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IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 are pivotal in autophagy, cellular senescence, and the inflammatory response in AMD, corresponding with 24 drugs with therapeutic potential for AMD, providing definite molecular mechanisms for further research and new possibilities for AMD treatment in the future.

IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 may be new targets for AMD gene therapy and drug development.

IL-6, VEGF-A, TP53, IL-1β, and TGF-β1 may be new targets for AMD gene therapy and drug development.

To investigate the ocular and systemic factors related to glaucoma and to be adjusted for interindividual comparison of ocular blood flow measurement results by laser speckle flowgraphy (LSFG) obtained from the optic nerve head (ONH) in normal Japanese individuals.

A multicenter, prospective cross-sectional study was conducted. The ONH tissue-area and vessel-area mean blur rate (MT and MV) were evaluated using LSFG and ONH structural parameters using planimetric methods. Multivariate linear mixed-effects modeled regression analysis was used to identify the contributing factors to the MT and MV. The explanatory variables were age; gender; smoking history; body mass index; mean arterial pressure (MAP); heart rate; intraocular pressure; axial length (AL); disc, rim, cup, and β-peripapillary atrophy (β-PPA) areas; and central retinal artery and vein equivalents.

In total, 195 eyes of 126 healthy individuals with an average age of 48.1 years were included. Multivariate analysis showed that MAP and disc area had a negative (

< 0.001) correlation, whereas β-PPA area had a positive correlation with MT (

= 0.010). Age and AL had a negative correlation (

= 0.001 and

= 0.011, respectively), whereas cup area had a positive correlation (

= 0.012) with MV.

Interindividual comparison of MT or MV must be adjusted for both systemic factors (blood pressure or age) and local ocular factors (AL and disc, cup, or β-PPA area).

Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

Our results provided reference data on the LSFG measurement and are important in comparing ocular blood flow between individuals using LSFG.

To assess whether age can be predicted from deep learning analysis of peripapillary spectral-domain optical coherence tomography (SD-OCT) B-scans and to determine the importance of specific retinal areas on the predictions.

Deep learning (DL) convolutional neural networks were developed to predict chronological age in healthy subjects using peripapillary SD-OCT B-scan images. Models were built using the whole B-scan, as well as using specific regions through image ablation. Cross-validation was used for training and testing the model. Mean absolute error (MAE) and correlations between predicted and observed age were used to evaluate model performance.

A total of 7271 images from 542 eyes of 278 healthy subjects were included. Bevacizumab clinical trial DL predictions of age using the whole B-scan were strongly correlated with chronological age (MAE = 5.82 years;

= 0.860,

< 0.001). The model also accurately discriminated between the lowest and highest tertiles of age, with an area under the receiver operating characteristic curve of 0.962. In general, class activation maps tended to show a diffuse pattern of activation throughout the scan image. For specific structures of the B-scan, the layers with the strongest correlations with chronological age were the choroid and vitreous (both

= 0.736), whereas retinal nerve fiber layer had the lowest correlation (

= 0.492).

A DL algorithm was able to accurately predict age from whole peripapillary SD-OCT B-scans.

DL models applied to SD-OCT scans suggest that aging appears to affect several layers in the posterior eye segment.

DL models applied to SD-OCT scans suggest that aging appears to affect several layers in the posterior eye segment.

To determine whether artifacts in optical coherence tomography (OCT) images are associated with the success or failure of adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in subjects with achromatopsia (ACHM).

Previously acquired OCT and non-confocal, split-detector AOSLO images from one eye of 66 subjects with genetically confirmed achromatopsia (15

and 51

) were reviewed along with best-corrected visual acuity (BCVA) and axial length. OCT artifacts in interpolated vertical volumes from CIRRUS macular cubes were divided into four categories (1) none or minimal, (2) clear and low frequency, (3) low amplitude and high frequency, and (4) high amplitude and high frequency. Each vertical volume was assessed once by two observers. AOSLO success was defined as sufficient image quality in split-detector images at the fovea to assess cone quantity.

There was excellent agreement between the two observers for assessing OCT artifact severity category (weighted kappa = 0.88). Overall, AOSLO success was 47%. For subjects with OCT artifact severity category 1, AOSLO success was 65%; for category 2, 47%; for category 3, 11%; and for category 4, 0%. There was a significant association between OCT artifact severity category and AOSLO success (

= 0.0002). Neither BCVA nor axial length was associated with AOSLO success (

= 0.07 and

= 0.75, respectively).

Artifacts in OCT volumes are associated with AOSLO success in ACHM. Subjects with less severe OCT artifacts are more likely to be good candidates for AOSLO imaging, whereas AOSLO was successful in only 7% of subjects with category 3 or 4 OCT artifacts. These results may be useful in guiding patient selection for AOSLO imaging.

Using OCT to prescreen patients could be a valuable tool for clinical trials that utilize AOSLO to reduce costs and decrease patient testing burden.

Using OCT to prescreen patients could be a valuable tool for clinical trials that utilize AOSLO to reduce costs and decrease patient testing burden.

Delivery of Advanced Therapy Medicinal Products to the submacular space is increasingly evolving into a therapeutic modality. Cell replacement for age-related macular degeneration (AMD) and gene therapy for RPE65 are recent successful examples. Herein, a nonhuman primate (NHP) model was used to investigate surgical means to detach the macula.

Sixteen eyes of 13 healthy macaques underwent a 25-gauge vitrectomy and subretinal injection of balanced salt solution monitored by microscope-integrated intraoperative optical coherence tomography (miOCT). The animals were followed with OCT and histology.

The miOCT monitoring allowed a more precise definition of surgical trauma ranging from an initial full-thickness foveal tear, or induction of a cystoid macular edema (CME), until no foveal defect was discernible, as the technique improved. However, as the subretinal fluid wave detached the fovea, the aforementioned lesions formed, whereas persistent retinal adhesion reproducibly proved to remain in the distal parafoveal semi-annulus.

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