Subretinal Exudation: The First Presentation of Untreated Choroidal Melanomas.

Introduction: This case series aims to present the unusual clinical manifestation of subretinal exudation in patients diagnosed with untreated choroidal melanoma. A total of 886 patients were diagnosed and treated for primary choroidal melanoma between November 2017 and June 2023 at St. Paul's Eye Unit, Royal Liverpool University Hospital, UK. The fundus photographs were screened for lipid exudates by two independent clinical experts. The patients' demographics, clinical manifestations, and imaging features were analysed, whereas the location of exudation was documented with fundus photographs and optical coherence tomography (OCT). The histopathological and genetic results were also analysed in cases with tumour biopsy available. Case Presentations: Eight cases with subretinal exudates were identified (n = 8/886, 0.90%). No gender predilection was noticed (male/female 1:1), whereas the mean age was 51 years (range 39-79). Four patients were asymptomatic at presentation, 2 patients reported reduced visual acuity, and 2 patients presented with photopsia. OCT scans revealed the presence of subretinal fluid and subretinal exudates, while the ultrasound showed medium or low internal reflectivity in 7 out of 8 cases. The biopsy analysis was available in 4 cases, all showing low-risk spindle cell choroidal melanoma with disomy 3. Conclusion: Lipid exudates are an atypical fundoscopic finding in patients with untreated choroidal melanoma. The subretinal location could differentiate them from other retinal vascular conditions and facilitate early diagnosis and intervention. Interestingly, all cases tested cytogenetically were of low metastatic risk; these exudates may, therefore, be a positive clinical prognostic sign.

Geographic Atrophy-associated Intraretinal Neovascularization (GAIN): A novel clinical entity.

KEY MESSAGES     : WHAT IS KNOWN : Geographic atrophy could be associated with MNV or other vascular alterations. Intraretinal fluid could be present in GA also without neovascularization. WHAT IS NEW : GAIN is a novel clinical entity characterized by GA and an intraretinal neovascular network. GAIN could be exudative or non-exudative.

Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration.

Age-related macular degeneration (AMD), a prevalent and progressive degenerative disease of the macula, is the leading cause of blindness in elderly individuals in developed countries. The advanced stages include neovascular AMD (nAMD), characterized by choroidal neovascularization (CNV), leading to subretinal fibrosis and permanent vision loss. Despite the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in stabilizing or improving vision in nAMD, the development of subretinal fibrosis following CNV remains a significant concern. In this review, we explore multifaceted aspects of subretinal fibrosis in nAMD, focusing on its clinical manifestations, risk factors, and underlying pathophysiology. We also outline the potential sources of myofibroblast precursors and inflammatory mechanisms underlying their recruitment and transdifferentiation. Special attention is given to the potential role of mast cells in CNV and subretinal fibrosis, with a focus on putative mast cell mediators, tryptase and granzyme B. We summarize our findings on the role of GzmB in CNV and speculate how GzmB may be involved in the pathological transition from CNV to subretinal fibrosis in nAMD. Finally, we discuss the advantages and drawbacks of animal models of subretinal fibrosis and pinpoint potential therapeutic targets for subretinal fibrosis.

Hyperautofluorescent material inside areas of macular atrophy may reveal non-lipofuscin fluorophores in late stage AMD.

PURPOSE: To characterize fundus autofluorescence (FAF) in complete (cRORA) and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) by fluorescence lifetime imaging ophthalmology (FLIO). METHODS: Overall, 98 macular atrophy (MA) lesions in 42 eyes of 37 age-related macular degeneration (AMD) patients (mean age: 80.9 ± 5.8 years), 25 of them classified as iRORA and 73 as cRORA by OCT, were investigated by FLIO in a short (SSC: 498-560 nm) and a long wavelength channel (LSC: 560-720 nm). Differences of FAF lifetimes and peak emission wavelength (PEW) between atrophic lesions and intact retinal pigment epithelium (RPE) in the outer ring of the ETDRS grid were considered. RESULTS: FAF lifetimes in MA were longer and PEW were significantly (p < 0.001) shorter than in intact RPE by 112 ± 78 ps (SSC), 91 ± 64 ps (LSC), 27 ± 18 nm (PEW) in iRORA and by 227 ± 112 ps (SSC), 167 ± 81 ps (LSC), and 54 ± 17 nm (PEW) in cRORA. 37% of iRORA and 24% of cRORA were hyperautofluorescent in SSC. Persistent sub-RPE-BL material in MA was newly found as a hyperautofluorescent entity with lifetimes considerably longer than that of drusen and RPE. CONCLUSIONS: Despite RPE and, thus, lipofuscin are greatly absent in MA, considerable FAF, preferably at short wavelengths, was found in those lesions. Drusen, persistent sub-RPE-BL material, basal laminar deposits, persistent activated RPE, and sclera were identified as putative sources of this fluorescence. FLIO can help to characterize respective fluorophores.

MERLIN: Two-Year Results of Brolucizumab in Participants With Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid.

PURPOSE: To report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination). DESIGN: Multicenter, randomized, double-masked Phase 3a study. PARTICIPANTS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment). METHODS: Study eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination. MAIN OUTCOME MEASURES: All available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses. RESULTS: Brolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9-37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively. CONCLUSIONS: Consistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.

Non-redundant role of leishmanolysin-like (Lmln) zinc-metallopeptidase in retinal homeostasis.

PURPOSE: To determine if Lmln, a Zn-metallopeptidase, is important for retinal homeostasis. METHODS: Combining an unbiased N-ethyl-N-nitrosourea mutagenesis pipeline in mice with optical coherence tomography (OCT) screening and automated meiotic mapping, we identified an allele (nemeth) that seemed to be associated with outer nuclear layer (ONL) thinning. Since nemeth was predicted to lead to a nonsense mutation of the Lmln gene, we targeted Lmln using CRISPR/Cas-9 technology and characterized the impact on retinal anatomy and function. RESULTS: OCT imaging demonstrated an outer retinal degeneration in Lmln-/- mice (P = 7.3 × 10-9 for ONL at 2 m) that progressed over the first 6 months of life and then stabilized. Light microscopy showed loss of ONL nuclei (P ranged between .00033 and .0097 for posterior measurements), and a TUNEL assay revealed a small but significant increase in apoptosis (P = .034). Lmln-/- mice accumulated fundus spots (P = .0030 by 2 m of age) and activated subretinal microglia (p ranged from .0007 to 8 × 10-13 for Gal3+ cells). Scotopic electroretinography demonstrated a decrease in retinal function in Lmln-/- mice both at 6 m (only a-wave, P < .01 for all stimuli) and at 10 m of age (P < .01 for both a-wave and b-wave with all stimuli). CONCLUSIONS: Our work revealed a previously unknown essential requirement for Lmln in maintaining retinal anatomy and function. Further studies using this new model will be aimed at determining the cellular expression of Lmln and its mechanisms of action within the retina.

Aqueous humor cytokine levels in patients with subretinal fibrosis in neovascular age-related macular degeneration.

PURPOSE: To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity. METHODS: The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB). RESULTS: Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P < 0.05), and VEGF, bFGF and TGF-α levels were significantly higher in SRFi patients than controls (all P < 0.05). No significant differences in 4 cytokine levels were observed between nAMD and SRFi patients in aqueous humor. We also identified a positive correlation between the aqueous humor levels of IL-6 and VEGF in the SRFi group, while bFGF and TGF-α in the nAMD group. Moreover, VEGF levels were strongly related to BCVA, and bFGF levels were positively related to the maximum thickness of subretinal hyperreflective material (SHRM) in fibrosis due to nAMD. CONCLUSION: VEGF and bFGF levels in aqueous humor were elevated in macular neovascularization with and without subretinal fibrosis. TGF-α levels exclusively differed in neovascular AMD with fibrosis. Cytokines are distributed differently and play a synergistic role in different stages (angiogenesis and fibrogenesis) of nAMD. The bFGF levels could predict the negative prognosis in fibrosis due to nAMD.

Bilateral Acute Proptosis With Papilledema and Sub-retinal Fluid As Initial Manifestations of Acute Lymphoblastic Leukemia in a Child.

A five-year-old boy presented with bilateral acute proptosis, papilledema, and sub-retinal fluid. Notably, choroidal thickening exceeded 600 microns. These ocular findings were the initial manifestations of acute lymphoblastic leukemia. This case underscores the importance of recognizing uncommon ocular presentations in pediatric leukemia for timely diagnosis and management.

Elderly Patient With Bilateral Central Serous Chorioretinopathy Misdiagnosed as Bilateral Wet Age-Related Macular Degeneration: A Case Report.

This report presents a unique case of a 77-year-old diabetic male patient with bilateral central serous chorioretinopathy (CSCR), who was receiving multiple bilateral intravitreal injections for a presumed diagnosis of wet age-related macular degeneration (AMD). The fundus examination did not show any signs of AMD or diabetic retinopathy (DR). The spectral domain optical coherence tomography (OCT) revealed bilateral subretinal fluid. The neovascular membrane was not visible on OCT angiography. Fundus fluorescein angiography (FFA) confirmed the absence of choroidal neovascularization (CNV). Notably, this represents a unique case of an elderly patient with CSCR mimicking occult CNV.

A Case of Incidental and Uncomplicated Subretinal Triamcinolone Acetonide.

Introduction: Posterior subtenon injection of triamcinolone acetonide (PSTA) is commonly done to treat refractory cases of macular edema. Complications may arise from the procedure as well as from the use of the periocular steroid medications. Side effects include subconjunctival hemorrhage, progression of cataract, scleral perforation (resulting in subretinal, subhyaloid, or intravitreal injection of the drug), retinal detachment, ptosis, orbital fat prolapse, orbital abscess, infectious scleritis, ocular hypertension, and scleral abscess. Here we describe a case of inadvertent subretinal triamcinolone acetonide (TA) deposition from a PSTA procedure without any adverse vision-threatening outcomes. Case Presentation: We report a patient who presented with a history of superior temporal left eye macula-off rhegmatogenous retinal detachment, which was successfully repaired with a scleral buckle (SB), pars plana vitrectomy, and gas placement. Due to persistent diplopia, the SB was removed after 1 year post-operatively. Due to the development of cystoid macular edema, a PSTA was performed after the patient failed topical steroids and NSAIDs. The procedure was halted early due to unexpected resistance during the injection. A dilated fundus exam showed the presence of subretinal triamcinolone acetonide. The patient was observed and found to have no complications with almost complete resolution of the triamcinolone acetonide after 3 months. Conclusion: In previous SB patients, it is important to highlight the risk of globe penetration, subretinal deposition of TA, formation of retinal breaks, or reopening of prior retinal breaks with posterior subtenon injection, which could have adverse effects on the local retina as well as the risk of retinal detachment.

The Usefulness of 55° Wide-Field Spectral-Domain Optical Coherence Tomography in Monitoring the Features of Peripheral Subretinal Fluid Remnants after Rhegmatogenous Retinal Detachment Surgery.

BACKGROUND: This study aimed to assess the effectiveness of 55° wide-field (WF) spectral-domain (SD) optical coherence tomography (OCT) for detecting peripheral subretinal fluid (SRF) after surgery for rhegmatogenous retinal detachment (RRD). METHODS: In this retrospective observational study, the retinal periphery was examined to evaluate the possible presence of persistent SRF after surgery. OCT scans were acquired in infrared mode to use any peripheral vessel as a landmark for better repeatability in monitoring fluid remnants. RESULTS: A total of 80 patients (10% with high myopia) were examined using 55° WF SD OCT after successful pars plana vitrectomy (83.8%) or scleral buckling (16.3%) for RRD. A total of 18 patients (22.5%), 16 of whom underwent pars plana vitrectomy and 2 who underwent scleral buckling, showed SRF at the OCT examination during the follow-up. Potential risk factors associated with SRF persistence were analyzed, revealing a significative association with young age (p = 0.009). After a follow-up period of 7.05 ± 2.44 months (ranging from 3 to 12 months), a complete resorption in all patients (100%) within 12 months was observed. Best-corrected visual acuity significantly improved in both groups over time. CONCLUSION: Using 55° WF SD-OCT successfully assessed the course of SRF reabsorption, offering a viable alternative for all those realities where technologies such as ultra-wide-field (UWF) OCT are not available.

Prothrombin deficiency with recurrent subretinal hemorrhage.

Ocular hemorrhage has been recorded in congenital factor deficiencies like hemophilia A, but it has never been documented in prothrombin deficiency. Here, we describe an unusual case of sudden vision loss in the right eye caused by subretinal hemorrhage following a coughing episode in a 67-year-old woman. Notably, the patient underwent left eye enucleation 12 years previously under similar circumstances due to subretinal hemorrhage. During the interview, it was discovered that the patient had a history of prothrombin deficiency, which was subsequently confirmed through laboratory testing. Aside from recurrent ocular bleeding and 1 instance of bleeding following dental extraction in childhood, there is no other history of bleeding. Subsequent molecular studies revealed a homozygous missense mutation at G1499A (Arg500Gln), a variant previously identified as R457Q. Although the likelihood of prothrombin deficiency initiating subretinal hemorrhage is low, it is likely to worsen retinal hemorrhage and contribute to difficulty in controlling bleeding. A comprehensive coagulation workup is essential in patients with ocular hemorrhage. Determining factor II activity should be included in individuals exhibiting variably prolonged prothrombin time and activated partial thromboplastin time with correction in mixing studies. Additional investigations, such as genetic sequencing and family studies, are advised for those with isolated low prothrombin levels.

Retro Mode Imaging for Detection and Quantification of Sub-RPE Drusen and Subretinal Drusenoid Deposits in Age-Related Macular Degeneration.

Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm2 (deviated left mode (DL)) and 105.4 ± 45.5 mm2 (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm2) and BAF imaging (49.1 ± 42.9 mm2) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD.

Changes in the outer nuclear layer and choroidal vascularity during the manifest and quiescent phases of acute central serous chorioretinopathy.

To investigate alteration of outer nuclear layer (ONL) and choroidal vascularity index (CVI) in different status of central serous chorioretinopathy (CSC). A retrospective review of 65 CSC eyes with subretinal fluid (manifest CSC) and 40 control eyes was conducted in a single tertiary university hospital. Differences in best-corrected visual acuity (BCVA), ONL, and CVI were compared. CVI was assessed both in the entire choroid (CVI-EC) and around the 1500 µm leakage area (CVI-1500). Measurements were repeated after the subretinal fluid resorption (quiescent CSC), and compared. CSC eyes showed worse BCVA, thinner ONL and greater CVI than controls. Quiescent CSC showed a recovery of ONL compared to the manifest CSC, along with the BCVA improvement. The resolution of the CSC revealed a decrease across all three choroidal areas (total, stromal and luminal), with a more pronounced reduction in the stromal than in the luminal choroidal area, leading to an increase in the CVI. This phenomenon was shown in both CVI-EC and CVI-1500. Conclusively, ONL thickness can be used as a quantitative biomarker for photoreceptor function in CSC. Increased CVI may reflect a disease activity. The stromal choroidal area is particularly sensitive in illustrating leakage from the choroidal vasculature.

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study.

Purpose: This study investigates the efficacy of transitioning patients with neovascular age-related macular degeneration (nAMD) from aflibercept (T1) to biosimilar ranibizumab (T2), an approach not previously documented in literature. Methods: In this multicenter observational study, patients over 50 years of age with nAMD were shifted from intravitreal aflibercept (IVI AFL) to biosimilar ranibizumab (B-RBZ) due to financial constraints. This study employed standardized ophthalmological methods to assess visual acuity (VA), central macular thickness (CMT), and subretinal and intraretinal fluid. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and linear regression. Results: A total of 29 eyes (12 males and 17 females) were analyzed. Mean age was 72.55 ±6.43 years. VA improved significantly during T1, with a mean increase from 55.0 ± 10.2 to 70.0 ± 8.5 ETDRS letters at the switch time point (p < 0.01), then a slight decrease to 62.3 ± 8.9 at 12 months (p < 0.05) was noted during T2. The mean CMT decreased notably from 400 ± 50 to 290 ± 45 µm at the switch. The final CMT at 12 months after switching to B-RBZ was 280 ± 40 µm (p < 0.01). There was a significant decrease in the retinal and intra retinal fluid during T1, followed by a gradual increase during T2. A significant correlation (p < 0.05) was noted between the presence of intraretinal fluid and increased injection frequency of B-RBZ. Conclusion: The switch from IVI AFL to IVI B-RBZ in patients with nAMD demonstrated efficacy in maintaining the VA and macular anatomy, with some challenges in fluid management.

[Use of artificial intelligence for recognition of biomarkers in intermediate age-related macular degeneration]. / Einsatz von künstlicher Intelligenz zur Erkennung von Biomarkern bei der intermediären altersabhängigen Makuladegeneration.

Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research. In this context AI provides a solution by fully automatic segmentation and therefore delivers exact, reproducible and quantitative analyses of AMD-related biomarkers. Furthermore, the application of AI in iAMD facilitates the risk assessment and the development of structural endpoints for new forms of treatment. For example, the quantitative analysis of drusen volume and hyperreflective foci with AI algorithms has shown a correlation with the progression of the disease. These technological advances therefore improve not only the diagnostic precision but also support future targeted treatment strategies and contribute to the prioritized target of personalized medicine in the diagnostics and treatment of AMD.

Association between three-dimensional morphological features and functional indicators of neovascular age-related macular degeneration.

PURPOSE: To investigate the correlation between morphological lesions and functional indicators in eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a prospective observational study of treatment-naïve nAMD eyes. Various morphological lesions and impaired retinal structures were manually measured at baseline and month-3 in three-dimensional optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images, including the volumes (mm3) of macular neovascularization (MNV), avascular subretinal hyperreflective material (avascular SHRM), subretinal fluid (SRF), intraretinal fluid (IRF), serous pigment epithelial detachment (sPED) and the impaired area (mm2) of ellipsoid zone (EZ), external limiting membrane (ELM) and outer nuclear layer (ONL). RESULTS: Sixty-three eyes were included. The volume of avascular SHRM showed persistent positive associations with the area of EZ damage, both at baseline, month-3, and change values (all P < 0.001). Poor BCVA (month-3) was associated with larger volumes of baseline IRF (ß = 0.377, P < 0.001), avascular SHRM (ß = 0.306, P = 0.032), and ELM impairment area (ß = 0.301, P = 0.036) in multivariate model. EZ and ELM impairment were primarily associated with baseline avascular SHRM (ß = 0.374, p = 0.003; ß = 0.388, P < 0.001, respectively), while ONL impairment primarily associated with MNV (ß = 0.475, P < 0.001). CONCLUSION: The utilization of three-dimensional measurements elucidates the intrinsic connections among various lesions and functional outcomes. In particular, avascular SHRM plays an important role in prognosis of nAMD.

Multimodal Imaging of Bilateral Retinal Pigment Epithelial Immunoglobulin Light Chain Deposition in Patients with Systemic Immunoglobulin Light Chain Deposition.

OBJECTIVE: To describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DESIGN: A retrospective observational case series. PARTICIPANTS: We examined 6 eyes in 3 patients (1 with multiple myeloma, 1 with membranous nephropathy, and 1 with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch's membrane complex and acquired serous retinal detachment. METHODS: Fundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain OCT, swept-source OCT (SS-OCT), en face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. MAIN OUTCOME MEASURES: Multimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. RESULTS: Bilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch's membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and "angiographically silent" serous retinal detachment in patients with systemic immunoglobulin light chain deposition. CONCLUSIONS: We have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER.

OBJECTIVE: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies. DESIGN: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies. PARTICIPANTS: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study. INTERVENTION: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing. MAIN OUTCOME MEASURES: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval). RESULTS: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16. CONCLUSIONS: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER). FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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 (SDDs) and leptochoroid. DESIGN: Retrospective, cohort study. SUBJECTS: The study compared patients affected by LVM with cohorts displaying a similar phenotypic spectrum. This included patients with acquired vitelliform lesions (AVLs) and those with SDDs alone. METHODS: A total of 60 eyes of 60 patients were included, of which 20 eyes had LVM, 20 eyes had AVLs, and the remaining had SDDs. Patients >50 years of age with complete medical records and multimodal imaging for ≥6 months of follow-up, including color fundus photography or MultiColor imaging, OCT, fundus autofluorescence, and OCT angiography 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 with both LVM (P = 0.001) and SDD subgroups (P < 0.001). The proportion of late-stage complications significantly differed among subgroups (chi-square = 7.5, P = 0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, whereas the remaining eyes presented a similar proportion of complications, including 20% in the AVL group after 27.6 months and 20% in the SDD group 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 the LVM group 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 SDDs 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 their higher propensity for faster progression and elevated rate of complications, particularly atrophic conversion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.