 and P=0.001 for RPD, RDP+ORA and drusen, respectively). The ganglion cell layer (GCL) was thinner in all patients affected either by RPD, RPD+ORA or drusen compared with healthy subjects (P=0.02, P=0.03 and P=0.004, respectively)., Conclusion: Significant retinal vascular loss is a common feature of patients with non-exudative age-related macular degeneration, more pronounced in those featuring RPD and RPD+ORA. It is associated with retinal thinning, localised particularly at the GCL, compared with controls., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background/aims: To analyse choroidal vascular density of affected and non-affected areas in active and inactive serpiginouschoroiditis (SC) by means of optical coherence tomography angiography (OCT-A)., Methods: In this cross-sectional and observational study, 22 eyes of 11 patients diagnosed with SC were included. All patients underwent blue-light fundus autofluorescence (spectralis Heidelberg retinalangiography+OCT) and swept-source OCT-A (AngioPlex Elite 9000 SS-OCT, Carl Zeiss Meditech) to analyse qualitative features and choroidal vessel density of areas considered affected, and the inner and the outer border of the lesions. Unaffected areas of otherwise healthy retina have also been studied., Results: All inactive inflammatory lesions were characterised by atrophy of choriocapillaris with an impairment of its detectable flow and greater visibility of choroidal vessels. On the other hand, all active inflammatory lesions showed an area of complete absence of decorrelation signal. The pathological border was characterised by a statistically significant lower choroidal vessel density compared with both the outer border and the unaffected area (0.650±0.113 vs 0.698±0.112, (p<0.001)). Although not statistically significant, vessel density of the outer border of inactive lesions was lower than vessel density of unaffected areas (0.650±0.113 vs 0.698±0.112, p=0.441). Active inflammatory lesions showed an area of complete absence of decorrelation signal at the level of the choriocapillaris and whole choroid., Conclusion: OCT-A represents a new imaging technique that provides useful information about the leading changes of choroidal vascular network in active and inactive lesions of SC., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To analyse static characteristics and dynamic functionality of retinal vessels in eyes with central serous chorioretinopathy (CSCR) by means of Dynamic Vessel Analyzer (DVA)., Methods: Patients presenting with treatment-naïve CSCR and normal subjects (controls) matched for age and sex between May 2015 and November 2015 were enrolled in the study. Participants underwent a complete ophthalmological examination, including dynamic and static retinal vessels analysis by DVA., Results: A total of 28 eyes of 28 subjects (14 eyes for each group) were included in the analysis. Dynamic analysis during stimulation by flickering light showed mean venous dilation of 3.3%±2.0% in patients with CSCR and 5.5%±2.6% in controls (p=0.0258); mean arterial dilation did not differ between patients and controls (3.2%±2.5% and 4.2%±1.5%, p=0.2). No differences were reported at static retinal analysis between patients with CSCR and control subjects. Subfoveal choroidal thickness as evaluated by optical coherence tomography was 438.6±86.1 µm in CSCR eyes, significantly increased compared with control subjects (301.5±72.5 µm, p=0.0001)., Conclusions: Dynamic analysis revealed a reduced retinal venous dilation in response to flicker light stimulation in CSCR eyes. The decreased retinal vein response to flicker light stimulation, possibly due to increased sympathetic tone and potentially leading to venous stasis, together with the increased choroidal thickness may help understand CSCR and give insights in its pathogenesis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To analyse the effects of intravitreal dexamethasone implant in patients suffering from diabetic macular oedema (DME) on the basis of their visual and functional response to antivascular endothelial growth factor (VEGF) loading dose, in order to early shift to corticosteroids in poorly responding patients., Design: Retrospective monocentric study., Methods: Data of patients with diabetes shifted to 0.7 mg dexamethasone implant after three injections of ranibizumab (RNB) and followed-up to 12 months were reviewed. Main outcome was the evaluation of short-term changes after dexamethasone implant injection, stratifying patients on the basis of best-corrected visual acuity (BCVA) and central macular thickness (CMT) after RNB loading dose. Secondary outcome was to investigate clinical gain maintenance at long-term follow-up., Results: Overall, 45 eyes of 45 patients (23 males, 51.1%), mean age 69.7±9 years, were included in the analysis. After 3 injections of RNB, 30 eyes (66.7%) had a poor visual response (-4.3±10.7 letters), while 15 eyes (33.3%) disclosed good visual outcome (+13.9±9.2 letters). Patients with poor visual response were associated with limited morphological improvement (p=0.04). After 1 month from dexamethasone, only poor responders showed relevant increase in BCVA (p=0.006) and reduction in CMT (p=0.002), in comparison to good visual response patients, featuring only minor clinical effects (p=0.3). The same trend was maintained up to 12 months, after a mean of 1.9±1.1 dexamethasone administrations., Conclusion: Visual and anatomical responses after RNB loading dose are significant predictors of both early term and long-term visual acuity improvement after switching to corticosteroids in patients with DME unresponsive to anti-VEGF., Competing Interests: Competing interests: MVC, MC, LQ, AR: none; GQ consultant for Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California, USA), Heidelberg (Germany), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), Zeiss (Dublin, USA). Francesco Bandello consultant for Alcon (Fort Worth, Texas, USA), Alimera Sciences, Allergan, Farmila-Thea (Clermont-Ferrand, France), Bausch & Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (Évry, France), Novartis Bayer Shering-Pharma, Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee, Belgium), Zeiss, Pfizer (New York, USA), Santen (Osaka, Japan), Sifi (Aci Sant’Antonio, Italy)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: To describe the vascular changes in patients affected by non-neovascular age-related macular degeneration (AMD), featuring reticular pseudodrusen (RPD), drusen, or both RPD and drusen by means of optical coherence tomography angiography (OCT-A)., Methods: Cross-sectional observational case series. Patients with non-neovascular AMD presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Patients underwent best-corrected visual acuity, biomicroscopy, infrared reflectance, short-wavelength fundus autofluorescence and OCT-A (AngioPlex, CIRRUS HD-OCT 5000, Carl Zeiss Meditech, Dublin, USA). Main outcome was quantification of vessel density, stromal tissue, and vascular/stromal (V/S) ratio at the choriocapillaris (CC), the Sattler and Haller's and the whole choroid layers among different groups of patients with non-neovascular AMD by means of binarised OCT-A scans., Results: 45 eyes of 34 patients were enrolled (15 eyes of 11 patients with RPD, group 1; 15 eyes of 11 patients with drusen, group 2; 15 eyes of 12 patients with mixed phenotype, group 3). The CC, the Sattler and Haller's and the whole choroid vessel density were reduced in all groups of patients (p=0.023, p=0.007 and p=0.011 in group 1, group 2 and group 3 for the CC; p=0.021, p=0.037 and p=0.043 in group 1, group 2 and group 3 for the Sattler and Haller's density; p=0.016, p=0.002 and p<0.001 in group 1, group 2 and group 3 for the choroidal density), with significantly lower V/S ratios compared with healthy controls., Conclusions: Patients with non-neovascular AMD show significant choroidal vascular depletion and fibrotic replacement, suggesting a possible role in the pathogenesis and progression of the disease., Competing Interests: Competing interests: FB consultant for Alcon (Fort Worth,Texas,USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan Inc (Irvine, California,USA), Farmila-Thea (Clermont-Ferrand, France), Bausch And Lomb (Rochester, New York, USA), Genentech (San Francisco, California, USA), Hoffmann-La-Roche (Basel, Switzerland), Novagali Pharma (Évry, France), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), Sanofi-Aventis (Paris, France), Thrombogenics (Heverlee,Belgium), Zeiss (Dublin, USA), Pfizer (New York, USA), Santen (Osaka, Japan), Sifi (Aci Sant'Antonio, Italy). GQ consultant for: Alcon (Fort Worth, Texas, USA), Alimera Sciences (Alpharetta, Georgia, USA), Allergan (Irvine, California,USA), Bayer Shering-Pharma (Berlin, Germany), Bausch and Lomb (Rochester, New York, USA), Molecular partners (Zurich, Switzerland), Novartis (Basel, Switzerland), Ophthotech (New York, New York, USA), (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: To describe the vascular abnormalities in patients affected by Stargardt disease (STGD1) by means of optical coherence tomography angiography (OCT-A)., Methods: Cross-sectional case series, with the following inclusion criteria: diagnosis of STGD1, clear ocular media, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, applanation tonometry, short-wavelength fundus autofluorescence (SW-FAF) (HRA Heidelberg, Germany), 3×3 Swept Source OCT-A (Topcon Corporation, Japan). Foveal avascular zone (FAZ) area was manually outlined and removed from the vessel density analysis (ImageJ). Main outcome was vessel density assessment in the superficial capillary plexus (SCP), in the deep capillary plexus (DCP), and in the choriocapillaris (CC) of patients with STGD1., Results: Nineteen patients (36 eyes) were recruited for the study (10 females, 52.6%). Mean age was 33±5.7 years and mean BCVA was 0.6±0.3 logarithm of the minimum angle of resolution. Thirty-six healthy age-matched subjects (one eye for each patient) acted as a control group. Qualitative analysis of OCT-A revealed areas of reduced vascular density in superficial and DCPs. CC showed focal defects partially corresponding to the flecks on SW-FAF imaging. Quantitative analysis of OCT-A disclosed a statistically significant difference in the density of the SCP (0.302±0.062 vs 0.365±0.042; p=0.0002) and the DCP (0.303±0.081 vs 0.399±0.045; p<0.001) compared with controls. To analyse CC, patients with STGD1 were divided into two groups, according to the presence of chorioretinal atrophy. Patients with atrophy showed significantly lower CC density compared with controls (p=0.0003) and patients without atrophy (p=0.001). Patients with STGD1 showed a larger FAZ at the SCP level compared with controls (p=0.012)., Conclusions: Vascular impairment in patients affected by STGD1 is concentrated in superficial and the deep retinal plexuses. Patients with atrophic changes have a greater reduction in CC density compared with controls ('dark atrophy'). Morphological vascular evaluation may become an important step for predicting STGD1 treatment outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To investigate the possible differences in choroidal thickness (CT) between non-neovascular (NNV) and neovascular (NV) age-related macular degeneration (AMD)., Methods: A retrospective, observational chart review of consecutive patients diagnosed with NNV AMD in one eye and with NV AMD in the fellow eye was carried out. NNV AMD was classified into four subgroups according to the Beckman Initiative for Macular Research AMD Classification Committee Meeting. CT was manually assessed using enhanced depth imaging optical coherence tomography from 1500 µm nasal to 1500 µm temporal to the fovea. Parametric and non-parametric tests were used to compare quantitative variables, a χ 2 test was used to compare categorical variables and logistic regression was used to evaluate associations of CT with other variables of interest., Results: In this study, 322 eyes from 161 patients were included and 102 (63.35%) were female and 59 (36.65%) were male, with a mean age of 80.80±8.45 years (range 58-99 years). Mean follow-up was 11.2±10.8 months (range 1-38 months). In NNV AMD eyes, the choroid was significantly thicker in the subfoveal and temporal regions of the macula, if compared with NV AMD fellow eyes. Differences in CT between NNV AMD and NV AMD fellow eyes were higher at earlier stages of NNV AMD., Conclusions: Subfoveal and temporal choroid was significantly thicker in NNV AMD compared with NV AMD fellow eyes. There was a significant choroidal thinning at advanced stages of NNV AMD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: To evaluate the effects of dexamethasone implant in eyes affected by recalcitrant diabetic macular oedema (DME) associated with proliferative diabetic retinopathy (PDR)., Methods: Thirteen consecutive patients with centre-involving DME associated with PDR, central macular thickness (CMT) ≥300 µm, previous therapy with panretinal photocoagulation, focal/grid laser treatment and anti-vascular endothelial growth factor injection were prospectively enrolled. A complete ophthalmological examination included: best-corrected visual acuity (BCVA) assessment, spectral-domain optical coherence tomography and fluorescein angiography. After the first dexamethasone implant, each patient was evaluated on a bi-monthly basis and re-treated according to persistence/recurrence of DME from the fourth month on. Primary outcome measures were the changes in mean BCVA and CMT at the 12-month examination. Secondary outcome measures included changes to the outer retinal layers., Results: BCVA improved from 0.99±0.31 LogMAR (logarithm of the minimum angle of resolution; Snellen Equivalent: 20/196) to 0.77±0.25 LogMAR (Snellen Equivalent: 20/117) (p<0.001) at the 12-month examination. CMT passed from baseline value 510±169 µm to 423±171 µm (p=0.018) at 12 months. The data showed a significant improvement in the integrity of the external limiting membrane (ELM, p=0.02), the ellipsoid zone (EZ, p=0.025) and retinal pigment epithelium (RPE, p=0.008), significantly correlated with the upturn in BCVA., Conclusions: Dexamethasone implant results in a recovery of morphology of the outer retinal layers even in patients displaying a compromised clinical situation. The qualitative status of the ELM and EZ might provide prognostic value for the final visual acuity and disease regression., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background/aims: To describe the morphological features of choroidal neovascularisation (CNV) and to report the ability of optical coherence tomography angiography (OCT-A) to detect the presence of myopic CNV by means of this new technique., Methods: Myopic CNV cases were individuated from a pool of patients with pathological myopia consecutively presenting between October 2015 and March 2016. OCT-A images were assessed for classification of morphological features, and to estimate sensitivity and specificity., Results: Thirty-six eyes of 28 consecutive patients with myopic CNV were included. In 4 out of 36 eyes it was not possible to classify the CNV 'shape', 'core', 'margin' and 'appearance' because the vascular network was not clearly visualised due to the poor quality of the examination. CNV shape on OCT-A was rated as circular in 9 eyes and irregular in 23 eyes. CNV core was visible in 11 eyes. CNV margin was considered as well defined in 16 eyes and poorly defined in 16 eyes. CNV appearance showed an 'interlacing' aspect in 16 eyes and a 'tangled' aspect in the other 16 eyes. A total of 11 CNVs were defined as active, 9 of which (81.8%) were interlacing, while a total of 21 were inactive, 14 of which (66.7%) were tangled. OCT-A sensitivity turned out to be 90.48% and specificity was 93.75%., Conclusions: We describe the OCT-A features of myopic CNV secondary to pathological myopia and demonstrate its high sensitivity and specificity for neovascular detection. Qualitative evaluation of OCT-A characteristics may allow one to recognise different patterns, possibly corresponding to different degrees of neovascular activity., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Aims: To describe the vascular abnormalities in patients affected by retinitis pigmentosa (RP) by means of optical coherence tomography angiography (OCT-A)., Methods: Cross-sectional case series; patients with RP presenting at the Medical Retina Service of the Department of Ophthalmology, University Vita-Salute San Raffaele in Milan were recruited. Inclusion criteria were: diagnosis of RP, clear ocular media, adequate pupillary dilation, and stable fixation. Patients underwent best-corrected visual acuity (BCVA), biomicroscopy, short-wavelength fundus autofluorescence (SW-FAF), and 3×3 Swept Source OCT-A. 30 healthy subjects were chosen as controls. The main outcome was identification of abnormalities in density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), along with abnormalities of the choriocapillaris (CC)., Results: 16 patients (32 eyes) were recruited (6 females, 37.4%). Mean age was 53±18 years; mean BCVA was 0.5±0.3 LogMAR. Vessel density analysis disclosed a statistical significant difference in the SCP (29.5±6.8 vs 34.1±4.3; p=0.009) and in the DCP (28.7±7.5 vs 35.5±5.7; p=0.001) between the patients and the controls. No difference was found at the level of the CC (51±4.4 vs 51.3±2.2; p=0.716). RP patients showed a bigger foveal avascular zone at the DCP level compared to controls (p<0.001)., Conclusions: This study showed that most of the vascular impairment in patients affected by RP localised in the DCP, with relative sparing of the SCP and CC. DCP alterations were more pronounced outside the hyper-autofluorescent ring on SW-FAF. Vascular impairment may preclude good treatment outcomes in RP patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)