OCT risk factors for 2-year foveal involvement in non-treated eyes with extrafoveal geographic atrophy and AMD.

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

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

PURPOSE: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

RISK FACTORS OF VISION LOSS AND MULTIPLE RECURRENCES IN MYOPIC MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the factors associated with maximum visual improvement (peak vision) gain and the risk factors of peak vision loss and multiple recurrences in myopic macular neovascularization undergoing antivascular endothelial growth factor therapy. METHODS: Retrospective study of 310 eyes with active myopic macular neovascularization and median follow-up of 3.5 years. We defined peak vision gain as the maximum best-corrected visual acuity value reached under treatment and peak vision loss as best-corrected visual acuity never scoring as peak vision. We used multiple-event Prentice, Williams, and Peterson models to compute recurrences' incidence and Cox regression to identify risk factors for peak vision gain, peak vision loss, and multiple recurrences. RESULTS: Eyes with worse baseline best-corrected visual acuity {hazard ratio (HR) = 2.59 (95% confidence interval [CI]: 1.63-4.11) for 0.1 logMAR increase, P < 0.001} had higher chance to achieve peak vision. Peak vision was lost in 162 eyes (52%). Older age (HR = 1.22 [95% CI: 1.02-1.43] for 10-year increase, P = 0.02) and recurrences (HR = 1.10 [95% CI: 1.01-1.22] for event, P = 0.04) predicted nonsustained peak vision. Older age (HR = 1.13 [95% CI: 1.04-1.27] for 10-year increase, P = 0.006), larger myopic macular neovascularization (HR = 1.06 [95% CI: 1.01-1.13] for 1-mm 2 increase, P = 0.04), and juxtafoveal location (HR = 1.88 [95% CI: 1.28-2.77] vs. extrafoveal, P = 0.001) predicted multiple recurrences. CONCLUSION: Myopic macular neovascularization eyes lose vision mainly because of multiple recurrences. Patients at risk for recurrences should undergo more attentive monitoring to avoid vision loss.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

PURPOSE: To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. METHODS: Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. RESULTS: Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. CONCLUSION: Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

PUNCTATE INNER CHOROIDOPATHY-LIKE REACTIONS IN UNRELATED RETINAL DISEASES.

PURPOSE: To report a cohort of patients with a punctate inner choroidopathy (PIC)-like reaction in concurrent, unrelated, chorioretinal disorders. METHODS: This was a retrospective observational study of patients seen at two referral centers with lesions consistent with PIC on multimodal imaging; patients with lesions resembling idiopathic multifocal choroiditis were also included. Active PIC-like lesions appeared as focal hyperreflective lesions splitting the retinal pigment epithelium/Bruch membrane (RPE/BrM) complex on optical coherence tomography. Chronic PIC-like lesions included subretinal fibrosis, multifocal punched-out chorioretinal atrophy, and curvilinear streaks. Patients' demographics, additional imaging features, and treatment responses were collected and summarized. RESULTS: Twenty-two eyes of 16 patients with a PIC-like reaction were included (75% females; median age 40 years). Underlying diagnoses included hereditary retinal conditions (10 patients, 63%) and acquired etiologies, all characterized by the RPE/BrM or outer retinal disruption. Fifteen eyes (68%) had active PIC-like lesions; seven eyes (32%) had chronic PIC-like lesions. Active PIC-like lesions regressed with time and responded to systemic steroids. Subretinal fibrosis (3 eyes, 20%), macular atrophy (3 eyes, 20%), and concomitant subretinal fibrosis and macular atrophy (5 eyes, 33%) developed on follow-up. Recurrences occurred in five eyes (23%). CONCLUSION: RPE/BrM or outer retina disruption may trigger a PIC-like reaction in susceptible patients, presumably because of the loss of immune privilege. A PIC-like reaction may influence the clinical progression and the visual prognosis of the primary chorioretinal disease.

CLINICAL ASSOCIATIONS AND PROGNOSTIC IMPLICATIONS OF REPAIR TISSUE PROLIFERATION IN EYES WITH RETINAL PIGMENT EPITHELIUM TEARS.

PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF FOCAL CHOROIDAL EXCAVATION AND THE CHOROIDAL STROMA VARIATIONS WITH OCCURRENCE OF EXCAVATION.

PURPOSE: To describe retinal and choroidal vascular changes, and choroidal stroma variations occurring in focal choroidal excavation (FCE). METHODS: Study design was a cross-sectional case series. Consecutive patients affected by FCE and healthy controls were recruited. All patients underwent complete ophthalmologic assessment and multimodal imaging, including structural optical coherence tomography and optical coherence tomography angiography. Choroidal thickness and stromal index were calculated from structural optical coherence tomography images. Moreover, we measured vessel density values of the superficial capillary plexus, deep capillary plexus and choriocapillaris at the level of the macula. RESULTS: Twenty-two patients (28 eyes; mean age 57.2 ± 16.4) and 28 control eyes (mean age of 56.5 ± 9.8) were included. Five patients (23%) were asymptomatic, whereas 17 patients (77%) complained of visual symptoms. FCE was associated with choroidal neovascularization in 10 eyes (35%). Choroidal stromal component was lower in FCE patients than controls, whereas choroidal thickness was unremarkable. Stromal index values calculated in the region proximal to the FCE was significantly lower than the values obtained from the external region. Deep capillary plexus vessel density was lower in FCE than controls. Choriocapillaris was altered in the region surrounding the FCE, whereas it was normal in the external region. CONCLUSION: Deep capillary plexus and choriocapillaris plexus were significantly altered in FCE patients. Moreover, choroidal stroma was significantly reduced in the areas closer to FCE compared to the surrounding choroid in patients, as well as compared to healthy controls, suggesting the hypothesis of weakening of the architectural support, creating a more friable point, which can favor FCE development.

THE EXPANDING CLINICAL SPECTRUM OF CHOROIDAL EXCAVATION IN MACULAR DYSTROPHIES.

PURPOSE: To assess the prevalence and the clinical course of focal choroidal excavation (FCE) in patients affected by macular dystrophies. METHODS: Prospective case series. All the patients underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. The presence of choroidal neovascularization (CNV) was assessed on the basis of the leakage detected on fluorescein angiography. RESULTS: A total of 162 eyes from 81 patients with macular dystrophy were included in the study. FCE was diagnosed in seven eyes (4.3% of the eyes), including four eyes with Best vitelliform dystrophy, two eyes with pattern dystrophy associated with pseudoxanthoma elasticum, and one case of Stargardt disease. In eyes with FCE and macular dystrophy, the mean best-corrected visual acuity was 0.4 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at baseline and was stable to 0.41 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at the final visit. In four of these seven eyes, FCE was associated with a subfoveal CNV. The CNV was managed with one intravitreal anti-vascular endothelial growth factor injection, achieving the complete anatomical stabilization of the CNV and recovery of the best-corrected visual acuity. CONCLUSION: Focal choroidal excavation can be infrequently encountered in patients with macular dystrophies. The presence of CNV may complicate FCE in these patients, and anti-vascular endothelial growth factor seems to be an effective treatment with no progression of FCE over time.

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment.

PURPOSE: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. RESULTS: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. CONCLUSIONS: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.

RETINAL PIGMENT EPITHELIUM APERTURE: A Previously Unreported Finding in the Evolution of Avascular Pigment Epithelium Detachment.

PURPOSE: To describe retinal pigment epithelium (RPE) aperture and to generate hypotheses about pathogenesis of this previously unreported finding in the evolution of avascular pigment epithelium detachment (PED) secondary to age-related macular degeneration. METHODS: Medical records and multimodal imaging results from 10 patients with RPE apertures were reviewed between January 2009 and December 2014 by 2 institutions. Main outcome measures were analysis of RPE aperture imaging characteristics, including aperture areas and PED diameters, and their temporal course. Lesions preceding RPE aperture development were also evaluated. RESULTS: Eleven RPE apertures were identified in 10 eyes of 10 patients (1 male, 9 females; mean age 73.1 ± 6.7 years) and included for analysis. The RPE apertures appeared as round discontinuities either at the apex or at the base of avascular PED. No rippling or retraction of the RPE was found at the sites of aperture. The RPE apertures enlarged homogeneously (mean round area of hypoautofluorescence significantly increased from 0.18 ± 0.13 to 0.93 ± 1.2; P = 0.005), and PED flattened (PED maximal height on spectral domain optical coherence significantly decreased from 445.2 ± 259 to 206.4 ± 218; P = 0.04) after a mean of 38.6 ± 16.3 months. Analysis of lesions preceding RPE apertures revealed areas of focal hyperautofluorescence at the site of development, in some cases appearing as drusenoid material connected with the base of avascular PED. CONCLUSION: The RPE aperture represents a previously unreported possible evolution of avascular PED, which should be distinguished by typical RPE tears. Analysis of lesions preceding RPE apertures suggests focal atrophic progression of drusenoid material in its pathogenesis.

Stereotactic radiotherapy for polypoidal choroidal vasculopathy: a pilot study.

PURPOSE: To evaluate low-voltage X-ray stereotactic radiotherapy (SRT) delivered in conjunction with intravitreal ranibizumab for the treatment of active macular polypoidal choroidal vasculopathy (PCV). METHODS: At baseline, all eyes received an intravitreal injection of ranibizumab, followed by 16-Gy X-ray SRT to the macula. Further ranibizumab injections were given pro re nata. The primary outcome measure was regression of the polyps assessed by indocyanine green angiography. Secondary outcome measures were best-corrected visual acuity (BCVA) and central foveal thickness (CFT) changes on optical coherence tomography. Local or systemic adverse events were evaluated as well. RESULTS: We examined 12 eyes of 12 patients with PCV. At month 12, an angiographic regression of the polyps was observed in 10 of the 12 eyes. The mean BCVA improved by 7.6 letters: from 65.08 ± 11.4 to 72.7 ± 14.75 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The mean CFT decreased from 372.3 ± 79.6 to 215.9 ± 57.9 µm (p < 0.01). No local or systemic adverse events were reported. CONCLUSIONS: The preliminary data support the safety of low-voltage X-ray SRT for the treatment of macular PCV and show polyp closure, reduction in CFT and improvement in the mean BCVA. Additional research is warranted to confirm the efficacy and longer-term safety of this therapy in this population.

Intravitreal ranibizumab for choroidal neovascularization with large submacular hemorrhage in age-related macular degeneration.

PURPOSE: To evaluate the effects of intravitreal ranibizumab injections in the treatment of choroidal neovascularization with large submacular hemorrhage secondary to age-related macular degeneration. METHODS: Prospective interventional case series. Patients presenting occult choroidal neovascularization with flat large submacular hemorrhage >50% of the entire lesion were considered. The protocol required 3 monthly consecutive injections, followed by repeat injections over the 12-month follow-up on the basis of optical coherence tomography parameters and angiographic features. RESULTS: Twenty-three patients were enrolled in the study and prospectively followed up. Mean best-corrected visual acuity and mean central macular thickness at the baseline were 0.82 ± 0.22 (logarithm of the minimum angle of resolution ± standard deviation) and 342 ± 56 µm, respectively. At 12-month examination, mean visual acuity improved significantly to 0.68 ± 0.41 (P = 0.04), and mean central macular thickness decreased to 236 ± 26 µm (P < 0.0001). A progressive resolution of macular bleeding was registered in 22 of 23 patients. No side effect or complication was registered. CONCLUSION: Intravitreal ranibizumab can be considered a beneficial approach for the management of choroidal neovascularization with flat large submacular hemorrhage secondary to age-related macular degeneration.

Intravitreal ranibizumab for naive extrafoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: To investigate the effect of intravitreal ranibizumab on extrafoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: Eighteen eyes affected by extrafoveal choroidal neovascularization secondary to age-related macular degeneration were prospectively enrolled in this study. After an initial intravitreal ranibizumab, all patients were reevaluated monthly over 12 months of follow-up. Further retreatments were performed on a pro re nata basis, depending on detection of any type of fluid on optical coherence tomography and/or the presence of leakage on fluorescein angiography. Primary outcome measures were mean changes in best-corrected visual acuity and the proportion of eyes gaining at least 15 letters (3 Early Treatment Diabetic Retinopathy Study [ETDRS] lines) at the end of the follow-up. Secondary outcome measures were central macular thickness variations and changes in choroidal neovascularization size. RESULTS: Mean best-corrected visual acuity presented a significant improvement during the follow-up period, being 0.3 ± 0.2 logMAR at baseline and 0.2 ± 0.2 logMAR at the 12-month examination (P < 0.001). An improvement of at least 3 EDTRS lines was achieved by 6 eyes (33.3%), whereas 6 patients (33.3%) gained 1 to 2 lines. The mean central macular thickness at baseline was 314 ± 87 µm, changing to 268 ± 65 µm at the 12-month examination (P = 0.003). The mean lesion size was 1.4 ± 1.4 mm and remained stable throughout the follow-up, being 1.8 ± 2.9 mm at 12 months (P = 0.64). CONCLUSION: Intravitreal ranibizumab administered after a pro re nata regimen with monthly evaluation is a beneficial approach for the management of extrafoveal choroidal neovascularization secondary to age-related macular degeneration over 12 months of follow-up. Further studies are warranted to confirm our preliminary results.

Endothelial progenitor cells and response to ranibizumab in age-related macular degeneration.

BACKGROUND: Choroidal neovascularization (CNV) is the main cause of vision loss in age-related macular degeneration (AMD). In experimental CNV, endothelial progenitor cells (EPCs) contribute to the formation of new vessels. The aim of this study was to investigate whether the behavior of EPCs in patients with AMD supports a role for EPCs in human CNV. METHODS: The number of circulating EPCs that are considered pure endothelial precursors and EPCs with monocytic characteristics, and the plasma levels of regulatory cytokines were evaluated in 23 patients with AMD with active CNV and 20 matched controls. In the patients, this profile was re-evaluated after ranibizumab. RESULTS: When compared with controls, the patients with AMD showed a lower number of both EPC types (P = 0.03) and higher plasma levels (P = 0.03) of stromal cell-derived factor 1. Three monthly injections of ranibizumab returned to control levels the number of circulating EPCs considered pure endothelial precursors and of stromal cell-derived factor 1, but not of monocytic EPCs. CONCLUSION: The observations indicate responsiveness of circulating EPCs to the CNV process in AMD. They suggest the hypothesis that increased stromal cell-derived factor 1 production at the CNV site (reflected in higher plasma levels) recruits EPCs from the circulation, and that antivascular endothelial growth factor therapy selectively decreases the recruitment of cells to be incorporated into new vessels.

Central Bouquet Hemorrhages in Pathologic Myopia: Clinical Characteristics and Prognostic Relevance.

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

Integrating Machine Learning and Traditional Survival Analysis to Identify Key Predictors of Foveal Involvement in Geographic Atrophy.

Purpose: The purpose of this study was to investigate the incidence of foveal involvement in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), using machine learning to assess the importance of risk factors. Methods: Retrospective, longitudinal cohort study. Patients diagnosed with foveal-sparing GA, having GA size ≥ 0.049 mm² and follow-up ≥ 6 months, were included. Baseline GA area, distance from the fovea, and perilesional patterns were measured using fundus autofluorescence. Optical coherence tomography assessed foveal involvement, structural biomarkers, and outer retinal layers thickness. Onset of foveal involvement was recorded. Foveal survival rates were estimated using Kaplan-Meier curves. Hazard ratios (HRs) were assessed with mixed model Cox regression. Variable Importance (VIMP) was ranked with Random Survival Forests (RSF), with higher scores indicating greater predictive significance. Results: One hundred sixty-seven eyes (115 patients, average age = 75.8 ± 9.47 years) with mean follow-up of 50 ± 29 months, were included in this study. Median foveal survival time was 45 months (95% confidence interval [CI] = 38-55). Incidences of foveal involvement were 26% at 24 months and 67% at 60 months. Risk factors were GA proximity to the fovea (HR = 0.97 per 10-µm increase, 95% CI = 0.96-0.98), worse baseline visual acuity (HR = 1.37 per 0.1 LogMAR increase, 95% CI = 1.21-1.53), and thinner outer nuclear layer (HR = 0.59 per 10-µm increase, 95% CI = 0.46-0.74). RSF analysis confirmed these as main predictors (VIMP = 16.7, P = 0.002; VIMP = 6.2, P = 0.003; and VIMP = 3.4, P = 0.01). Lesser baseline GA area (HR = 1.09 per 1-mm2 increase, 95% CI = 1.01-1.16) and presence of a double layer sign (HR = 0.42, 95% CI = 0.20-0.88) were protective but less influential. Conclusions: This study identifies anatomic and functional factors impacting the risk of foveal involvement in GA. These findings may help identify at-risk patients, enabling tailored preventive strategies.

Photoreceptor Integrity in MEWDS: Longitudinal Structure-Function Correlations.

Purpose: The purpose of this study was to investigate structure-function correlations in multiple evanescent white dot syndrome (MEWDS) using microperimetry (MP) and spectral-domain optical coherence tomography (SD-OCT). Methods: Single-center prospective observational study including 14 eyes from 13 patients with MEWDS monitored over a median of 49.5 days (interquartile range = 29-92 days). Investigations focused on best-corrected visual acuity (BCVA), foveal granularity, and the Photoreceptor Reflectivity Ratio (PRR) as a measure of photoreceptor integrity. MP assessed average retinal threshold sensitivity (RTS) and bivariate contour ellipse area (BCEA) for fixation stability. A linear mixed model was used to test associations and interactions among RTS, time, and clinical variables. A hierarchical linear mixed model was used to analyze structure-function relationships, addressing both individual and location-specific variations. Results: Overall, 2340 MP locations were tested. PRR revealed a transient decrease within 30 days post-presentation, indicative of early photoreceptor disruption, followed by a progressive increase, signaling recovery. Significantly lower foveal sensitivity (RTS = 14.8 ± 7.4 vs. 22.5 ± 4.4 decibel [dB], P = 0.04) and increased fixation spread (63% BCEA = 1.26 ± 0.97 vs. 0.48 ± 0.35 deg2, P = 0.06) were noted in eyes with foveal granularity compared to those without. A significant increase in RTS was demonstrated over time (0.066 dB/day, P < 0.001), with a central-to-peripheral gradient of improvement. The interaction between follow-up time and baseline BCVA (P < 0.001) indicated more rapid improvement in eyes with worse initial vision. There was a robust, nonlinear association between PRR and RTS across all tested locations (P < 0.001), becoming asymptotic for sensitivity losses exceeding 20 dB. Conclusions: Photoreceptor reflectivity accurately aligned with visual function in MEWDS on longitudinal examinations. The central-to-peripheral gradient of improvement may suggest specific vulnerabilities underlying the area around the disc.

Distinct Pathways of Macular Atrophy in Type 3 Macular Neovascularization Associated With AMD.

Purpose: To explore the occurrence of macular atrophy (MA) in eyes with age-related macular degeneration (AMD)-associated Type 3 macular neovascularization (MNV) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Importantly, we aimed at describing the existence of separate pathways leading to MA. Methods: We analyzed 41 participants (41 eyes) with treatment-naïve Type 3 MNV who were followed up for a duration of 12 months after beginning the anti-VEGF therapy. At the one-year follow-up visit, optical coherence tomography (OCT) scans were reviewed for the presence of MA. MA regions of interest (ROIs) were selected and traced back to their original dominant baseline lesion (i.e., precursor) through previous serially captured OCT scans. Baseline lesions included precursors associated with the development and exudation of MNV and causes external to the neovascularization itself. Results: At the one-year follow-up visit, MA was graded to be present in 38 (92.7%) out of 41 eyes. These 78 MA ROIs were divided into two subgroups according to the precursor lesion, yielding a group of 53 MA lesions with precursors associated with the development and exudation of MNV (i.e., MA caused by physical harm from Type 3 neovessels, collapse of a serous pigment epithelium detachment, and fibrosis) and 25 MA regions with precursors external to the neovascularization itself (i.e., MA caused by drusen or subretinal drusenoid deposits). Conclusions: Eyes with Type 3 MNV are commonly complicated by MA and precursors of MA include causes associated with the development and exudation of MNV, as well as lesions unrelated to the neovascularization process itself.

Choroidal Hyper-Reflective Foci in Geographic Atrophy.

Purpose: The purpose of this study was to describe the presence of choroidal hyper-reflective foci (HRF) on optical coherence tomography (OCT) in patients with geographic atrophy (GA). The relationship between the presence and quantity of choroidal HRF and other clinical and imaging factors was also investigated. Methods: A total of 40 participants (40 eyes) with GA and age-related macular degeneration (AMD) were retrospectively analyzed. OCT images were reviewed for the presence, characteristics, and localization of choroidal HRF. The amount of choroidal HRF was quantified in different choroidal layers by two different (i.e. threshold reflectivity and manual counting) methodologies. The primary outcome was to describe and quantify choroidal HRF and correlate them with GA lesion size. Results: Structural OCT images showed that all patients had multiple hyper-reflective deposits in different layers of the choroid. These hyper-reflective deposits in the choroid were located near Bruch's membrane or the edges of the blood vessels, particularly in the Sattler's layer, and none were observed inside the vessels. Choroidal HRF exhibited variable size and shape and varying effects on the posterior signal, including shadowing or hypertransmission. Mean ± SD number of choroidal HRF per B-scan was 21.5 ± 15.4 using the threshold reflectivity methodology and 25.1 ± 16.0 using the manual counting methodology. A significant correlation between the untransformed GA size and number of HRF was found, considering both quantitative strategies. Conclusions: Hyper-reflective dots in the choroid of subjects with GA may be readily identified with structural OCT. These HRF might represent a natural component of the choroid that becomes more visible due to the absence of the retinal pigment epithelium.

Morphometric Risk Factors for Drusenoid Pigment Epithelium Detachment Collapse and Retinal Pigment Epithelium Atrophy Expansion.

Purpose: The purpose of this study was to investigate factors associated with drusenoid pigment epithelium detachment (dPED) growth rate, incidence of dPED collapse, and retinal pigment epithelium (RPE) atrophy enlargement rate following dPED collapse and their impact on visual acuity (VA). Methods: This was a retrospective longitudinal study on 44 eyes. Serial spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF) imaging were performed. Qualitative features and quantitative dPED-related metrics were assessed. The surface-to-volume ratio (S/V) was computed to evaluate dPED shape irregularity. AF imaging was utilized to measure RPE atrophy area in eyes experiencing dPED collapse. Regression models were used to analyze associations among VA, dPED growth rate, and RPE atrophy enlargement rate. Cox regression was used to identify risk factors for dPED collapse. Results: Significant correlations were observed between dPED area, surface, and volume (P < 0.05 for all pairs). The dPED metrics were inversely correlated with the S/V. Incidence of dPED collapse was 22 per 100 eye-years over a mean follow-up of 59 ± 41 months. Eyes experiencing collapsed dPED had worse baseline VA (P < 0.001). RPE hypertransmission (hazard ratio [HR] = 3.68, P = 0.004) and hyper-reflective foci (HR = 3.45, P = 0.02) were risk factors for dPED collapse; a higher S/V ratio was protective (HR = 0.78, P = 0.03). A faster rate of RPE atrophy enlargement was associated with a faster rate of dPED volume increase (r = 0.47, P = 0.02) and worse VA over time (P = 0.02). Conclusions: Risk stratification in patients with dPED can be aided by identifying risk factors for dPED collapse. Identifying factors associated with RPE atrophy enlargement may have implications for treatment decision making.