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To improve understanding of intraocular pressure (IOP) and its variance, this project identifies systemic and ocular characteristics of healthy eyes of adult volunteers including IOP variation, ocular biometrics, and aqueous humor dynamics (AHDs). These data serve as baseline controls for further studies from the Eye Dynamics and Engineering Network (EDEN) Consortium.Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design.Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol.Participants from the University of Michigan, Mayo Clinic, and University of Nebraska Medical Center underwent measurements of ocular biometrics, AHD, and IOP using 4 tonometers. Intraocular pressure data during 3 study visits without glaucoma medications were used in the analysis. The PhenX Toolkit survey acquired standardized data on medical history, surgical history, medications, smoking and alcohol exposures, and physical measures.The variability of IOP measurements within eyes was assessed as visit-to-visit IOP variation, within-visit IOP variation, and within-visit positional IOP variation. The concordance (or correlation) between eyes was also assessed.Average positional change of4.7 mmHg was detected with a range of 0.5-11.0 mmHg. Pearson correlation of IOP between eyes within a visit was 0.87 (95% confidence interval [CI], 0.82-0.91) for Goldmann applanation tonometry, 0.91 (95% CI, 0.88-0.94) for Icare rebound tonometry, and 0.91 (95% CI, 0.88-0.94) for pneumatonometry. There was a 4% to 12% asymmetric fluctuation of 3 mmHg or more between eyes between visits using rebound tonometry, 9% with Goldmann applanation tonometry, and 3% to 4% by pneumotonometry. The coefficient of variation between visits for the same eye ranged from 11.2% to 12.9% for pneumatonometry, from 13.6% to 17.4% for rebound tonometry, and 15.8% to 16.2% for Goldmann applanation tonometry.The current study from the EDEN Consortium describes measurement methods and data analyses with emphasis on IOP variability. Future papers will focus on changes in ocular biometrics and AHD with timolol or latanoprost treatment.

Though roughly 30–50% of aqueous outflow resistance resides distal to Schlemm’s canal (SC), the morphology of the conventional outflow pathway distal to SC has not been thoroughly evaluated. This study examined the morphological changes along proximal and distal aspects of the conventional aqueous outflow pathway and their association with decreased outflow facility in an experimental model of glaucoma in cynomolgus macaques. Nd:YAG laser burns were made to 270–340 degrees of the trabecular meshwork (TM) of one eye (n = 6) or both eyes (n = 2) of each monkey to induce ocular hypertension. Distinct regions of the TM were left unlasered. Contralateral eyes (n = 5) were not lasered and were utilized as controls. Monkeys were sacrificed ≥ 60 months after their last laser treatment. All eyes were enucleated and perfused at 15 mmHg for 30 minutes to measure outflow facility. Two pairs of eyes were also perfused with fluorescein to examine segmental outflow. All eyes underwent perfusion-fixation for 1 hr. Anterior segments were cut into radial wedges and processed for light and electron microscopy. Width, height, and cross-sectional area (CSA) of SC were compared between high- and low-flow regions of control eyes, and between non-lasered regions of laser-treated eyes and control eyes. Number and CSA of intrascleral veins (ISVs) were compared between non-lasered and lasered regions of laser-treated eyes and control eyes, and between high- and low-flow regions of control eyes. Scleral collagen fibril diameter was compared between control eyes and lasered and non-lasered regions of laser-treated eyes. Median outflow facility was significantly decreased in laser-treated eyes compared to control eyes (P = 0.02). Median CSA and height of SC were smaller in high- flow regions than low-flow regions of control eyes (P < 0.05). Median width of SC was not significantly different between high- and low-flow regions of control eyes (P > 0.05). Median CSA, width, and height of SC were not different between non-lasered regions and control eyes (P > 0.05). SC was partially or completely obliterated in lasered regions. Median number of ISVs was significantly decreased in lasered regions compared to non-lasered regions (P < 0.01) and control eyes (P < 0.01). Median CSA of ISVs did not differ between these groups (P > 0.05). Median number and CSA of ISVs were not significantly different between high- and low-flow regions of control eyes (P > 0.05). Lasered regions displayed looser scleral stroma and smaller median diameter of collagen fibrils adjacent to the TM compared to non-lasered regions (P < 0.05) and control eyes (P < 0.05). Dense TM, partial to complete obliteration of SC, and a decreased number of patent ISVs may account in part for the decreased outflow facility in monkey eyes with laser-induced ocular hypertension. The significance of changes in scleral structure in laser-treated eyes warrants further investigation.

Due to their similarities in anatomy, physiology, and pharmacology to humans, mice are a valuable model system to study the generation and mechanisms modulating conventional outflow resistance and thus intraocular pressure. In addition, mouse models are critical for understanding the complex nature of conventional outflow homeostasis and dysfunction that results in ocular hypertension. In this review, we describe a set of minimum acceptable standards for developing, characterizing, and utilizing mouse models of open-angle ocular hypertension. We expect that this set of standard practices will increase scientific rigor when using mouse models and will better enable researchers to replicate and build upon previous findings.