Advancements in Imaging and Therapeutic Options for Dry Age-Related Macular Degeneration and Geographic Atrophy.

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.

Pachy-Reticular Pseudodrusen.

PURPOSE: To characterize the features of a peculiar association between reticular pseudodrusen (RPD) and pachychoroid (namely "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 intermediate age-related macular degeneration (AMD) population, we selected eyes with RPD and pachychoroid (i.e. choroidal thickness > 250 µm). A control group of RPD eyes but without pachychoroid (i.e. a choroidal < 250 µm) was included. METHODS: Number and stages of RPD were evaluated in each ETDRS subfield. Furthermore, choroidal perfusion was investigated using choroidal vascularity index (CVI), and choriocapillaris perfusion density (PD) on structural optical coherence tomography (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. Pachy-RPD patients were significantly younger than patients with RPD and normal/leptochoroid (mean age 75±16 and 82±7-year-old, respectively)(p=0.002). Total RPD number was comparable between the two 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 lower advanced stages) in comparison to RPD in normal/leptochoroid. Furthermore, pachy-RPD eyes showed greater perfusion indexes 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.

International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

Structural and functional characterization of retinal impairment in T1DM patients without diabetic retinopathy: a 3-year longitudinal study.

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.

Peripapillary pachychoroid syndrome treated with dexamethasone implant: A case report.

PURPOSE: To describe a case of peripapillary pachychoroid syndrome (PPS) in a diabetic patient with cystoid macular edema (CME), treated with intravitreal dexamethasone implant (IDI) injection. This report also illustrates the history of the disease after repeated IDI and dexamethasone topical treatment. METHODS: A case report. RESULTS: A 77-year old male patient with PPS and good diabetic control was treated with dexamethasone implant for CME. After an initial morphofunctional improvement associated with a first IDI, the disease relapsed after the second dexamethasone implant injection. This was associated with a significant increase in both intraretinal fluid and choroidal thickness, with subsequent visual acuity (VA) decrease. At this point, a topical dexamethasone treatment was performed and, despite a morphological improvement, VA worsened compared with baseline, likely because of anatomical damage. CONCLUSION: In this report, the importance of the recognition of PPS is underlined and the possible occurrence of a "rebound" effect due to repeated IDI is described.

Deep learning for automatic prediction of early activation of treatment naïve non-exudative MNVs in AMD.

BACKGROUND: Around 30% of non-exudative macular neovascularizations(NE-MNVs) exudate within 2 years from diagnosis in patients with age-related macular degeneration(AMD).The aim of the study is to develop a deep learning classifier based on optical coherence tomography(OCT) and OCT angiography(OCTA) to identify NE-MNVs at risk of exudation. METHODS: AMD patients showing OCTA and fluorescein angiography (FA) documented NE-MNV with a 2-years minimum imaging follow-up were retrospectively selected. Patients showing OCT B-scan-documented MNV exudation within the first 2 years formed the EX-GROUP while the others formed QU-GROUP.ResNet-101, Inception-ResNet-v2 and DenseNet-201 were independently trained on OCTA and OCT B-scan images. Combinations of the 6 models were evaluated with major and soft voting techniques. RESULTS: Eighty-nine (89) eyes of 89 patients with a follow-up of 5.7 ± 1.5 years were recruited(35 EX GROUP and 54 QU GROUP). Inception-ResNet-v2 was the best performing among the 3 single convolutional neural networks(CNNs).The major voting model resulting from the association of the 3 different CNNs resulted in improvement of performance both for OCTA and OCT B-scan (both significantly higher than human graders' performance). Soft voting model resulting from the combination of OCTA and OCT B-scan based major voting models showed a testing accuracy of 94.4%. Peripheral arcades and large vessels on OCTA enface imaging were more prevalent in QU GROUP. CONCLUSIONS: Artificial intelligence shows high performances in identifications of NE-MNVs at risk for exudation within the first 2 years of follow up, allowing better customization of follow up timing and avoiding treatment delay. Better results are obtained with the combination of OCTA and OCT B-scan image analysis.

Phenotypic characterization of predictors for development and progression of geographic atrophy using optical coherence tomography.

PURPOSE: To evaluate the impact of optical coherence tomography (OCT) phenotypes preceding atrophy related to age-related macular degeneration (AMD) on the progression of atrophic lesions. METHODS: In this observational retrospective cohort study, a total of 70 eyes of 60 consecutive patients with intermediate AMD 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.Main outcome measures were geographic atrophy (GA) progression rate (mm2/year) and square root-transformation GA (mm2/year). RESULTS: The best-fit model for GA (OR: 1.81, p<0.001) and square root-transformation GA (OR: 1.36, p<0.001) areas revealed that the main baseline predictor was the presence of an RPE-basal lamina-(BL)-Bruch's membrane (BrM) splitting. Large drusen at baseline appeared protective for the GA area lesion expansion over time (OR: 0.52, p<0.001) when considered with other confounders. CONCLUSION: A thin RPE-BL-BrM splitting without evidence of neovascularization on OCT angiography likely represents an OCT signature for late basal laminar deposits. Identifying this phenotype can help identify individuals with a higher risk of rapid progression and atrophy expansion.

Artificial intelligence in age-related macular degeneration: state of the art and recent updates.

Age related macular degeneration (AMD) represents a leading cause of vision loss and it is expected to affect 288 million people by 2040. During the last decade, machine learning technologies have shown great potential to revolutionize clinical management of AMD and support research for a better understanding of the disease. The aim of this review is to provide a panoramic description of all the applications of AI to AMD management and screening that have been analyzed in recent past literature. Deep learning (DL) can be effectively used to diagnose AMD, to predict short term risk of exudation and need for injections within the next 2 years. Moreover, DL technology has the potential to customize anti-VEGF treatment choice with a higher accuracy than expert human experts. In addition, accurate prediction of VA response to treatment can be provided to the patients with the use of ML models, which could considerably increase patients' compliance to treatment in favorable cases. Lastly, AI, especially in the form of DL, can effectively predict conversion to GA in 12 months and also suggest new biomarkers of conversion with an innovative reverse engineering approach.

Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.

INTRODUCTION: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up. METHODS: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed. RESULTS: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6 years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6 years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001). CONCLUSIONS: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

OCT angiography 2023 update: focus on diabetic retinopathy.

Optical coherence tomography angiography (OCTA) has become part of the clinical practice and its growing applications are in continuous development. Coherently with the growing concern about the human and economic cost of diabetes, diabetic retinopathy (DR) was the most popular topic for OCTA studies in the past year. The analysis of the literature reveals that applications of OCTA in DR are in continuous growth. In particular, ultrawide field (UWF) OCTA and artificial intelligence (AI) based on OCTA images are affirming as the new frontiers of scientific research in the field. Diagnostic accuracy of AI methods based on OCTA is equal or superior to the one based on OCT methods and also bears potential to detect systemic associations. UWF OCTA is noninvasive method that is reaching similar accuracy of FA in detection of neovascularization and intraretinal microvascular abnormalities (IRMAs) and has allowed better characterization of microvascular peripherical changes in DR. Lastly, deep capillary plexus (DCP) characteristics seem to play a pivotal role in the development of diabetic macular edema (DME) and refinement of biomarkers for different phenotypes of DME and diabetic macular ischemia (DMI) is currently on its way.

Expert Consensus on Geographic Atrophy in the EU: A Call for Urgent Policy Action.

Geographic atrophy is an eye disease that greatly interferes with the daily lives of patients and their families, posing a serious threat to the aging European demographic. Over the past 30 months, this initiative has assembled leading experts in the field of ophthalmology to share insights on the necessary policy steps that need to be taken to overcome this challenge on an EU-wide scale. Through analyzing best practices in Germany, Italy, France, and Spain, this consensus paper sets out a series of policy recommendations, which, if implemented, could greatly benefit all individuals affected by geographic atrophy. Amongst other features, these countries have provided valuable examples of awareness campaigns and an overall commitment to inclusive and comprehensive policies. The policy recommendations emerging from this paper include the adoption of comprehensive screening programs, retinal disease screening in the EU Driving License Directive, the development of a white paper at the European Commission, and the creation of Council recommendations on eye health screening. Given the significant improvements made at the national level throughout the EU, countries will require unitary support at the European level to further develop their policies and successfully address the burden of geographic atrophy.

NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

BACKGROUND: To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration. METHODS: A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography. RESULTS: Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy. CONCLUSION: Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.

Optical Coherence Tomography Angiography: A 2023 Focused Update on Age-Related Macular Degeneration.

Optical coherence tomography angiography (OCTA) has extensively enhanced our comprehension of eye microcirculation and of its associated diseases. In this narrative review, we explored the key concepts behind OCTA, as well as the most recent evidence in the pathophysiology of age-related macular degeneration (AMD) made possible by OCTA. These recommendations were updated since the publication in 2020, and are targeted for 2023. Importantly, as a future perspective in OCTA technology, we will discuss how artificial intelligence has been applied to OCTA, with a particular emphasis on its application to AMD study.

Deep-learning based automated quantification of critical optical coherence tomography features in neovascular age-related macular degeneration.

PURPOSE: To validate a deep learning algorithm for automated intraretinal fluid (IRF), subretinal fluid (SRF) and neovascular pigment epithelium detachment (nPED) segmentations in neovascular age-related macular degeneration (nAMD). METHODS: In this IRB-approved study, optical coherence tomography (OCT) data from 50 patients (50 eyes) with exudative nAMD were retrospectively analysed. Two models, A1 and A2, were created based on gradings from two masked readers, R1 and R2. Area under the curve (AUC) values gauged detection performance, and quantification between readers and models was evaluated using Dice and correlation (R2) coefficients. RESULTS: The deep learning-based algorithms had high accuracies for all fluid types between all models and readers: per B-scan IRF AUCs were 0.953, 0.932, 0.990, 0.942 for comparisons A1-R1, A1-R2, A2-R1 and A2-R2, respectively; SRF AUCs were 0.984, 0.974, 0.987, 0.979; and nPED AUCs were 0.963, 0.969, 0.961 and 0.966. Similarly, the R2 coefficients for IRF were 0.973, 0.974, 0.889 and 0.973; SRF were 0.928, 0.964, 0.965 and 0.998; and nPED were 0.908, 0.952, 0.839 and 0.905. The Dice coefficients for IRF averaged 0.702, 0.667, 0.649 and 0.631; for SRF were 0.699, 0.651, 0.692 and 0.701; and for nPED were 0.636, 0.703, 0.719 and 0.775. In an inter-observer comparison between manual readers R1 and R2, the R2 coefficient was 0.968 for IRF, 0.960 for SRF, and 0.906 for nPED, with Dice coefficients of 0.692, 0.660 and 0.784 for the same features. CONCLUSIONS: Our deep learning-based method applied on nAMD can segment critical OCT features with performance akin to manual grading.

Combined wide-field imaging in grading diabetic retinopathy.

OBJECTIVES: To detect retinal neovascularization elsewhere (NVE), of the optic disc (NVD) and intraretinal microvascular abnormalities (IRMA) in treatment naive diabetic retinopathy (DR) and compare these findings by using 90° Wide-Field Colour Fundus Photography (WF CFP), Wide-Field Spectral-Domain Optical Coherence Tomography Angiography (OCTA) and the combination of WF CFP and OCTA through overlay software. METHODS: Patients with treatment naive severe non-proliferative DR or proliferative DR were prospectively enrolled. All patients underwent WF-CFP and OCTA in the same day. Two readers independently analysed WF-CFP, SD-OCTA and the overlay of the two techniques. The degree of agreement between the two raters and between different techniques (WF CFP, OCTA, WF CFP combined to OCTA) were measured with Cohen's Kappa coefficient. RESULTS: Thirty-one eyes from 21 patients (10 males, mean age 63 ± 15 years) were included. Inter-rater agreement by using WF-CFP in detection of NVE, NVD and IRMA was respectively 0.62, 0.22 and 0.55. OCTA scored values of inter-rater agreement of 0.86, 0.87 and 0.92 in detection of NVE, NVD and IRMA, respectively. By combining WF-CFP and SD-OCTA, inter-rater agreement in detection of NVE, NVD and IRMA was 0.93, 0.94 and 0.89, respectively. CONCLUSION: Inter-rater agreement in detection of NVE, NVD and IRMA was substantial, fair and moderate, respectively. OCTA provided almost perfect values of inter-rater agreement in NVE, NVD and IRMA detection. Combining WF-CFP and OCTA further empowered concordance values in detection of NVE and NVD. Combining OCTA and WF-CFP is the best performance to detect NVE and NVD.

FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

'Structural OCT changes distinguishing between myopic macular haemorrhages due to choroidal neovascularization and spontaneous Bruch's membrane rupture: the "myopic 2 binary reflective sign".

OBJECTIVE: To evaluate the sensitivity and specificity of structural optical coherence tomography (OCT) in comparison to fluorescein angiography (FA) and OCT angiography (OCTA) in discerning between macular haemorrhages (MH) due to myopic choroidal neovascularization (m-CNV) and idiopathic macular haemorrhage (IMH) in myopic patients and to suggest a new OCT biomarker to discern these two entities. METHODS AND ANALYSIS: In this longitudinal retrospective study, patients affected by MH and pathological myopia were included. All patients underwent OCTA and FA to discern bleeding from m-CNV or IMH. Furthermore, all patients underwent a structural OCT and 2 expert graders evaluated the presence of the myopic 2 binary reflective sign as a biomarker to discern between IMH and bleeding from m-CNV. RESULTS: Forty-seven eyes of 47 patients were enrolled. By means of angiographic examinations, 34 out of 47 eyes with MH (57%) were diagnosed as m-CNV, whereas 13 eyes (43%) as IMH. Using structural OCT, the graders identified the presence of the myopic 2 binary reflective sign in 13 out of 13 eyes with IMH. In 33 out of 34 cases with m-CNV, the 2 graders established the absence of the sign. This accounted for 100% of sensibility and 97% of specificity of structural OCT in discerning between MH from m-CNV and IMH. CONCLUSION: Structural OCT can discern with good reliability between IMH and bleeding from m-CNV based on the presence/ absence of the myopic 2 binary reflective sign. This could be of paramount relevance in the clinical setting for the diagnosis and treatment of HM patients.