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

Purpose: To assess the rate and risk factors of cystoid macular edema (CME) both after isolated vitrectomy and after subsequent phacoemulsification in eyes with primary non-complicated rhegmatogenous retinal detachment (RRD) or idiopathic epiretinal membrane (ERM)., Methods: Retrospective observation of institutional patients undergoing vitrectomy for RRD or vitrectomy with internal limiting membrane peeling for ERM from 2016 to 2021, further analyzing those who later underwent phacoemulsification. The CME rate was assessed within the first 6 months after both vitrectomy and cataract surgery., Results: We included 187 phakic eyes with ERM and 311 with RRD undergoing isolated vitrectomy. Post-vitrectomy CME occurred in 12.8% of ERM cases compared to 1% in RRD cases (p<0.0001). Stage-4 ERMs and intraoperative laser were found associated with CME. After uncomplicated phacoemulsification, the CME rate was higher in eyes vitrectomized for ERM (13.8%) compared to RRD (2%, p=0.0055). Post-vitrectomy CME was found to be associated with an increased risk of post-cataract CME (OR 13.588, p=0.0187)., Conclusions: In eyes undergoing phacoemulsification post-vitrectomy, the risk of CME is higher when vitrectomy was performed for ERM compared to RRD. The ERM-related intraretinal changes, together with the required surgical stress, may play a role in making these eyes more susceptible to CME., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Objective: To characterize clinical and prognostic implications of leptovitelliform maculopathy (LVM), a distinctive phenotype of vitelliform lesion characterized by the coexistence of subretinal drusenoid deposits (SDDs) and leptochoroid., Design: Retrospective, cohort study., Subjects: The study compared patients affected by LVM with cohorts displaying a similar phenotypic spectrum. This included patients with acquired vitelliform lesions (AVLs) and those with SDDs alone., Methods: A total of 60 eyes of 60 patients were included, of which 20 eyes had LVM, 20 eyes had AVLs, and the remaining had SDDs. Patients >50 years of age with complete medical records and multimodal imaging for ≥6 months of follow-up, including color fundus photography or MultiColor imaging, OCT, fundus autofluorescence, and OCT angiography were included., Main Outcome Measures: Choroidal vascularity index (CVI); proportion of late-stage complications (macular neovascularization, atrophy)., Results: The AVL subgroup exhibited a significantly higher CVI compared with both LVM (P = 0.001) and SDD subgroups (P < 0.001). The proportion of late-stage complications significantly differed among subgroups (chi-square = 7.5, P = 0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, whereas the remaining eyes presented a similar proportion of complications, including 20% in the AVL group after 27.6 months and 20% in the SDD group after 36.9 months. Kaplan-Meier estimates of survival demonstrated a significant difference in atrophy development between groups (P < 0.001), with a median survival of 3.9 years for the LVM group and 7.1 years for controls. The presence of LVM correlated with a fourfold increase in the likelihood of developing complications., Conclusions: Leptovitelliform maculopathy, characterized by the association of vitelliform lesions with SDDs and leptochoroid, represents a distinct clinical phenotype in the broader spectrum of vitelliform lesions. The importance of a clinical distinction for these lesions is crucial due to their higher propensity for faster progression and elevated rate of complications, particularly atrophic conversion., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: Ashish Sharma; Consultant- Intas, Lupin, Bayer, Allergan, Novartis. Peter K Kaiser; Aerie, Allegro, Allergan, Allgenesis, Alzheon, Annexon Biosciences, AsclepiX, Aviceda, Bayer, Bausch and Lomb, Biogen Idec, Bionic Vision Technologies, Boehringer Ingelheim, Carl Zeiss Meditec, Clearside Biomedical, DelSiTech, DTx Pharma, Duet Therapeutics, Eyevensys, Galecto Biotech, Galimedix, Gemini Therapeutics, Glaukos, Innovent, iRenix, Iveric Bio, jCyte, Kanaph Therapeutics, Kanghong, Kodiak, LensGen, NGM Biopharmaceuticals, Inc., Novartis, Ocugenix, Oculis, Ocuphire, OcuTerra Therapeutics Inc., Omeros, Opthea, Oxurion, Palatin, Regeneron, RegenxBio, Retinal Sciences, Retrope, Roivant, Samsung Bioepis, Sandoz, Santen, Stealth Biotherapeutics, Sustained Nano Systems, Takeda, Théa, Ramin Tadayoni; AbbVie Allergan, Alcon, Apellis, Bayer, Boehringer Ingelheim, Genentech, Iveric Bio, KHB, Novartis, Oculis, Roche, Thea, Zeiss. Frank G Holz-F.G. Holz reports research grants and personal fees from Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, Roche/Genentech, Geuder, Heidelberg Engineering, ivericBio, Pixium Vision, Novartis, Zeiss; personal fees from Alexion, Grayburg Vision, LinBioscience, Stealth BioTherapeutics, Aerie, Oxurion. Luke Nicholson Optos (research funding), Bayer (Speaker fees), Abbvie (Speaker fees, advisory board), Roche (Speaker fees, Heidelberg (Speaker fees)). Clara Vazquez-Alfageme None. Sobha Sivaprasad- Dr Sivaprasad reported receiving financial support from AbbVie, Amgen, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Eyebiotech, Eyepoint Phamaceuticals, Janssen Pharmaceuticals, Nova Nordisk, Optos, Ocular Therapeutix, Kriya Therapeutics, OcuTerra, Roche, Stealth Biotherapeutics. Dr Sivaprasad is Editor in Chief of Eye. Taku Wakabayashi; None. Se Joon Woo- Dr Woo reported serving as a consultant for Samsung Bioepis and Panolos Bioscience; being cofounder of Retimark; serving as an advisory board member of Novartis and Novelty Nobility; receiving grants and personal fees from Samsung Bioepis, Novartis, Novelty Nobility, Alteogen, Kookje, and Curacle; and receiving lecture fees from Novartis, Bayer, Allergan, AbbVie, Alcon, Taejoon, SCAI Therapeutics, and Alteogen. David Sarraf; Amgen, Bayer, Endogena Therapeutics, Genentech, Iveric Bio, Novartis and Optovue/Visionix and receives research grants from Amgen, Boehringer, Genentech, Heidelberg, Optovue/Visionix, Regeneron, and Topcon. Nilesh Kumar; Lupin and Intas. Nikulaa Parachuri-None. Carl D Regillo-Adverum, Allergan, Annexon, Bausch and Lomb, Clearside, Eyepoint, Genentech/Roche, Iveric, Novartis, Kodiak, Notal, Merck, Ocular therapeutics, Regenxbio, Stealth, Takeda, Zeiss and receives research support from Adverum, Allergan, Annexon, Eyepoint, Genentech/Roche, Novartis, Kodiak, Iveric, Regenxbio, Regeneron. Kourous A Rezaei- Consultant for Alcon Laboratories. Arshad M Khanani- Consultant: Adverum, Aerpio, Alimera, Allergan, Apellis, Asclepix, Aviceda, Bausch and Lomb, Broadwing Bio, Chengdu Kanghong, Cholgene, 4DMT, Dutch Ophthalmic Research Center, Gemini, Genentech, Glaukos, Graybug, Gyroscope, Iveric Bio, Janssen, Kato Pharma, Kodiak, Oculis, Opthea, Oxurion, Novartis, Polyphotonix, Recens Medical, Regeneron, Retrotope, Regenxbio, Roche, Surrozen, Thea, Unity Bio Research Support: Adverum, Apellis, Asclepix, Chengdu Kanghong, 4DMT, Gemini, Genentech, Graybug Vision, Gyroscope, Iveric Bio, Kodiak, Neurotech, NGM Bio, Ocular Therapeutix, Oculis, Opthea, Oxurion, Novartis, Recens Medical, Regenxbio, Roche, Unity Bio Equity: Aviceda, Gyroscope, Recens Medical, Retrotope, PolyphotonixSpeaker: Allergan, Genentech, Novartis. Francesco Bandello; CONSULTANT: Allergan, Bayer, Boehringer- Ingelheim, FidiaSooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. Mahesh Shanamugam; None. Lalit Verma; Consultant to Novartis, Bayer, Intas. Mangat Ram Dogra; None. NS Muralidhar; None. Manisha Agarwal; None. Anat Loewenstein; CONSULTANT: Allergan, Novartis, Roche, Notal Vision, Fiorsightslabs, Beyeonics, Bayer Health Care. Baruch D Kuppermann CLINICAL RESEARCH: Alcon, Alimera, Allegro, Allergan, Apellis, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron, ThromboGenics; CONSULTANT: Alimera, Allegro, Allergan, Cell Care, Dose, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, jCyte, Novartis, Ophthotech, Regeneron, Revana, Theravance Biopharma, Dr Kuppermann acknowledges an unrestricted grant from Research to Prevent Blindness to the Gavin Herbert Eye Institute at the University of California, Irvine.

Purpose: Uveitis embraces a heterogeneous group of vision-threatening inflammatory conditions. Understanding uveitis epidemiology, etiology, and clinical findings is fundamental for a prompt diagnosis and optimal patient management. The aim of the study is to report the epidemiology of uveitis in a national referral center in Northern Italy and investigate the visual prognosis., Methods: This retrospective study was conducted at Uveitis Service (Ospedale San Raffaele) between June 2016 and May 2023. Demographic data, clinical characteristics, and etiological diagnoses of uveitis patients were collected, and visual prognosis was longitudinally explored., Results: 1105 patients with uveitis were included in the study, while 47 patients presented neoplastic masquerade syndrome and have been excluded. The population had a slight majority of females (M/F ratio = 0.76), mean age was 47 years. 25% presented infectious uveitis, primarily due to herpetic etiology, toxoplasmosis, and tuberculosis. Non-infectious uveitis was the most prevalent diagnosis (38%), with sarcoidosis, HLA-B27-associated uveitis, and Fuch's uveitis as prominent causes. Anatomically, anterior segment was most frequently involved (41%). Significant improvement in visual acuity was observed at follow-up, particularly in patients with infectious uveitis., Conclusions: Our study sheds light into the epidemiological landscape of uveitis in Northern Italy, reflecting changing patterns due to factors such as migration and changing sexual habits. In particular, higher percentages of syphilis have been observed, compared to other European reports. The distribution of non-infectious uveitis reflects other epidemiological European series. Higher percentages of neoplastic masquerade syndromes support the need of early recognition. Our findings offer precious insights for uveitis epidemiology and daily clinical practice.

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

Purpose: To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO)., Methods: This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up., Results: Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046)., Conclusions: Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO., Competing Interests: Competing interests: AS: consultant: for Novartis, Allergan, Bayer, Lupin, Intas, Biogen. TW: None. CDR- consultant: 4DMT, Adverum, Allergan, Annexon, Apellis, Aviceda, Bausch and Lomb, Boehringer-Ingelheim, Clearside, Eyepoint, Genentech/Roche, Iveric, Janssen, Kodiak, Merck, NGM, Novartis, Ocugen, Opthea, Regenxbio, Stealth, Thea, Zeiss and receives research support from 4DMT, Adverum, Allergan, Annexon, Apellis, Eyepoint, Genentech/Roche, Iveric, Janssen, Kodiak, NGM, Novartis, Ocugen, Opthea, Regenxbio, Regeneron. CMGC: Novartis, Bayer, Roche, Boehringer-Ingelheim, Topcon, Zeiss and Chui Ming Gemmy Cheung is a member of the Eye editorial board. AL reports other from Allergan, other from Novartis, other from Roche, other from Notal Vision, other from Forsightslabs, other from Beyeonics, other from Bayer Health Care. DZ: consultant for Novartis, Abbvie, Bayer and Roche. DG: None. AH: None. SO: consultant for Novartis, Allergan, Bayer, Bauch & Lomb. HBÖ: None. NP: None. NK: None. BDK: CLINICAL RESEARCH: Alcon, Alimera, Allegro, Allergan, Apellis, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron, ThromboGenics; consultant: Alimera, Allegro, Allergan, Cell Care, Dose, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, jCyte, Novartis, Ophthotech, Regeneron, Revana, Theravance Biopharma. FB: consultant: Allergan, Bayer, Boehringer- Ingelheim, FidiaSooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. GQ: consultant: Alimera Sciences, Allegro, Allergan Inc, Amgen, Bayer Shering-Pharma, Baush & Lomb, Boehringer-Ingelheim, CenterVue, Heidelberg, KBH, LEH Pharma, Lumithera, Nevacar, Novartis, Roche, Sandoz, Sifi, Sooft-Fidia, Topcon, Thea, Zeiss., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To differentiate intraretinal fluid (IRF) cysts from degenerative pseudocysts in neovascular age-related macular degeneration (AMD) by quantitative multimodal imaging., Design: Observational, cross-sectional., Participants: Patients affected by macular neovascularization secondary to AMD., Methods: All patients were analyzed by OCT, OCT angiography (OCTA), and dense automatic real-time (ART) OCTA. New-onset cysts were considered IRF, whereas those cysts that were found to be persistent for at least 3 months were categorized as degenerative pseudocysts. Intraretinal cysts were automatically segmented to calculate cyst circularity. Peri-cyst space was quantitatively analyzed to assess the presence of perfusion signal and hyperreflective foci (HF)., Main Outcome Measures: Best-corrected visual acuity, cyst circularity, peri-cyst perfusion, peri-cyst HF, fibrosis, and outer retinal atrophy., Results: We analyzed 387 cysts collected from 35 eyes of 35 patients with neovascular AMD (14 men; mean age, 80 ± 5 years). We classified 302 IRF cysts and 85 degenerative pseudocysts. Intraretinal fluid cysts were characterized by significantly higher circularity (0.86; range, 0.81-0.91), perfusion signal in the peri-cyst space, and peri-cyst HF in 89% of cases (all P < 0.05). Degenerative pseudocysts showed significantly lower circularity (0.68; range, 0.64-0.76), no perfusion signal in the peri-cyst space, and peri-cyst HF in only 29% of cases (all P < 0.05). The adopted quantitative metrics significantly correlated with disease duration, number of injections, fibrosis, and outer retinal atrophy., Conclusions: Intraretinal fluid cysts can be discriminated from degenerative pseudocysts using a quantitative multimodal imaging approach. These findings are clinically relevant and should be included in future training models for artificial intelligence algorithms to improve the diagnostic power and fluid monitoring in neovascular AMD., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Extensive macular atrophy with pseudodrusen-like appearance (EMAP) was first described in France in 2009 as a symmetric and rapidly progressive form of macular atrophy primarily affecting middle-aged individuals. Despite the recent identification of a significant number of cases in Italy and worldwide, EMAP remains an underrecognized condition. The clinical triad typical of EMAP consists of vertically oriented macular atrophy with multilobular borders, pseudodrusen-like deposits across the posterior pole and mid-periphery, and peripheral pavingstone degeneration. Nonetheless, recent research has portrayed EMAP as a highly stage-dependent condition, allowing the identification of novel disease hallmarks, including a diffuse separation between the Bruch's membrane and the retinal pigment epithelium, along with consistent sparing of a region temporal to the macula. Additionally, retinal electrophysiology is particularly useful in distinguishing EMAP from age-related macular degeneration (AMD). Supported by unpublished data from the largest EMAP cohorts worldwide, this review aims to provide a comprehensive and updated description of EMAP, now recognized as a severely blinding disease characterized by diffuse chorioretinal atrophy and photoreceptor dysfunction. Furthermore, we propose a set of diagnostic criteria that incorporate clinical, imaging, and functional tests, to facilitate the recognition of this clinical entity. Lastly, we aim to shed light on its pathogenesis by comparing it with AMD and monogenic retinal disorders exhibiting similar phenotypes., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To identify baseline optical coherence tomography (OCT) predictors of the 3-year macular atrophy (MA) development for type 3 macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD) treated by anti-VEGF therapy., Design: Multicenter, retrospective, longitudinal study., Participants: We included patients with treatment-naïve type 3 MNV secondary to nAMD at baseline, treated with anti-VEGF during a 3-year follow-up., Methods: Patients were identified from six retinal referral institutions: 1) San Raffaele University, Milan, Italy 2) University of Genova, Genova, Italy; 3) Doheny Eye Institute, Los Angeles, USA; 4) Stein Eye Institute, Los Angeles, USA; 5) University of Paris Est, Creteil, France; 6) IRCCS Bietti Foundation, Rome, Italy. Several baseline predictors of 3-year MA area were analyzed based on structural OCT and demographics., Main Outcome Measures: Multivariate analysis in order to identify baseline independent predictors of the 3-year MA development for type 3 MNV secondary to nAMD treated by anti-VEGF therapy., Results: We included 131 eyes of 131 patients (mean age 80±6-year-old, 81% females). Best-corrected visual acuity was 0.49±0.40 LogMAR at the baseline and significantly decreased to 0.59±0.43 LogMAR at the end of 3-year follow-up (p<0.001). Patients were treated with 11±6 anti-VEGF injections and developed atrophy in 75% of cases (from 18% at the baseline). Eyes that developed 3-year MA were treated with a significantly lower number of injections compared to eyes without MA (9.9±5.5 vs 14.7±7.2 injections, p<0.001). The most relevant independent predictors at baseline of MA area at 3-year follow-up were: area of MA at baseline (p<0.001), AMD phenotype (presence of reticular pseudodrusen) (p=0.017), baseline presence of nascent geographic atrophy (p=0.008), and the baseline presence of subretinal hyper-reflective material (p=0.002)., Conclusions: Macular atrophy development is a frequent complication of type 3 MNV treated with anti-VEGF injections. Several factors could be considered as baseline predictors of atrophy development during the anti-VEGF treatment., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target., Methods: This retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment., Results: Six eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported., Conclusion: PBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Federico Beretta, Ilaria Zucchiatti: none.Riccardo Sacconi is a consultant for: AbbVie (North Chicago, Illinois, USA), Bayer Shering-Pharma (Berlin, Germany), Carl Zeiss Meditec (Dublin, USA), Hoffmann-La-Roche (Basel, Switzerland), Novartis (Basel, Switzerland).Francesco Bandello is a consultant for: AbbVie (North Chicago, Illinois, USA), Alcon (Fort Worth,Texas,USA), Alimera Sciences (Alpharetta, Georgia, 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 is a consultant for: AbbVie (North Chicago, Illinois, USA), Alimera Sciences (Alpharetta, Georgia, USA), Amgen (Thousand Oaks, USA), Heidelberg (Germany), KBH (Chengdu, China), LEH Pharma (London, UK), Lumithera (Poulsbo, USA), Novartis (Basel, Switzerland), Bayer Shering-Pharma (Berlin, Germany), Sandoz (Berlin, Germany), Sifi (Catania, Italy), Soof-Fidia (Albano, Italy), Zeiss (Dublin, USA).

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM)., Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis., Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED., Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance., (© 2024. The Author(s).)

Purpose: To analyze the progression of structural and functional retinal impairment in type 1 diabetes mellitus (T1DM) patients with no clinical signs of diabetic retinopathy (DR) during a 3-year follow-up., Methods: This was an observational longitudinal study. Post-pediatric T1DM patients without clinical signs of DR, and sex- and age-matched healthy subjects were recruited at San Raffaele Hospital (Milan, Italy). Each patient underwent a comprehensive ophthalmological evaluation, including optical coherence tomography (OCT), OCT-angiography (OCT-A), retinal static and dynamic vessel analysis (DVA), and microperimetry., Results: 21 eyes of 21 T1DM patients (10 females; 24 ± 2 years old), and 21 age and sex-matched healthy subjects were enrolled. At baseline, T1DM eyes revealed a significantly decreased vessel length density using OCT-A (p < 0.001 and p = 0.046 in 3 × 3 and 6 × 6 mm images) and a significantly increased vessel density index (p = 0.013 and p = 0.087 in 3 × 3 and 6 × 6 mm images) of deep capillary plexus. DVA detected a significantly decreased vessel response to flicker light (p = 0.002). A significantly increased thickness of ganglion cellular layer 6-mm-diameter subfields in inferior and superior quadrants was found in diabetic patients (p < 0.001 in both subfields). At 3-years-follow-up no significant longitudinal changes were disclosed in all analyses., Conclusions: Concomitant subclinical microvascular and neurodegenerative damages could be early signs of DR onset that precede functional alterations and clinical signs of DR development. These alterations demonstrated a stable trend over time., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Purpose: To describe a phenotypical manifestation characterized by the identification of peripheral linear streaks associated with retinitis pigmentosa (RP)., Methods: Study design is a prospective observational case series. All consecutive patients affected by RP underwent a complete ophthalmological examination. The diagnosis of peripheral linear streaks was based on the identification of curvilinear atrophic streaks in the periphery of the retina., Results: Overall, six out of 140 patients (4.2%) were affected by peripheral linear streaks associated with RP. A single patient showed also punched out chorioretinal lesions at the posterior pole, with macular neovascularization development over the follow-up, treated with ranibizumab injections., Conclusions: RP phenotypical manifestation characterized by peripheral linear streaks is infrequent and may provide additional evidence to support the contribution of inflammation in the pathogenesis of RP., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: to evaluate long-term effectiveness and safety of fluocinolone acetonide (FAc) implant used as second-line treatment in patients with persistent diabetic macular edema (DME)., Methods: retrospective data chart review of 241 pseudophakic eyes of 178 patients treated with FAc from July 2017 to December 2021 in 10 medical retinal units in Italy. The primary endpoint was the change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) at 2 years. A Student's paired t-test was used. Additional therapies for DME and intraocular pressure (IOP)-related events were also evaluated., Results: efficacy of FAc was assessed in a subset of 111 eyes with at least 24 months of follow-up. Mean BCVA increased at 2 years by 5.1 ETDRS letters (95%CI = 2.6-7.5; p  < 0.001) while mean CMT decreased by 189 µm (95% CI 151-227; p  < 0.001). Thirty-eight of these eyes (34.2%) needed additional intravitreal treatments, mainly anti-VEGF. Safety was evaluated on the entire cohort of 241 eyes treated with FAc. Overall, 66 eyes (27.4%) required emergent IOP-lowering medications (typically within the first-year post FAc) while 14 eyes (5.8%) underwent trabeculectomy, mostly during the second year of follow-up., Conclusion: FAc implant provides a substantial long-term functional and anatomical benefit when used as second-line treatment in eyes with DME. IOP rise can be adequately managed with topical agents although some eyes may require IOP-lowering surgery., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To characterize acquired vitelliform lesions associated with leptochoroid (i.e., diffuse choroidal thinning) and reticular pseudodrusen (RPD) and compare this phenotype to the acquired vitelliform lesion (AVL) in the dystrophic spectrum., Methods: This retrospective, observational case-control study enrolled 56 patients (56 eyes) affected by vitelliform lesions (AVL), including 27 patients with AVL associated with RPD and leptochoroid (i.e., choroidal thinning) referred to as LeptoVitelliform Maculopathy (LVM), and 29 AVL patients without other funduscopic abnormalities. The main structural features analysed were the integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), the presence of hyporeflective spaces, and hypertransmission. Choroidal vascular index (CVI) was calculated using ImageJ software., Results: Patients with LVM were 6.69 years older and presented smaller vitelliform lesions considering both vertical (P < 0.001) and horizontal diameters (P < 0.001) with a similar visual impairment compared to the AVL group (P = 0.27). The LVM subgroup showed a greater alteration of the ELM (p < 0.001) and choroidal hypertransmission (i = 0.007), accompanied by less frequent RPE bumps (P = 0.001) and hyporeflective spaces within the vitelliform material (P = 0.002). Furthermore, the LVM group presented a lower CVI with a significant attenuation on both the luminal and stromal compartments compared to AVL (P < 0.001, both)., Conclusions: The phenotypic combination of subretinal vitelliform lesion and RPD may delineate a distinct phenotype that shares with AVL only the presence of vitelliform material and a similar visual deterioration. The presented findings of LVM highlight significant structural and microvascular alterations that may hold prognostic relevance, warranting future longitudinal studies., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Vitreoretinal lymphoma (VRL) is a rare lymphoma affecting the vitreous and the retina. Clinical diagnosis is challenging and often delayed and may lead to aggravated prognosis. This study aims to review multimodal imaging findings in VRL., Methods: We performed a comprehensive narrative review of the multimodal imaging findings that might be useful in the detection of VRL lesions., Results: The most frequent ocular manifestations of VRL are vitritis, and retinal and sub-retinal Pigmented Epithelium (RPE) infiltrations. Color Fundus Photography (CFP) detects vitreous haze, optic nerve, retinal and sub-RPE infiltration. Ultra-wide field imaging allows visualization of different patterns of vitreous haze and monitoring of VRL evolution through the detection of chorio-retinal atrophy (CRA). Fundus Autofluorescence shows granular hypo- and hyper-autofluorescent pattern. Optical Coherence Tomography (OCT) reveals vitreous cells, vertical hyper-reflective lesions and sub-RPE infiltrates. Fluorescein Angiography (FA) shows hypo or hyperfluorescent round lesions at the late stages of the examination, while Indocyanine Green Angiography (ICGA) detects round areas of focal hypo-fluorescence in the early phases that gradually enlarge in the late phases. B-scan ultrasonography detects vitreous opacities and homogeneous hyperreflective corpuscular material in the vitreous, and is a strongly recommended tool in suspecting VRL and is particularly useful when vitreous haze is impeding retinal examination., Conclusion: Diagnostic vitrectomy with cytopathological analysis remains the gold standard for VRL diagnosis, however multimodal imaging allows the identification of suggestive retinal and vitreal lesions for early suspicion, diagnosis, and treatment and monitoring disease progression and response to treatment.

Purpose: To report and characterize ocular features of asymptomatic vitreoretinal lymphoma (VRL) associated with primary central nervous system lymphoma (PCNSL), by examining clinical and multimodal imaging characteristics and comparing with symptomatic VRL., Design: Retrospective cross-sectional study., Methods: Patients with cytologically or molecularly confirmed VRL were included. Patients were classified into three groups: primary VRL (PVRL), symptomatic VRL associated with PCNSL (PCNSL-S), or asymptomatic VRL associated with PCNSL (PCNSL-AS). Data encompassing demographics, visual symptoms, visual acuity (VA), and imaging characteristics were collected. Cross-sectional analyses of quantitative and categorical variables among groups were performed with one-way ANOVA and multinomial linear regression analyses., Results: The study included 104 eyes from 56 patients with VRL. Twenty-nine patients (52%) were diagnosed with PVRL, and 27 patients (48%) were diagnosed with VRL associated with PCNSL. Among these, 17 (63%) reported visual symptoms (PCNSL-S), whereas 10 (37%) were asymptomatic (PCNSL-AS). PCNSL-AS patients exhibited better VA than PVRL patients (0.11 vs 0.76 LogMAR, P = 0.04) and distinct clinical features, with lower rates of anterior segment involvement (odds ratio [OR] = 0.02; 95% confidence interval [CI] 0.12-0.84; P < .01) and vitritis (OR = 0.32; 95% CI 0.11-0.91; P = .03). Subretinal infiltration was less common in PCNSL-AS cases compared to PVRL (OR = 0.14; 95% CI 0.02-1.11; P = 0.06) and PCNSL-S (OR: 0.08; 95% CI 0.01-0.69 P = 0.05) and was associated with worse VA (estimate = 0.55 LogMAR; 95% CI 0.29-0.8; P < .01)., Conclusions: This study describes distinctive clinical and imaging features of asymptomatic VRL associated with PCNSL, characterized by better VA and less severe ocular involvement. The findings highlight the pivotal role of multimodal imaging in facilitating early detection of VRL in the staging of PCNSL. Future guidelines for PCNSL management should consider the necessity of diagnosing patients with asymptomatic VRL., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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

Purpose: To characterize the features of a peculiar association between reticular pseudodrusen (RPD) and pachychoroid (pachy-RPD) and to compare them with eyes affected by RPD and normal/leptochoroid., Design: Observational, retrospective, case-control study., Participants: Among a cohort of patients with intermediate age-related macular degeneration (AMD), we selected eyes with RPD and pachychoroid (i.e., choroidal thickness of >50 μm). A control group of RPD eyes but without pachychoroid (i.e., a choroidal thickness of <250 μm) was included., Methods: Number and stages of RPD were evaluated in each ETDRS subfield. Furthermore, choroidal perfusion was investigated using the choroidal vascularity index (CVI), and choriocapillaris perfusion density (PD) on structural OCT and OCT angiography., Main Outcome Measures: Description of the multimodal imaging features of pachy-RPD and differences with RPD associated with normal/leptochoroid., Results: Among 111 RPD eyes, 37 were included in the pachy-RPD group and 74 in the control group. Patients with pachy-RPD were significantly younger than patients with RPD and normal/leptochoroid (mean age, 75 ± 16 and 82 ± 7 years, respectively; P = 0.002). Total RPD number was comparable between the 2 groups (P = 0.220). However, pachy-RPD eyes showed a significantly higher number of stage 1 RPD in comparison to the controls (P < 0.001), and a lower number of stage 3 (P < 0.001) and stage 4 RPD (P = 0.052). The CVI and choriocapillaris PD were greater in pachy-RPD than in the control group (P < 0.001 and P= 0.010, respectively)., Conclusions: Pachy-RPD are characterized by a different distribution of RPD stages (i.e., more early stages and fewer advanced stages) in comparison to RPD with normal/leptochoroid. Furthermore, pachy-RPD eyes showed greater perfusion indices of the choroid. These features suggest that the presence of pachychoroid could be a protective factor in the RPD evolution to the advanced AMD forms., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Retinal microaneurysms (MAs) are among the earliest signs of diabetic retinopathy (DR) and can be classified in several subtypes by non-invasive multimodal retinal imaging. The main aim of the present study is to characterize retinal MAs perfusion properties and their blood flow network connectivity by means of Dense Automatic-RealTime (DART) OCTA technology, checking the relationship with the multimodal retinal imaging classification and testing the clinical impact of DART., Methods: A cross-sectional, observational study setting was chosen. Multimodal retinal imaging included confocal multicolour, OCT, OCTA and DART OCTA. We classified retinal MAs accordingly with the recently proposed multimodal retinal imaging classification and we tested the role of DART OCTA for detecting retinal MAs blood flow network connectivity. We also tested the relationship with clinical parameters., Results: We included 206 retinal MAs of 36 DR eyes. We categorized retinal MAs as red (70; 34%), mixed (106; 51%) and green (30; 15%), corresponding to precise characteristics on structural OCT and both (regular) enface and DART OCTA images. The agreement between en-face and DART OCTA techniques for detecting MAs perfusion was very high (overall ICC 0.98; p < 0.01). However, DART OCTA provided clearer visualization than enface OCTA for detecting the blood flow network connectivity of retinal MAs, especially looking at the afferent and efferent MAs capillaries. Multimodal retinal imaging classification of retinal MAs provided significant correlations with DR duration, DR stage, and macular capillary non-perfusion., Conclusions: DART OCTA provided several new insights on retinal MAs characteristics and their blood flow network connectivity., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To report a case of multifocal vitelliform lesions in a patient affected by metabolic encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) with the m.3243A>G variant., Observations: A 37-year-old woman affected by MELAS was referred to our center for progressive vision deterioration. On fundus examination, she presented bilateral macular atrophy associated in the left eye with neurosensory detachment, along with several bilateral vitelliform lesions close to the vascular arcades. We describe the dynamic evolution of the vitelliform lesions, which could either enlarge and coalesce or undergo atrophic evolution., Conclusions: Mitochondrial retinopathy due to the m.3243A>G variant can be associated with multifocal vitelliform lesions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

Purpose: To explore changes in reticular pseudodrusen (RPD) number and location after the development of macular neovascularization (MNV) in eyes with prior intermediate age-related macular degeneration, focusing on different retinal regions differently affected by MNV., Methods: This retrospective longitudinal study included intermediate age-related macular degeneration eyes with RPD that developed MNV. Reticular pseudodrusen were assessed at baseline when MNV was diagnosed (MNV stage) and after anti-vascular endothelial growth factor treatment. Three regions of interest were considered: MNV area, subretinal fluid (SRF) area, and a marginal area of 1,000 µm around SRF (marginal zone). Reticular pseudodrusen counts were compared with age- and sex-matched control eyes with RPD that did not develop MNV., Results: Reticular pseudodrusen number exhibited a significant decrease after MNV development in the MNV area (P = 0.048) and in the area with SRF (P = 0.078). A statistically significant decrease was also disclosed in the marginal area around SRF (P = 0.002), associated with larger SRF areas. Control eyes did not show any significant change in the RPD count., Conclusion: Reticular pseudodrusen reduction after MNV development suggests a complex interplay involving the MNV itself, the presence of SRF, and trophic changes. The results of this study highlight the role of MNV in retinal nutritional balance and provide intriguing results in the RPD life cycle.

Purpose: This study aims to quantify the volume of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal pigment epithelium (sub-RPE) fluid in treatment-naïve Type 3 macular neovascularization (MNV) eyes with age-related macular degeneration (AMD) and to investigate the correlation of these fluid volumes with visual acuity (VA) outcomes at baseline and following antivascular endothelial growth factor (VEGF) treatment., Design: Retrospective, clinical cohort study., Methods: In this study, we analyzed patients diagnosed with exudative AMD and treatment-naïve Type 3 MNV undergoing a loading dose of anti-VEGF therapy. Using a validated deep-learning segmentation strategy, we processed optical coherence tomography (OCT) B-scans to segment and quantify IRF (i.e., both in the inner and outer retina), SRF, and sub-RPE fluid volumes at baseline. The study correlated baseline fluid volumes with baseline and short-term VA outcomes postloading dose of anti-VEGF injections., Results: Forty-six eyes from 46 patients were included in this study. Visual acuity was 0.51 ± 0.30 LogMAR at baseline and 0.33 ± 0.20 LogMAR after the loading dose of anti-VEGF (P = .001). Visual acuity at the follow-up visit was 0.40 ± 0.17 LogMAR in patients with no complete resolution of retinal fluid and 0.31 ± 0.20 LogMAR in eyes without retinal fluid after treatment (P = .225). In the multivariable analysis, the IRF volume in the inner retina (P = .032) and the distance of the MNV from the fovea (P = .037) were predictors of visual acuity at baseline. The baseline IRF volume in the inner retina also predicted the visual acuity at follow-up (P = .023)., Conclusion: The present study highlights the fluid volume in the inner retina as a crucial predictor of short-term visual outcomes in Type 3 MNV, underscoring the detrimental effect of IRF on neuroretinal structures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To provide an analysis of structural optical coherence tomography (OCT) and enface infrared reflectance (IR) differences between non-exudative macular neovascularizations (NE MNVs) secondary to age-related macular degeneration (AMD) and NE MNVs secondary to pachychoroid spectrum., Methods: Patients diagnosed with NE-MNV documented by OCTA and dye angiography in the context of either AMD or pachychoroid spectrum were retrospectively included in AMD group and PACHY group respectively. Only treatment-naïve NE MNVs showing persistence of non-exudative status for at least 1 year after diagnosis were considered. Availability of good quality structural OCT B scan and IR enface acquisitions both at baseline and at 1 year follow up was also required., Results: The study population included 15 eyes of 15 patients in AMD group and 13 eyes of 13 patients in PACHY group. AMD group showed at baseline a significantly wider pigment epithelium detachment (PED) apex angle (p = 0.02), higher homogeneity of the PED (p = 0.015), higher PED shadowing(p = 0.03). Both groups experienced a widening of apex angle (flattening of the PED) during follow-up. Ten (76.9%) patients in PACHY group showed a hyporeflective halo at the margins of the PED at baseline compared to 3/15 (20.0%) patients in AMD group (0.007), with no significant changes at 1 year follow up (p = 0.47)., Conclusion: NE-MNVs in pachychoroid eyes are characterized by sharper and more inhomogeneous PEDs with a lighter choroidal shadowing compared to NE-MNVs in AMD eyes. Moreover, they often show a hyporeflective halo around the lesion with IR imaging., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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.)

Purpose: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient., Case Description: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision., Discussion: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity., Conclusion: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To analyze the alterations at the level of the inner retina in patients affected by Stargardt disease (STGD1)., Methods: Cross-sectional investigation involving STGD1 patients with genetically confirmed diagnosis, who underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and microperimetry., Results: Overall, 31 patients (62 eyes) with genetically confirmed STGD1 were included in the study. Mean inner retinal thickness, vessel density of plexa, and retinal sensitivity resulted significantly reduced in STGD patients, compared with healthy controls ( p  < 0.05), both in the outer and in the inner ETDRS rings. Overall, 43% of eyes revealed an inner retinal thinning, whereas 21% and 35% showed a thicker or within normal range inner retina., Conclusions: Inner retina is irregularly altered in STGD1, showing variable quantitative alterations as detected on OCT. Inner retinal status might represent a useful biomarker to better characterize STGD1 and to ascertain the effects of new treatment approaches., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate the pathophysiology and prognostic significance of acute Henle fiber layer (HFL) hyperreflectivity in placoid diseases by examining its relationship with impaired choroidal flow and persistent photoreceptor disruption., Methods: Retrospective-prospective observational study on patients with placoid diseases. Indocyanine green angiography and optical coherence tomography were performed during the acute phase and follow-up. Impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption, their colocalization index, and their associations with initial and final visual acuity were explored., Results: Sixteen eyes from eight patients (mean age, 25.3 ± 6.44 years) were included (median follow-up, 13.5 months). Quantitative analysis revealed significant correlations between areas of impaired choroidal flow, HFL hyperreflectivity, and persistent ellipsoid zone disruption (correlation coefficients of 0.69, 0.63, and 0.46, respectively). Impaired choroidal flow area exceeded HFL hyperreflectivity (P = 0.002) and ellipsoid zone disruption (P = 0.003). A noteworthy 94% nonrandom overlap between HFL hyperreflectivity and ellipsoid zone disruption was observed. Worse initial visual acuity correlated with foveal involvement (P = 0.0002), thicker choroid (P = 0.001), larger impaired choroidal flow areas (P = 0.02), and thinner outer retina post lesion inactivation (P = 0.04)., Conclusion: Henle fiber layer hyperreflectivity predicted photoreceptor recovery potential in placoid diseases. If HFL hyperreflectivity corresponds to acute HFL damage, it may suggest more severe involvement of the entire photoreceptor length.

Purpose: To compare the clinical implications of central bouquet hemorrhages (CBHs) to primarily subretinal hemorrhages, both occurring in the setting of pathologic myopia with lacquer crack formation., Design: Multicenter retrospective cohort study., Participants: Twenty-five eyes (11 primarily subretinal hemorrhages and 14 CBH) were monitored over a median of 35 (interquartile range [IQR], 9.50-54) months., Main Outcomes Measures: Comprehensive ophthalmic examinations and OCT were reviewed. The study employed linear mixed-effects models to compare the impact of CBH versus primarily subretinal hemorrhages on baseline visual acuity (VA), rate of VA improvement, and final VA, adjusting for the follow-up period. Times of hemorrhages reabsorbtion and rate of ellipsoid zone (EZ) layer disruption on OCT were recorded., Results: Eyes with CBH exhibited significantly worse baseline VA (0.93 ± 0.45 logarithm of the minimum angle of resolution [logMAR]; 20/160 Snellen vs. 0.36 ± 0.26 logMAR [20/50 Snellen], P < 0.001), a slower rate of VA improvement (P = 0.04), and a trend toward worse final VA (0.48 ± 0.47 logMAR [20/60 Snellen] vs. 0.16 ± 0.16 logMAR [20/30 Snellen], P = 0.06) compared with eyes with primarily subretinal hemorrhages. The CBH group experienced longer median reabsorption times (10 [IQR, 4.6-23.3] months vs. 2.3 [IQR, 2-3.2] months), and a higher prevalence of EZ layer disruption (86% vs. 0%), than the group with primarily subretinal hemorrhages. Central bouquet hemorrhage reabsorption was followed by the appearance of vertical hyperreflective lines in the central fovea in 67% of eyes, persisting for up to 6 years of follow-up., Conclusions: Central bouquet hemorrhage signifies a distinct condition in pathologic myopia, characterized by worse visual outcomes, prolonged structural impact, and possible irreversible damage, compared with primarily subretinal hemorrhages. Central bouquet hemorrhage regression should be taken into account in the differential diagnosis of vertical hyperreflective lesions in the central fovea on OCT in eyes with pathologic myopia., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the clinical and multimodal imaging features of sympathetic ophthalmia in the acute and chronic phases., Methods: Retrospective cohort study of consecutive patients with sympathetic ophthalmia seen at a tertiary referral center. Charts, imaging studies, and histopathological specimens were reviewed. The clinical features and multimodal imaging in the sympathizing eye were analyzed by sorting features into those seen in the acute and chronic phase., Results: Ten patients were included in the analysis and all of them had previous ocular trauma or complicated retinal detachment. In the acute phase, 70% had anterior uveitis, 70% had vitritis, and 100% had active posterior uveitis; posterior uveitis included multifocal choroiditis (80%), optic disc swelling (40%), multiple serous retinal detachments (20%), MEWDS-like findings (10%), and retinal vasculitis with chorioretinitis (10%). In the chronic phase, posterior manifestations included widespread patches of chorioretinal atrophy in the mid- and far-periphery (80%), peripapillary subretinal fibrosis (50%), and nummular perivascular atrophy (50%)., Conclusions: Sympathetic ophthalmia shows different posterior segment manifestations in the acute and chronic phase. Active sympathetic ophthalmia should be ruled out in eyes with a MEWDS-like presentation or rapidly progressing chorioretinitis, and history of trauma in the fellow eye. Peripapillary subretinal fibrosis and perivascular nummular atrophy may be useful features to suspect SO once acute inflammation has resolved.

There is a lack of knowledge about the effect of flavanols-rich dark chocolate intake on the anatomy and functionality of retinal vessels. The aim of this study prospective, randomized, blind, crossover clinical trial (ClinicalTrials.gov Identifier: NCT05227248, 07/02/2022) was to evaluate the effect of dark-chocolate intake on the functionality and anatomy of the retinal vessels in healthy subjects using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCT-A). Twenty eyes of 20 healthy subjects (mean age, 24.4 ± 1.6 years; 12 females) were enrolled. Participants were randomized to consume 20 g of dark chocolate or 7.5 g of milk chocolate. Visual function, DVA and OCT-A parameters were evaluated before chocolate consumption and two hours later. One week later, the same participants were tested before and after consuming the opposite chocolate. Using OCT-A, no differences were disclosed in terms of perfusion density changes after dark-chocolate and milk-chocolate intake analyzing all chorioretinal plexuses (p > 0.09 in all analyses). Using DVA, a significant increase in the arterial dilation percentage after flicker stimulation was disclosed comparing baseline (2.750 ± 2.054%) with values after the dark chocolate intake (4.145 ± 3.055%, p = 0.016). This difference was not disclosed after the milk chocolate intake (p = 0.465). We disclosed that a reasonable amount of flavanols-rich chocolate in healthy subjects has benefic functional short-term effects in retinal vessels measured with DVA. This suggests a potential role of dark chocolate intake on retinal vessels. Further studies with long-term follow-up are warranted to show if the chronic assumption of dark chocolate could play a favorable role in the prevention of retinal diseases., (© 2024. The Author(s).)

Purpose: To report a challenging case of corneal descemetocele following Nd:YAG laser capsulotomy for posterior capsule opacification in a patient with Steven Johnson syndrome (SJS)., Observations: A single-eye 52 year-old man, with a history of Steven Johnson syndrome, presented with severe eye pain and profound vision reduction in his left eye two days after undergoing Nd:YAG laser capsulotomy using the standard Abraham contact lens. A corneal descemetocele was identified and subsequently confirmed by anterior segment optical coherence tomography. He was promptly treated with the application of a therapeutic contact lens and sustained antibiotic regimen (preservative-free fluoroquinolone drops every 4 hours for 6 weeks) until healing of the corneal epithelium. Throughout the following eight weeks AS-OCT showed favorable anatomical and functional outcomes, achieving a substantial spontaneous healing., Conclusions and Importance: Corneal descemetocele may occur after Nd:YAG laser capsulotomy in patients with Steven Johnson syndrome. This case strengthens the critical importance of a careful preoperative assessment and meticulous postoperative management in high-risk patients, such as those with Steven Johnson syndrome, even after seemingly routine and safe ophthalmic procedures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

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

Non-exudative choroidal and/or macular neovascularizations (NV) represent nowadays a common finding in different retinal disorders. The introduction of non-invasive techniques such as structural optical coherence tomography (OCT) and OCT angiography (OCTA) allowed for easy detection and follow-up of non-exudative NVs. Recognized as a distinct entity, these lesions demonstrate a high variability in terms of pathophysiology, morphology, and prognostic implications. In the absence of a consensus regarding correct classification of subtypes of non-exudative NVs, accurate management through strict follow-up strategies and prompt treatment is required. In this review we offer a comprehensive overview of the non-exudative NV spectrum in various retinal diseases aiming to provide a deeper insight into this clinical entity., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: This study aimed to delineate the characteristics, prevalence, and outcomes of neovascularization (NV), particularly aneurysmal type 1 NV, in patients with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE), and to introduce a clinical classification based on multimodal imaging., Design: Retrospective longitudinal cohort study., Participants: Eighty-five patients (168 eyes) with AS secondary to PXE at 2 tertiary referral centers., Methods: Data collection included demographic, medical, and ocular histories. Diagnostic methods comprised fundus photography, autofluorescence, indocyanine green angiography, OCT, and OCT angiography., Main Outcome Measures: Prevalence of type 1 NV, visual acuity (VA), risk of exudation., Results: Type 1 NV was identified in 127 eyes (76%), with 85 of these (67%) showing exclusively type 1 NV. These lesions often originated around the disc, at sites of Bruch membrane dehiscences, and followed the path of AS, extending to the macula in 101 eyes (80%). Despite 65% of type 1 NV remaining nonexudative, 35% evolved into exudative over 5 years, and 11 eyes experienced midperipheral subretinal hemorrhages. Aneurysmal dilations, observed in 57% of eyes, substantially increased exudation risk (hazard ratio = 3.86, P = 0.02). Despite treatment, VA significantly deteriorated in exudative type 1 NV (P = 0.02). Type 2 NV, detected in 42 eyes (33%), often coexisted with type 1 NV and was associated with poorer visual outcomes and higher rates of macular atrophy. A classification of AS was developed, ranging from empty AS (stage 0, no NV) to advanced NV (stage 3, both type 1 and type 2 NV)., Conclusions: Type 1 NV predominates in AS. Although predominantly nonexudative, its progression correlates with substantial visual impairment, similar to the deficits observed with type 2 NV. Aneurysmal type 1 NV poses a significant exudation risk, underscoring the need for vigilant monitoring., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to non-exudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment., Design: Retrospective, longitudinal cohort study., Methods: This study evaluated 80 eyes from 60 patients (mean age 74.2±10 years) with progressing non-neovascular AMD using blue-light fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). The study monitored the onset of foveal involvement and analyzed VA changes over an average follow-up of 60±26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomical changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomical changes were explored using generalized linear mixed-effects models., Results: VA declined consistently by an average of 0.010 LogMAR per month (SE: 0.0003, p<0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE: 0.02, p<0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (p<0.05). The most rapid declines in VA typically occurred about 9 months (IQR 0-27 months) prior to detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], p=0.02) and smaller baseline GA lesions (p=0.01) were associated with faster deterioration preceding visible foveal damage., Conclusion: This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with non-exudative AMD., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To assess the associations between visual acuity (VA) and retinal thickness in age-related macular degeneration (AMD) eyes treated with anti-vascular endothelial growth factor (VEGF) therapy., Methods: Sixty-eight patients with neovascular AMD (68 eyes) undergoing anti-VEGF therapy with two years of follow-up imaging data after the initiation of treatment were retrospectively included. Linear and nonlinear regression analyses with curve fitting estimation were performed to explore the relationship between visual acuity and OCT-based parameters at the 3-month and 24-month follow-up visits. Regression analyses were also performed between visual acuity and the retinal thickness deviation which was calculated as the absolute value of the difference between measured and normative retinal thickness values., Results: The VA was not associated with either foveal (R 2  = 0.011 and p  = .401 at 3 months; R 2  = 0.032 and p  = .142 at 24 months) or parafoveal (R 2  = 0.045 and p  = .081 at 3 months; R 2  = 0.050 and p  = .055 at 24 months) retinal thicknesses. Compared with the linear models, a quadratic function yielded a relative increase in the R 2 coefficients. Conversely, the VA was linearly associated with foveal retinal thickness deviation (R 2  = 0.041 and p  = .037 at 24 months) and parafoveal retinal thickness deviation (R 2  = 0.062 and p  = .040 at 3 months; R 2  = 0.088 and p  = .014 at 24 months) values., Conclusions: Although there was no linear relationship between retinal thickness and VA, a weak but statistically significant linear relationship could be observed when a retinal thickness deviation was considered. This suggests that deviation-based parameters may be beneficial for structure-function correlations in the context of anti-VEGF therapy for neovascular AMD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Limited data is available on treatment satisfaction with the management of wet age-related macular degeneration (wAMD) among patients in Italy. In this cross-sectional real-world study, treatment satisfaction with anti-vascular endothelial growth factor (anti-VEGFs) was assessed in patients with wAMD in Italy., Patients and Methods: This was a non-interventional, cross-sectional survey involving patients with wAMD receiving anti-VEGFs. The survey was administered through a virtual assistant via phone. Patients' treatment satisfaction was assessed using a newly developed Novartis Tailored Treatment Satisfaction Questionnaire (NVS TTSQ) and the validated Macular Disease Treatment Satisfaction Questionnaire (MacTSQ)., Results: Overall, 154 evaluable patients were enrolled in 5 centers across Italy. The mean (SD) age of the patients was 76.8 years (7.01). Overall treatment satisfaction score assessed by NVS TTSQ was 40.50 (7.11), with a mean of 9.97 (1.84) on the information domain and 22.98 (4.57) on the unmet need domain. Patients were satisfied with diagnosis communication (4.99 [1.30]), information provided on treatment administration (4.58 [1.49], range 0-6), the waiting room (4.40 [1.43]), and management of visits and injections at the center (5.14 [1.12]), general management of maculopathy at the center (5.22 [1.01]). Patients were not satisfied with their independence in terms of disease management (2.56 [2.45]); they would like additional information about the disease (5.38 [1.03]) and to discuss the injection procedures (4.02 [1.94]) with already-treated patients. The overall treatment satisfaction score on MacTSQ scale was 55.84 (10.13)., Conclusion: Patients with wAMD are satisfied with the overall management of their disease in Italy. However, patients would like to have more information on prognosis and management of the disease., Competing Interests: Enrico Peiretti is a scientific advisor for Bayer and Novartis. He received travel grants from Alcon, Baush and Lomb, Sifi, and Allergan. Chiara Ascardi, Marta Bartezaghi, and Lorenzo De Santi were full-time employees of Novartis Farma S.p.A., Milano, MI, Italy at the time of the study. Francesco Bandello is a consultant/advisor for Abbvie, Alimera, Bayer, Boehringer-Ingelheim, Fidia Sooft, Hofmann La Roche, Novartis, Ntc Pharma, Oxurion Nv, and Sifi. Francesco Boscia is a consultant/advisor for Alcon, Abbvie, Bayer, Novartis, Roche, and Zeiss. Monica Varano serves as an advisory board member of Abbvie, Astellas, Bayer, Biogen, Novartis, and Roche. Giovanni Staurenghi is a consultant/advisor for Abbvie, Apellis Pharmaceuticals, Inc., Annexon Bioscience, Bayer Healthcare Pharmaceuticals, Boehringer, Centervue, Inc., Genentech, Heidelberg Engineering, Hoffman La Roche, Ltd., Iveric Bio, Medscape, Novartis Pharmaceuticals, Optos, Inc., and RetinAI. He received grant support from Carl Zeiss Meditec, Centervue, Inc., Heidelberg Engineering, Hoffman La Roche, Ltd., Nidek, Inc., Novartis Pharmaceuticals, Optos, Inc., and RetinAI. He received lecture and speaker bureau fees from Carl Zeiss, Heidelberg Engineering, Hoffman La Roche, Ltd., Meditec, Nidek, Inc., and Novartis Pharmaceuticals. He also received patent royalties from Ocular Instruments Inc. The authors report no other conflicts of interest in this work., (© 2024 Peiretti et al.)

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with dry AMD (d-AMD) leading to geographic atrophy (GA) and significant visual impairment. Multimodal imaging plays a crucial role in d-AMD diagnosis and management, allowing for detailed classification of patient phenotypes and aiding in treatment planning and prognosis determination. Treatment approaches for d-AMD have recently witnessed profound change with the development of specific drugs targeting the complement cascade, with the first anticomplement agents recently approved for GA treatment. Additionally, emerging strategies such as gene therapy and laser treatments may offer potential benefits, though further research is needed to fully establish their efficacy. However, the lack of effective therapies capable of restoring damaged retinal cells remains a major challenge. In the future, genetic treatments aimed at preventing the progression of d-AMD may emerge as a powerful approach. Currently, however, their development is still in the early stages., (© 2024. The Author(s).)

Objective: This study was aimed primarily at describing the results of aqueous real-time polymerase chain reaction (RT-PCR) and reporting the rate of therapeutic modifications directly attributable to this procedure (profitability). Our secondary outcome was to compare demographic and clinical characteristics between patients with RT-PCR positivity and those with RT-PCR negative results., Design: Retrospective observational study conducted at the Uveitis Service of San Raffaele Hospital (Milan, Italy) between November 2016 and July 2022., Participants: Patients with infectious uveitis suspect (anterior, intermediate, posterior uveitis, or panuveitis)., Methods: Patients with suspected infectious uveitis underwent aqueous RT-PCR for detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), and Toxoplasma gondii., Results: Sixty-five eyes of 61 patients (60 ±16 years of age; 54% males) were included. Aqueous RT-PCR tested positive in 58% and negative in 42% of patients. CMV and HSV-1 were the most frequently detected pathogens. RT-PCR confirmed clinical suspicion in 38% of patients and altered the presumed etiologic diagnosis and treatment in 20% of patients. Profitability was associated with CMV positivity. HSV-1 positivity was related to iris atrophy. CMV positivity was correlated with keratic precipitates. Vitritis and retinitis were related to VZV, CMV, and T. gondii detection. Synechiae, retinitis, and neuritis were related to positive tests regardless of the pathogen investigated. Early complications related to paracentesis were rarely reported., Conclusion: Aqueous RT-PCR was a safe semi-invasive tool to confirm a presumptive diagnosis and to change initial suspicion in ambiguous cases of herpetic uveitis. Thus aqueous RT-PCR may alter therapeutic management., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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.)

Purpose: To evaluate the impact of optical coherence tomography phenotypes preceding atrophy related to age-related macular degeneration on the progression of atrophic lesions., Methods: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate age-related macular degeneration with a minimum follow-up of 24 months were included. The atrophy was quantified using fundus autofluorescence, also considering the directionality of atrophy as centrifugal and centripetal progression rates. The main outcome measures were geographic atrophy (GA) progression rate (mm 2 /year) and square root transformation of GA (mm 2 /year)., Results: The best-fit model for GA (odds ratio: 1.81, P < 0.001) and square root transformation of GA (odds ratio: 1.36, P < 0.001) areas revealed that the main baseline predictor was the presence of a retinal pigment epithelium-basal lamina-Bruch membrane splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (odds ratio: 0.52, P < 0.001) when considered with other confounders., Conclusion: A thin retinal pigment epithelium-basal lamina-Bruch membrane splitting without evidence of neovascularization on optical coherence tomography angiography likely represents an optical coherence tomography signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Pigmented paravenous chorioretinal atrophy (PPCRA) is an uncommon form of chorioretinal atrophy characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinal pigment epithelial atrophy that are distributed along the retinal veins. Most patients are asymptomatic, and evidence suggest that PPCRA is slowly progressing. Unless macular involvement is present, the majority of patients usually retain a normal visual function. Our ability to diagnose PPCRA has recently improved thanks to multimodal imaging, especially with the advent of ultra-widefield (UWF) imaging. Blood tests and functional and genetic testing can help with the correct differential diagnosis of pseudo-PPCRA or other disorders with similar characteristics. Although the cause of PPCRA is unknown, it is possible that it has a genetic basis. In this review we provide a summary of the multimodal imaging characteristics of PPCRA, and discuss its possible pathogenesis, based on the genes that have been associated with this disease.

Purpose: Our aim was to report a comprehensive multimodal imaging case of unilateral frosted branch angiitis in a 40-year-old White woman., Methods: Case report involving clinical examination, ultra-wide field fundus photograph, ultra-wide field fluorescein angiography, optical coherence tomography (OCT) and OCT angiography., Results: A 40-year-old patient presented with unilateral acute vision loss. On fundus examination, extensive retinal veins sheathing, macular edema, and vascular congestion were observed while ultra-wide field fluorescein angiography revealed a hyperfluorescent "hot" optic disc and blood retinal barrier disruption. Optical coherence tomography angiography displayed foveal avascular zone enlargement and excluded papillary neovascularization. Extensive laboratory workup for infectious, autoimmune, and inflammatory disorders was negative; thus, a diagnose of acute idiopathic unilateral frosted branch angiitis was made. Intravitreal injection of dexamethasone implant was administered with a good clinical response., Conclusion: Multimodal imaging is crucial to correctly diagnose and treat frosted branch angiitis. To the best of our knowledge, the use of optical coherence tomography angiography as a complementary tool to the diagnostic process in frosted branch angiitis has been described in literature just once as a photographic essay of cytomegalovirus-related frosted branch angiitis 1 and it might be of great value for better characterizing clinical features of this disorder and for following disease activity in a noninvasive fashion.

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