Bruch's Membrane Research Articles

Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.

The complement system is crucial for immune surveillance, providing the body's first line of defence against pathogens. However, an imbalance in its regulators can lead to inappropriate overactivation, resulting in diseases such as age-related macular degeneration (AMD), a leading cause of irreversible blindness globally affecting around 200 million people. Complement activation in AMD is believed to begin in the choriocapillaris, but it also plays a critical role in the subretinal and retinal pigment epithelium (RPE) spaces. Bruch's membrane (BrM) acts as a barrier between the retina/RPE and choroid, hindering complement protein diffusion. This impediment increases with age and AMD, leading to compartmentalisation of complement activation. In this review, we comprehensively examine the structure and function of BrM, including its age-related changes visible through in vivo imaging, and the consequences of complement dysfunction on AMD pathogenesis. We also explore the potential and limitations of various delivery routes (systemic, intravitreal, subretinal, and suprachoroidal) for safe and effective delivery of conventional and gene therapy-based complement inhibitors to treat AMD. Further research is needed to understand the diffusion of complement proteins across BrM and optimise therapeutic delivery to the retina.

Prevalence and Characteristics of Peripapillary Gamma Zone in Children With Different Refractive Status: The Hong Kong Children Eye Study.

This study aimed to assess the prevalence and characteristics of the peripapillary gamma zone in myopic, emmetropic, and hyperopic eyes of Chinese children. Overall, 1274 children aged 6 to 8 years from the Hong Kong Children Eye Study underwent ocular examinations, including measurements of cycloplegic auto-refraction and axial length (AL). The optic disc was imaged using a Spectralis optical coherence tomography (OCT) unit and a protocol involving 24 equally spaced radial B-scans. The Bruch's membrane opening (BMO) was identified in over 48 meridians in each eye. The peripapillary gamma zone was defined as the region between the BMO and the border of the optic disc, identified by the OCT. The prevalence of the peripapillary gamma zone was higher in myopic eyes (36.3%) than in emmetropic (16.1%) and hyperopic eyes (11.5%, P < 0.001). AL (per 1 mm; odds ratio [OR]) = 1.861, P < 0.001) and a more oval disc shape (OR = 3.144, P < 0.001) were associated with the presence of a peripapillary gamma zone after adjusting for demographic, systemic, and ocular variables. In the subgroup analysis, a longer AL was associated with the presence of a peripapillary gamma zone in myopic eyes (OR = 1.874, P < 0.001), but not in emmetropic (OR = 1.033, P = 0.913) or hyperopic eyes (OR = 1.044, P = 0.883). A peripapillary zone was not observed in the region nasal to the optic nerve in myopic eyes, in contrast to its presence in the same region in 1.9% of emmetropic eyes and 9.3% of hyperopic eyes; these intergroup differences were statistically significant (P < 0.001). Although peripapillary gamma zones were observed in the eyes of both myopic and non-myopic children, their characteristics and distribution patterns were substantially different.

Precision Medicines for Retinal Lipid Metabolism-Related Pathologies.

Oxidation of lipids and lipoproteins contributes to inflammation processes that promote the development of eye diseases. This is a consequence of metabolism dysregulation; for instance, that of the dysfunctional peroxisomal lipid metabolism. Dysfunction of lipid peroxidation is a critical factor in oxidative stress that causes ROS-induced cell damage. Targeting the lipid metabolism to treat ocular diseases is an interesting and effective approach that is now being considered. Indeed, among ocular structures, retina is a fundamental tissue that shows high metabolism. Lipids and glucose are fuel substrates for photoreceptor mitochondria; therefore, retina is rich in lipids, especially phospholipids and cholesterol. The imbalance in cholesterol homeostasis and lipid accumulation in the human Bruch's membrane are processes related to ocular diseases, such as AMD. In fact, preclinical tests are being performed in mice models with AMD, making this area a promising field. Nanotechnology, on the other hand, offers the opportunity to develop site-specific drug delivery systems to ocular tissues for the treatment of eye diseases. Specially, biodegradable nanoparticles constitute an interesting approach to treating metabolic eye-related pathologies. Among several drug delivery systems, lipid nanoparticles show attractive properties, e.g., no toxicological risk, easy scale-up and increased bioavailability of the loaded active compounds. This review analyses the mechanisms involved in ocular dyslipidemia, as well as their ocular manifestations. Moreover, active compounds as well as drug delivery systems which aim to target retinal lipid metabolism-related diseases are thoroughly discussed.

Longitudinal Changes of Bruch's Membrane Opening, Anterior Scleral Canal Opening, and Border Tissue in Experimental Juvenile High Myopia.

To investigate the relative positional changes between the Bruch's membrane opening (BMO) and the anterior scleral canal opening (ASCO), and border tissue configuration changes during experimental high myopia development in juvenile tree shrews. Juvenile tree shrews were assigned randomly to two groups: binocular normal vision (n = 9) and monocular -10 D lens treatment starting at 24 days of visual experience to induce high myopia in one eye while the other eye served as control (n = 12). Refractive and biometric measurements were obtained daily, and 48 radial optical coherence tomography B-scans through the center of the optic nerve head were obtained weekly for 6 weeks. ASCO and BMO were segmented manually after nonlinear distortion correction. Lens-treated eyes developed high degree of axial myopia (-9.76 ± 1.19 D), significantly different (P < 0.001) from normal (0.34 ± 0.97 D) and control eyes (0.39 ± 0.88 D). ASCO-BMO centroid offset gradually increased and became significantly larger in the experimental high myopia group compared with normal and control eyes (P < 0.0001) with an inferonasal directional preference. The border tissue showed a significantly higher tendency of change from internally to externally oblique configuration in the experimental high myopic eyes in four sectors: nasal, inferonasal, inferior, and inferotemporal (P < 0.005). During experimental high myopia development, progressive relative deformations of ASCO and BMO occur simultaneously with changes in border tissue configuration from internally to externally oblique in sectors that are close to the posterior pole (nasal in tree shrews). These asymmetric changes may contribute to pathologic optic nerve head remodeling and an increased risk of glaucoma later in life.

Ocular Deformations in Spaceflight-Associated Neuro-Ocular Syndrome and Idiopathic Intracranial Hypertension.

Spaceflight-associated neuro-ocular syndrome (SANS) shares several clinical features with idiopathic intracranial-hypertension (IIH), namely disc edema, globe-flattening, hyperopia, and choroidal folds. Globe-flattening is caused by increased intracranial pressure (ICP) in IIH, but the cause in SANS is uncertain. If increased ICP alone causes SANS, then the ocular deformations should be similar to IIH; if not, alternative mechanisms would be implicated. Using optical coherence tomography (OCT) axial images of the optic nerve head, we compared "pre to post" ocular deformations in 22 patients with IIH to 25 crewmembers with SANS. We used two metrics to assess ocular deformations: displacements of Bruch's membrane opening (BMO-displacements) and Geometric Morphometrics to analyze peripapillary shape changes of Bruch's membrane layer (BML-shape). We found a large disparity in the mean retinal nerve-fiber layer thickness between SANS (108um; 95% confidence interval [CI]=105-111um) and IIH (300um; 95% CI=251-350.1um). The pattern of BML-shape and BMO-displacements in SANS were significantly different from IIH (P < 0.0001). Deformations in IIH were large and preponderantly anterior, whereas the deformations in SANS were small and bidirectional. The degree of disc edema did not explain the differences in ocular deformations. This study showed substantial differences in the degree of disc edema and the pattern of ocular deformations between IIH and SANS. The precise cause for these differences is unknown but suggests that there may be fundamental differences in the underlying biomechanics of each consistent with the prevailing hypothesis that SANS is consequent to multiple factors beyond ICP alone. We propose a hypothetical model to explain the differences between IIH and SANS based on the pattern of indentation loads.

Анализ влияния отслойки ретинального пигментного эпителия при экссудативной форме возрастной макулярной дегенерации на долгосрочные результаты лечения

Retinal pigment epithelial detachments (RPE) develops in more than 80 % of eyes with exudative age-related macular degeneration (eAMD) [1, 2]. RPED is a pathological condition in which the retinal pigment epithelium separates from the underlying Bruch's membrane due to the formation of a fibrovascular membrane, drusenoid material, fluid and/ or blood accumulation [3]. Recent published data from studies have shown controversial results of treatment with anti-VEGF therapy in patients with ARD on the background of eAMD, possibly due to different diagnostic capabilities and interpretation of the results by specialists. Purpose. To study the response to anti-VEGF therapy in patients with various RPED in eAMD. Material and methods. The study included 221 patients: with serous vascular (55 eyes) and fibrovascular detachment of RPE (176 eyes). To determine the maximum height of the retinal pigment epithelium detachment, it was necessary to manually set a line from Bruch's membrane to the retinal pigment epithelium in the scan where the maximum detachment of the retinal pigment epithelium was detected. Antiangiogenic therapy was carried out using the drug Aflibercept (Eylea® / Eulea®, Bayer Pharma AG, Mullerstrasse 178, 13353 Berlin, Germany) according to the standard method using the treat &amp; extend regimen (treat and prolong). Results. A significant increase in BCVA was found in patients with 1st type neovascularization and PCV during the first year of therapy from 0.51 ± 0.18 to 0.58 ± 0.23 and from 0.66 ± 0.23 to 0.76 ± 0.20 (p &lt; 0.05), with a further gradual significant decrease and return from baseline BCVA by 3rd year to 0.51 ± 0.25 (p &lt; 0.05) in the group with 1st type CNV, in patients with PCV, there was also a decrease in BCVA, but this was unreliable. BCVA values in all four groups decreased by the 6th year of observation. There was a significant decrease in the height of RPED in the group with the 1st and 3rd types of neovascularization, as well as in patients with PCV during the first 2 years of therapy (p &lt; 0.05). Сonclusions. Thus, a significant increase in BCVA in the first year of therapy in patients with ARD is more common in 1st type CNV and with PCV. At the same time, in all groups, after 6 years of treatment, a downward trend in BCVA can be observed. Also, in all groups, there was a decrease in the height of RP, which indicates a good response of the fluid under RP to the ongoing anti-VEGF therapy. Keywords: exudative form of retinal pigment epithelium detachment, anti-VEGF therapy, aflibercept, retinal pigment epithelium detachment

Retinal Nerve Fiber Layer Thickness/Minimum Rim Width Ratio Differentiates Glaucoma from Other Optic Neuropathies.

Global peripapillary retinal nerve fiber layer thickness/Bruch membrane opening- minimum rim width ratio is an objective and effective parameter to separate glaucomatous optic neuropathies (GONs) from nonglaucomatous optic neuropathies (NGONs). This study was undertaken to evaluate the diagnostic capability of the peripapillary retinal nerve fiber layer (pRNFL)/ Bruch membrane opening-minimum rim width (BMO-MRW) ratio to differentiate glaucomatous optic neuropathies (GONs) from nonglaucomatous optic neuropathies (NGONs). This retrospective study included patients with an optic neuropathy (ON), visual loss for>6 months and a confirmed single etiology. pRNFL thickness and BMO-MRW were measured with spectral-domain OCT (Spectralis®, Heidelberg Engineering, Heidelberg, Germany). The diagnostic accuracies of pRNFL, BMO-MRW and the global pRNFL/BMO-MRW ratio were evaluated with the areas under receiver operating characteristics curves (AUROCs). One eye each from 171 patients was investigated: 50 primary open-angle glaucomas, 15 normal pressure glaucomas, 50 optic neuritises, 15 nonarteritic anterior ischemic ONs, 24 compressive ONs, 10 dominant optic atrophies and 7 nutritional ONs. The global pRNFL/BMO-MRW ratio had the highest AUROC [0.97 vs. 0.92; P =0.01]. It was able to distinguish between GONs and NGONs with a cut-off value of 0.34. Increased mean deviation of the visual field-defect severity was associated with a higher ratio for GONs and a lower ratio for NGONs. Compared to NGONs and for the same degree of pRNFL thinning, lower BMO- MRW was found to be a specific marker of glaucoma, reflecting the neuroglial architecture changes within the optic nerve head typical of glaucoma and supporting fundamental pathophysiological differences.

OCT Optic Nerve Head Morphology in Myopia II: Peri-Neural Canal Scleral Bowing and Choroidal Thickness in High Myopia—An American Ophthalmological Society Thesis

To use optical coherence tomography (OCT) to characterize optic nerve head (ONH) peri-neural canal (pNC) scleral bowing (pNC-SB) and pNC choroidal thickness (pNC-CT) in 69 highly myopic and 138 healthy, age-matched, control eyes. Cross-sectional, case control study. Within ONH radial B-scans, Bruch membrane (BM), BM opening (BMO), anterior scleral canal opening (ASCO), and pNC scleral surface were segmented. BMO and ASCO planes and centroids were determined. pNC-SB was characterized within 30° foveal-BMO (FoBMO) sectors by 2 parameters: pNC-SB-scleral slope (pNC-SB-SS), measured within 3 pNC segments (0-300, 300-700, and 700-1000 μm from the ASCO centroid); and pNC-SB-ASCO depth relative to a pNC scleral reference plane (pNC-SB-ASCOD). pNC-CT was calculated as the minimum distance between the scleral surface and BM at 3 pNC locations (300, 700, and 1100 μm from the ASCO). pNC-SB increased and pNC-CT decreased with axial length (P < .0133; P < .0001) and age (P < .0211; P < .0004) among all study eyes. pNC-SB was increased (P < .001) and pNC-CT was decreased (P < .0279) in the highly myopic compared to control eyes, and these differences were greatest in the inferior quadrant sectors (P < .0002). Sectoral pNC-SB was not related to sectoral pNC-CT in control eyes, but was inversely related to sectoral pNC-CT (P < .0001) in the highly myopic eyes. Our data suggest that pNC-SB is increased and pNC-CT is decreased in highly myopic eyes and that these phenomena are greatest in the inferior sectors. They support the hypothesis that sectors of maximum pNC-SB may predict sectors of greatest susceptibility to aging and glaucoma in future longitudinal studies of highly myopic eyes. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Using a combination of peripapillary atrophy area and choroidal thickness for the prediction of different types of myopic maculopathy.

To analyse the topographic characteristics in macular choroidal thickness (mChT) and ocular biometry in myopic maculopathy and to explore the potential cut-off value for prediction of myopic maculopathy (MM). All participants underwent detailed ocular examinations. MM was subdivided into thin choroid, Bruch's membrane (BM) defects, choroidal neovascularization (CNV), and myopic tractional maculopathy (MTM) according to OCT-based classification system. Peripapillary atrophy area (PPA), tilt ratio, torsion, and mChT were individually measured. A total of 1947 participants were included. In multivariate logistics models, older age, longer axial length, larger PPA area, and thinner average mChT were more likely to have MM and different type of MM. Female participants were more likely to have MM and BM defects. A lower tilt ratio was more likely to be associated with CNV and MTM. The area under the curve (AUC) of single tilt ratio, PPA area, torsion, and topographic of mChT for MM, thin choroid, BM Defects, CNV, and MTM were 0.6581 to 0.9423, 0.6564 to 0.9335, 0.6120 to 0.9554, 0.5734 to 0.9312, 0.6415 to 0.9382, respectively. After combining PPA area and average mChT for predicting MM, thin choroid, BM defects, CNV, and MTM, the AUC of the combination were 0.9678, 0.9279, 0.9531, 0.9213, 0.9317, respectively. Progressive and continuous PPA area expanding and thin choroid play a role in the development of myopic maculopathy. The present study showed that a combination of peripapillary atrophy area and the choroidal thickness could be used to predict MM and each type of MM.

Association Between Parapapillary Microvasculature Dropout and Central Retinal Vessel Trunk in Primary Open Angle Glaucoma.

Central retinal vessel trunk displacement is an important factor in the generation and development of deep-layer microvasculature dropout in primary open angle glaucoma. To investigate the association between the microvasculature dropout and the central retinal vessel trunk in primary open angle glaucoma eyes. In total, 112 eyes from 112 patients with primary open-angle glaucoma were included. Matched 26 no microvasculature dropout eyes and 26 microvasculature dropout eyes, they had similar axial length and global retinal nerve fiber layer thickness. Central retinal vessel trunk shift index was calculated as the distance of the central retinal vessel trunk from the Bruch membrane opening center relative to that of the Bruch membrane opening border. The correlation of the presence, extent, and location of microvasculature dropout and the displacement extent and location of the central retina vessel trunk was analyzed. The central retinal vessel trunk shift index differed significantly between the 2 matched groups. Multivariate logistic analyses showed that in 112 eyes from 112 patients, eyes with microvasculature dropout was significantly associated with larger shift index than eyes without microvasculature dropout. The angular circumference of microvasculature dropout was significantly associated with adjusted shift index (a linear mixed model was constructed, exclude the influence of axial length and global retinal nerve fiber layer thickness on shift index). The location of the microvasculature dropout and central retinal vessel trunk contralateral were significantly correlated. In primary open angle glaucoma eyes, microvasculature dropout and the central retinal vessel trunk were significantly correlated. Because the central retinal vessel trunk represents the structural stability of the lamina cribrosa, microvasculature dropout seems to correlate with lamina cribrosa's structural stability.

Choriocapillaris Flow Signal Impairment in Patients With Pseudoxanthoma Elasticum.

To quantify choriocapillaris flow alterations in patients with pseudoxanthoma elasticum (PXE) in pre-atrophic stages and its association with structural changes of the choroid and outer retina. Thirty-two eyes of 21 patients with PXE and 35 healthy eyes of 35 controls were included. The density of choriocapillaris flow signal deficits (FDs) was quantified on 6 × 6-mm optical coherence tomography angiography (OCTA) images. Spectral-domain optical coherence tomography (SD-OCT) images were analyzed for thicknesses of the choroid and outer retinal microstructure and correlated with choriocapillaris FDs in the respective Early Treatment Diabetic Retinopathy Study subfield. The multivariable mixed model analysis for choriocapillaris FDs revealed significantly higher FDs associated with the group (PXE patients vs. controls +13.6; 95% confidence interval [CI] 9.87-17.3; P < 0.001), with increasing age (+0.22% per year; 95% CI 0.12-0.33; P < 0.001), and with retinal location (significantly higher FDs in nasal compared to temporal subfields). Choroidal thickness (CT) did not differ significantly between both groups (P = 0.078). The CT and choriocapillaris FDs were inversely correlated (-1.92 µm per %FDs; interquartile range -2.81 to -1.03; P < 0.001). Larger values of the choriocapillaris FDs were associated with significant thinning of the overlying photoreceptor layers (outer segments: -0.21 µm per %FDs, P < 0.001; inner segments: -0.12 µm per %FDs, P = 0.001; outer nuclear layer: -0.72 µm per %FDs; P < 0.001). Patients with PXE display significant alterations of the choriocapillaris on OCTA even in pre-atrophic stages and in the absence of significant choroidal thinning. The analysis favors choriocapillaris FDs over choroidal thickness as a potential early outcome measure for future interventional trials in PXE. Further, increased FDs in nasal compared to temporal locations mirror the centrifugal spread of Bruch's membrane calcification in PXE.

Animal model of subretinal fibrosis without active choroidal neovascularization

Subretinal fibrosis can occur during neovascular age-related macular degeneration (nAMD) and consequently provokes progressing deterioration of AMD patient's vision. Intravitreal anti–vascular endothelial growth factor (VEGF) injections decrease choroidal neovascularization (CNV), however, subretinal fibrosis remains principally unaffected. So far, no successful treatment nor established animal model for subretinal fibrosis exists. In order to investigate the impact of anti-fibrotic compounds on solely fibrosis, we refined a time-dependent animal model of subretinal fibrosis without active choroidal neovascularization (CNV). To induce CNV-related fibrosis, wild-type (WT) mice underwent laser photocoagulation of the retina with rupture of Bruch's membrane. The lesions volume was assessed with optical coherence tomography (OCT). CNV (Isolectin B4) and fibrosis (type 1 collagen) were separately quantified with confocal microscopy of choroidal whole-mounts at every time point post laser induction (day 7–49). In addition, OCT, autofluorescence and fluorescence angiography were carried out at designated timepoints (day 7, 14, 21, 28, 35, 42, 49) to monitor CNV and fibrosis transformation over time. From 21 to 49 days post laser lesion leakage in the fluorescence angiography decreased. Correspondingly, Isolectin B4 decreased in lesions of choroidal flat mounts and type 1 collagen increased. Fibrosis markers, namely vimentin, fibronectin, alpha-smooth muscle actin (α-SMA) and type 1 collagen were detected at different timepoints of tissue repair in choroids and retinas post laser. These results prove that the late phase of the CNV-related fibrosis model enables screening of anti-fibrotic compounds to accelerate the therapeutic advancement for the prevention, reduction, or inhibition of subretinal fibrosis.

Mechanobiological implications of age-related remodelling in the outer retina

The outer retina consists of the light-sensitive photoreceptors, the pigmented epithelium, and the choroid, which interact in a complex manner to sustain homeostasis. The organisation and function of these cellular layers are mediated by the extracellular matrix compartment named Bruch's membrane, situated between the retinal epithelium and the choroid. Like many tissues, the retina experiences age-related structural and metabolic changes, which are relevant for understanding major blinding diseases of the elderly, such as age-related macular degeneration. Compared with other tissues, the retina mainly comprises postmitotic cells, making it less able to maintain its mechanical homeostasis over the years functionally. Aspects of retinal ageing, like the structural and morphometric changes of the pigment epithelium and the heterogenous remodelling of the Bruch's membrane, imply changes in tissue mechanics and may affect functional integrity. In recent years, findings in the field of mechanobiology and bioengineering highlighted the importance of mechanical changes in tissues for understanding physiological and pathological processes. Here, we review the current knowledge of age-related changes in the outer retina from a mechanobiological perspective, aiming to generate food for thought for future mechanobiology studies in the outer retina.

Anatomic Peculiarities Associated with Axial Elongation of the Myopic Eye.

To describe anatomical peculiarities associated with axial elongation in the human myopic eye. Reviewing the results of previous histomorphometrical investigations of enucleated human globes, as well as reviewing findings obtained in population-based studies and hospital-based clinical investigations of myopic patients and non-myopic individuals. Myopic axial elongation is associated with a change from a mostly spherical eye shape to a prolate ellipsoid form. It is combined with choroidal and scleral thinning, most pronounced at the posterior pole and less pronounced in the fundus midperiphery. In the fundus midperiphery, the retina and density of the retinal pigment epithelium (RPE) and photoreceptors decrease with a longer axial length, while in the macular region, retinal thickness, RPE cell density, and choriocapillaris thickness are not related to axial length. With axial elongation, a parapapillary gamma zone develops, leading to an enlargement of the optic disc-fovea distance and a decrease in angle kappa. Axial elongation is also correlated with an increase in the surface and volume of Bruch's membrane (BM), while BM thickness remains unchanged. Axial elongation causes moderately myopic eyes to show a shift of BM opening to the foveal direction so that the horizontal disc diameter becomes shorter (with a consequent vertical ovalization of the optic disc shape), a temporal gamma zone develops, and the optic nerve exit takes an oblique course. Features of high myopia are an enlargement of the RPE opening (myopic parapapillary beta zone) and BM opening (secondary macrodisc), elongation and thinning of the lamina cribrosa, peripapillary scleral flange (parapapillary delta zone) and peripapillary choroidal border tissue, secondary BM defects in the macular region, myopic maculoschisis, macular neovascularization, and cobblestones in the fundus periphery. These features combined may be explained by a growth in BM in the fundus midperiphery leading to axial elongation.

Visual outcomes of macular melanocytic lesions after early or delayed proton beam therapy.

During their initial management, some macular melanocytic lesions can be closely monitored to wait for a documented growth before advocating a treatment by irradiation. However, the visual outcomes of this strategy have not yet been assessed. This study compares the visual outcomes of macular melanocytic lesions that underwent delayed proton beam therapy (PBT) after an initial observation to those treated early. A total of 162 patients with suspicious melanocytic lesions whose margins were located within 3mm of the fovea were recruited from two French ocular oncology centers. Overall, 82 patients treated with PBT within 4months after the initial visit (early PBT group) were compared to 24 patients treated with delayed PBT (delayed PBT group) and 56 patients not treated with PBT (observation group). Visual acuity was not significantly different between baseline and last visit in the observation group (p = 0.325). Between baseline and last visit, the median [IQR] loss in visual acuity was significant in both the early (0.7 [0.2; 1.8], p < 0.001) and the delayed (0.5 [0.2; 1.5], p < 0.001) PBT groups. After irradiation, there was no significant difference between the early and delayed PBT groups for visual loss (p = 0.575), diameter reduction (p = 0.190), and thickness lowering (p = 0.892). In multivariate analysis, history of diabetes mellitus and Bruch's membrane rupture remained significantly associated with greater visual loss (p = 0.036 and p = 0.002, respectively). For small lesions in which there is no clear diagnosis of malignant melanoma, an initial close monitoring to document tumor growth does not impact visual prognosis, despite the potential complications associated with the untreated tumor. However, the survival should remain the main outcome of the treatment of these lesions.

Optical Coherence Tomography Based Choroidal Thickness and Its Determinants in Healthy Saudi Population: A Cross-Sectional Study.

Purpose To study choroidal thickness (CT) and its determinants based on optical coherence tomography (OCT) in the healthy adult Saudi population. Materials and methods This cross-sectional study was conducted in 2021 at a tertiary eye hospital in Saudi Arabia. The autorefractor-based refractive status (spherical equivalent) of each eye was documented. CT was measured from the enhanced depth OCT images at the fovea to the 1500 µm nasal and temporal to the fovea. CT was defined as the distance from a hyper-reflective line representing retinal pigment epithelium (RPE)-Bruch's membrane to the choroid-scleral junction. The CT was correlated with demographic and other variables. Results The study sample included 288 eyes of 144 participants (mean age 31.5±8.3 years; males 94, 65.3%). Emmetropia, myopia, and hypermetropic spherical equivalent were noted in 53 (18.4%), 152 (52.5%), and 83 (28.8%) eyes, respectively. The mean sub-foveal (SFCT), nasal, and temporal CT were 329.4±56.7μm, 302.3±63.5 μm, and 312.8± 56.7μm, respectively. CT varied significantly by location (p<0.001). CT was negatively correlated with age (r = -0.177, P<0.001). CT in emmetropic and myopic eyes was 319.7±53 μm and 313.1±53 μm, respectively. The difference in CT based on refractive status (p= 0.49) or sex was non-significant (p= 0.6). Regression analysis suggested that age (p<0.001), refractive error (p= 0.02), scanning time (p<0.001), and scanning location (p= 0.006) were significant predictors of CT. Conclusion CT measurements of the eyes of healthy Saudis can be used as reference values for studies evaluating CT changes due to various chorioretinal diseases.

Deep Optic Nerve Head Structures Associated With Increasing Axial Length in Healthy Myopic Eyes of Moderate Axial Length

To elucidate which swept-source optical coherence tomography (OCT)-derived optic nerve head (ONH) parameters are associated with longer axial length (AXL) in healthy myopic eyes. Prospective cross-sectional observational study. Two hundred eleven healthy eyes of 140 participants (96 emmetropic-mild myopic [AXL: 22.2-24.5 mm], 83 moderately myopic [24.5-26.0 mm], and 32 highly myopic [26.0-27.4 mm] eyes) were enrolled. Bruch membrane opening (BMO), anterior scleral canal opening (ASCO) area and ovality, minimum rim width, parameters defining misalignment between the BMO and ASCO planes, OCT-defined region of perineural canal retinal epithelium atrophy and externally oblique choroidal border tissue, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), circumpapillary choroidal thickness (cpChT), lamina cribrosa parameters, and peripapillary scleral (PPS) angle were calculated from BMO-centered radial scans reconstructed from 3D raster scans. Multivariate linear mixed models were used to elucidate ONH parameters that are independently associated with AXL. Longer AXL was associated with a greater misalignment between ASCO and BMO planes, larger region of externally oblique choroidal border tissue, thinner cpChT, larger PPS angle, larger ASCO area, and thicker cpRNFLT (all P < .040 after Bonferroni's correction for number of included explanatory variables). A greater misalignment between BMO and ASCO planes, thinner choroid, a more posteriorly bowed PPS, an enlargement of ASCO, and thicker cpRNFLT were each associated with longer AXL. An enhanced understanding of these AXL-associated configurations should provide essential information to improve our ability to detect glaucoma-induced ONH morphology in myopic eyes.

Retinal microvasculature observations of fellow eyes after intra-arterial chemotherapy for unilateral retinoblastoma using optical coherence tomography angiography.

To investigate the characteristics of the retinal microvasculature of the fellow eyes in patients with unilateral retinoblastoma (RB) after intra-arterial chemotherapy (IAC) through optical coherence tomography angiography. This retrospective study enrolled 11 fellow eyes of patients with unilateral RB receiving IAC (group I), nine fellow eyes of patients with unilateral RB receiving IAC and intravenous chemotherapy (IVC) (group II), and 14 age-matched normal eyes (control group). Optical coherence tomography angiography was performed on all individuals. Vascular density of superficial capillary plexus and deep capillary plexus (DCP), foveal avascular zone related parameters, and retinal thickness were measured and compared among the three groups. There was no statistical difference in age and logMAR visual acuity among the three groups. Compared with the control group, the vascular density of the DCP was lower in group I and II. Decreased vascular density of FD-300 and thinner thickness of outer plexus layer to Bruch's membrane were detected in group II compared with the control group. The vascular density and retinal thickness showed no differences between group I and II. The decreased vascular density in the DCP without measurable visual impairment was observed in fellow eyes after IAC or IAC + IVC for unilateral RB. Further studies with a larger sample would be necessary to determine the clinical significance of these findings.

Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence.

To demonstrate two distinct pathways to geographic atrophy (GA) that originate from soft drusen/ pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDDs), respectively, and are characterized by their final quantitative autofluorescence (qAF) levels. 23 eyes of 18 patients with GA underwent spectral-domain optical coherence tomography (SD-OCT) and qAF imaging on the qAF-ready Heidelberg Spectralis. 52 GA Regions-of-interest (ROIs), or clusters of adjacent lesions, were selected, and the ROIs were divided into groups by the dominant iAMD precursors on prior serial tracked SD-OCT scans. Mean qAF values and structural SD-OCT findings of groups were compared. Group 1 lesions (soft drusen/PED precursors, 18/52) were isolated, with lower mean qAF (35.88 ± 12.75 units); group 3 lesions (SDD precursors, 12/52) were multilobular, with significantly higher mean qAF (71.62 ± 12.12 units, p < 0.05). Group 2 lesions, (mixed precursors, 22/52) had intermediate mean qAF (58.13 ± 67.92 units). Significantly greater prevalence of split RPE/ Bruch's membrane complex in SDD-associated GA, suggesting basal laminar deposit (BLamD), than in drusen-associated lesions was the major structural difference. Quantitative autofluorescence (qAF) of GA lesions may reflect two distinct pathogenic pathways and structural outcomes, originating from soft drusen/PED and subretinal drusenoid deposits (SDDs), with the final qAF values lower or higher, respectively. Basal laminar deposit specifically in and adjacent to SDD-associated lesions may account for their greater autofluorescence. The potential importance of this paradigm is that it could direct, simplify and facilitate research on geographic atrophy by dividing the disease into two components that may be studied separately.

Progressive degeneration of the retina in Loxl3 mutant mouse model of Stickler syndrome

Stickler syndrome is a multisystem collagenopathy with affected individuals exhibiting a high rate of ocular complications. Lysyl oxidase-like 3 (LOXL3) is a human disease gene candidate with a critical role in catalyzing collagen crosslinking. A homozygous missense variant of LOXL3 was reported in Stickler syndrome with severe myopia. However, the underlying mechanisms of the LOXL3 missense mutation that causes Stickler syndrome are unknown. In this study, a mouse model of Stickler syndrome induced by LOXL3 mutation (c.2027G ​> ​A, p.Cys676Try) was obtained using CRISPR/Cas9 gene editing techniques. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, and cleft palate, and Loxl3 mutation also induced skeletal dysplasia and progressive visual degeneration. Furthermore, we observed the damage of the bruch's membrane (BrM) and an increase in the levels of glial fibrillary acidic protein (GFAP) and Rpe65 in the Loxl3 mutant mice. Thus, we provided the critical in vivo evidence that Loxl3 possibly has a pivotal role in maintaining the eye function.