Translational Vision Science & Technology最新文献

Purpose: Tonography is the standard method for non-invasive measurement of aqueous humor outflow facility. However, assessment of tonography tracing quality is currently subjective, and acceptance of poor-quality data or inappropriately discarding valid data can bias results. The purpose of this study was to develop an objective method for assessing the quality of tonography tracings.

Methods: Pneumatonography tracings were obtained from glaucoma and ocular hypertension patients as part of an ongoing multicenter study of aqueous humor dynamics. Intraocular pressure (IOP) was captured digitally at 40 Hz over 2 minutes. Root mean square error (RMSE) of a linear best-fit line was obtained for each tracing. Each tracing was also graded by seven experienced tonographers using a scale of 1 (worst) to 10 (best) for quality (Expert score). A Reference set of 35 tracings was used to determine the relationship between RMSE values and Expert scores using a logarithmic curve. This relationship was used to calculate a predicted score in a second Test set of 20 tracings. A logarithmic curve was used to account for the fixed range of Expert scores and unbounded upper range for RMSE values. The differences between the predicted scores and the Expert scores were evaluated using Bland-Altman analysis.

Results: There was a very strong correlation between predicted and Expert scores (R = 0.94). The mean difference between Expert and predicted scores was -1.01 ± 0.84, and the limits of agreement were between -2.65 and +0.63.

Conclusions: Objective assessment of pneumatonography tracings can be performed using RMSE of a fitted line and calculation of a predicted quality score that closely matches scores given by expert graders.

Translational relevance: Tonography tracing quality can now be objectively assessed.

Purpose: CNGA3 achromatopsia is a rare hereditary syndrome caused by dysfunction of cone photoreceptors. Visual information is therefore obtained only by rod photoreceptors, resulting in low acuity, photoaversion, and color blindness. Trials using gene therapy have been initiated recently, in which clinical improvement was subtle.

Methods: To explain this suboptimal outcome, we used diffusion tensor imaging to assess visual pathway integrity in 3 CNGA3 achromatopsia patients before and after gene therapy, and compared them with 16 normally sighted adults.

Results: No significant differences from normal subjects in optic tract and radiation were detected. Fiber integrity reduction was observed in the occipitocallosal fibers. These differences showed some normalization after treatment, but intersubject variability was evident. Specifically, the observed changes were related to radial diffusivities, reflecting fiber myelination or glial cell alterations.

Conclusions: Despite the fundamental role of cone photoreceptors in human sight, primary visual pathways in patients are comparable with those of healthy individuals and thereby fiber integrity is probably not an obstacle for recovery. Preliminary results suggest that the splenial fibers are less cohesive in naïve patients and regain some integrity after treatment. These findings add to previous reports on this rare population and suggest that novel information is processed within the visual cortex after treatment.

Translational relevance: Patients with complete color blindness were treated using a novel gene augmentation therapy. Unfortunately, the patients did not experience a sudden eureka moment of being able to perceive the full spectrum of colors. In this study, we rule out fiber disintegration as the cause of their limited recovery.

Purpose: To explore the relationship between hormone levels and diabetic retinopathy (DR).

Methods: This cross-sectional study recruited 2432 patients with type 2 diabetes from Tianjin Medical University General Hospital between 2016 and 2019. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between hormone levels and DR.

Results: DR was diagnosed in 953 patients (39.19%), with no significant gender difference in prevalence. Among men, DR prevalence increased with testosterone level increasing (Q4 vs. Q1: odds ratio [OR] = 1.64; 95% confidence interval [CI], 1.11-2.41) but decreased with prolactin levels increasing (Q4 vs. Q1: OR = 0.65; 95% CI, 0.44-0.96). Among women, high follicle-stimulating hormone (FSH) (Q4 vs. Q1: OR = 2.22; 95% CI, 1.40-3.52) and luteinizing hormone (LH) levels (Q4 vs. Q1: OR = 1.77; 95% CI, 1.20-2.63) were linked with increased DR prevalence. No associations were found in premenopausal women, but postmenopausal women with high prolactin level had increased DR prevalence (Q2 vs. Q1: OR = 1.56; 95% CI, 1.01-2.19). Dose-response relationships were suggested for FSH (P = 0.087) and testosterone (P = 0.088) with DR prevalence, though caution is advised due to the risk of type I error arising from multiple comparisons. Other risk factors included low body mass index (OR = 0.98), smoking (OR = 1.32), long diabetes duration (OR = 1.02), and high systolic blood pressure (OR = 1.01).

Conclusions: Prolactin (negatively) and testosterone (positively) were correlated with DR risk in men. FSH and testosterone showed suggestive dose-response relationship with DR prevalence in postmenopausal women. Further research is needed for type 1 diabetes.

Translational relevance: Sex hormones play a crucial role in DR development, affecting men and women differently.

Purpose: This study compares clinical characteristics of retinitis pigmentosa (RP) associated with mutations in the EYS and USH2A genes in a Southeast Asian cohort.

Methods: Prospective single-center study of families with EYS- or USH2A-associated RP seen at the Singapore National Eye Centre. Comprehensive ophthalmic evaluations, multimodal imaging, genetic testing, and longitudinal follow-up identified clinically useful differentiating features between the two genotypes.

Results: A total of 300 families with RP were enrolled, with EYS- and USH2A-associated RP, accounting for 24.7% of all probands and 50.7% of solved or likely solved cases. USH2A cases were predominantly nonsyndromic RP (75%). EYS-associated RP was more severe in functional and structural outcomes, and patients were more myopic than USH2A (SE -3.31 vs. -0.69; P < 0.0001). EYS RP displayed peripapillary nasal sparing on autofluorescence imaging more frequently than USH2A (57.6% vs. 26.7%; P = 0.006), whereas USH2A cases more often had a parafoveal ring (73.3% vs. 30.3%; P = 0.0002). Multiple logistic regression identified diagnostic features with 83.2% accuracy in distinguishing between EYS and USH2A, validated in a second unrelated clinical cohort.

Conclusions: EYS- and USH2A-associated RP have overlapping clinical presentations but can often be distinguished based on a constellation of phenotypic features including disease onset and severity, refractive error, and fundus autofluorescence. These diagnostic features may support a more effective diagnostic strategy for these common forms of RP.

Translational relevance: Distinct clinical features differentiating EYS- and USH2A-associated RP provide valuable diagnostic tools that may inform personalized management and facilitate targeted interventions in clinical practice.

Purpose: Continuous visual stimulus tracking could be used as an easy alternative to standard automated perimetry (SAP) for visual function screening. With continuous visual stimulus tracking, we simplified the perimetric task to following a moving dot on a screen with the eyes. Here, we determined whether tracking performance (the agreement between gaze and stimulus position) enables the detection and quantification of glaucomatous visual function loss (in terms of SAP), and whether it shows a learning effect.

Methods: We evaluated the tracking performance of 36 cases with early, moderate, or severe glaucoma (median with interquartile range [IQR] age = 70 [67-74] years) and 36 controls (median = 70, IQR = 67-72 years). All participants monocularly tracked a moving stimulus (Goldmann size III) at 3 Weber contrast levels: 40, 160, and 640%, while their eye movements were recorded.

Results: Glaucoma decreased the tracking performance, with the most severe reduction in the severe glaucoma cases. A distinction between groups was possible, but depended on the contrast level: tracking performance of early glaucoma cases was significantly different from controls only at 40% contrast. Within the cases, glaucomatous visual function loss (SAP Mean Sensitivity [MS]) was best correlated with tracking performance when using 160% contrast. There was no significant learning effect.

Conclusions: Overall, the data indicate that it is possible to detect and quantify glaucomatous visual function loss with continuous visual stimulus tracking.

Translational relevance: Continuous visual stimulus tracking is an easy, fast, and intuitive technique that has the potential for diagnostic applications in detection of new glaucoma cases and monitoring of previously diagnosed cases.

Purpose: To examine relationships between retinal structure and visual function in geographic atrophy (GA) by analyzing spatial agreement between absolute scotomas and macular structure, focusing on (1) choroidal hypertransmission, a key feature of complete retinal pigment epithelium and outer retinal atrophy (cRORA), and (2) fundus autofluorescence (FAF)-defined GA.

Methods: Mesopic microperimetry (using a novel T-shaped pattern) and multimodal imaging were recorded longitudinally in a phase II GA trial. Horizontal and vertical optical coherence tomography (OCT) line scans (corresponding to the T axes) were graded for choroidal hypertransmission; FAF images were graded for GA. Spatial concordance between zones of absolute scotoma and atrophy was quantified by the Dice similarity coefficient (DSC).

Results: The analysis population comprised 24 participants (mean follow-up 26.8 months). For concordance between absolute scotoma and choroidal hypertransmission, estimated mean DSC was 0.70 (95% confidence interval [CI], 0.64-0.77). This was significantly higher than for FAF-defined GA (0.67; 95% CI, 0.61-0.74; estimated mean difference = 0.03, 95% CI, 0.02-0.05, P < 0.001). Mean OCT choroidal reflectivity was strongly associated with likelihood and severity of scotoma.

Conclusions: Spatial concordance between absolute scotomas and GA structural features is moderately high and slightly higher for choroidal hypertransmission than FAF-defined GA. This supports choroidal hypertransmission, a key cRORA feature, as an outcome measure in interventional trials. OCT provides more information to explain visual function than FAF alone. However, given some discordance for both structural features, performing microperimetry alongside imaging remains important.

Translational relevance: These findings provide insights into the complex relationship between retinal structure and visual function and contribute to a nuanced understanding of outcome measures.

Purpose: To determine biomarkers of macular neovascularization (MNV) in neovascular age-related macular degeneration through the application of an automatic algorithm based optical coherence tomography angiography (OCTA) analysis.

Methods: In this retrospective, observational, single-center, cross-sectional study, patients with a diagnosis of age-related macular degeneration complicated by type 1 MNV were included. MNV was detected with OCTA and scans were analyzed with a qualitative and quantitative open-source image processing package. For each analyzed image, we automatically acquired the following data: Total MNV area, vessel area, vessel density (VD), total number of branches, total number of vascular junctions, mean vessel length, mean vessel diameter, fractal dimension (FD), junction density, and vessel tortuosity.

Results: The following morphological parameters revealed a significant negative correlation with best-corrected visual acuity: MNV area - Spearman ρ = -0.309 (P = 0.002); vessel area - Spearman ρ = -0.315 (P = 0.002); total number of vascular junctions - Spearman ρ = -0.285 (P = 0.005), and VL - Spearman ρ = -0.304 (P = 0.003). Immature MNV lesions were significantly associated with better vessel area than mature and hypermature lesions.

Conclusions: Several automated MNV-associated morphological parameters can correlate with the best-corrected visual acuity. Further studies are warranted to determine if these OCTA biomarkers can be applied to guide anti-vascular endothelial growth factor therapy and predict response to treatment.

Translational relevance: The analysis of MNV biomarkers may have prognostic value in terms of visual function.

Purpose: To evaluate the performance of various approaches of processing three-dimensional (3D) optical coherence tomography (OCT) images for deep learning models in predicting area and future growth rate of geographic atrophy (GA) lesions caused by age-related macular degeneration (AMD).

Methods: The study used OCT volumes of GA patients/eyes from the lampalizumab clinical trials (NCT02247479, NCT02247531, NCT02479386); 1219 and 442 study eyes for model development and holdout performance evaluation, respectively. Four approaches were evaluated: (1) en-face intensity maps; (2) SLIVER-net; (3) a 3D convolutional neural network (CNN); and (4) en-face layer thickness and between-layer intensity maps from a segmentation model. The processed OCT images and maps served as input for CNN models to predict baseline GA lesion area size and annualized growth rate.

Results: For the holdout dataset, the Pearson correlation coefficient squared (r2) in the GA growth rate prediction was comparable for all the evaluated approaches (0.33∼0.35). In baseline lesion size prediction, prediction performance was comparable (0.9∼0.91) except for the SLIVER-net (0.83). Prediction performance with only the thickness map of the ellipsoid zone (EZ) or retinal pigment epithelium (RPE) layer individually was inferior to using both. Addition of other layer thickness or intensity maps did not improve the prediction performance.

Conclusions: All explored approaches had comparable performance, which might have reached a plateau to predict GA growth rate. EZ and RPE layers appear to contain the majority of information related to the prediction.

Translational relevance: Our study provides important insights on the utility of 3D OCT images for GA disease progression predictions.

Purpose: To investigate the association between aqueous humor (AH) suppressant eye drops and the concentration of aflibercept at 1 month after intravitreal injection.

Methods: This retrospective study included 17 eyes of 17 patients with neovascular age-related macular degeneration (nAMD) who used eye drops for their glaucoma and received their first intravitreal aflibercept (IVA) at two centers between July 2013 and November 2020. As controls, we enrolled 40 age-, sex-, and axial length-matched eyes of 40 patients with nAMD who were not using any medication that would affect AH circulation. AH was collected 1 month after the first IVA. Aflibercept levels were measured by enzyme-linked immunosorbent assay and were compared between controls and cases using the Kruskal-Wallis test and Dunn's test. The drugs were categorized into two groups based on their mechanism of action on the AH: outflow drugs (e.g., prostaglandin analog) and inflow drugs (e.g., carbonic anhydrase inhibitor, beta-blockers, and alpha-2 agonists).

Results: Mean (interquartile range) aflibercept levels in the AH in controls and in cases who used outflow and inflow drugs were 6.83 µg/mL (1.94-10.34), 9.93 µg/mL (2.58-17.44), and 15.95 µg/mL (7.20-22.57), respectively. A Kruskal-Wallis test showed a significant difference among the control, inflow, and outflow drugs (P = 0.0075). Dunn's test showed that aflibercept levels in the aqueous humor were significantly higher in cases using inflow drugs compared to both controls and cases using outflow drugs (P = 0.0085 and P = 0.044, respectively).

Conclusions: Aflibercept levels in the AH 1 month after the first IVA were higher in cases using eye drops that reduce AH secretion than in controls.

Translational relevance: Our results, together with previous studies in animals, suggest that combined use of these eye drops might extend the half-life of intravitreally injected drugs.

Purpose: To evaluate the safety and efficacy of the magnetic levator prosthesis (MLP) relative to active control with KT Tape, an elastic therapeutic tape used clinically to mechanically open the lids, and to a sham MLP worn in-office only.

Methods: This was a double-masked, randomized crossover single-center trial of patients with severe unilateral or bilateral paralytic blepharoptosis defined as occlusion of the visual axis without frontalis recruitment. Patients were allocated to MLP or tape first and then crossed over after 2 weeks of use and a 2-week washout. Primary outcome was maximum eyelid closure on spontaneous blink measured in video frames with ImageJ. Primary patient-reported outcome was the Glasgow Benefit Inventory and, secondarily, comparison of the amount of eye opening and proportions of complete volitional blinks.

Results: Of 16 patients randomized, 15 completed the crossover. MLP and tape equally improved eye opening over sham (MLP, 6.8 mm [95% confidence interval (CI), 5.2-8.4]; tape, 7.0 mm [5.4-8.6]; sham, 3.9 mm [2.3-5.5], all P < 0.001). Spontaneous blinks were significantly better with MLP (2.4 mm [95% CI, 1.5-3.7] compared to tape, 4.1 mm [2.6-6.5], P < 0.001). Incomplete volitional blinks were much more common when wearing tape compared to when wearing the MLP (P < 0.001), which was not different from sham. There was a significant perceived benefit of both MLP and tape (P < 0.001). There were three related nonserious adverse events over 3539 hours of tape use and two related nonserious adverse events over 4632 hours of MLP use.

Conclusions: The MLP was superior to KT tape and sham for the treatment of severe blepharoptosis.

Translational relevance: First randomized controlled clinical trial of the MLP. (https://clinicaltrials.gov/study/NCT04678115?cond=Blepharoptosis&term=kinesiotape&rank=1, NCT04678115).