OBJECTIVE: Current literature reveals an association between anthropometric measures of adiposity (AnthM) and age-related macular degeneration (AMD), but few have explored the disease association with imaging methods. This study aimed to explore the relationship between AMD status and dual-energy X-ray absorptiometry measures (DEXAMs) among a representative sample of the US population, and compare the association with AnthM.
METHODS: Using a representative sample in the National Health and Nutrition Examination Study 2005-2006 (n=1632), DEXAMs across the whole body and waist (ie, android), and relative fat distributions (eg, percentage fat, android-to-total body ratio) were analysed between no AMD (baseline) and any AMD. Bivariate analyses across AMD status were similarly performed for AnthM (ie, body mass index, waist circumference and skinfold thicknesses) and potential confounders (ie, demographics and health-related variables). Significant adiposity measures were analysed using logistic regression, adjusting for confounders.
RESULTS: The participants in the sample were aged 40-69 years, were majority female (52%) and mainly Caucasian (76.5%). Bivariate analysis revealed having any AMD had positive significant associations with android-to-total fat ratio and subscapular skinfold thickness (SSFT). Other AnthM and DEXAMs were not significant. After adjusting age, gender and prescription of cholesterol-lowering medicine, only SSFT remained significantly associated.
CONCLUSIONS: SSFT represents an independent risk factor for AMD presence compared with other AnthM and DEXAMs. SSFT is an established method of measuring fat under the skin (ie, subcutaneous fat). Hence, subcutaneous fat may be more relevant in explaining the adiposity-AMD link due to physiological properties specific to the tissue. Limitations include the restricted age range and low numbers of participants with late AMD.

Background/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.

OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients.
METHODS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively.
RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk.
CONCLUSIONS: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients.
UNASSIGNED: CRD42023394226.

A scoping review of 45 peer-reviewed manuscripts involving intraocular pressure (IOP) change and concurrent optical coherence tomography angiography (OCTA) assessments was performed to aggregate knowledge, summarize major findings, and identify gaps in literature and methodology relating to the effect of IOP change on OCTA. Articles were identified through PubMed/Medline, Google Scholar, Cochrane, Web of Science, and article reference lists. A total of 838 results were identified, and 45 articles met the inclusion and exclusion criteria for detailed analysis. OCTA metrics including vessel density (VD), perfusion density, and flow density of the superficial capillary plexus and the radial peripapillary capillaries were analyzed in relation to relative temporal IOP changes. Overall, IOP changes were found to affect superficial vascular plexus (VD) measurements on OCTA, especially when IOP elevated above the physiologic normal range (10-21 mmHg). No significant association was found between diurnal IOP variation and OCTA metrics. Cataract surgery improved the whole-image signal strength and VD regardless of changes in IOP. Beta-blockers were associated with paradoxically reduced vessel density in normal tension glaucoma patients in two studies. Although glaucoma surgical intervention studies were inconsistent and limited by scan quality and low sample sizes, patients requiring glaucoma surgery exhibited attenuated postoperative superficial VD recovery despite significant IOP reductions with surgical intervention. In addition to ensuring near-perfect signal strength with minimal media opacities and controlling for high myopia, central corneal thickness, and the presence of retinopathy, clinicians should consider the statistically significant impact of IOP on OCTA metrics when interpreting results.

Aging is the greatest risk factor for chronic human diseases, including many eye diseases. Geroscience aims to understand the effects of the aging process on these diseases, including the genetic, molecular, and cellular mechanisms that underlie the increased risk of disease over the lifetime. Understanding of the aging eye increases general knowledge of the cellular physiology impacted by aging processes at various biological extremes. Two major diseases, age-related cataract and age-related macular degeneration (AMD) are caused by dysfunction of the lens and retina, respectively. Lens transparency and light refraction are mediated by lens fiber cells lacking nuclei and other organelles, which provides a unique opportunity to study a single aging hallmark, i.e., loss of proteostasis, within an environment of limited metabolism. In AMD, local dysfunction of the photoreceptors/retinal pigmented epithelium/Bruch\'s membrane/choriocapillaris complex in the macula leads to the loss of photoreceptors and eventually loss of central vision, and is driven by nearly all the hallmarks of aging and shares features with Alzheimer\'s disease, Parkinson\'s disease, cardiovascular disease, and diabetes. The aging eye can function as a model for studying basic mechanisms of aging and, vice versa, well-defined hallmarks of aging can be used as tools to understand age-related eye disease.

Documenting the organization of the retinal capillaries is of importance to understand the visual consequences of vascular diseases which may differentially affect the microvascular layers. Here we detailed the spatial organization of the macular capillaries in ten healthy human subjects using a prototypic adaptive optics-enhanced optical coherence tomography angiography (AO-OCTA) system. Within the central 6° × 6°, the radial peripapillary capillaries and the superficial, intermediate and deep vascular plexuses (SVP, IVP and DVP, respectively) were consistently resolved. In 8 out of the 10 eyes, the capillary segments composing the perifoveal arcade (PFA) were perfused only by the SVP, while drainage of the PFA showed more variability, comprising a case in which the PFA was drained by the DVP. Around the center, a distinct central avascular zone could be documented for each layer in 7 of the 10 cases; in three eyes, the IVP and SVP merged tangentially around the center. In all eyes, the foveal avascular zone was larger in the DVP than in the SVP and IVP. In one eye with incomplete separation of the inner foveal layers, there was continuity of both the SVP and the IVP; a central avascular zone was only present in the DVP. The diversity of perfusion and drainage patterns supported a connectivity scheme combining parallel and serial organizations, the latter being the most commonly observed in perifoveal vessels. Our results thus help to further characterize the diversity of organization patterns of the macular capillaries and to robustly analyze the IVP, which will help to characterize early stages of microvascular diseases.

The dog retina contains a central macula-like region, and there are reports of central retinal disorders in dogs with shared genetic etiologies with humans. Defining central/peripheral gene expression profiles may provide insight into the suitability of dogs as models for human disorders. We determined central/peripheral posterior eye gene expression profiles in dogs and interrogated inherited retinal and macular disease-associated genes for differential expression between central and peripheral regions. Bulk tissue RNA sequencing was performed on 8 mm samples of the dog central and superior peripheral regions, sampling retina and retinal pigmented epithelium/choroid separately. Reads were mapped to CanFam3.1, read counts were analyzed to determine significantly differentially expressed genes (DEGs). A similar analytic pipeline was used with a published bulk-tissue RNA sequencing human dataset. Pathways and processes involved in significantly DEGs were identified (Database for Annotation, Visualization and Integrated Discovery). Dogs and humans shared the extent and direction of central retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. Many genes implicated in heritable retinal disorders in dogs and humans were differentially expressed between central and periphery. Approximately half of genes associated with human age-related macular degeneration were differentially expressed in human and dog tissues. We have identified similarities and differences in central/peripheral gene expression profiles between dogs and humans which can be applied to further define the relevance of dogs as models for human retinal disorders.

OBJECTIVE: To investigate the recurrent non-arteritic retinal artery occlusion (RAO) in the same or opposite eye.
METHODS: We searched the RAO registry at Seoul National University Bundang Hospital and included patients with recurrent RAO in the present study. Ophthalmic and systemic features were analysed to identify risk factors and visual outcomes.
RESULTS: Of the 850 patients in the non-arteritic RAO cohort, 11 (1.3%) experienced a second RAO recurrence, either in the same (5 patients; 0.6%) or opposite (6 patients; 0.7%) eye. The same eye group experienced an earlier recurrence (1-2 months, median 1 month) than the opposite eye group, where the time to recurrence was notably longer (8-66 months, median 22 months). Best corrected visual acuity (BCVA) in the same eye group decreased after the recurrence of RAO. In the same eye group, initial BCVA ranged from 20/200 to counting fingers (CF), while BCVA during RAO recurrence ranged from CF to hand motion. When RAO recurred in the opposite eye, the reduction in visual acuity was less severe than the reduction of the initial episode: initial episode ranged from 20/400 to light perception and recurrent episode ranged from 20/25 to 20/400. Patients exhibited varying degrees of carotid (81.8%) and cerebral (9.1%) artery occlusions. Additionally, one patient in each group (total 2 patients, 18.2%) experienced a stroke 6 months after RAO recurrence.
CONCLUSIONS: Since the RAO recurrences could lead to devastating visual impairment, it is essential to emphasise the importance of risk factor screening to patients while collaborating with neurologists and cardiologists.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that can result in fatal end-stage renal disease, heart failure, and cerebro-occlusive events. Vague clinical symptoms and rarity often mean diagnosis and potential treatment is delayed. Ophthalmic findings in FD patients can be helpful in establishing an early diagnosis and timely treatment. Spectral domain optical coherence tomography (SD-OCT) imaging in FD patients shows hyper-reflective foci (HRF) in characteristic patterns within the inner retinal layers. We found that the HRF was localised in linear distributions at the deep and superficial borders of the retinal inner nuclear layer, likely reflecting anatomic vascular plexuses and FD-related sphingolipid deposition within the vessel walls. These results highlight the potential use of SD-OCT in FD and how it may aid diagnosis in undifferentiated patients, prognostication, and disease monitoring.

Sorsby macular dystrophy is an autosomal dominant disorder secondary to heterozygous mutations in the TIMP3 gene in 22q12. It begins with fine, pale, drusen-like deposits or confluent, faint yellow material or sheets beneath the retinal pigment epithelium, but it eventually progresses to either geographic atrophy with pigmentary clumps or scars due to the choroidal neovascular membrane around the fourth decade of life. We describe a patient who presented with a progressive loss of unilateral visual acuity, wrongly suggesting an infectious or inflammatory disease.