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.

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.

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.

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.

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.

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.

NON-EXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

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

Long-term predictors of anti-VEGF treatment response in patients with neovascularization secondary to CSCR: a longitudinal study.

PURPOSE: To identify the baseline predictors of anti-VEGF treatment response at 3 years in patients affected by choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR). METHODS: In this retrospective longitudinal study, medical records of patients diagnosed with CNV secondary to CSCR and treated using anti-VEGF injections between April 2015 and May 2020 were reviewed. The potential qualitative and quantitative predictors of treatment response were identified or measured based on the multimodal imaging examination available for each patient at the baseline, including structural OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT-angiography (OCT-A). Univariate and multivariate analyses were performed. RESULTS: Twenty-nine eyes from 29 patients affected by CNV complicating CSCR were included in the study. At the end of the 3-year follow-up, the mean BCVA was 20/50 Snellen equivalent (0.38 ± 0.36 LogMAR), and no significant difference with baseline BCVA (0.37 ± 0.29 LogMAR) was found (p = 0.9). Twenty out of 29 eyes (69%) had active lesions at the end of the follow-up. At multivariate analysis, none of the included features was independently associated with the 3-year BCVA outcome. Pigment epithelium detachment (PED) height (ß = 0.017, p = 0.028) and outer limiting membrane (OLM) preservation at the fovea (ß = -5.637, p = 0.026) were independently associated with the CNV activity at 3 years. CONCLUSION: PED height and OLM obliteration at the fovea might be considered baseline predictors of lesion activity at 3-year follow-up in patients with CNV secondary to CSCR treated with anti-VEGF therapy.

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.

Novel IMPG2 variant causing adult macular vitelliform dystrophy: A case report.

INTRODUCTION: Adult-onset vitelliform macular dystrophy (AVMD) is an inherited maculopathy characterized by metamorphopsias and decrease in visual acuity occurring between the fourth and the sixth decade. It is characterized by an 'egg yolk' macular lesion eventually evolving towards foveal atrophy and fibrosis. It is usually an autosomal dominant inherited disorder with variable penetrance, mainly related to variants in BEST1, PRPH2, IMPG1, and IMPG2 genes. CASE DESCRIPTION: A 47-year-old woman complaining of "wavy" vision was referred to our clinic. Her past medical history and reported family history did not reveal any ocular disease. Complete ophthalmological evaluation was performed. Funduscopic examination and multimodal imaging revealed a round vitelliform lesion in both eyes, leading to a diagnosis of AVMD. Genetic analysis revealed a novel, likely pathogenetic, heterozygous c.478G > T (p.Glu160Ter), (NM_016247) variant in the IMPG2 gene. DISCUSSION: Our patient exhibits a novel pathogenetic variant in a gene associated with AVMD. Heterozygous variants in the IMPG2 gene have been reported in multiple individuals with vitelliform macular dystrophy, with an autosomal dominant mode of inheritance. Genetic screening is essential to characterize patients, to predict vision loss in patients with a positive family history and to characterize eligible patients for new potential emerging therapies. Genotype-phenotype correlation studies are needed to have a clearer picture of pathogenetic mechanisms. Our study characterizes the phenotype related to a novel IMPG2 pathogenic variant through multimodal imaging.

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.

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.

A Brazilian case of exudative perifoveal vascular anomalous complex responsive to aflibercept intravitreal injections.

PURPOSE: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections. CASE DESCRIPTION: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05 ml/2 mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity. DISCUSSION: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one. CONCLUSION: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis.

'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.

Subretinal hyperreflective material in retinal and chorioretinal disorders: A comprehensive review.

Subretinal hyperreflective material (SHRM) is a common and remarkable optical coherence tomography (OCT) biomarker whose importance is emerging in several retinal and chorioretinal diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, pathologic myopia, posterior uveitis, vitelliform lesions and macular dystrophies, and rarer disorders. Multimodal imaging, also thanks to the introduction of OCT angiography, allowed a deeper characterisation of SHRM components and its morphological changes after treatment, suggesting its usefulness in clinical practice. We discuss and summarize the nature, multimodal imaging characteristics, and prognostic and predictive significance of SHRM in the different retinal and choroidal disorders in which it has been described.

Shedding Light on Photobiomodulation Therapy for Age-Related Macular Degeneration: A Narrative Review.

BACKGROUND: Photobiomodulation (PBM) relies on the pathophysiological mechanism whereby red to near-infrared light can target mitochondrial activity and promote ATP synthesis. Preclinical and clinical studies have shown promising results in treating intermediate age-related macular degeneration (AMD), since PBM can produce photochemical reactions in endogenous retinal chromophores. Currently, PBM is approved by the Food and Drug Administration and by the European Medicines Agency for the treatment of intermediate AMD. This narrative review aimed to evaluate the available evidence on the effectiveness and safety of PBM in treating intermediate AMD. METHODS: A comprehensive search was conducted using the PubMed database, employing the keywords "photobiomodulation" and "age-related macular degeneration." All English-language studies published up to June 2023 were reviewed, and the search was expanded to include relevant references from selected articles. The included publications were analyzed for this review. RESULTS: The available studies on PBM in AMD demonstrated promising but inconsistent results. PBM showed potential in improving best-corrected visual acuity (BCVA) and contrast sensitivity (CS) in patients with AMD. Some studies also suggested a reduction in AMD lesions, such as drusen volume. However, the long-term efficacy and optimal treatment parameters of PBM in AMD remained to be fully determined due to the limitations of the available studies. These included variations in irradiation techniques, wavelengths, exposure times, and treatment sessions, making it challenging to generalize the effectiveness of PBM. Furthermore, the lack of accurate classification of AMD phenotypes in the available studies hindered the understanding of which phenotypes could truly benefit from this treatment. Finally, the strength of evidence varied among studies, with limited sample sizes, unpublished results, and only three randomized sham-controlled trials. CONCLUSIONS: Currently, the effectiveness of PBM in promoting drusen resorption or preventing progression to advanced forms of AMD, as observed in the cited studies, remains uncertain.

Subclinical Angioid Streaks with Pseudodrusen: A New Phenotype of Age-Related Macular Degeneration.

INTRODUCTION: To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. METHODS: This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences. RESULTS: Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%. CONCLUSIONS: Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.