Posterior Polar Annular Choroidal Dystrophy: Genetic Insights and Differential Diagnosis in Inherited Retinal Diseases.

Posterior polar annular choroidal dystrophy (PPACD) is a rare ocular disorder and presents as symmetric degeneration of the retinal pigment epithelium (RPE) and the underlying choriocapillaris, encircling the retinal vascular arcades and optic disc. This condition distinctively preserves the foveal region, optic disc, and the outermost regions of the retina. Despite its distinct clinical presentation, due to the infrequency of its occurrence and the limited number of reported cases, the pathophysiology, and the genetic foundations of PPACD are still largely uncharted. This review aims to bridge this knowledge gap by investigating potential genetic contributors to PPACD, assessing current findings, and identifying genes that warrant further study. Emphasis is also placed on the crucial role of multimodal imaging in diagnosing PPACD, highlighting its importance in understanding disease pathophysiology. By analyzing existing case reports and drawing comparisons with similar retinal disorders, this paper endeavors to delineate the possible genetic correlations in PPACD, providing a foundation for future genetic research and the development of targeted diagnostic strategies.

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.

PHENOTYPIC CHARACTERIZATION OF PREDICTORS FOR DEVELOPMENT AND PROGRESSION OF GEOGRAPHIC ATROPHY USING OPTICAL COHERENCE TOMOGRAPHY.

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.

Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents.

Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFß and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment.

SUBRETINAL LIPID GLOBULES AN EARLY BIOMARKER OF MACULAR NEOVASCULARIZATION IN EYES WITH INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To explore the association between subretinal lipid globules (SLGs) detected in eyes with intermediate age-related macular degeneration with the presence of nonexudative macular neovascularization. METHODS: This was a retrospective analysis of 113 consecutive patients with bilateral intermediate age-related macular degeneration (226 eyes) followed for a least 6 months. All eyes underwent multimodal imaging with fundus autofluorescence, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Subretinal lipid globules were identified on spectral-domain optical coherence tomography as round hyporeflective lesions measuring 31 to 157 µ m located between the ellipsoid zone and the retinal pigment epithelium/Bruch membrane complex. Nonexudative macular neovascularization was detected with optical coherence tomography angiography. The features of NE-MNV lesions detected in eyes with SLGs were compared with those in eyes without SLGs. RESULTS: Subretinal lipid globules were identified in 15 eyes of which 14 eyes (93.3%) demonstrated NE-MNV on optical coherence tomography angiography. In the remaining 98 eyes without SLGs, 18 (18.4%) displayed NE-AMD on optical coherence tomography angiography. The macular neovascularization area was larger in the SLG subgroup (+0.38 vs. +0.21 mm 2 , P = 0.008) and showed faster horizontal growth (+727 µ m, CI 95% 250.4, 1,205.4) than MNV in eyes without SLGs (+64.9 µ m, CI 95%, 24.3, 154) on optical coherence tomography B-scans. After a mean of 11.6 months, the conversion rate to exudative MNV was similar between eyes with SLGs and those without SLGs [8/26 (38.5%) versus 3/13 (27.3%), P = 0.56)]. CONCLUSION: The detection of SLGs in eyes with intermediate age-related macular degeneration was strongly correlated with the presence of NE-MNV. Although these MNV lesions were larger and grew faster than NE-MNV detected in eyes lacking SLGs, the rates of conversion to exudative MNV appeared similar.

The Role of Diabetic Choroidopathy in the Pathogenesis and Progression of Diabetic Retinopathy.

Diabetic choroidopathy was first described on histopathological specimens of diabetic eyes. This alteration was characterized by the accumulation of PAS-positive material within the intracapillary stroma. Inflammation and polymorphonuclear neutrophils (PMNs) activation are crucial elements in choriocapillaris impairment. The evidence of diabetic choroidopathy in vivo was confirmed with multimodal imaging, which provides key quantitative and qualitative features to characterize the choroidal involvement. The choroid can be virtually affected in each vascular layer, from Haller's layer to the choriocapillaris. However, the damage on the outer retina and photoreceptor cells is essentially driven by a choriocapillaris deficiency, which can be assessed through optical coherence tomography angiography (OCTA). The identification of characteristic features of diabetic choroidopathy can be significant for understanding the potential pathogenic and prognostic implications in diabetic retinopathy.

The Role of Alpha-Synuclein Deposits in Parkinson's Disease: A Focus on the Human Retina.

Parkinson's disease (PD) is a neurodegenerative condition characterized by the progressive deterioration of dopaminergic neurons in the central and peripheral autonomous system and the intraneuronal cytoplasmic accumulation of misfolded α-synuclein. The clinical features are the classic triad of tremor, rigidity, and bradykinesia and a set of non-motor symptoms, including visual deficits. The latter seems to arise years before the onset of motor symptoms and reflects the course of brain disease. The retina, by virtue of its similarity to brain tissue, is an excellent site for the analysis of the known histopathological changes of PD that occur in the brain. Numerous studies conducted on animal and human models of PD have shown the presence of α-synuclein in retinal tissue. Spectral-domain optical coherence tomography (SD-OCT) could be a technique that enables the study of these retinal alterations in vivo. The objective of this review is to describe recent evidence on the accumulation of native or modified α-synuclein in the human retina of patients with PD and its effects on the retinal tissue evaluated through SD-OCT.

A COMMON FINDING IN FOVEAL-SPARING EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN IMPLICATES BASAL LAMINAR DEPOSITS.

PURPOSE: To characterize structural and clinical alterations preceding the diffuse macular atrophy in extensive macular atrophy with pseudodrusen (EMAP) and their evolution toward atrophic changes. METHODS: A retrospective chart review was performed of patients with early-onset reticular pseudodrusen (i.e., pre-EMAP) younger than 55 years and EMAP with foveal sparing. Patients were included if they had complete medical records and multimodal imaging. RESULTS: A total of 12 patients were reviewed, of whom 4 of 12 patients (7 eyes) presented a pre-EMAP stage, characterized by the presence of pseudodrusen-like deposits without atrophic changes, while the remaining 8 of 12 patients (10 eyes) exhibited EMAP with foveal sparing (60.1 ± 6.4 years). Subretinal deposits of various stages tended to fade, leaving subretinal pigment epithelium accumulation of hyperreflective material with a physical separation between the retinal pigment epithelium-basal lamina and the Bruch membrane, along with the persistence of hyperreflective material after retinal pigment epithelium loss. These findings preceded atrophy development in a pre-EMAP stage and the EMAP stage with foveal sparing. CONCLUSION: Our findings presented distinct multimodal imaging features in eyes with reticular pseudodrusen depicting a peculiar phenotype of rapidly progressing atrophy in midlife. The disease spectrum may include other forms of geographic atrophy allied by thickened basal laminar deposits.

Choroidal Vasculature Changes in Age-Related Macular Degeneration: From a Molecular to a Clinical Perspective.

The contribution of choroidal vasculature to the pathogenesis of age-related macular degeneration (AMD) has been long debated. The present narrative review aims to discuss the primary molecular and choroidal structural changes occurring with aging and AMD with a brief overview of the principal multimodal imaging modalities and techniques that enable the optimal in vivo visualization of choroidal modifications. The molecular aspects that target the choroid in AMD mainly involve human leukocyte antigen (HLA) expression, complement dysregulation, leukocyte interaction at Bruch's membrane, and mast cell infiltration of the choroid. A mechanistic link between high-risk genetic loci for AMD and mast cell recruitment has also been recently demonstrated. Recent advances in multimodal imaging allow more detailed visualization of choroidal structure, identifying alterations that may expand our comprehension of aging and AMD development.

Role of CD 20+ T cells and related cytokines in mediating retinal microvascular changes and ocular complications in chronic-plaque type psoriasis.

OBJECTIVE: To assess the role of CD3+ CD20+ CD4- CD8- double-negative (DN) or CD3+CD20+ CD4/CD8+ T cells and the related pro-inflammatory cytokines in the humor aqueous, in mediating retinal microvascular changes in patients with chronic plaque-type moderate to severe psoriasis. DESIGN: A total of 76 patients (57.6 ± 11.7 years) with chronic plaque-type psoriasis were initially evaluated. Nineteen patients (19 eyes) and 19 healthy volunteers (19 eyes) were subjected to dermatological evaluation with Psoriasis Area Severity Index (PASI) and the Dermatology life quality index (DLQI). Retinal images were processed using an automatized software. On the same day, a venous sample was collected and analyzed using multiparametric flow cytometry. Three out of 6 patients who presented cataract, consented to perform surgery with humor aqueous collection. The samples were analyzed using a Multi-Analyte ELISA kit for the simultaneous quantification of IL1α, IL1ß, IL2, IL4, IL6, IL8, IL10, IL12, IL17A, IFNγ, TNF-α, GMCSF. RESULTS: The CD3+CD4+/CD8+CD20+CD56- T cells expression was greater in the psoriatic patients (+73.9%, P < 0.001) compared to controls, but not the DN T cells (-8.2%, P = 0.30). Ocular complications were diagnosed in 61.1% of patients, microvascular parameters including artero-venous ratio (P = 0.04), subfoveal choriocapillaris/Sattler's layer, and choroidal thickness (CT, both P < 0.001) were significantly altered in psoriasis subgroup. The increased circulating levels of the CD3+CD4+/CD8+CD20+CD56- T cells were associated with thinning of subfoveal CT (P = 0.03) and Haller's layer (P = 0.01). Instead, the DN T cells presented an inverse relationship with disease duration (P = 0.02), DLQI score (P = 0.02), and the use of biological therapy (P = 0.05). The related cytokine patterns possibly modified in this cellular context have been investigated. No significant differences were observed in cytokines levels between psoriasis and controls, the most significant difference was detected on IL-6, without reaching statistical significance (fold change of 1.4, P = 0.13). CONCLUSION: Our findings demonstrated that CD20+ T cell subpopulation is highly represented in psoriasis regardless of the use of immunomodulatory therapies, and the diffuse microvascular alterations suggested possible endothelial damage as mainstream for the genesis of psoriatic-mediated complications as further supported by the comparable concentrations of cytokines, at least as humor aqueous content, with respect to healthy eyes.

Linear and planar reflection artifacts on swept-source and spectral-domain optical coherence tomography due to hyperreflective crystalline deposits.

PURPOSE: To describe novel spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) linear and planar reflection artifacts produced by hyperreflective crystalline deposits (HCD). METHODS: Imaging from 10 eyes with HCD producing linear and planar artifacts on OCT was retrospectively analyzed. All eyes had SD-OCT (Spectralis HRA + OCT, Heidelberg Engineering, Germany) and SS-OCT angiography (PLEX Elite 9000, Carl Zeiss Meditec, Inc., Dublin, CA) acquired on the same day. The horizontal extent of planar artifacts and the corresponding HCD on B-scans was measured using a digital caliper. Artifact features from HCD in eyes with non-neovascular age-related macular degeneration (AMD) were analyzed and compared to those seen in two eyes with the "onion sign," an OCT signature previously shown to represent cholesterol crystals (CC) in the sub-retinal pigment epithelium-basal laminar space of eyes with neovascular AMD. A third eye with the "onion sign" was imaged with dense B-scan (DB)-OCTA. RESULTS: Ten eyes of ten patients (77.4 ± 8.7 years) with HCD were analyzed. On SS-OCTA, HCD produced linear artifacts of high signal intensity passing through the HCD and spanning the entire scan depth. On SD-OCT, HCD produced planar artifacts located anterior to both the retina and a hyporeflective space representing normal vitreous signal. The horizontal extent of the artifact did not differ significantly from the corresponding HCD on OCT B-scans (P = 0.62). The OCT artifacts produced by the "onion sign" appeared similar to those of HCD. The additional eye with neovascular AMD imaged with DB-OCTA was characterized by a single, vertical, linear false-flow signal crossing retinal layers. CONCLUSIONS: To the authors' knowledge, this is the first description of SD- and SS-OCT/OCTA artifacts corresponding to both HCD and the "onion sign." These artifacts are likely due to highly reflective CC previously shown on histology to correspond to both of these OCT signatures.

RELATIONSHIP BETWEEN CHOROIDAL VASCULAR HYPERPERMEABILITY, CHORIOCAPILLARIS FLOW DENSITY, AND CHOROIDAL THICKNESS IN EYES WITH PACHYCHOROID PIGMENT EPITHELIOPATHY.

PURPOSE: To use swept-source optical coherence tomography and swept-source optical coherence tomography angiography to investigate potential relationships between choroidal vascular hyperpermeability (CVH) seen with indocyanine green angiography (ICGA), choriocapillaris flow density, and choroidal thickness in eyes with pachychoroid pigment epitheliopathy. METHODS: Patients with pachychoroid pigment epitheliopathy were prospectively imaged with 12-mm × 12-mm swept-source optical coherence tomography, 12-mm × 12-mm swept-source optical coherence tomography angiographyA, and ICGA. Binarized choriocapillaris OCTA images were superimposed with ICGA images in which CVH area had been isolated. Choriocapillaris flow density within or outside the quadrants of CVH was calculated and the ratio of these two values was determined. The presence of CVH and choroidal thickness was evaluated at 9 locations within a central 3-mm × 3-mm area to explore the relationship between these 2 factors. RESULTS: Ten eyes from 10 patients were enrolled in the present study. Choriocapillaris flow density within quadrants of CVH area was significantly lower compared with quadrants without CVH (P < 0.001). The mean choriocapillaris flow density ratio was 0.86 ± 0.10 (range: 0.65-0.99). From among the 90 locations in 10 study eyes, 48 were within areas of CVH. Choroidal thickness was greater in quadrants of CVH compared with areas without CVH (P < 0.001, 455 ± 122 µm vs. 297 ± 93 µm). CONCLUSION: Reduced choriocapillaris flow density, increased choroidal thickness, and CVH appear to co-localize in eyes with pachychoroid pigment epitheliopathy.

Postural changes revealing orbital venous malformation using ultrasound in blue rubber bleb nevus syndrome.

A 62-year-old white woman presented with a diagnosis of blue rubber bleb nevus syndrome (BRBNS). The right eye appeared enophthalmic, yet the patient complained of episodes of right proptosis on bending forward. The remainder of the examination was unremarkable. Orbital ultrasound (US) in an upright posture revealed a single low reflectivity cavity (4.27 mm x 2.82 mm) of uncertain interpretation. In a forward-leaning posture the lesion increased in size (maximum thickness of 13.72 mm), demonstrating multiple low reflectivity spaces with highly reflective septae. This case first reports the use of US with postural changes to assess the presence of orbital venous malformation in BRBNS. The expansile nature upon postural changes supports the venous origin of the orbital lesion.

Vitreo-macular interface disorders in retinitis pigmentosa.

PURPOSE: To investigate the prevalence and progression of vitreo-macular interface disorders (VMID) phenotypes and their natural history in retinitis pigmentosa (RP). METHODS: A total of 257 eyes of 145 RP patients with VMID were retrospectively evaluated. Patients were divided according to the VMID subtypes into epiretinal membranes (ERMs), vitreo-macular traction (VMT) group, and macular hole (MH). Serial eye-tracked spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA) changes were analyzed for a mean follow-up of 36.95 months. The status of posterior vitreous cortex was also considered. A control group of 65 eyes belonging to 65 RP patients with no macular changes was also recruited. RESULTS: VMID and control groups had the same baseline BCVA (0.50 vs 0.44 LogMAR) and did not differ in terms of phakic status. Different VMID groups had similar BCVA at baseline (p = 0.98). ERM represented the most prevalent disorder (207/257 eyes, 80.5%), followed by 35/257 (13.6%) VMT, and 15/257 Lamellar MH (LMH) eyes (5.8%). There were no cases of full thickness MH. Throughout the 36.9 months of follow-up, BCVA decreased an average 0.09 LogMAR from 0.31 to 0.4 in VMID patients and 0.01 in controls. VMID subgroup analysis showed a significant BCVA decrease in ERM patients (- 20.29%, p < 0.001), while VMT and LMH did not change significantly. Foveal thickness also remained stable over time. Complete PVD was present in 11 eyes in ERM, VMT, and LMH. CONCLUSIONS: Our study confirms the high prevalence of VMID in RP patients; however, only ERMs determined a significant loss of vision over 24 months. The high prevalence of VMID in RP patients suggests that macular alteration other than edema represents part of disease spectrum.

PREDICTIVE FACTORS FOR DEVELOPMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Spectral-Domain Optical Coherence Tomography Study.

PURPOSE: To investigate the risk factors predictive for the development of neovascular age-related macular degeneration (NVAMD) by means of spectral-domain optical coherence tomography. METHODS: Retrospective study of 73 eyes graded Stage 2 and Stage 3 according to the AMD International Grading System with minimum follow-up of 24 months. Drusenoid pigment epithelial detachment, hyperreflective foci, external limiting membrane, inner ellipsoid band, and retinal pigment epithelium integrity were analyzed at baseline and last follow-up. Binary logistic regression model analyzed significant predictors of neovascular conversion. RESULTS: The discontinuity of external limiting membrane, inner ellipsoid band, and retinal pigment epithelium bands were significantly more prevalent in the NVAMD group at baseline and last follow-up (P < 0.001). Hyperreflective foci represented the single most important predictor of neovascular conversion (Exp [B], 15.15; P = 0.005) as confirmed by Kaplan-Meier curve (P = 0.002). Drusenoid pigment epithelial detachment width was significantly greater in NVAMD group than control subjects at baseline and last follow-up (P < 0.001), and its delta value also resulted a significant neovascular predictor (Exp [B], 0.99; P = 0.04). CONCLUSION: Hyperreflective foci significantly increase the risk of NVAMD progression. The delta width of drusenoid pigment epithelial detachment also predicts disease progression, integrating the stratification of NVAMD progression risk.

ASSOCIATION BETWEEN CHOROIDAL CAVERNS AND CHOROIDAL VASCULAR HYPERPERMEABILITY IN EYES WITH PACHYCHOROID DISEASES.

PURPOSE: To investigate the association between choroidal caverns, choroidal vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid disease. METHODS: This was a retrospective review of swept-source optical coherence tomography and indocyanine green angiography imaging performed on eyes with pachychoroid disease. RESULTS: Imaging from 21 eyes with pachychoroid disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy) from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available for review. In all study eyes, pachyvessels traversed the areas of CVH visible in mid- and late-phase indocyanine green angiography. A total of 504 choroidal caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445 (88%) were seen within the areas of CVH compared with 59 (12%), which were detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an increased choroidal thickness when compared with eyes with ≤1 cavern (P < 0.001). CONCLUSION: Choroidal caverns, found primarily in the areas of indocyanine green angiography CVH traversed by pachyvessels, were detected in 52% of eyes with pachychoroid disease. The presence of choroidal caverns in these cases may indicate a loss of normal choroidal architecture associated with dilated Haller layer veins and increased choroidal thickness.

Factors Influencing Fixation Stability Area: A Comparison of Two Methods of Recording.

SIGNIFICANCE: The authors analyze factors influencing bivariate contour ellipse area (BCEA) in healthy and pathologic eyes and how such factors may affect isolated (static BCEA) or microperimetric fixation (dynamic BCEA). They conclude that aging increases both dynamic BCEA and examination time, whereas static BCEA offers less variance and the maximum distinction with pathologic eyes. PURPOSE: The aim of this study was to assess factors influencing BCEA and the recording method that offer less variability and thus maximum distinction between healthy and pathologic eyes. METHODS: A total of 136 eyes were retrospectively reviewed, 85 eyes without ophthalmic disorders (logMAR acuity ≦0.0) and 51 eyes with late age-related macular degeneration (AMD) were enrolled. All patients underwent two consecutive examinations, a 30-second isolated fixation (static BCEA) and a microperimetric test with continuous fixation recording (dynamic BCEA). All the examinations were carried out using MP1 microperimeter (NAVIS software version 1.7.6; Nidek Technologies, Padova, Italy). RESULTS: Dynamic BCEA was significantly correlated with age (r = 0.38, P < .001), total (r = 0.32, P = .03), and tracking time (r = 0.33, P = .02) in controls, whereas no significant relationships were found in the AMD group. The greatest difference between static and dynamic BCEA was observed in 70- to 79-year decade in healthy subjects (P < .01). Logistic regression analysis showed that late AMD status was significantly predicted by ±2 SD and ±3 SD static BCEA (both P = .03). CONCLUSIONS: Dynamic BCEA is influenced by a certain degree of variability in advanced-age healthy subjects. In such cases, the use of ±2 SD and ±3 SD static BCEAs seems to offer a more accurate detection of fixation stability changes in the AMD group with respect to normal subjects.

VITELLIFORM LESIONS ASSOCIATED WITH LEPTOCHOROID AND PSEUDODRUSEN.

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 (SDD) and leptochoroid. DESIGN: Retrospective, cohort study. SUBJECTS: The study compares patients affected by leptovitelliform maculopathy with cohorts displaying a similar phenotypic spectrum. This includes patients with acquired vitelliform lesions (AVL) and those with SDD alone. METHODS: A total of 60 eyes of 60 patients were included, of whom 20 eyes had LVM, 20 eyes had AVL, and the remaining had SDD. Patients older than 50 years with complete medical records and multimodal imaging for at least 6 months of follow-up, including color fundus photograph (CFP) or MultiColor, optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA) 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 to both LVM (p<0.001) and SDD subgroups (p<0.001). The proportion of late-stage complications significantly differed among subgroups (χ2=7.5, p=0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, while the remaining eyes presented a similar proportion of complications, including 20% in AVL after 27.6 months and 20% in SDD 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 LVM 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 SDD 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 a higher propensity for faster progression and an elevated rate of complications, particularly toward atrophic conversion.