Comparison of MicroRNA Expression in Aqueous Humor of Normal and Primary Open-Angle Glaucoma Patients Using PCR Arrays: A Pilot Study.

Purpose: MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that have been detected in human aqueous humor (AH). Prior studies have pooled samples to obtain sufficient quantities for analysis or used next-generation sequencing. Here, we used PCR arrays with preamplification to identify and compare miRNAs from individual AH samples between patients with primary open-angle glaucoma (POAG) and normal controls. Methods: AH was collected before cataract surgery from six stable, medically treated POAG patients and eight age-matched controls. Following reverse transcription and preamplification, individual patient samples were profiled on Taqman Low Density MicroRNA Array Cards. Differentially expressed miRNAs were stratified for fold changes larger than ±2 and for significance of P < 0.05. Significant Kyoto Encyclopedia of Genes and Genomes pathways influenced by the differentially expressed miRNAs were identified using the predicted target module of the miRWalk 2.0 database. Results: This approach detected 181 discrete miRNAs, which were consistently expressed across all samples of both experimental groups. Significant up-regulation of miR-518d and miR-143, and significant down-regulation of miR-660, was observed in the AH of POAG patients compared with controls. These miRNAs were predicted to reduce cell proliferation and extracellular matrix remodeling, endocytosis, Wnt signaling, ubiquitin-mediated proteolysis, and adherens junction function. Conclusions: This pilot study demonstrates that miRNA expression within the AH of POAG patients differs from age-matched controls. AH miRNAs exhibit potential as biomarkers of POAG, which merits further investigation in a larger case-controlled study. This technique provides a cost-effective and sensitive approach to assay miRNAs in individual patient samples without the need for pooling.

Optical coherence tomography angiography of optic disc perfusion in glaucoma.

PURPOSE: To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-four normal subjects and 11 patients with glaucoma were included. METHODS: One eye of each subject was scanned by a high-speed 1050-nm-wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. RESULTS: In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group (P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R(2) = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. CONCLUSIONS: Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

Optical coherence tomography-based corneal power measurement and intraocular lens power calculation following laser vision correction (an American Ophthalmological Society thesis).

PURPOSE: To use optical coherence tomography (OCT) to measure corneal power and improve the selection of intraocular lens (IOL) power in cataract surgeries after laser vision correction. METHODS: Patients with previous myopic laser vision corrections were enrolled in this prospective study from two eye centers. Corneal thickness and power were measured by Fourier-domain OCT. Axial length, anterior chamber depth, and automated keratometry were measured by a partial coherence interferometer. An OCT-based IOL formula was developed. The mean absolute error of the OCT-based formula in predicting postoperative refraction was compared to two regression-based IOL formulae for eyes with previous laser vision correction. RESULTS: Forty-six eyes of 46 patients all had uncomplicated cataract surgery with monofocal IOL implantation. The mean arithmetic prediction error of postoperative refraction was 0.05 ± 0.65 diopter (D) for the OCT formula, 0.14 ± 0.83 D for the Haigis-L formula, and 0.24 ± 0.82 D for the no-history Shammas-PL formula. The mean absolute error was 0.50 D for OCT compared to a mean absolute error of 0.67 D for Haigis-L and 0.67 D for Shammas-PL. The adjusted mean absolute error (average prediction error removed) was 0.49 D for OCT, 0.65 D for Haigis-L (P=.031), and 0.62 D for Shammas-PL (P=.044). For OCT, 61% of the eyes were within 0.5 D of prediction error, whereas 46% were within 0.5 D for both Haigis-L and Shammas-PL (P=.034). CONCLUSIONS: The predictive accuracy of OCT-based IOL power calculation was better than Haigis-L and Shammas-PL formulas in eyes after laser vision correction.