Translational Vision Science & Technology最新文献

Purpose: Previous researches have suggested an important association between gut microbiota (GM) and vascular pathologies such as atherosclerosis. This study aimed to explore the association between 196 GM taxa and retinal vein occlusion (RVO).

Methods: This study used Mendelian randomization (MR), linkage disequilibrium score regression (LDSC), and polygenic overlap analysis. Genome-wide association study (GWAS) data associated with 196 GM taxa was obtained from the MiBioGen consortium, involving a large number of European-ancestry participants. GWAS data of RVO was obtained from the FinnGen consortium and another study that also involved European-ancestry participants. Inverse-variance weighted was used as the primary approach for MR estimation. Moreover, LDSC and polygenic overlap analyses were performed to evaluate the genetic correlation between GM taxa and RVO.

Results: The MR results identified the association of six GM taxa, including class Bacilli, order Lactobacillales, family Streptococcaceae, genus Clostridium innocuum group, genus Family XIII AD3011 group, and genus Subdoligranulum with the development of RVO. In addition, the polygenic overlap analysis supported the genetic association between GM and RVO.

Conclusions: Our findings confirmed the association between six GM taxa and the development of RVO, thereby highlighting the effects of GM on retinal vascular health.

Translational relevance: The results may provide the rationale for developing GM-based strategies for preventing the onset of RVO.

Purpose: Geographic atrophy (GA), an advanced form of dry age-related macular degeneration (AMD), has limited treatment options. This study introduces a novel mouse model featuring an expanding GA patch that can be used to test mechanisms and therapeutics.

Methods: C57Bl/6J male mice (n = 96) aged 9-10 weeks received an intraperitoneal (IP) injection of 20 mg/kg sodium iodate (NaIO3). In vivo confocal scanning laser ophthalmoscope (cSLO) and optical coherence tomography imaging were done at one, four, eight, and 16 weeks after injection, with GA area measurements taken at weeks 8 and 16. Mice were euthanized on weeks 8 and 16 for histological analysis.

Results: Administration of 20 mg/kg intraperitoneal NaIO3 caused variable damage levels. Approximately 22% of cases showed damage (speckled autofluorescence) covering 35% to 90% of the 102° field of view cSLO image at one week after injection. These mice developed an expanding patch of GA by week 8, with a mean 1.45-fold increase in area by week 16. This region showed complete photoreceptor and retinal pigment epithelium loss and complement activation at the atrophy edge, whereas the inner retina remained undamaged. Mice with less damage (48% of cases) only developed incomplete outer retinal degeneration, and mice with more damage (30% of cases) had too much GA for measurable expansion.

Conclusions: Although expanding GA formed in only 22% of mice, the model's simplicity and predictability for GA development via one-week post-injection imaging make it suitable for GA therapeutic experimentation.

Translational relevance: This murine model provides a valuable tool for testing GA therapies, mirroring clinical endpoints relevant to human trials.

Purpose: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects.

Methods: We have developed an alternative strategy that uses anti-syndecan-2 polyclonal antibody (anti-Sdc2 pAb) to block VEGF-A-induced permeability without interfering with other VEGF-A activities. The effect of anti-Sdc2 pAb therapy was assessed in vitro using a transendothelial electrical resistance (TEER) assay, as well as staining of the endothelial cell junction, and in vivo in the laser-induced choroidal neovascularization (CNV) model.

Results: Anti-Sdc2 pAb blocked VEGF-A-induced permeability in vitro, and both local intravitreal injections and systemic intravenous treatments with anti-Sdc2 pAb were as effective as intravitreal anti-VEGF therapy in reducing edema, size of retinal lesions, and local inflammation in this model. Post-injury neovascularization was not affected by treatment with anti-Sdc2 pAb.

Conclusions: These findings indicate that anti-Sdc2 pAb therapy can be an effective alternative to anti-VEGF-A approaches for suppression of edema and to prevent retinal lesions in wet neovascular AMD (nAMD).

Translational relevance: Intravitreal anti-Sdc2 treatment may avoid side effects observed with the long-term anti-VEGF therapy, and systemic treatment with an anti-Sdc2 pAb antibody can address the issues associated with repeated intravitreal injections.

Purpose: The purpose of this study was to investigate the dynamic changes in aqueous concentrations of angiopoietin (Ang)-1/2 and vascular endothelial growth factor (VEGF) during injection in treatment-naïve patients with diabetic macular edema (DME) receiving faricimab during the induction phase (3 consecutive monthly doses) and retrospectively analyze the data.

Methods: Thirty-five eyes of 26 patients (age = 63.1 ± 12.9 years) with treatment-naïve DME received faricimab injections monthly, 3 consecutive times. Additionally, 59 eyes of 59 patients (age = 63.9 ± 8.8 years) who underwent cataract surgery were recruited as controls. Aqueous humor samples were collected from each injection or surgery and stored at -80°C, and the concentration of each cytokine was quantified using a multiple enzyme-linked immunosorbent assay (Luminex). The clinical parameters of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at each visit were also recorded.

Results: Three induction phases of faricimab significantly suppressed each aqueous cytokine, rapidly for VEGF, gradually for Ang-2, and slightly for Ang-1. The Ang-1/2 ratio was lower (<1.0) at baseline and gradually increased, but did not reach a control ratio of 1.58. The baseline CFT correlated with VEGF, but not with the Ang-2, Ang-1, or Ang-1/2 ratios. After three injections, CFT did not correlate with VEGF, but it positively correlated with Ang-2 and negatively correlated with Ang-1, and it strongly negatively correlated with the Ang-1/2 ratio.

Conclusions: The Ang-1/2 ratio in the aqueous humor significantly negatively correlated with the degree of residual edema after faricimab treatment for DME.

Translational relevance: The Ang-1/2 ratio in aqueous humor is thus a useful biomarker of the treatment response for DME.

Purpose: To analyze choroidal and choriocapillaris changes in eyes affected by active unilateral central serous chorioretinopathy (CSC).

Methods: A total of 17 eyes suffering from naïve CSC were enrolled. In addition, 17 healthy fellow eyes were analyzed, and 10 eyes were enrolled as controls. Main outcome measures were choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and pigment epithelial detachment (PED) presence and maximum height (PED-MH). In addition, choriocapillaris and choroidal flow analysis in the two concentric areas surrounding the fovea were analyzed.

Results: CCT was higher in affected eyes than healthy ones (P = 0.007). CVI was significantly higher in affected eyes (P = 0.027) and in fellow eyes (P = 0.027) compared to healthy. The choriocapillaris analysis showed interesting results in the first ring, with statistically significant differences between diseased eyes and fellow eyes and in diseased eyes compared to healthy ones. Besides, in the second ring analysis a lower flow in choriocapillaris was found in diseased eyes compared with healthy (P = 0.019). The choroidal flow analysis showed lower flow in affected eyes in the first and second ring when comparing diseased eyes with healthy controls (P = 0.006).

Conclusions: Choroidal and choriocapillaris flow abnormalities occur in both eyes affected by CSC and fellow eyes with different trends depending on the area of study reinforcing the key role of choroid and choriocapillaris in the pathogenesis of disease.

Translational relevance: Understanding choroidal and choriocapillaris flow abnormalities in CSC eyes could give us new biomarkers able to monitor disease.

Purpose: To examine the 5-year incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population.

Methods: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital. Baseline examinations were performed from 2014 to 2015, with 5-year follow-up examinations conducted between 2019 and 2020. Fundus photographs were graded according to the Beckman Initiative guidelines.

Results: A total of 5658 participants with gradable photographs at both examinations were included in the study, comprising 58.0% women, with a mean age of 54.9 ± 11.0 years. The 5-year incidence of any, early, intermediate, and late AMD were 6.1% (95% confidence interval [CI], 5.5%-6.8%), 5.0% (95% CI, 4.4%-5.6%), 3.4% (95% CI, 2.9%-3.9%), and 0.3% (95% CI, 0.2%-0.4%), respectively. In multivariate analysis, incident early AMD was associated with older age (P < 0.001; odds ratio [OR], 1.04; 95% CI, 1.02-1.06), female sex (P = 0.011; OR, 1.42; 95% CI, 1.08-1.86), and a higher estimated glomerular filtration rate (P = 0.020; OR, 1.15; 95% CI, 1.02-1.30), whereas having diabetes was a protective factor (P = 0.019; OR, 0.61; 95% CI, 0.41-0.92). Incident intermediate AMD was associated with older age (P < 0.001; OR, 1.05; 95% CI, 1.04-1.07), a higher high-density lipoprotein cholesterol level (P < 0.001; OR, 1.97; 95% CI, 1.38-2.83) and a lower triglyceride level (P = 0.008; OR, 0.77; 95% CI, 0.64-0.93).

Conclusions: A higher estimated glomerular filtration rate level was a risk factor for incident early AMD. A higher high-density lipoprotein cholesterol level and lower triglyceride level were risk factors for incident intermediate AMD. This finding may point to the role of renal circulation and lipid metabolism in incident AMD.

Translational relevance: This community-based longitudinal study may provide a valuable understanding of AMD and its associated factors for targeted prevention and management strategies.

Purpose: To evaluate changes in the retinal microvasculature using widefield swept-source optical coherence tomography angiography (SS-OCTA) following three anti-vascular endothelial growth factor (anti-VEGF) loading injections for diabetic macular edema (DME).

Methods: Thirty-four treatment-naïve patients with DME received an initial three loading injections, followed by injections on an as-needed basis. Macular ischemia was evaluated based on the foveal avascular zone (FAZ) area, perfusion density, and vessel density on a 3 × 3-mm SS-OCTA image. Midperipheral ischemia was analyzed by dividing a 12 × 12-mm image into 16 boxes to compare changes in the nonperfusion area (NPA). Participants were categorized as aggravated, stable, or improved based on changes in the NPA after three injections.

Results: Of the 34 included patients, eight (23.5%) demonstrated aggravation of the NPA, 23 (67.6%) remained stable, and three (8.8%) exhibited improvement. Although FAZ area, perfusion, and vessel density increased, the differences were not significant compared to baseline. The number of injections and glycated hemoglobin (HbA1c) levels in the NPA aggravation group were significantly higher than in the stable and improvement groups. Logistic regression analysis revealed that NPA aggravation was independently associated with the number of anti-VEGF injections.

Conclusions: Changes in NPA following anti-VEGF loading injections varied among patients with DME and were significantly associated with HbA1c levels and injection frequency. Worsening mid-peripheral NPA after the anti-VEGF injections independently risked DME recurrence.

Translational relevance: We revealed that worsening mid-peripheral retinal ischemia after anti-VEGF loading injections contributes to the recurrence of DME.

Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD. The article outlines opportunities to address gaps and unmet needs that should lead to additional progress toward the development of treatments for patients with IRDs and non-neovascular AMD in the future.

Purpose: Identify optimal metabolic features and pathways across diabetic retinopathy (DR) stages, develop risk models to differentiate diabetic macular edema (DME), and predict anti-vascular endothelial growth factor (anti-VEGF) therapy response.

Methods: We analyzed 108 aqueous humor samples from 78 type 2 diabetes mellitus patients and 30 healthy controls. Ultra-high-performance liquid chromatography-high-resolution-mass-spectrometry detected lipidomics and metabolomics profiles. DME patients received ≥3 anti-VEGF treatments, categorized into strong and weak response groups. Machine learning (ML) screened prospective metabolic features, developing prediction models.

Results: Key metabolic features identified in the metabolomics and lipidomics datasets included n-acetyl isoleucine (odds ratio [OR] = 1.635), cis-aconitic acid (OR = 3.296), and ophthalmic acid (OR = 0.836) for DR. For early-DR, n-acetyl isoleucine (OR = 1.791) and decaethylene glycol (PEG-10) (OR = 0.170) were identified as key markers. L-kynurenine (OR = 0.875), niacinamide (OR = 0.843), and linoleoyl ethanolamine (OR = 0.941) were identified as significant indicators for DME. Trigonelline (OR = 1.441) and 4-methylcatechol-2-sulfate (OR = 1.121) emerged as predictors for strong response to anti-VEGF. Predictive models achieved R² values of 99.9%, 97.7%, 93.9%, and 98.4% for DR, early-DR, DME, and strong response groups in the calibration set, respectively, and validated well with R² values of 96.3%, 96.8%, 79.9%, and 96.3%.

Conclusions: This research used ML to identify differential metabolic features from metabolomics and lipidomics datasets in DR patients. It implies that metabolic indicators can effectively predict early disease progression and potential weak responders to anti-VEGF therapy in DME eyes.

Translational relevance: The identified metabolic indicators may aid in predicting the early progression of DR and optimizing therapeutic strategies for DME.