Vogt-Koyanagi-Harada-like Syndrome Induced by Checkpoint Inhibitor Cemiplimab.

Checkpoint inhibition targeting programmed cell-death protein 1 has demonstrated efficacy for a wide range of indications including cutaneous malignancy. However, immune-related adverse events (irAEs), including infrequent but visually impactful ocular irAEs, require careful consideration of treatment options, including medication withdrawal, local corticosteroids, or rarely immunomodulation. This case presents a 53-year-old woman who developed uveitis and mucous membrane ulcers after treatment for numerous cutaneous neoplasms, primarily squamous cell carcinoma, with the programmed cell-death protein 1 inhibitor cemiplimab. Ophthalmic examination revealed diffuse choroidal depigmentation consistent with a Vogt-Koyanagi-Harada-like syndrome. Topical and periocular steroids were used to treat the intraocular inflammation, and cemiplimab was discontinued. Because of ongoing severe uveitis, systemic corticosteroids and corticosteroid-sparing immunosuppression were initiated. Specifically, azathioprine and methotrexate were introduced, but each was stopped due to side effects, prompting the initiation of adalimumab (ADA) treatment. While ADA controlled intraocular inflammation, the squamous cell carcinomas were noted to progress, resulting in the discontinuation of ADA. However, a uveitis recurrence was observed. After a discussion of risks and benefits of biologic immunosuppressive therapy, including the risk of vision loss, ADA was restarted with successful disease quiescence at a 16-month follow-up. The cutaneous neoplasms were managed with topical and intralesional therapies, such as 5-fluorouracil. Recent dermatologic examinations suggested no new cutaneous lesions. This scenario presents the effective use of ADA in an ocular irAE that balances the management of sight-threatening ocular inflammation with the risk of promoting recurrent or de novo neoplastic disease.

Eye Dynamics and Engineering Network Consortium: Baseline Characteristics of a Randomized Trial in Healthy Adults.

PURPOSE: 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. DESIGN: Multicenter open-label clinical trial in healthy adults randomized to 1 week treatment with 2 approved glaucoma drugs in a crossover design. PARTICIPANTS: Among 135 healthy participants, 122 participants (aged 55.2 ± 8.8 years; 92 females, 30 males) completed the protocol. METHODS: 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. MAIN OUTCOME 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. RESULTS: Average positional change of > 4.7 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. CONCLUSIONS: 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. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Pragmatic adjunctive usage of netarsudil: A retrospective chart review from a tertiary care center.

Purpose: This retrospective chart review of netarsudil (Rhopressa) characterizes intra-ocular pressure (IOP) reduction, drug tolerance, drug cost, and compliance in a tertiary university Midwest clinic in a variety of glaucoma diagnoses on patients prescribed netarsudil 01/2017 to 5/2020. Methods: Patient demographics, primary diagnosis, indication for medication, prescription date, prescription fill status, duration of use, discontinuation reason, and number of IOP-lowering medications were noted. Confounding medication changes were excluded from IOP analysis. The IOP difference between the first visit after starting netarsudil and the baseline (mean before starting netarsudil on the stable medication regimen) was calculated. Results: A total of 133 patients were prescribed netarsudil (age 69 ± 20 years, 59% females, 79% white, 86% primary glaucoma) as adjunct glaucoma medication (mean medications 3.2 ± 0.9). Indications were lowering IOP (mean baseline IOP 20.0 ± 6 mmHg) and drug regimen simplification. Prescription was not filled by 22/133 subjects because of the cost (68%) and the need for surgery (23%). No demographic factors were associated with prescription fill status. A total of 101 eyes of 76 patients were used for IOP analysis. The mean change in IOP was -0.8 ± 6.4 mmHg, (IOP decrease in 67%, increase or no change in 33% eyes). Netarsudil was discontinued in 52% (50/96) patients; the reasons include surgery for IOP control (42%), allergies (30%), cost (14%), and paradoxical rise in IOP (12%). Conclusion: Netarsudil was used as adjunct third or fourth line medication at a glaucoma practice in Midwestern USA. 17% of prescriptions went unfilled; netarsudil was discontinued in 52% of patients. IOP response was variable in this population with severe complex glaucoma.

Changes in Ocular Biometric Parameters Over a 24-Hour Period in Ocular Hypertensive Patients.

Purpose: To identify 24-h changes in ocular biometric parameters in subjects with ocular hypertension (OHT), and to determine if an intraocular pressure (IOP)-lowering drug alters these parameters. Methods: Thirty volunteers with OHT (58.6 ± 9.2 years of age) were enrolled in this randomized, double-masked, placebo-controlled, crossover study. Participants self-administered 0.2% brimonidine or placebo 3 times daily for 6 weeks. Measurements of seated and supine IOP, central cornea thickness (CCT), anterior chamber depth (ACD), axial length (AXL), and lens thickness were made at 8 am, 3 pm, 8 pm, and 3 am. Statistical tests were Student's 2-tailed paired t-tests or 2-way analysis of variance (ANOVA) followed by one-way ANOVA and post hoc testing. Results: Time of day had a significant effect on IOP, CCT, ACD, and AXL. In placebo-treated eyes, CCT was greater at 3 am than at any other time (P < 0.01), ACD and AXL were greater at 3 am and 8 pm than at 3 pm (P < 0.01). Daytime IOPs were higher than nighttime (seated, P = 0.007; supine, P = 0.018), and supine IOP at night was higher than seated IOP during the day (P < 0.001). Brimonidine did not lower IOP at night nor did it alter the 24-h patterns of CCT, ACD, and AXL. Conclusions: Ocular biometric parameters exhibit characteristic 24-h fluctuations in patients with OHT. At night compared with day, the supine IOP increases, the cornea thickens, the anterior chamber deepens, and the AXL increases. Brimonidine does not alter these parameters at times when it lowers IOP (day) nor when it does not (night). Clinical Trial Registration number: NCT0132419.

What do patients with glaucoma see: a novel iPad app to improve glaucoma patient awareness of visual field loss.

PURPOSE: Glaucoma patients with peripheral vision loss have in the past subjectively described their field loss as 'blurred' or 'no vision compromise'. We developed an iPad app for patients to self-characterise perception within areas of glaucomatous visual field loss. METHODS: Twelve glaucoma patients with visual acuity ≥20/40 in each eye, stable and reliable Humphrey Visual Field (HVF) over 2 years were enrolled. An iPad app (held at 33 cm) allowed subjects to modify 'blur' or 'dimness' to match their perception of a 2×2 m wall-mounted poster at 1 m distance. Subjects fixated at the centre of the poster (spanning 45° of field from centre). The output was degree of blur/dim: normal, mild and severe noted on the iPad image at the 54 retinal loci tested by the HVF 24-2 and was compared to threshold sensitivity values at these loci. Monocular (Right eye (OD), left eye (OS)) HVF responses were used to calculate an integrated binocular (OU) visual field index (VFI). All three data sets were analysed separately. RESULTS: 36 HVF and iPad responses from 12 subjects (mean age 71±8.2y) were analysed. The mean VFI was 77% OD, 76% OS, 83% OU. The most common iPad response reported was normal followed by blur. No subject reported dim response. The mean HVF sensitivity threshold was significantly associated with the iPad response at the corresponding retinal loci (For OD, OS and OU, respectively (dB): normal: 23, 25, 27; mild blur: 18, 16, 22; severe blur: 9, 9, 11). On receiver operative characteristic (ROC) curve analysis, the HVF retinal sensitivity cut-off at which subjects reported blur was 23.4 OD, 23 OS and 23.3 OU (dB). CONCLUSIONS: Glaucoma subjects self-pictorialised their field defects as blur; never dim or black. Our innovation allows translation of HVF data to quantitatively characterise visual perception in patients with glaucomatous field defects.

Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model.

PURPOSE: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). METHODS: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). RESULTS: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. CONCLUSION: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

The Effects of Topical Timolol and Latanoprost on Calculated Ocular Perfusion Pressure in Nonglaucomatous Volunteers.

Purpose: To characterize the effects of timolol and latanoprost on calculated ocular perfusion pressure (OPP) in a multicenter, prospective, crossover-design study. Methods: Nonglaucomatous volunteers were evaluated at baseline, after 1 week of timolol 0.5% dosed twice daily, and after 1 week of latanoprost 0.005% dosed nightly (randomized treatment order; 6-week washout period). Pneumatonometric intraocular pressure (IOP) and brachial blood pressure (BP) were evaluated at each visit. Using 3 commonly used equations, OPP was calculated based on IOP and BP. The OPPs at each visit were compared by using linear mixed-effects models. Results: This analysis includes 121 participants (242 eyes; 75% female, 87% White, mean age 55 years). Mean OPP (standard deviation) calculated with mean arterial pressure was 46.8 (8.1) mmHg at baseline, 48.5 (7.9) mmHg with timolol (P = 0.005), and 49.6 mmHg (8.2) with latanoprost (P < 0.001). When compared with baseline, OPP calculated with diastolic BP was significantly increased with both timolol (1.3 mmHg) and latanoprost (3.1 mmHg). The OPP calculated with systolic BP was increased with latanoprost (2.8 mmHg) but decreased with timolol (-1.3 mmHg). Timolol reduced systolic BP by 3.2 mmHg. Compared with timolol, latanoprost conferred greater increases in OPP calculated with both systolic and diastolic BP compared with baseline; however, the difference in treatment effects on OPP calculated with mean arterial pressure was not significantly different (P = 0.068). Conclusion: In this crossover study of nonglaucomatous volunteers, latanoprost increased OPP. However, timolol's benefit to OPP may be limited in part because it reduced systolic BP. Clinical Trial Registration number: NCT01677507.

Predictors of Intraocular Pressure Lowering after Phacoemulsification and iStent Implantation.

PURPOSE: To explore the demographic and clinical variables associated with intraocular pressure (IOP) lowering after cataract extraction (CE) alone or CE in combination with the iStent (Glaukos Corporation) placement (CE+IS). DESIGN: Retrospective data extraction and survival analysis of consecutive patients identified over a 2-year period. PARTICIPANTS: Patients with mild to moderate glaucoma who underwent CE (48 eyes of 32 patients) or CE+IS (61 eyes of 37 patients) were analyzed. METHODS: Inability to reduce the number of medications or the IOP by at least 20% compared with baseline on 2 consecutive visits was considered surgical failure. Using Cox proportional hazards models, survival analysis was performed, and demographic and clinical variables were evaluated as risk factors. MAIN OUTCOME MEASURES: Time to failure after surgical procedure. RESULTS: CE+IS had lower odds of failure than CE alone (hazard ratio [HR], 2.01; P = 0.047). In White patients, CE+IS showed greater odds of success compared with CE alone (HR, 2.86; P = 0.007). For non-White patients, no difference was found in the outcomes for the 2 procedures (HR, 0.59; P = 0.48). In the multivariate analysis, non-White race (HR, 8.75; P = 0.0002) and longer axial length (HR, 1.61; P = 0.03) were associated with greater hazard of failure after CE+IS. In the CE group, greater odds of failure were associated with steeper corneal curvature (HR, 1.74; P = 0.008), shallower anterior chamber (HR, 0.22; P = 0.008), and longer axial length (HR, 1.58; P = 0.01). CONCLUSIONS: Addition of the iStent to CE improved the duration of IOP lowering in White patients, but not in non-White patients. Associations between IOP lowering after CE and biometric parameters may allow for leveraging these clinical parameters for better case selection for these procedures.

The Effects of Acute Intracranial Pressure Changes on the Episcleral Venous Pressure, Retinal Vein Diameter and Intraocular Pressure in a Pig Model.

PURPOSE: Orbital veins such as the retinal veins and episcleral veins drain into the cavernous sinus, an intracranial venous structure. We studied the effects of acute intracranial pressure (ICP) elevation on episcleral venous pressure, intraocular pressure and retinal vein diameter in an established non-survival pig model. METHODS: In six adult female domestic pigs, we increased ICP in 5 mm Hg increments using saline infusion through a lumbar drain. We measured ICP (using parenchymal pressure monitor), intraocular pressure (using pneumatonometer), episcleral venous pressure (using venomanometer), retinal vein diameter (using OCT images) and arterial blood pressure at each stable ICP increment. The average baseline ICP was 5.4 mm Hg (range 1.5-9 mm Hg) and the maximum stable ICP ranged from 18 to 40 mm Hg. Linear mixed models with random intercepts were used to evaluate the effect of acute ICP increase on outcome variables. RESULTS: With acute ICP elevation, we found loss of retinal venous pulsation and increased episcleral venous pressure, intraocular pressure and retinal vein pressure in all animals. Specifically, acute ICP increase was significantly associated with episcleral venous pressure (ß = 0.31; 95% CI 0.14-0.48, p < .001), intraocular pressure (ß = 0.37, 95%CI 0.24-0.50; p < .001) and retinal vein diameter (ß = 11.29, 95%CI 1.57-21.00; p = .03) after controlling for the effects of arterial blood pressure. CONCLUSION: We believe that the ophthalmic effects of acute ICP elevation are mediated by increased intracranial venous pressure producing upstream pressure changes within the orbital and retinal veins. These results offer exciting possibilities for the development of non-invasive ophthalmic biomarkers to estimate acute ICP elevations following significant neuro-trauma.

Glaucomatous visual fields and neurocognitive function are independently associated with poor lane maintenance during driving simulation.

BACKGROUND: Driving simulators are a safe alternative to on-road vehicles for studying driving behavior in glaucoma drivers. Visual field (VF) loss severity is associated with higher driving simulator crash risk, though mechanisms explaining this relationship remain unknown. Furthermore, associations between driving behavior and neurocognitive performance in glaucoma are unexplored. Here, we evaluated the hypothesis that VF loss severity and neurocognitive performance interact to influence simulated vehicle control in glaucoma drivers. METHODS: Glaucoma patients (n = 25) and suspects (n = 18) were recruited into the study. All had > 20/40 corrected visual acuity in each eye and were experienced field takers with at least three stable (reliability > 20%) fields over the last 2 years. Diagnosis of neurological disorder or cognitive impairment were exclusion criteria. Binocular VFs were derived from monocular Humphrey VFs to estimate a binocular VF index (OU-VFI). Montreal Cognitive Assessment (MoCA) was administered to assess global and sub-domain neurocognitive performance. National Eye Institute Visual Function Questionnaire (NEI-VFQ) was administered to assess peripheral vision and driving difficulties sub-scores. Driving performance was evaluated using a driving simulator with a 290° panoramic field of view constructed around a full-sized automotive cab. Vehicle control metrics, such as lateral acceleration variability and steering wheel variability, were calculated from vehicle sensor data while patients drove on a straight two-lane rural road. Linear mixed models were constructed to evaluate associations between driving performance and clinical characteristics. RESULTS: Patients were 9.5 years older than suspects (p = 0.015). OU-VFI in the glaucoma group ranged from 24 to 98% (85.6 ± 18.3; M ± SD). OU-VFI (p = .0066) was associated with MoCA total (p = .0066) and visuo-spatial and executive function sub-domain scores (p = .012). During driving simulation, patients showed greater steering wheel variability (p = 0.0001) and lateral acceleration variability (p < .0001) relative to suspects. Greater steering wheel variability was independently associated with OU-VFI (p = .0069), MoCA total scores (p = 0.028), and VFQ driving sub-scores (p = 0.0087), but not age (p = 0.61). CONCLUSIONS: Poor vehicle control was independently associated with greater VF loss and worse neurocognitive performance, suggesting both factors contribute to information processing models of driving performance in glaucoma. Future research must demonstrate the external validity of current findings to on-road performance in glaucoma.

Comparing the trabecular outflow by the response to topical pilocarpine in patients with and without glaucoma filtering surgery.

PURPOSE: To compare the trabecular outflow by the response to topical pilocarpine administration in patients with and without prior glaucoma filtering surgery. STUDY DESIGN: Prospective, cross-sectional, randomized, double-blinded study. METHODS: Open-angle glaucoma (OAG) patients without any prior glaucoma surgery, and those with prior trabeculectomy or tube shunt surgery aged 18-90 years were included. Both groups were randomized into pilocarpine or artificial tears (ATs). Intraocular pressure (IOP) was measured before and 90 min after the instillation of eye drops. RESULTS: A total of 189 eyes of 189 patients were included: 92 eyes in the pilocarpine and 97 eyes in the ATs group. There was a mean ± standard deviation of - 0.81 ± 3.08 mmHg decrease in IOP with pilocarpine in those without prior surgery, significantly higher than the ATs group (0.55 ± 2.31 mmHg; p = 0.02). No significant change in IOP with pilocarpine was noted in the surgical group compared to the ATs group (p = 0.90). In the surgery group, greater IOP reduction was observed with pilocarpine in those who had undergone surgery within the last three years than those who had surgery three or more years prior (- 1.56 ± 2.64 versus 1.41 ± 2.77 mmHg; p = 0.001). CONCLUSION: Less IOP reduction was observed with pilocarpine in patients who had filtering surgery more than three years previously compared to those with more recent surgery.

Effect of Near Work on Intraocular Pressure in Emmetropes.

OBJECTIVE: To determine whether accommodation induced by reading alters intraocular pressure (IOP) in healthy, young, emmetropic adults and to document the duration and magnitude of this effect. DESIGN: Cross-sectional study. Participants. Fifteen healthy, emmetropic young adults. METHODS: Subjects performed 20 minutes of near work (reading at 33 cm) followed by 20 minutes of far work (reading at 520 cm) while IOP was measured using an iCare tonometer at baseline and every 5 minutes thereafter. Statistical analysis was performed using repeated measures ANOVA. Main Outcome Measures. Intraocular pressure. RESULTS: IOP decreased significantly compared to baseline IOP after 10 minutes of near work (average change of -1.60 ± 2.2 (SD) mm Hg, p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (p < 0.05). IOP remained lower than baseline IOP throughout all subsequent near and far work. The difference in IOP at the end of experimentation compared to baseline IOP was -1.87 ± 1.81 mm Hg (. CONCLUSIONS: Near work decreases IOP in healthy emmetropes, and this effect is sustained for at least 20 minutes after discontinuing prolonged near work. Providers may need to consider this effect when measuring IOP in clinical practice.

Pneumotonometer Accuracy Using Manometric Measurements after Radial Keratotomy, Clear Corneal Incisions and Lamellar Dissection in Porcine Eyes.

Purpose/Aim of the study: Measured intraocular pressure (IOP) after corneal incisions may not be reflective of the true IOP because of changes in corneal biomechanical properties. The purpose of this study is to investigate the effect of various corneal incisions on pneumotonometer accuracy in enucleated porcine eyes.Materials and Methods: A pneumotonometer was used to measure IOP (IOPp) at manometrically controlled pressure levels of 10, 20, 30 and 40 mmHg in enucleated porcine eyes. IOP measurements at each level were repeated after one of the following corneal incisions: radial keratotomy (8 eyes), lamellar dissection (10 eyes), clear cornea standard phacoemulsification incisions (10 eyes). The pneumotonometer error, defined as the difference between IOPp and manometric pressure (IOPm), was calculated for each pressure level. The error before the corneal incisions was compared to the error after the corneal incisions to assess the accuracy of the pneumotonometer.Results: The pneumotonometer underestimates true IOP at all pressure levels, both before and after the corneal procedures. There was a statistically significant greater underestimation of IOP after radial keratotomy incisions at pressure levels of 20, 30 and 40 mmHg (p = .013, 0.004, and 0.002, respectively). There was no statistically significant difference in the amount of pneumotonometer underestimation error after lamellar dissection or standard cataract incisions.Conclusion: The pneumotonometer underestimates true IOP in enucleated porcine eyes at all pressure levels between 10-40 mmHg. Radial keratotomy incisions caused a statistically significant greater underestimation error in pneumotonometry measurements at pressures of 20-40 mmHg. Lamellar dissection and clear corneal cataract incisions did not cause an additional error in pneumotonometry measurements in enucleated porcine eyes.

Differences in ocular biometrics and aqueous humour dynamics between Chinese and Caucasian adults.

BACKGROUND: Glaucoma prevalence and subtype profile vary across different racial and ethnic groups. This study provides a comparative evaluation of differences in aqueous humour dynamics (AHD) and ocular biometrics in healthy Chinese and Caucasian adults of two different age groups. METHODS: Data from two independent studies with identical designs were compared. Cohorts included young adults (20-30 years old, 32 Chinese and 39 Caucasians) and older adults (>50 years old, 37 Chinese and 46 Caucasians). Parameters of AHD and ocular biometrics were evaluated. Group comparisons were made by generalised estimating equation methods. RESULTS: Differences in young adult Caucasians compared with similarly aged Chinese were thinner central cornea (-29.27 µm, p<0.001), lower intraocular pressure (IOP) (-2.33 mm Hg, p<0.001), larger anterior chamber volume (ACV) (28.78 µL, p<0.001) and faster uveoscleral outflow rate (Fu) (0.82 µL/min, p<0.001). Differences in older adult Caucasians compared with similarly aged Chinese were slower aqueous flow rate (Fa) (-0.28 µL/min, p=0.042), lower IOP (-1.97 mm Hg, p<0.001) and larger ACV (33.15 µL, p<0.001). Considering all subjects together by race, Caucasian subjects had slower Fa (-0.22 µL/min, p=0.035), thinner corneas (-0.52 µm, p=0.003), lower IOP (-2.11 mm Hg, p<0.001), higher ACV (30.39 µL, p<0.001) and faster Fu (0.63 µL/min, p<0.001). CONCLUSION: Differences in AHD and biometrics between Caucasian and Chinese adults include larger ACVs which may contribute to the wider angles reported in Caucasians, and slower Fa rates coupled with faster Fu rates which may contribute to their lower IOP and lower overall risk of glaucoma.

Effect of Timolol on Aqueous Humor Outflow Facility in Healthy Human Eyes.

PURPOSE: Hyposecretion of aqueous humor has been postulated to adversely affect the health of the trabecular meshwork and outflow resistance. However, the effect of medications that reduce aqueous humor production on outflow facility in living human eyes is unclear. This study evaluated the effect of timolol, an aqueous humor flow suppressant, on outflow facility in healthy eyes. DESIGN: Prospective, before-and-after study. METHODS: In a multicenter study, 113 healthy participants over 40 years of age were included. Intraocular pressure (IOP) was measured with the participant in the sitting position by using a pneumatonometer. The outflow facility was measured with the participant in the supine position by 2-minute pneumatonography. After participants self-administered drops of timolol 0.5% for 1 week, twice daily in each eye, both measurements were repeated. RESULTS: Mean IOP decreased from 15.1 ± 3.0 mm Hg at baseline to 12.4 ± 2.4 mm Hg (P < 0.001) after 1 week of timolol use. Mean outflow facility decreased from 0.23 ± 0.08 µL/min/mm Hg at baseline to 0.18 ± 0.08 µL/min/mm Hg (P < 0.001) after timolol. The change in outflow facility was negatively correlated with baseline outflow facility (r = -0.51; P < 0.001). CONCLUSIONS: Timolol reduces outflow facility in healthy human eyes, and this effect is greater in eyes with higher baseline outflow facility. This phenomenon may be related to reduced aqueous humor flow, but the precise mechanism remains to be determined.

The Water-Drinking Test Revisited: An Analysis of Test Results in Subjects with Glaucoma.

PURPOSE: The Water-Drinking Test (WDT) has been shown to predict the diurnal IOP change. This study evaluates the factors that may affect the WDT results. METHODS: This study was conducted on 203 glaucoma patients who had undergone trabeculectomy (53) or tube surgery (31), or had a medically controlled open-angle (82) or closed-angle (37) glaucoma. IOP was measured at baseline and then every 15 minutes over a one-hour period after drinking water. The main outcome measures were IOP change (increase in IOP from baseline) at all measurement time points, IOP peak (highest IOP after drinking water), IOP fluctuation (difference between IOP peak and baseline), and assessing the association of these IOPs with a patient's demographic and management modalities. RESULTS: The mean age of the participants was 54±18 years, and 113 (56%) were male. Female patients showed greater IOP fluctuation than males (7.28 vs. 5.92 mm Hg; P=0.016), and a greater IOP peak (22.7 vs. 20.1 mm Hg; P=0.001). The observed associations between gender and IOP changes were only significant in <50 years. IOP at 60 minutes was greater in tube than trabeculectomy (5.6 vs. 3.1 mm Hg; P=0.007). The number of topical medications showed a direct independent association with IOP changes (P<0.001). Compared to other classes of topical medications, latanoprost showed lower WDT-IOP profile (P=0.0003). CONCLUSIONS: WDT-IOP change was diminished in subjects on latanoprost, and was greater in females <50 years, and those on greater number of medications.

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: a multi-cohort analysis.

Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10-27) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10-5); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.

Mechanism of Action of Selective Laser Trabeculoplasty and Predictors of Response.

Purpose: This study was designed to evaluate the changes in aqueous humor dynamics (AHD) produced by selective laser trabeculoplasty (SLT) and to explore if baseline AHD parameters are predictive of IOP response to SLT. Methods: Thirty-one consecutive subjects diagnosed with ocular hypertension or primary open-angle glaucoma scheduled to undergo SLT as their primary IOP-lowering therapy were enrolled in this prospective observational study. Subjects underwent baseline assessment of AHD in both eyes. Variables assessed were IOPs at 9 AM and noon, aqueous humor flow rate (fluorophotometry), episcleral venous pressure (EVP, venomanometry), outflow facility (pneumatonography and fluorophotometry) and uveoscleral outflow (calculated using modified Goldmann equation). All subjects underwent 360 degrees SLT and AHD measurements were repeated 3 months later. Results: Compared with baseline, IOPs after SLT were significantly lower at 9 AM (22.9 ± 5.1 vs. 19.7 ± 3.0 mm Hg; P = 0.001) and noon (23.4 ± 4.6 vs. 20.0 ± 3.5 mm Hg; P < 0.001). Outflow facility by fluorophotometry was significantly increased from 0.17 ± 0.11 µL/min/mm Hg at baseline to 0.24 ± 0.14 µL/min/mm Hg at 3 months (P = 0.008). Outflow facility by tonography (baseline: 0.16 ± 0.07 µL/min/mm Hg vs. 3 months: 0.22 ± 0.16 µL/min/mm Hg; P = 0.046) was similarly increased. No change in aqueous flow or EVP was observed. There were no changes in IOP or AHD in the contralateral untreated eye. Using multiple linear regression models, higher baseline aqueous flow, lower baseline outflow facility, and possibly lower uvescleral outflow were associated with more IOP lowering with SLT. Conclusions: The IOP-lowering effect of SLT is mediated through an increase in outflow facility. There is no contralateral effect. Higher aqueous flow and lower outflow facility may be predictive of better response to SLT.

Comparison of Aqueous Outflow Facility Measurement by Pneumatonography and Digital Schiøtz Tonography.

Purpose: It is not known if outflow facilities measured by pneumatonography and Schiøtz tonography are interchangeable. In this study we compared outflow facility measured by pneumatonography to outflow facility measured by digital Schiøtz tonography. Methods: Fifty-six eyes from 28 healthy participants, ages 41 to 68 years, were included. Intraocular pressure (IOP) was measured in the sitting and supine positions with a pneumatonometer. With the subject in the supine position, IOP was recorded for 2 minutes by using a pneumatonometer with a 10-g weight and for 4 minutes by using a custom digital Schiøtz tonometer. Outflow facility was determined from the changes in pressure and intraocular volume and a standard assumed ocular rigidity coefficient for each instrument, respectively, and by using an ocular rigidity coefficient calculated by measuring pressure without and with a weight added to the pneumatonometer tip. Results: The outflow facility was 0.29 ± 0.09 µL/min/mm Hg by Schiøtz tonography and 0.24 ± 0.08 µL/min/mm Hg by pneumatonography (P < 0.001) when using the standard assumed constant ocular rigidity coefficient. Mean calculated ocular rigidity coefficient was 0.028 ± 0.01 µL-1, and outflow facility determined by using this coefficient was 0.23 ± 0.08 µL/min/mm Hg by Schiøtz tonography and 0.21 ± 0.07 µL/min/mm Hg by pneumatonography (P = 0.003). Outflow facilities measured by the two devices were correlated when the ocular rigidity was assumed (r = 0.60, P < 0.001) or calculated (r = 0.70, P < 0.001). Conclusions: Outflow facilities measured by pneumatonography were correlated with those measured by Schiøtz tonography, but Schiøtz tonography reported approximately 10% to 20% higher facilities when using the standard method. When ocular rigidity was determined for each eye, differences were smaller. Measurements from these devices cannot be compared directly.