Background The purpose of this study was to define a minimum set of outcome measures for patients affected by non-advanced age-related macular degeneration (AMD).Methods A structured Delphi consensus process was conducted by a panel of worldwide experts in treatment outcome registries, imaging, nutrition and other AMD aspects. The experts answered anonymously to a series of surveys, each followed by a face-to-face meeting to discuss the pooled results. Supporting literature was shared among the group members by a facilitator before each round. Finally, all the results were discussed and the consensus document was created based on the level of agreement between experts.Results Six rounds were conducted until a formal consensus was achieved. Five main sections were identified: demographic characteristics, health factors, functional, imaging and clinical outcomes. A minimum set of 28 outcome measures was subsequently developed and approved by all members. Based on the priority of various items, 24 fields were designated as mandatory, while the remaining were deemed optional. Five items are required only at baseline, 12 are to be assessed annually for changes and the remaining 0 1must be collected at each clinical assessment.Conclusion This newly defined minimum set of outcome measures for non-advanced AMD could be employed in future real-world data collection registries aimed at gathering comprehensive and longitudinally extensive clinical data on a global scale. This may help to elucidate the natural progression of non-advanced AMD and its response to new therapies.

AIMS:To compare 1-year and 2-year outcomes of eyes with persistent and non-persistent diabetic macular oedema (DME) treated with vascular endothelial growth factor (VEGF) inhibitors. METHODS:This was a cohort study using the Fight Retinal Blindness! (FRB!) international outcomes registry. Participants had treatment-naïve eyes with centre-involving DME starting intravitreal VEGF inhibitor therapy from 2014 to 2023. Eyes were grouped as those with persistent DME and those with non-persistent DME. Main outcome measures were mean visual acuity (VA) change and central subfoveal thickness change after 1 and 2 years of treatment. RESULTS:This study included 877 eyes, of which 40% had persistent DME. The mean VA change in eyes with persistent DME was less than that in eyes with non-persistent DME at 1 (+3.6 vs. +6.5 letters; p<0.001) and 2 (+3.6 vs. +6.3 letters; p<0.001) years. The persistent group had a lower mean reduction in central subfield thickness at 1 (-74 vs -111 µm; p<0.001) and 2 (-90 vs -114 µm; p<0.001) years and received more mean injections at 1 (7.6 vs 6.5; p<0.001) and 2 (11.8 vs 9.5; p<0.001) years. CONCLUSION:Eyes with persistent DME had significantly lower improvement in mean VA, lower reduction in CST and more injections 1 and 2 years after the initiation of VEGF inhibitor therapy. Eyes with persistent DME likely had a higher treatment burden because they had more aggressive disease that was more difficult to control. More effective agents would likely deliver better outcomes in this significant group of patients with DME.

PURPOSE:To highlight the role of en face OCT in the measurement of choroidal hypertransmission defects (hyperTDs) in complete retinal pigment epithelial and outer retinal atrophy (cRORA), and to refine the definition of retinal pigment epithelium (RPE)-related alterations associated with cRORA. DESIGN:Consensus meeting. PARTICIPANTS:Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS:As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed the role of en face OCT in the assessment of cRORA. A structured study was conducted, consisting of an exercise to assess en face OCT cases, reviewed jointly during the eighth CAM meeting, and to explore the utility of this advanced tool for disease staging and progression. Additionally, definitions previously applied to RPE abnormalities were discussed and refined leading to modifications. The current report summarizes the methods used during the consensus meeting and the outcomes achieved as pertains to the application of en face OCT for cRORA grading and simplification of the RPE assessment criteria. MAIN OUTCOME MEASURES:Defining the role of en face OCT in the detection and quantification of hyperTDs, improving classification of cRORA, and refining the terminology related to RPE alterations to enhance grading consistency. RESULTS:During the consensus case discussions, high levels of agreement were achieved for hyperTD detection using en face OCT. The CAM group affirmed the role of en face OCT as a critical adjunct to traditional B-scan analysis, for more precise measurement of the area of cRORA lesions and for distinguishing threshold cRORA from smaller incomplete retinal pigment epithelial and outer retinal atrophy lesions. Additionally, merger of RPE attenuation and RPE disruption into a unified category termed "abnormal RPE band" significantly reduced interreader variability, leading to greater consistency among graders. CONCLUSIONS:The integration of en face OCT with cross sectional B-scan imaging enhances the accurate classification and area measurement of early atrophic alterations in age-related macular degeneration, improving diagnostic consistency and lesion assessment. The consensus panel's adoption of the abnormal RPE band term as a unified category for RPE abnormalities may reduce confusion regarding the definition of RPE degeneration and has the potential to improve interreader variability. FINANCIAL DISCLOSURE(S):The authors have no proprietary or commercial interest in any materials discussed in this article.

Background Whole blood viscoelastic tests (VETs) are key for detecting fibrinolysis during orthotopic liver transplantation (OLT). The Quantra System introduces a novel parameter, clot stability to lysis (CSL), for quantifying fibrinolysis. The objective was to assess CSL performance relative to established VET measures. Methods Data were drawn from a multicenter, prospective study of adults undergoing OLT, with Quantra and ROTEM delta testing performed in parallel. This sub-analysis focused on fibrinolysis-positive samples, emphasizing discordant findings between platforms. Results Among 125 enrolled patients, 13 intraoperative samples involving the use of heparin showed discordant results. Calibrated automated thrombinography revealed that Quantra reagents produce slower, reduced thrombin generation compared to ROTEM, diminishing thrombin activatable fibrinolysis inhibitor (TAFI) activity. This enhances sensitivity of Quantra to detect fibrinolysis in these samples. Conclusions Quantra's CSL parameter demonstrated improved detection of fibrinolysis in heparinized samples and may support individualized fibrinolysis management during OLT. Broader clinical validation is warranted.

To investigate the influence of macular drusen phenotypes on dark adaptation (DA) in intermediate age-related macular degeneration (iAMD). This cross-sectional, multicentric study enrolled 57 eyes of 43 iAMD patients. Drusen were subclassified as cuticular, soft, reticular pseudodrusen (RPD), or combined soft + RPD based on multimodal imaging. Dark adaptometry (AdaptDx; 20-minute test-time) assessed DA function through rod intercept time (RIT), last measured log sensitivity (LMLS; primary outcome) and area under the DA curve (AUDAC; secondary outcome). OCT volumes (30°x20° field) were analyzed using an AI-enhanced algorithm providing a quantification of chorioretinal layers and pigment epithelium detachments (PED) volumes. Multivariable tobit and linear regression analyzed associations between drusen phenotypes and DA outcomes. Drusen phenotype distribution was: cuticular 13 eyes (22.8

The treatment of diabetic macular oedema (DMO) likely involves a series of treatment episodes separated by gaps during which no vascular endothelial growth factor inhibitor injections are delivered. Our aim is to differentiate the episodes and gaps with the isolation forests algorithm using the Fight Retinal Blindness! registry. We analysed 11 786 injection intervals (12 803 injections) and found that the period between adjacent injections≥38 weeks (95% CI 34 to 43 weeks) apart could be regarded as a treatment gap. The results will allow treatment episodes to be isolated so that the treatment patterns of DMO can be characterised more accurately.

Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.

Purpose Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, particularly neovascular AMD (nAMD). This study aimed to investigate the real-world treatment patterns, effectiveness, and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies for anti-VEGF naïve nAMD patients in Italy. Methods RADIANCE is a retrospective, observational, multicenter cohort study conducted at 13 clinical sites across Italy. The study enrolled all consecutive patients with nAMD, naïve to any intraocular anti-VEGF treatment and who initiated therapy with aflibercept, ranibizumab, or bevacizumab between January 2017 and November 2018. The primary objective of this study was to evaluate changes in visual acuity (VA) 52 weeks after initiating treatment with anti-VEGF. Results A total of 405 patients were enrolled; of these, 263 patients had at least two VA measurements and were included in the completer analysis (CA) set. At 52 weeks, the median VA change from baseline in the CA set was +1 letter, with 41.1% showing ≥ 5-letter improvement. Stratified by anti-VEGF agent, no statistically significant differences were observed. Overall, patients received a median of 5.0 (25th–75th percentile 3–6) injections of the initial anti-VEGF agent during the first year. Patients receiving ≥ 6 injections in the first year showed better VA outcomes. Undertreatment was evident at decreasing injection frequency over time. Conclusion The results of the RADIANCE study suggest an overall moderate effectiveness after 1 year of treatment with anti-VEGF in naïve patients with nAMD in Italy. Real-world outcomes demonstrated suboptimal treatment with no significant differences among anti-VEGF agents.

Faricimab, a bispecific antibody targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A), introduces a novel therapeutic option for diabetic macular oedema (DMO) and neovascular age-related macular degeneration (nAMD). This consensus document, developed by an expert panel of Italian retina specialists, provides practical recommendations for the integration of faricimab into clinical practice. The panel reviewed pivotal clinical trials, YOSEMITE and RHINE for DMO and TENAYA and LUCERNE for nAMD, which demonstrated faricimab’s noninferiority to aflibercept in vision outcomes while offering extended dosing intervals up to 16 weeks. Key benefits include rapid and sustained fluid resolution, enhanced macular dryness, and reduced treatment burden for patients and healthcare systems. Recommendations cover treatment initiation, tailored management using treat-and-extend protocols, and strategies for switching from other anti-VEGF therapies. The consensus highlights faricimab’s potential to optimise outcomes for patients with DMO and nAMD while addressing real-world challenges, such as undertreatment and clinic resource constraints.

Purpose:To investigate whether consensus can be reached on the acceptability of end-stage atrophy onset as a clinical end point in early intervention trials of age-related macular degeneration (AMD), and the criteria for defining such an end point. Design:A modified Delphi study. Participants:International panel of experts in AMD, retinal imaging, and histopathology that are part of the Classification of Atrophy Meetings group. Methods:A modified Delphi study was undertaken to determine if there is consensus on the acceptability of the onset of end-stage atrophic AMD as a clinical end point to evaluate early interventions and the criteria for defining such an end point. Two initial rounds of online surveys were conducted. Aggregate results and anonymized comments were provided after each round, followed by a face-to-face meeting before a final survey round was completed. Main Outcome Measures:Statements where consensus was reached, defined as ≥80% of responses within the 3-point bracket for agreement or disagreement based on a 9-point Likert rating scale, from a total of 33 statements included in the final round of the survey. Results:Consensus was reached for the statement that the onset of end-stage atrophic AMD was an appropriate clinical end point to evaluate early interventions (82% responses in agreement). Consensus was also reached for the statement that such an end point should be defined based on anatomical changes that have been previously shown in clinical studies to be associated with marked, but not necessarily complete, functional loss (95% responses in agreement). Consensus was nearly reached for the specific criterion that ≥90% of such atrophic AMD lesions should have ≥1 test location that was ≤10 decibels on 2 microperimetry tests (77% responses in agreement). Conclusions:There was expert group consensus that the onset of end-stage atrophy is an appropriate clinical end point to evaluate early interventions in AMD, and that such an end point should show evidence of marked functional loss in prior clinical studies. We believe these findings will help to define incident clinical end points that are acceptable to regulatory authorities. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background:Trauma-induced coagulopathy (TIC) occurs in a quarter of trauma patients and is associated with death due to uncontrolled bleeding. Current guidelines recommend viscoelastic testing (VET) to assess coagulopathy and guide transfusions. The Quantra with the QStat Cartridge is a point-of-care (POC) VET device that measures changes in clot stiffness (CS) during coagulation and fibrinolysis using ultrasound detection of resonance. This study aimed to evaluate the performance of the QStat Cartridge in trauma patients compared with rotational thromboelastometry (ROTEM) delta and thromboelastography (TEG) 6s VET devices. Methods:A multicenter prospective observational study was conducted in adult patients meeting criteria for a full trauma team response at eight US level 1 trauma centers. Citrated blood samples drawn on arrival at the hospital or after blood transfusions were analyzed in parallel on QStat, ROTEM or TEG. Correlation between QStat and equivalent VET measurements was assessed by linear regression. Concordance was assessed by agreement of results relative to device-specific normal reference ranges. Results:259 severely injured patients were enrolled, yielding 271 samples for analysis. Moderate to strong correlations between QStat and corresponding ROTEM and TEG measurements were observed (r=0.64-0.88). The concordance between CS results was 84.5% for QStat CS and EXTEM A10 and 83.3% for CS and citrated rapid TEG maximum amplitude. For fibrinogen-related results, concordance was 81.5% for QStat fibrinogen contribution to clot stiffness (FCS) and FIBTEM A10 and 93.8% for FCS and citrated functional fibrinogen maximum amplitude. For fibrinolysis measurements, the overall agreement between QStat clot stability to lysis and EXTEM ML or CK-LY30 was 97.5% and 92.9%, respectively. Conclusion:QStat provides comparable information to the ROTEM delta and TEG 6s in trauma patients and can be useful for diagnosing TIC and guiding treatment. The Quantra's simplicity of use, ability to deploy at the POC, and rapid availability of results may provide clinicians with a faster, more convenient means to assess and manage TIC. Level of evidence:Diagnostic test, level II. Trial registration number:NCT04312958.

Purpose To report a possible association between paracentral acute middle maculopathy (PAMM) and hemodynamically significant patent foramen ovale (PFO), and to propose a cardiovascular screening strategy for patients with unexplained isolated PAMM. Design Retrospective multicenter case series. Methods Electronic medical records and multimodal retinal imaging findings of consecutive patients with PAMM and hemodynamically significant PFO presenting at Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico and Ophthalmic Hospital, ASST Fatebenefratelli Sacco between January 2019 and December 2024. Initial spectral domain optical coherence tomography (SD-OCT) showed a band-like hyperreflective lesion at the inner nuclear layer (INL) in all cases. Results A total of five patients (three males; mean age 62 years, range 54–71) with PAMM were found to have a hemodynamically significant PFO. Four out of five had isolated PAMM and were included in this series. In three cases the PFO was discovered after the cardiologist referral; one patient was known for PFO and Factor V Leiden mutation. In all cases PFO was the only embolic source identified after an extensive workup. Management included surgical or percutaneous closure or antithrombotic therapy. Over a mean 12-month follow-up (range: 6–21), SD-OCT showed progressive attenuation and thinning of the INL; visual acuity improved or remained stable. None of the patients experienced recurrent retinal or cerebral ischemic events during follow-up. Conclusions Our series suggests that isolated PAMM is possibly linked to hemodynamically significant PFO, supporting the need for a targeted cardiovascular assessment, including bubble contrast echocardiography.

To investigate the choroidal features associated with the presence of flat irregular pigment epithelium detachments (FIPEDs) in patients with previous diagnosis of chronic central serous chorioretinopathy (CSC). This was a retrospective multicentric study that analysed the medical records and imaging findings of 199 patients with treated and untreated, chronic CSC. The diagnosis was established by multimodal imaging. Eyes with macular FIPEDs, defined as an irregular elevation of the RPE under which the Bruch’s membrane (BM) could be evident on structural optical coherence tomography (OCT) cross-sectional B-scans, were enrolled. OCT images were graded for the presence of dilated Haller vessels (pachyvessels) “compressing” and attenuating choriocapillaris and Sattler layer thickness beneath the FIPED. The presence of macular neovascularisation (MNV) was determined using indocyanine green angiography (ICGA) or OCT angiography imaging. FIPEDs were categorised as vascular (vFIPED) if any MNV was present within the FIPED; otherwise, these were graded as avascular FIPED (aFIPED). 217 eyes of 199 patients with chronic CSC and macular FIPED on structural OCT cross-sectional B-scans were included in the study. The mean age was 57.9 ± 13.8 years, and 79.3

Purpose: To characterize, using clustering analysis, the OCT morphological and clinical phenotypes of diabetic macular edema (DME) in a very large population (>2000 DME eyes) using standardized and validated OCT-based biomarkers. Methods: A cross-sectional study was conducted on OCT scans collected from 2355 eyes of 1688 patients with DME and performed during real-world clinical practice. OCT scans were automatically analyzed by a software able to automatically quantify OCT key biomarkers: intraretinal fluid (IRF), subretinal fluid (SRF), hyperreflective retinal foci (I-HRF), and external limiting membrane (ELM) and ellipsoid zone (EZ) interruption. Clustering analysis was performed using the above-mentioned biomarkers, including the distribution of IRF across the three ETDRS rings. Results: The overall population was predominantly composed of type 2 diabetes patients (89%), with a mean diabetes duration of 15.6 ± 10.7 years and mean best corrected visual acuity (BCVA) of 63 ± 18 ETDRS letters. Multivariate clustering identified four morphological phenotypes with distinct patterns of fluid distribution associated with different I-HRF counts, SRF volume, and percentages of ELM/EZ integrity (p < 0.0001). Conclusions: This large OCT analysis identified distinct morphological subtypes of DME, confirming the clinical relevance of key imaging biomarkers. The distribution and severity of DME features differ among clusters, supporting the importance of OCT-based phenotyping in tailoring treatment strategies and understanding disease evolution.

BACKGROUND:To evaluate the 10-year cumulative incidence, progression rates, and risk factors for macular atrophy (MA) in neovascular age-related macular degeneration (nAMD) patients receiving long-term anti-vascular endothelial growth factor (VEGF) therapy. METHODS:Retrospective, multicenter, cohort study including 148 eyes from 140 nAMD patients treated with a pro-re-nata (PRN) anti-VEGF regimen and followed for ≥ 10 years. Annual multimodal imaging-including blue autofluorescence [BAF], spectral-domain optical coherence tomography [SD-OCT] and near-infrared reflectance-was reviewed to detect and quantify MA using RegionFinder. Kaplan-Meier analysis estimated cumulative MA incidence, while mixed-effects Cox and linear regressions identified risk factors and progression rates. RESULTS:Baseline MA prevalence was 23.0%, increasing to 64.9% at 5 years and 79.8% at 10 years. Foveal involvement occurred in 47.4% of cases. Significant predictors for MA included baseline BCVA < 20/40 (HR = 1.50, p = 0.02), greater central subfield thickness (CST) fluctuations (HR = 1.04, p = 0.01), and more frequent submacular haemorrhages (HR = 1.34, p = 0.04). Type 3 macular neovascularization was associated with fovea-involving MA (HR = 2.03, p = 0.02). Mean MA size increased from 0.34 to 2.27 mm at 10 years, progressing at 0.20 mm/year (β = 0.15, p < 0.001). Eyes with incident MA exhibited faster progression (β = 0.03, p = 0.01) and worse BCVA decline compared to those with baseline MA (-1.96 vs. -1.42 letters/year, p < 0.001). CONCLUSIONS:nAMD patients treated with PRN anti-VEGF therapy demonstrated a high 10-year cumulative incidence of MA (79.8%), with poor baseline BCVA and CST fluctuations as key risk factors. Eyes with incident MA progressed faster and were associated with greater visual decline, suggesting a more visually impactful atrophy.

PURPOSE:To describe a rare case of posterior ocular involvement consistent with an autoimmune retinopathy (AIR) on multimodal retinal imaging in a patient with common variable immunodeficiency (CVID). METHODS:Observational case report. RESULTS:A 34-year-old male patient with a recent diagnosis of CVID was referred to our clinic following the incidental finding of retinal lesions in his eyes. He was asymptomatic and his best-corrected visual acuity (BCVA) was 20/20 in both eyes. Multimodal retinal imaging including optical coherence tomography and fundus autofluorescence revealed peripapillary and mid-peripheral hyperautofluorescent lesions associated with outer nuclear layer thinning and ellipsoid/interdigitation zones disruption in both eyes.PET/CT imaging ruled out systemic inflammation or malignancy and a diagnosis of a possible non-paraneoplastic AIR was established.During follow-up BCVA was stable, the patient remained asymptomatic, and the retinal imaging findings showed no progression. At 12 months, the patient reported new-onset occasional photopsias described as "shimmering lights." Despite these symptoms, BCVA and retinal imaging remained stable. CONCLUSION:This case supports a potential association between CVID and immune-mediated retinal pathology, highlighting the importance of comprehensive ophthalmic evaluation and multimodal retinal imaging in CVID patients and further research into this association.

BACKGROUND:To compare conventional internal limiting membrane (ILM) peeling versus inverted flap technique in small idiopathic macular hole. METHODS:Retrospective, multicentre cohort study including consecutive eyes with a ≤250 μm idiopathic macular hole treated with primary vitrectomy. The primary outcome was best-corrected visual acuity (BCVA) change and macular hole closure rate. Closure patterns on optical coherence tomography (OCT) and rates of external limiting membrane (ELM) and ellipsoid zone (EZ) recovery were considered as secondary outcomes. RESULTS:A total of 389 and 250 eyes were included in the conventional ILM peeling group and in the inverted flap group, respectively. Hole closure rate was comparable between the two groups (98.5% in the ILM peeling group and 97.6% in the inverted flap group). Mean BCVA was comparable between the two groups at baseline (p = 0.331). At 12 months, mean BCVA was 0.14 ± 0.19 logMAR in the conventional ILM peeling group and 0.17 ± 0.18 logMAR in the inverted flap group (p = 0.08). At 12 months, 73% of eyes had a U-shape closure morphology in the conventional ILM peeling group versus 55% in the inverted flap group. At 12 months, ELM recovery rate was 96% and 86% in the conventional ILM peeling group and in the inverted flap group, respectively (p < 0.001); EZ recovery rate was 78% and 69%, respectively (p = 0.04). CONCLUSIONS:The inverted flap technique provides no advantages in terms of visual outcome and closure rate in small idiopathic macular hole surgery. Additionally, this technique seems to impair postoperative restoration of external retinal layers compared with conventional peeling.

OBJECTIVES:This independent prospective study evaluated the short-term effects and safety of photobiomodulation (PBM) in early and intermediate age-related macular degeneration. METHODS:patients were treated with PBM in one eye. Functional parameters and drusen volume were measured at one (W4), three- (W12) and six-months (W24) after PBM. RESULTS:The study included 38 subjects who completed the PBM protocol. Two patients developed macular neovascularization during the study period. Best corrected visual acuity improved from 77.82 ± 5.83 ETDRS letters at baseline to 82.44 ± 5.67 at W12 (p < 0.01), then declined to 80.05 ± 5.79 at W24 (p < 0.01 vs. baseline). Low luminance visual acuity showed a similar pattern, improving from 61.18 ± 8.58 ETDRS letters at baseline to 66.33 ± 8.55 at W12 (p < 0.01), and decreasing to 62.05 ± 9.71 at W24 (p = 0.02). Contrast sensitivity improved at W12 (20.11 ± 9.23 ETDRS letters, p < 0.01), but returned to baseline by W24 (16.45 ± 9.12, p = 0.5). Scotopic microperimetry showed a decrease in mean absolute retinal sensitivity from 9.24 ± 3.44 dB to 7.47 ± 4.41 dB at W24 (p < 0.01), while relative sensitivity decreased only at W24 (p = 0.04). Drusen volume decreased at W4 (0.018 ± 0.009 mm3, p < 0.01) and W12 (0.017 ± 0.009 mm3, p < 0.01), with a slight increase at W24 (0.019 ± 0.012 mm3, p = 0.154). CONCLUSIONS:PBM resulted in temporary improvements in visual function and a reduction in drusen volume, but these effects were not sustained at six months. The long-term efficacy and impact on disease progression are uncertain, necessitating further research to confirm these findings and determine optimal patient selection.