Bruch's Membrane Research Articles

Comprehensive review of angioid streaks.

Angioid streaks are irregular breaks in the brittle Bruch's membrane and commonly present as pigmented linear lines radiating from the optic disc. They may be associated with systemic disease in up to 50% of the patients. Systemic diseases such as pseudoxanthoma elasticum, Paget's disease, and hemoglobinopathies are commonly associated with angioid streaks. However, they may be idiopathic in a small number of cases. Patients may be asymptomatic until complications such as choroidal neovascular membrane and subretinal hemorrhage involving the fovea develop. Due to the brittle nature of Bruch's membrane, even minor trauma could lead to subretinal hemorrhage in these eyes. Diagnosis is commonly made through clinical examination and investigations such as fundus autofluorescence and optical coherence tomography. Treatment consists of management of the choroidal neovascular membrane commonly through intravitreal antivascular endothelial growth factor injections. In this review, we provide an overview of angioid streaks right from their epidemiology to their management.

Characterization of drusen formation in a primary porcine tissue culture model of dry AMD

Age-related macular degeneration (AMD) affects millions of individuals worldwide and is a leading cause of blindness in the elderly. In dry AMD, lipoproteinaceous deposits called drusen accumulate between the retinal pigment epithelium (RPE) and Bruch's membrane, leading to impairment of oxygen and nutrient trafficking to the neural retina, and degeneration of the overlying photoreceptor cells. Owing to key differences in human and animal ocular anatomy and the slowly progressing nature of the disease, AMD is not easily modeled invivo. In this study, we further characterize a "drusen-in-a-dish" primary porcine RPE model system by employing vital lipid staining to monitor sub-RPE deposition over time in monolayers of cells cultured on porous transwell membranes. We demonstrate for the first time using a semi-automated image analysis pipeline that the number and size of sub-RPE deposits increases gradually but significantly over time and confirm that sub-RPE deposits grown in culture immunostain positive for multiple known components found in human drusen. As a result, we propose that drusen-in-a-dish cell culture models represent a high-throughput and cost-scalable alternative to animal models in which to study the pathobiology of drusen accumulation and may serve as useful tools for screening novel therapeutics aimed at treating dry AMD.

Relationship between the length of macular Bruch's membrane on fundus photograph and myopia occurrence in pre-myopia children aged 3–6 years: A 3-year longitudinal study

PurposeTo evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3–6 years. MethodsThis study included 204 pre-myopia (-0.50D<spherical equivalent (SE) ≤+0.75D) children with three years follow-up in Beijing Hyperopia Reserve Research. All participants underwent a comprehensive eye examination. The length of macular Bruch's membrane (BM) and the temporal vascular arcade angle were measured upon fundus photographs. ResultsMean age at initial visit was 4.28 ± 0.98 years and mean SE was 0.45 ± 0.29D. Both at baseline and after 3 years of follow-up, axial length was longer in boys than that in girls. (all P < 0.001) Children were divided into two groups according to the refractive status of children at the final follow-up: Myopia group (SE≤-0.50D) and Non-myopia group (SE>-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008–0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055–0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) ConclusionsInitial SE and the length of macular BM in pre-myopia children aged 3–6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process.

Exploration of Choroidal Thinning Located Temporal to the Fovea: A Pilot Study.

Background/Objectives: Posterior staphyloma (PS) is a hallmark of pathological myopia, corresponding to a circumscribed outpouching of the eyeball with choroidal thinning and inward scleral deformation at its edges. Its pathogenesis is still unclear, thus constituting a research priority as the prevalence of myopia is increasing worldwide. Recently, it has been suggested that the optic nerve sheaths or oblique muscles are potential promoters of PS through the traction or compression effect that they apply to the eye wall. The inferior oblique muscle (IOM) inserts 1-2 mm from the macula. The projection of its insertion is accessible using Optical Coherence Tomography (OCT). Before launching prospective studies, we sought to detect any choroidal thinning (ChT) in the temporal vicinity of the macula and to measure the distance between it and the fovea (FT-distance). Methods: This retrospective cross-sectional pilot study included 120 eyes. Using Spectralis®-OCT, the area centered by the Bruch's membrane opening-fovea axis was analyzed for ChT and FT-distance. Results: Of the 112 defined eyes, 70% (78 eyes) had ChT. Pachymetry was significantly thinner (p = 0.018) in eyes with than without ChT. The mean FT-distance was 3601.9 ± 93.6 µm. Conclusions: The location of ChT coincided with the insertion distance of the IOM, suggesting a link between them. The association between the presence of ChT and a thinner pachymetry suggests a reduced scleral resistance, as a thinner pachymetry is related to a thinner sclera. Our results suggest a link between ocular deformation and the IOM, which may be relevant for the pathogenesis of PS, warranting further investigation.

Sources of Discrepancy between Retinal Nerve Fiber Layer and Bruch’s Membrane Opening-Minimum Rim Width Thickness in Eyes with Glaucoma

To compare the discrepancies between circumpapillary retinal nerve fiber layer (RNFL) and Bruch's membrane opening-minimum rim width (BMO-MRW) thickness in glaucoma eyes. A cross-sectional observational study. One hundred eighty-six eyes (118 patients) with glaucoma. OCT optic nerve head volume scans of patients enrolled in the Advanced Glaucoma Progression Study at the final available visit were exported. The RNFL and BMO-MRW measurements were averaged into corresponding 7.5° sectors, and the nasal sector data were excluded from analyses. A 2-stage screening process was used to identify true mismatches between the RNFL and BMO-MRW measurements, in which either the RNFL or BMO-MRW value was in the less than first percentile range while its counterpart was in the greater than first percentile range on the temporal-superior-nasal-inferior-temporal curve. The prevalence of these mismatches was mapped, and corresponding images were reviewed to determine the underlying cause of these discrepancies. Proportion of mismatches between RNFL and BMO-MRW, location of mismatches between RNFL and BMO-MRW, anatomical causes of mismatches between RNFL and BMO-MRW. Mismatch analysis revealed true mismatches between RNFL and BMO-MRW in 7.7% of sectors. High BMO-MRW with low corresponding RNFL mismatches were most frequently located at the 45° and 322.5° sectors, whereas high RNFL with corresponding low BMO-MRW mismatches peaked at the 75° sector. Large blood vessels accounted for 90.9% of high RNFL with low BMO-MRW mismatches. Small to large blood vessels accounted for 62.9% of high BMO-MRW with low RNFL mismatches; the remaining mismatches could be attributed to retinoschisis or inclusion of outer retinal layers in BMO-MRW measurements. Although overall agreement between RNFL and BMO-MRW measurements is good in areas with advanced damage, blood vessels and other anatomical factors can cause discrepancies between the 2 types of structural measurements and need to be considered when evaluating the utility of such measurements for detection of change. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.

Dysregulated cholesterol metabolism is critical in the pathogenesis of AMD. Cellular senescence contributes to the development of numerous age-associated diseases. In this study, we investigated the link between cholesterol burden and the cellular senescence of photoreceptors. Retinas from rod-specific ATP binding cassette subfamily A member 1 (Abca1) and G member 1 (Abcg1) (Abca1/g1-rod/-rod) knockout mice fed with a high-fat diet were analyzed for the signs of cellular senescence. Real-time quantitative PCR and immunofluorescence were used to characterize the senescence profile of the retina and cholesterol-treated photoreceptor cell line (661W). Inducible elimination of p16(Ink4a)-positive senescent cells (INK-ATTAC) mice or the administration of senolytic drugs (dasatinib and quercetin: D&Q) were used to examine the impact of senolytics on AMD-like phenotypes in Abca1/g1-rod/-rod retina. Increased accumulation of senescent cells as measured by markers of cellular senescence was found in Abca1/g1-rod/-rod retina. Exogenous cholesterol also induced cellular senescence in 661W cells. Selective elimination of senescent cells in Abca1/g1-rod/-rod;INK-ATTAC mice or by administration of D&Q improved visual function, lipid accumulation in retinal pigment epithelium, and Bruch's membrane thickening. Cholesterol accumulation promotes cellular senescence in photoreceptors. Eliminating senescent photoreceptors improves visual function in a model of retinal neurodegeneration, and senotherapy offers a novel therapeutic avenue for further investigation.

Predict and Protect: Evaluating the Double-Layer Sign in Age-Related Macular Degeneration.

Advanced age-related macular degeneration (AMD) is a major cause of vision loss. Therefore, there is interest in precursor lesions that may predict or prevent the onset of advanced AMD. One such lesion is a shallow separation of the retinal pigment epithelium (RPE) and Bruch's membrane (BM), which is described by various terms, including double-layer sign (DLS). In this article, we aim to examine and clarify the different terms referring to shallow separation of the RPE and BM. We also review current evidence on the outcomes associated with DLS: firstly, whether DLS is predictive of exudative neovascular AMD; and secondly, whether DLS has potential protective properties against geographic atrophy. The range of terms used to describe a shallow separation of the RPE and BM reflects that DLS can present with different characteristics. While vascularised DLS appears to protect against atrophy but can progress to exudation, non-vascularised DLS is associated with an increased risk of atrophy. Optical coherence tomography (OCT) angiography (OCTA) is the principal method for identifying and differentiating various forms of DLS. If OCTA is unavailable or not practically possible, simplified classification of DLS as thick or thin, using OCT, enables the likelihood of vascularisation to be approximated. Research is ongoing to automate DLS detection by applying deep-learning algorithms to OCT scans. The term DLS remains applicable for describing shallow separation of the RPE and BM. Detection and classification of this feature provides valuable information regarding the risk of progression to advanced AMD. However, the appearance of DLS and its value in predicting AMD progression can vary between patients. With further research, individualised risks can be confirmed to inform appropriate treatment.

Two-year follow-up of a post-traumatic choroidal rupture with a lens luxation patient: a case report

Background: A choroidal rupture is a break in the choroid, Bruch membrane, and retinal pigment epithelium (RPE) that occurs most commonly as a result of blunt ocular trauma. It may be a secondary effect of direct or indirect trauma. This case illustrates an indirect post-traumatic choroidal rupture with lens luxation. Three months following the incident, the patient presented with impaired vision. The posterior segment was found to have a luxated lens during the objective examination of the eye. The funduscopy revealed a white, curvilinear, crescent-shaped streak that was concentric to the optic nerve. Case description: A 45-year-old male from East Java visited the ophthalmology outpatient clinic with a chief complaint of blurred vision in the left eye for three months, followed by pain in the left eye. On examination, the visual acuity was a one-meter counting finger. The lens was luxated to the posterior. The funduscopy examination revealed a curvilinear crescent-shaped streak. Vitrectomy and lensectomy were implemented. After four months of aphakia, the patient underwent a scleral fixation intraocular lens (IOL) implantation. The visual acuity was satisfactory, and no complications were observed during the two-year follow-up. Conclusion: We reported a post-traumatic choroidal rupture and a lens luxation with an optimal outcome after a two-year follow-up.

Functionalized Collagen I Membranes as a Bruch's Membrane Mimetic for Outer Retinal In Vitro Models.

Physiologically relevant in vitro models of the human outer retina are required to better elucidate the complex interplay of retinal tissue layers and investigate their role in retinal degenerative disorders. Materials currently used to mimic the function of Bruch's membrane fail to replicate a range of important structural, mechanical, and biochemical properties. Here, we detail the fabrication of a surface-functionalized, fibrous collagen I membrane. We demonstrate its ability to better replicate a range of important material properties akin to the function of human Bruch's membrane when compared with a commonly utilized synthetic polyethylene terephthalate alternative. We further reveal the ability of this membrane to support the culture of the ARPE-19 cell line, as well as human pluripotent stem cell-derived RPE-like cells and human umbilical vein endothelial cells. This material could provide greater physiological relevance to the native Bruch's membrane than current synthetic materials and further improve the outcomes of in vitro outer retinal models.

Extensive macular atrophy with pseudodrusen-like appearance: comprehensive review of the literature.

This review focuses on extensive macular atrophy with pseudodrusen-like appearance (EMAP), a recently described maculopathy presenting with pseudodrusen-like lesions and chorioretinal atrophy more pronounced in the vertical axis. Narrative review of the literature published until May 2024. The early onset age of EMAP (50-55 years) and its distinctive natural history, which includes night blindness followed by severe vision loss, differentiate it from atrophic age-related macular degeneration (AMD). A clear pathogenesis has not been determined, but risk factors include female gender and complement system abnormalities (altered levels of C3 and CH50). Moreover, lifelong exposure to pesticides has been suggested as risk factor for direct neuronal degeneration involving rods and cones. In the early phase of the disease, reticular pseudodrusen-like lesions appear in the superior perifovea and tend to coalescence horizontally into a flat, continuous, reflective material localized between the retinal pigmented epithelium and Bruch's membrane. Over time, EMAP causes profound RPE and outer retinal atrophy in the macular area, with a recent classification reporting a 3-stages evolution pattern. Blue autofluorescence showed rapidly evolving atrophy with either hyperautofluorescent or isoautofluorescent borders. Significant similarities between the diffuse-trickling phenotype of geographic atrophy and EMAP have been reported. Macular neovascularization is a possible complication. EMAP is specific form of early-onset atrophic macular degeneration with rapid evolution and no treatment. Further studies are needed to assess the best management.

Topographic Measurement of the Subretinal Pigment Epithelium Space in Normal Aging and Age-Related Macular Degeneration Using High-Resolution OCT.

A micrometer scale hyporeflective band within the retinal pigment epithelium basal lamina - Bruch's membrane complex (RPE-BL-BrM) was topographically measured in aging and age-related macular degeneration (AMD). In a prospective cross-sectional study, 90 normal eyes from 76 subjects (range = 23-90 years) and 53 dry AMD eyes from 47 subjects (range = 62-91 years) were enrolled. Isotropic volume raster scans over 6mm × 6mm (500 × 500 A-scans) were acquired using a high-resolution (2.7 µm axial resolution) spectral-domain optical coherence tomography (SD-OCT) prototype instrument. Six consecutive optical coherence tomography (OCT) volumes were computationally motion-corrected and fused to improve feature visibility. A boundary regression neural network was developed to measure hyporeflective band thickness. Topographic dependence was evaluated over a 6-mm-diameter Early Treatment Diabetic Retinopathy Study (ETDRS) grid. The hyporeflective band thickness map (median of 4.3 µm and 7.8 µm in normal and AMD eyes, respectively) is thicker below and radially symmetric around the fovea. In normal eyes, age-associated differences occur within 0.7 to 2.3mm from the foveal center (P < 0.05). In AMD eyes, the hyporeflective band is hypothesized to be basal laminar deposits (BLamDs) and is thicker within the 3-mm ETDRS circle (P < 0.0002) compared with normal eyes. The inner ring is the most sensitive location to detect age versus AMD-associated changes within the RPE-BL-BrM. AMD eyes with subretinal drusenoid deposits (SDDs) have a significantly thicker hyporeflective band (P < 0.001) than those without SDDs. The hyporeflective band is a quantifiable biomarker which differentiates AMD from aging. Longitudinal studies are warranted. The hyporeflective band may be a useful biomarker for risk stratification and disease progression.

Lacquer cracks in pathological myopia: a clinical review.

Lacquer cracks, described as breaks in the Bruch's membrane, are unique lesions in the spectrum of fundus changes associated with pathological myopia. Lacquer cracks are generally believed to be relatively innocuous lesions by themselves; however, progression to other features of myopic macular degeneration, such as patchy chorioretinal atrophy and choroidal neovascularization, may result in irreversible visual impairment. With the rising prevalence of pathological myopia to epidemic proportions, particularly in the Asian countries, ophthalmologists expect to encounter lacquer cracks more frequently in clinical practice. Therefore, it is crucial for the ophthalmic community to be aware of lacquer cracks and to actively look for these lesions in myopic patients so that early detection and close monitoring can help prevent blinding complications. This article provides a comprehensive review on lacquer cracks in eyes with pathological myopia from a clinical perspective.

Basal Linear Deposit: Normal Physiological Ageing or a Defining Lesion of Age-Related Macular Degeneration?

Objective: To determine if basal linear deposit (BLinD) is a specific lesion of age-related macular degeneration (AMD). Methods: The cohort was selected from a clinically and histopathologically validated archive (Sarks Archive) and consisted of 10 normal eyes (age 55-80 years) without any macular basal laminar deposit (BLamD) (Sarks Group I) and 16 normal aged eyes (age 57-88 years) with patchy BLamD (Sarks Group II). Only eyes with in vivo fundus assessment and corresponding high-resolution transmission electron microscopy (TEM) micrographs of the macula were included. Semithin sections and fellow-eye paraffin sections were additionally examined. BLinD was defined as a diffuse layer of electron-lucent vesicles external to the retinal pigment epithelium (RPE) basement membrane by TEM and was graded as follows: (i) Grade 0, absence of a continuous layer; (ii) Grade 1, a continuous layer up to three times the thickness of the RPE basement membrane (0.9 µm); (iii) Grade 2, a continuous layer greater than 0.9 µm. Bruch's membrane (BrM) hyalinisation and RPE abnormalities were determined by light microscopic examination of corresponding semithin and paraffin sections. Results: BLinD was identified in both normal (30%) and normal aged (62.5%) eyes. BLinD was thicker in normal aged eyes (p = 0.045; 95% CI 0.04-3.4). BLinD thickness positively correlated with both the degree of BrM hyalinisation (p = 0.049; 95% CI 0.05-2.69) and increasing microscopic RPE abnormalities (p = 0.022; 95% CI 0.188-2.422). RPE abnormalities were more likely to be observed in eyes with increased BrM hyalinisation (p = 0.044; 95% CI 0.61-4.319). Conclusions: BLinD is most likely an age-related deposit rather than a specific lesion of AMD. Its accumulation is associated with increasing BrM hyalinisation and microscopic RPE abnormalities, suggesting a relationship with dysregulated RPE metabolism and/or transport.

Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration

Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Retrospective study. Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6× 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 μm on the en face images generated using a slab extending from 64 to 400 μm beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. The mean sqrt area measurements and the number of hyperTDs were compared. The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc= 0.969 and rc= 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P= 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Aberrant lipid accumulation and retinal pigment epithelium dysfunction in PRCD-deficient mice

Progressive Rod-Cone Degeneration (PRCD) is an integral membrane protein found in photoreceptor outer segment (OS) disc membranes and its function remains unknown. Mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans and multiple dog breeds. PRCD-deficient models exhibit decreased levels of cholesterol in the plasma. However, potential changes in the retinal cholesterol remain unexplored. In addition, impaired phagocytosis observed in these animal models points to potential deficits in the retinal pigment epithelium (RPE). Here, using a Prcd−/− murine model we investigated the alterations in the retinal cholesterol levels and impairments in the structural and functional integrity of the RPE. Lipidomic and immunohistochemical analyses show a 5-fold increase in the levels of cholesteryl esters (C.Es) and lipid deposits in the PRCD-deficient retina, respectively, indicating alterations in total retinal cholesterol. Furthermore, the RPE of Prcd−/− mice exhibit a 1.7-fold increase in the expression of lipid transporter gene ATP-binding cassette transporter A1 (Abca1). Longitudinal fundus and spectral domain optical coherence tomography (SD-OCT) examinations showed focal lesions and RPE hyperreflectivity. Strikingly, the RPE of Prcd−/− mice exhibited age-related pathological features such as lipofuscin accumulation, Bruch's membrane (BrM) deposits and drusenoid focal deposits, mirroring an Age-related Macular Degeneration (AMD)-like phenotype. We propose that the extensive lipofuscin accumulation likely impairs lysosomal function, leading to the defective phagocytosis observed in Prcd−/− mice. Our findings support the dysregulation of retinal cholesterol homeostasis in the absence of PRCD. Further, we demonstrate that progressive photoreceptor degeneration in Prcd−/− mice is accompanied by progressive structural and functional deficits in the RPE, which likely exacerbates vision loss over time.

Drusen in the macula and parapapillary region.

To examine histological characteristics and differences between drusen beneath the retinal pigment epithelium (small hard drusen) located in the macula and located in the parapapillary region. We histomorphometrically examined human eyes enucleated due to uveal melanomas or secondary angle-closure glaucoma. The study included 106 eyes (age, 62.6 ± 15.2years) with macular drusen (n = 7 globes) or parapapillary drusen (n = 29 eyes) and 70 eyes without drusen. In all drusen, periodic-acid-Schiff-positive material was located between the RPE basal membrane and the inner collagenous layer of Bruch's membrane (BM). Macular drusen as compared with parapapillary drusen had lower height (15.2 ± 10.1µm versus 34.3 ± 19.8µm; P = 0.003), while both groups did not differ significantly in basal drusen width (74.0 ± 36.3µm versus 108.7 ± 101.0µm; P = 0.95). Eyes with macular drusen and eyes without drusen did not differ significantly in BM thickness (2.74 ± 0.44µm versus 2.55 ± 0.88µm; P = 0.57) or in RPE cell density (35.4 ± 10.4 cells/480µm versus 32.8 ± 7.5 cells/480µm; P = 0.53), neither in the drusen region nor in the drusen vicinity, while BM thickness (4.60 ± 1.490µm; P < 0.001) and RPE cell density (56.9 ± 26.8 cells/480µm; P = 0.005) were higher at the parapapillary drusen. Eyes with macular drusen, eyes with parapapillary drusen, and eyes without drusen did not differ significantly in choriocapillaris density (all P > 0.10) and thickness (all P > 0.35). Limitations of the study, among others, were a small number and size of drusen examined, diseases leading to enucleation, lack of serial sections, limited resolution of light microscopy, and enucleation-related and histological preparation-associated artefacts. The findings of this study, also taking into account its methodological limitations, suggest that macular drusen and parapapillary drusen shared the morphological feature of periodic-acid-Schiff-positive material between the RPE basal membrane and BM and that they did not vary significantly in choriocapillaris thickness and density. RPE cell density and BM thickness were higher in parapapillary drusen than in macular drusen.

Sodium-iodate injection can replicate retinal and choroid degeneration in pigmented mice: Using multimodal imaging and label-free quantitative proteomics analysis

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. Sodium iodate (NaIO3), a stable oxidizing agent, has been injected to establish a reproducible model of oxidative stress-induced RPE and photoreceptor death. The aim of our study was to evaluate the morphological and molecular changes of retina and retinal pigment epithelium (RPE)-choroid in NaIO3-treated mouse using multimodal fundus imaging and label-free quantitative proteomics analysis. Here, we found that following NaIO3 injection, retinal degeneration was evident. Fundus photographs showed numerous scattered yellow-white speckled deposits. Optical coherence tomography (OCT) images indicated disruption of the retinal layers, damage of the RPE layer and accumulation of hyper-reflective matter in multiple layers of the outer retina. Widespread foci of a high fundus autofluorescence (FAF) signal were noticed. Fundus fluorescein angiography (FFA) revealed diffuse intense transmitted fluorescence mixed with scattered spot-like blocked fluorescence. Indocyanine green angiography (ICGA) presented punctate hyperfluorescence. Due to the atrophy of the RPE and Bruch's membrane and choroidal capillary complex, the larger choroidal vessels become more prominent in ICGA and optical coherence tomography angiography (OCTA). Transmission electron microscope (TEM) illustrated abnormal material accumulation and damaged mitochondria. Bioinformatics analysis of proteomics revealed that the differentially expressed proteins participated in diverse biological processes, encompassing phototransduction, NOD-like receptor signaling pathway, phagosome, necroptosis, and cell adhesion molecules. In conclusion, by multimodal imaging, we described the phenotype of NaIO3-treated mouse model mimicking oxidative stress-induced RPE and photoreceptor death in detail. In addition, proteomics analysis identified differentially expressed proteins and significant enrichment pathways, providing insights for future research, although the exact mechanism of oxidative stress-induced RPE and photoreceptor death remains incompletely understood.

Prevalence, Features, and Outcomes of Type 1 Neovascularization in Eyes with Angioid Streaks

This study aimed to delineate the characteristics, prevalence, and outcomes of neovascularization (NV), particularly aneurysmal Type 1 NV, in patients with angioid streaks (AS) secondary to pseudoxanthoma elasticum (PXE), and to introduce a clinical classification based on multimodal imaging (MMI). Retrospective longitudinal cohort study. 85 patients (168 eyes) with AS secondary to PXE at two tertiary referral centers. Data collection included demographic, medical, and ocular histories. Diagnostic methods comprised fundus photography, autofluorescence, indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography. Prevalence of Type 1 NV, visual acuity (VA), risk of exudation. Type 1 NV was identified in 127 eyes (76%), with 85 of these (67%) showing exclusively Type 1 NV. These lesions often originated around the disc, at sites of Bruch's membrane dehiscences, and followed the path of AS, extending to the posterior pole in 101 eyes (80%). Despite 65% of Type 1 NV remaining non-exudative, 36% evolved into exudative over five years, and 11 eyes experienced mid-peripheral subretinal hemorrhages. Aneurysmal dilations, observed in 57% of cases, substantially increased exudation risk (hazard ratio = 3.86, p=0.02). Despite treatment, VA significantly deteriorated in exudative Type 1 NV (p=0.02). Type 2 NV, detected in 56 eyes (33%), often coexisted with Type 1 NV and was associated with poorer visual outcomes and higher rates of macular atrophy. A classification of AS was developed, ranging from empty AS (stage 0, no NV) to advanced NV (stage 3, both Type 1 and Type 2 NV). Type 1 NV predominates in AS. Although predominantly non-exudative, its progression correlates with substantial visual impairment, similar to the deficits observed with Type 2 NV. Aneurysmal Type 1 NV poses a significant exudation risk, underscoring the need for vigilant monitoring.

Optic Nerve Head Morphology and Macula Ganglion Cell Inner Plexiform Layer Thickness in Axially Anisometropic Rhesus Monkeys.

The purpose of this study was to determine the effects of axial elongation on optic nerve head morphology and macula inner retinal thickness in young rhesus monkeys. Both eyes of 26 anisometropic, 1-year-old rhesus monkeys were imaged using optical coherence tomography (OCT). Before imaging, the animals were sedated, their eyes were dilated, and axial length was measured using an optical biometer. OCT imaging included a 20 degrees, 24-line radial scan centered on the optic nerve head (ONH) and two 20 degrees × 20 degrees raster scans, one centered on the ONH and the other on the macula. Radial scans were analyzed using programs written in MATLAB to quantify the Bruch's membrane opening (BMO) area and position, minimum rim width (MRW), anterior lamina cribrosa surface (ALCS) position, size of any scleral crescent, circumpapillary retinal nerve fiber layer (RNFL), and choroid thickness (pCh). Macula total retinal thickness (mTRT) and ganglion cell inner plexiform layer (GCIPL) thicknesses were quantified from macula scans. Linear least square regression was determined for OCT measures and axial length of the right eye, and for inter-eye differences. Animals were 341 ± 18days old at the time of imaging. BMO area (R2 = 0.38), ALCS position (R2 = 0.45), scleral crescent area (R2 = 0.35), pCh thickness (R2 = 0.21), mTRT (R2 = 0.24), and GCIPL thickness (R2 = 0.16) were correlated with the axial length (all P < 0.05). For each of these parameters, the right-eye regression slope did not differ from the slope of the interocular difference (P > 0.57). There are posterior segment morphological differences in anisometropic rhesus monkeys related to axial length. Whether these differences increase the risk of pathology remains to be investigated.

PROGRESSION OF PERIPAPILLARY AND MACULAR CHORIORETINAL ATROPHY IN MULTIFOCAL CHOROIDITIS IS ASSOCIATED WITH PERIATROPHIC INFLAMMATORY PLUMES.

To investigate peripapillary atrophy and macular chorioretinal scars in eyes affected by multifocal choroiditis and panuveitis. This retrospective cohort study reviewed the medical records, fundus photographs, and spectral-domain optical coherence tomographic scans of 31 eyes from 19 patients. Patients had a mean age of 45 years (range 24-69 years). The average follow-up duration was 7 years (range, 2.5-14.5 years), with 14 patients undergoing immunosuppressive treatment. In the group of 31 eyes, 20 showed peripapillary plumes of ill-defined hyperreflectivity at the termination border of the retinal pigment epithelium. These plumes, extending from bare Bruch membrane to the outer nuclear layer, sometimes undermined the adjacent retinal pigment epithelium. They responded to corticosteroid treatment and resembled the material under the retinal pigment epithelium in acute lesions. Among 20 eyes with these peripapillary inflammatory lesions, 16 (80%) experienced increased atrophy, in contrast to none in the eyes without these lesions ( P < 0.001). Similar patterns were observed at the edges of macular chorioretinal atrophy. This observation occurred in patients using immunosuppressive medication who were otherwise thought to be under adequate control. In patients with multifocal choroiditis and panuveitis, previously unrecognized plumes of smoldering inflammatory activity at the borders of chorioretinal atrophy appears to be linked to atrophy expansion. The recognition of this phenomenon may require a reappraisal of treatment of multifocal choroidopathies to help mitigate the expansion of atrophy in these eyes.