Faculty Bibliography

PURPOSE: Previously, we demonstrated reduced Schlemm's canal cross-sectional area (SC-CSA) with increased perfusion pressure in a cadaveric flow model. The purpose of the present study was to determine the effect of acute IOP elevation on SC-CSA in living human eyes. METHODS: The temporal limbus of 27 eyes of 14 healthy subjects (10 male, 4 female, age 36 +/- 13 years) was imaged by spectral-domain optical coherence tomography at baseline and with IOP elevation (ophthalmodynamometer set at 30-g force). Intraocular pressure was measured at baseline and with IOP elevation by Goldmann applanation tonometry. Vascular landmarks were used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm's canal CSA at five locations within a 1-mm length of SC was measured in ImageJ as described previously. A linear mixed-effects model quantified the effect of IOP elevation on SC-CSA. RESULTS: The mean IOP increase was 189%, and the mean SC-CSA decrease was 32% (P < 0.001). The estimate (95% confidence interval) for SC-CSA response to IOP change was -66.6 (-80.6 to -52.7) mum(2)/mm Hg. CONCLUSIONS: Acute IOP elevation significantly reduces SC-CSA in healthy eyes. Acute dynamic response to IOP elevation may be a useful future characterization of ocular health in the management of glaucoma.

PURPOSE: Although glaucoma treatments alter aqueous humor (AH) dynamics to lower intraocular pressure, the regulatory mechanisms of AH circulation and their contributions to the pathogenesis of ocular hypertension and glaucoma remain unclear. We hypothesized that gadolinium-enhanced magnetic resonance imaging (Gd-MRI) can visualize and assess AH dynamics upon sustained intraocular pressure elevation and pharmacologic interventions. METHODS: Gadolinium contrast agent was systemically administered to adult rats to mimic soluble AH components entering the anterior chamber (AC) via blood-aqueous barrier. Dynamic Gd-MRI was applied to examine the signal enhancement in AC and vitreous body upon microbead-induced ocular hypertension and unilateral topical applications of latanoprost, timolol maleate, and brimonidine tartrate to healthy eyes. RESULTS: Gadolinium signal time courses in microbead-induced hypertensive eyes possessed faster initial gadolinium uptake and higher peak signals in AC than control eyes, reflective of reduced gadolinium clearance upon microbead occlusion. Opposite trends were observed in latanoprost- and timolol-treated eyes, indicative of their respective drug actions on increased uveoscleral outflow and reduced AH production. The slowest initial gadolinium uptake but strongest peak signals were found in AC of both brimonidine-treated and untreated fellow eyes. These findings drew attention to the systemic effects of topical hypotensive drug treatment. Gadolinium leaked into the vitreous of microbead-induced hypertensive eyes and brimonidine-treated and untreated fellow eyes, suggestive of a compromise of aqueous-vitreous or blood-ocular barrier integrity. CONCLUSIONS: Gadolinium-enhanced MRI allows spatiotemporal and quantitative evaluation of altered AH dynamics and ocular tissue permeability for better understanding the physiological mechanisms of ocular hypertension and the efficacy of antiglaucoma drug treatments.

Minimally invasive glaucoma surgeries (MIGS) can improve the conventional, pressure-dependent outflow by bypassing or ablating the trabecular meshwork (TM), or creating alternative drainage routes into the suprachoroidal or subconjunctival space. They have a highly favourable risk profile compared to penetrating surgeries, and lower intraocular pressure with variable efficacy that may depend on the extent of outflow segments accessed. Since they are highly standardised procedures that use clear corneal incisions, they can elegantly be combined with cataract and refractive procedures to improve vision in the same session. There is a growing need for surgeons to become proficient in MIGS to address the increasing prevalence of glaucoma and cataracts in a well-informed, aging population. Techniques of visualisation and instrumentation in an anatomically highly confined space with semitransparent tissues are fundamentally different from other anterior segment surgeries, and present even experienced surgeons with a substantial learning curve. Here, we provide practical tips, and review techniques and outcomes of TM bypass and ablation MIGS.

PURPOSE: The structure and biomechanics of the sclera and cornea are central to several eye diseases such as glaucoma and myopia. However, their roles remain unclear, partly because of limited noninvasive techniques to assess their fibrous microstructures globally, longitudinally, and quantitatively. We hypothesized that magic angle-enhanced magnetic resonance imaging (MRI) can reveal the structural details of the corneoscleral shell and their changes upon intraocular pressure (IOP) elevation. METHODS: Seven ovine eyes were extracted and fixed at IOP = 50 mm Hg to mimic ocular hypertension, and another 11 eyes were unpressurized. The sclera and cornea were scanned at different angular orientations relative to the main magnetic field inside a 9.4-Tesla MRI scanner. Relative MRI signal intensities and intrinsic transverse relaxation times (T2 and T2*) were determined to quantify the magic angle effect on the corneoscleral shells. Three loaded and eight unloaded tendon samples were scanned as controls. RESULTS: At magic angle, high-resolution MRI revealed distinct scleral and corneal lamellar fibers, and light/dark bands indicative of collagen fiber crimps in the sclera and tendon. Magic angle enhancement effect was the strongest in tendon and the least strong in cornea. Loaded sclera, cornea, and tendon possessed significantly higher T2 and T2* than unloaded tissues at magic angle. CONCLUSIONS: Magic angle-enhanced MRI can detect ocular fibrous microstructures without contrast agents or coatings and can reveal their MR tissue property changes with IOP loading. This technique may open up new avenues for assessment of the biomechanical and biochemical properties of ocular tissues in aging and in diseases involving the corneoscleral shell.

PURPOSE: To characterize the in vivo three-dimensional (3D) lamina cribrosa (LC) microarchitecture of healthy eyes using adaptive optics spectral-domain optical coherence tomography (AO-SDOCT). METHODS: A multimodal retinal imaging system with a light source centered at 1050 nm and AO confocal scanning laser ophthalmoscopy was used in this study. One randomly selected eye from 18 healthy subjects was scanned in a 6 degrees x 6 degrees window centered on the LC. Subjects also underwent scanning with Cirrus HD-OCT. Lamina cribrosa microarchitecture was semiautomatically segmented and quantified for connective tissue volume fraction (CTVF), beam thickness, pore diameter, pore area, and pore aspect ratio. The LC was assessed in central and peripheral regions of equal areas and quadrants and with depth. A linear mixed effects model weighted by the fraction of visible LC was used to compare LC structure between regions. RESULTS: The nasal quadrant was excluded due to poor visualization. The central sector showed greater CTVF and thicker beams as compared to the periphery (P < 0.01). Both superior and inferior quadrants showed greater CTVF, pore diameter, and pore mean area than the temporal quadrant (P < 0.05). Depth analysis showed that the anterior and posterior aspects of the LC contained smaller pores with greater density and thinner beams as compared to the middle third (P < 0.05). The anterior third also showed a greater CTVF than the middle third (P < 0.05). CONCLUSIONS: In vivo analysis of healthy eyes using AO-SDOCT showed significant, albeit small, regional variation in LC microarchitecture by quadrant, radially, and with depth, which should be considered in further studies of the LC.

For 30 years, the many diversity-related health sciences programs targeting the University of Pittsburgh undergraduate campus, school of medicine, schools of the health sciences, clinical practice plan, and medical center were run independently and remained separate within the academic health center (AHC). This lack of coordination hampered their overall effectiveness in promoting diversity and inclusion. In 2007, a group of faculty and administrators from the university and the medical center recognized the need to improve institutional diversity and to better address local health disparities. In this article, the authors describe the process of linking the efforts of these institutions in a way that would be successful locally and applicable to other academic environments. First, they engaged an independent consultant to conduct a study of the AHC's diversity climate, interviewing current and former faculty and trainees to define the problem and identify areas for improvement. Next, they created the Physician Inclusion Council to address the findings of this study and to coordinate future efforts with institutional leaders. Finally, they formed four working committees to address (1) communications and outreach, (2) cultural competency, (3) recruitment, and (4) mentoring and retention. These committees oversaw the strategic development and implementation of all diversity and inclusion efforts. Together these steps led to structural changes within the AHC and the improved allocation of resources that have positioned the University of Pittsburgh to achieve not only diversity but also inclusion and to continue to address the health disparities in the Pittsburgh community.