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Item Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer’s Disease(IOS Press, 2023) Mathew, Sunu; WuDunn, Darrell; Mackay, Devin D.; Vosmeier, Aaron; Tallman, Eileen F.; Deardorff, Rachael; Harris, Alon; Farlow, Martin R.; Brosch, Jared R.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Risacher, Shannon L.; Radiology and Imaging Sciences, School of MedicineBackground: The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina. Objective: To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. Methods: 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Results: Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. Conclusion: RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.Item Choroidal Thickness and Primary Open-Angle Glaucoma—A Narrative Review(MDPI, 2022-02-23) Verticchio Vercellin, Alice; Harris, Alon; Stone, Ari M.; Oddone, Francesco; Mendoza, Kristen Ann; Siesky, Brent; Ophthalmology, School of MedicineThe choroid provides the majority of blood flow to the ocular tissues and structures that facilitate the processes of retinal metabolism responsible for vision. Specifically, the choriocapillaris provides a structural network of small blood vessels that supplies the retinal ganglion cells and deep ocular tissues. Similar to retinal nerve fiber layer thickness, choroidal thickness (CT) has been suggested to represent a quantifiable health biomarker for choroidal tissues. Glaucoma is a disease with vascular contributions in its onset and progression. Despite its importance in maintaining ocular structure and vascular functionality, clinical assessments of choroidal tissues have been historically challenged by the inaccessibility of CT biomarker targets. The development of optical coherence tomography angiography and enhanced depth imaging created a framework for assessing CT and investigating its relationship to glaucomatous optic neuropathy onset and progression. Pilot studies on CT in glaucoma are conflicting—with those both in support of, and against, its clinical utility. Complicating the data are highly customized analysis methods, small sample sizes, heterogeneous patient groups, and a lack of properly designed controlled studies with CT as a primary outcome. Herein, we review the available data on CT and critically discuss its potential relevance and limitations in glaucoma disease management.Item Cross-Polarization Optical Coherence Tomographic Assessment of In situ Simulated Erosive Tooth Wear(Wiley, 2021) Romero, Maria Jacinta Rosario H.; Bezerra, Savio J.C.; Fried, Daniel; Yang, Vincent; Lippert, Frank; Eckert, George J.; Zero, Domenick T.; Hara, Anderson Takeo; Cariology, Operative Dentistry and Dental Public Health, School of DentistryThis clinical study tested cross-polarization optical coherence tomography (CP-OCT) monitoring of erosive tooth wear (ETW). Twenty participants completed a 14-day/arm, 3-arm crossover study simulating different ETW severities. Participants received two enamel specimens (per arm) and were randomized to: severe (s-ETW, lemon juice/pH:2.5/4.25%wt/vol citric acid), moderate (m-ETW, grapefruit juice/pH:3.5/1.03%wt/vol citric acid), and non-ETW (water). Enamel thickness was measured with CP-OCT (day[D] 0, 7, 14) and micro-computed tomography (μ-CT; D14). Enamel surface loss was determined with CP-OCT and optical profilometry (OP; D7, D14). CP-OCT showed higher enamel surface loss for D14 than D7 for m-ETW (P = .009) and s-ETW (P = .040) and differentiated severity at D14 (s-ETW > non-ETW, P = .027). OP was able to differentiate surface loss between days (D7 < D14, P < .001) for m-ETW and s-ETW, and ETW severity effect after 7 and 14 days (non-ETW < m-ETW < s-ETW, P < .001). At D14, CP-OCT and μ-CT were positively correlated (r = .87, ICC = .62). CP-OCT showed potential as a tool for clinical ETW monitoring.Item Double-Masked, Randomized, Phase 2 Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Neovascular Age-Related Macular Degeneration(Mary Ann Liebert, 2018-11-09) Callanan, David; Kunimoto, Derek; Maturi, Raj K.; Patel, Sunil S.; Staurenghi, Giovanni; Wolf, Sebastian; Cheetham, Janet K.; Hohman, Thomas C.; Kim, Kimmie; López, Francisco J.; Schneider, Susan; Ophthalmology, School of MedicinePURPOSE: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration. METHODS: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients (n = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections). RESULTS: In the abicipar 1 mg (n = 25), abicipar 2 mg (n = 23), and ranibizumab (n = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae. CONCLUSIONS: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.Item Exploratory Analysis of Objective Outcome Measures for the Clinical Assessment of Erosive Tooth Wear(MDPI, 2023-08-02) Romero, Maria Jacinta Rosario H.; Ungar, Peter S.; Fried, Daniel; Lippert, Frank; Zero, Domenick T.; Zunt, Susan; Eckert, George J.; Gutierrez Gossweiler, Ana; Elkington-Stauss, Dylan Jacob; Tamayo-Cabeza, Guillermo; Kelly, Adam B.; Bartels, Troy; Kita, Camille; Wewers, Elizabeth; Hara, Anderson T.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryThis study proposed using enamel surface texture and thickness for the objective detection and monitoring of erosive tooth wear (ETW), comparing them to the standard subjective Basic Erosive Wear Evaluation (BEWE). Thirty-two subjects (n = 597 teeth) were enrolled in this longitudinal observational clinical study. Enamel thickness (by cross-polarization optical coherence tomography, CP-OCT) and 3D dental microwear parameters, i.e., area-scale fractal complexity (Asfc), anisotropy (Str), and roughness (Sa) (by white-light scanning confocal profilometry), were obtained from buccal surfaces. Buccal, occlusal, and lingual surfaces were scored for BEWE and the maximum score per tooth (BEWEMax) was determined at baseline and 12 months (M12). Data outcome relationships were evaluated (alpha = 0.05). Enamel thickness decreased (p < 0.001), BEWE scores, Sa, and Str increased (p < 0.001), while Asfc did not change at M12. Baseline BEWEBuccal correlated strongly with BEWEMax (r = 0.86, p < 0.001) and moderately with BEWELingual (r = 0.42, p < 0.001), but not with enamel thickness (r = 0.03, p = 0.43). Change (Δ) in surface texture outcomes correlated poorly but significantly with ΔBEWEBuccal (r = −0.15–0.16, p < 0.001) and did not correlate with Δenamel thickness (r = 0.02–0.09, p > 0.06). Teeth with BEWE progression revealed a greater increase in ΔSa and ΔStr. These findings suggest that enamel surface roughness can potentially determine ETW severity, and CP-OCT may be relevant for clinically monitoring enamel thickness.Item Retinal nerve fiber layer thickness in glaucomatous Nepalese eyes and its relation with visual field sensitivity(Elsevier, 2014) Khanal, Safal; Thapa, Madhu; Racette, Lyne; Johnson, Richard; Davey, Pinakin Gunvant; Joshi, Mahesh Raj; Shrestha, Gauri Shankar; Medicine, School of MedicineBACKGROUND: To evaluate peripapillary retinal nerve fiber layer (RNFL) thickness in glaucomatous Nepalese eyes using spectral domain optical coherence tomography (SD-OCT) and study its relationship with visual field sensitivity. METHODS: A total of 120 eyes comprising primary open angle glaucoma (POAG), glaucoma suspects (GS), normal tension glaucoma (NTG) and healthy subjects (n=30 cases in each group) underwent a complete ophthalmic examination, including optic nerve head (ONH) evaluation and standard automated perimetry (SAP). RNFL thickness measurements around the optic disk were taken with circular spectral domain optical coherence tomography (SD-OCT) scans. Analysis of variance (ANOVA) was used for comparison of RNFL parameters among various study groups. The relationship of RNFL parameters with visual field (VF) global indices was evaluated with regression analysis. RESULTS: The mean pRNFL thickness was significantly less in the POAG (64.30±14.45μm, p<0.01), NTG (85.43±9.79μm, p<0.001) and GS (102.0±9.37μm, p<0.001) groups than in the healthy group (109.8±8.32μm). The RNFL was significantly thinner across all quadrants in all study group pairs (p<0.05) except for normal vs. GS (only superior and inferior quadrant, significant). Linear regression plots with RNFL thickness as a predictor of MD and LV demonstrated a strong and statistically significant degree of determination in the POAG group (R(2)=0.203 and 0.175, p=0.013 and 0.021). CONCLUSION: The RNFL thickness measurements with SD-OCT are lower in glaucomatous eyes as compared to age-matched GS and normal eyes in the Nepalese population. A high resolution SD-OCT could aid significantly in the early diagnosis of glaucoma in Nepal.Item Segmentation of human retinal layers from optical coherence tomography scans(ProQuest, 2015-02-09) Hammes, Nathan M.; Tsechpenakis, Gavriil; Tuceryan, Mihran; Fang, ShiaofenAn algorithm was developed in to efficiently segment the inner-limiting membrane (ILM) and retinal pigmented epithelium (RPE) from spectral domain-optical coherence tomography image volumes. A deformable model framework is described and implemented in which free-form deformations (FFD) are used to direct two deformable sheets to the two high-contrast layers of interest. Improved accuracy in determining retinal thickness (the distance between the ILM and the RPE) is demonstrated against the commercial state-of-the-art Spectralis OCT native segmentation software. A novel adaptation of the highest confidence first (HCF) algorithm is utilized to improve upon the initial results. The proposed adaptation of HCF provides distance-based clique potentials and an efficient solution to layer-based segmentation, reducing a 3D problem to 2D inference.