Faculty Bibliography

Since the introduction of commercial optical coherence tomography (OCT) systems, the ophthalmic imaging modality has rapidly expanded and it has since changed the paradigm of visualization of the retina and revolutionized the management and diagnosis of neuro-retinal diseases, including glaucoma. OCT remains a dynamic and evolving imaging modality, growing from time-domain OCT to the improved spectral-domain OCT, adapting novel image analysis and processing methods, and onto the newer swept-source OCT and the implementation of adaptive optics (AO) into OCT. The incorporation of AO into ophthalmic imaging modalities has enhanced OCT by improving image resolution and quality, particularly in the posterior segment of the eye. Although OCT previously captured in-vivo cross-sectional images with unparalleled high resolution in the axial direction, monochromatic aberrations of the eye limit transverse or lateral resolution to about 15-20 mum and reduce overall image quality. In pairing AO technology with OCT, it is now possible to obtain diffraction-limited resolution images of the optic nerve head and retina in three-dimensions, increasing resolution down to a theoretical 3 mum3. It is now possible to visualize discrete structures within the posterior eye, such as photoreceptors, retinal nerve fiber layer bundles, the lamina cribrosa, and other structures relevant to glaucoma. Despite its limitations and barriers to widespread commercialization, the expanding role of AO in OCT is propelling this technology into clinical trials and onto becoming an invaluable modality in the clinician's arsenal.

OBJECTIVE: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. METHODS: Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. RESULTS: The genetic risk score was associated with self-reported ANM (P = 2.2 x 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P >/=0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). CONCLUSIONS: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.This is an open-access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share thework provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.