Topical Medication Adherence and Visual Field Progression in Open-angle Glaucoma: Analysis of a Large US Health Care System.

PRCIS: Modeling of visual field and pharmacy data (Kaiser Permanente, 2001 to 2014) from open-angle/pseudoexfoliation glaucoma patients in clinical practice indicated a significant inverse association between the level of medication adherence and rate of visual field progression. PURPOSE: The aim was to quantify the effect of nonadherence to topical hypotensive medication on glaucomatous visual field progression in clinical practice. METHODS: Retrospective analysis of combined visual field and pharmacy data from Kaiser Permanente Southern California's HealthConnect electronic health record database. Patients with a diagnosis of primary open-angle glaucoma or pseudoexfoliation glaucoma (2001 to 2011) and ≥3 subsequent visual field tests of the same Swedish Interactive Threshold Algorithm type were followed up from first medication fill to final visual field test. Medication adherence (proportion of days covered) was estimated from pharmacy refill data. A conditional growth model was used to estimate the effect of adherence level in modifying the progression of mean deviation over time after adjusting for potential confounders, including age, sex, race/ethnicity, baseline glaucoma severity, and comorbidity. RESULTS: In total, 6343 eligible patients were included in the study and followed for (mean) 5.8 years; average treatment adherence during follow-up was 73%. After controlling for confounders and the interaction between time and baseline disease severity, the model indicated that mean deviation progression was significantly (P=0.006) reduced by 0.006 dB per year for each 10% (absolute) increase in adherence. Model estimates of time to glaucoma progression (mean deviation change -3 dB from baseline) were 8.3 and 9.3 years for patients with adherence levels of 20% and 80%, respectively. CONCLUSIONS: Improving patient adherence to topical glaucoma medication may result in slower deterioration in visual function over time.

Two-year outcomes of a pilot glaucoma suspect telemedicine monitoring program.

PURPOSE: The purpose of this study was to characterize a pilot program using e-health to monitor glaucoma suspects in a large integrated health system. METHODS: A retrospective chart review of patients enrolled in the first 2 years of a new glaucoma suspect telemedicine monitoring program was conducted. Patients were enrolled in the program after being diagnosed as glaucoma suspects in the regular clinic setting and were eligible for the program if they had better than 20/40 vision, intraocular pressure (IOP) <25 mmHg, a normal baseline visual field, and an optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) without clear evidence of glaucomatous optic nerve damage. Patients were followed annually thereafter with measurements of vision, IOP, and OCT RNFL, which were reviewed at a centralized telemedicine reading center. Patients were retained within the program unless there was evidence of disease progression, in which case they were referred to an ophthalmologist for further evaluation. The first 100 patients received a survey assessing their satisfaction with the program after their first visit. The number of patients who adhered to follow-up recommendations, who were referred to an ophthalmologist for additional evaluation, and who began on IOP-lowering medications was evaluated. RESULTS: A total of 225 patients were enrolled in this program. Of eligible patients, 97.3% attended their 1-year follow-up visit and 92.5% attended their 2-year follow-up visit. Over the course of 2 years, five patients were referred for further clinic evaluation due to concern for progressive RNFL loss, of which two were started on IOP-lowering medications. No patients were referred to the clinic for vision loss or elevated IOP. In all, 87% of patients said that they would be extremely or quite likely to recommend the program to a friend. More than 80% of patients said that the program was extremely or very helpful, convenient, and professional. CONCLUSION: This novel telemedicine program for monitoring low-risk glaucoma suspects achieved high patient retention. Significant disease progression was rare with a few patients requiring referrals back to the clinic setting or initiation of IOP-lowering therapy. Telemedicine is a promising method to follow patients who are glaucoma suspects.

The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.

PURPOSE: To identify sustained differences in intraocular pressure (IOP) after intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs. DESIGN: Database study. PARTICIPANTS: Patients seeing an ophthalmic provider who contributes to the database. METHODS: We identified a total of 23 776 unique patients who received only a single type of anti-VEGF medication (bevacizumab, aflibercept, or ranibizumab) by injection in the right eye in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups included patients with age-related macular degeneration only and patients who had not received an anti-VEGF injection for at least 1 year before the study. We examined those with at least 12, 18, and 25 injections for each of these 3 medications. For all groups, we used fellow, untreated eyes for comparison. MAIN OUTCOME MEASURES: The mean change in IOP from baseline at a minimum of 1 year of follow-up and the proportion of eyes with a clinically significant IOP increase (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg). RESULTS: All patients in all groups receiving all drugs showed a decrease in IOP from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant difference. A generalized linear model accounting for confounders associated bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes receiving injections compared with 1.5% in the associated untreated fellow eyes. Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8% for aflibercept, ranibizumab, and bevacizumab, respectively, which was significantly higher than untreated fellow eyes for bevacizumab and ranibizumab, but not for aflibercept. CONCLUSIONS: These analyses from real-world data indicate that anti-VEGF intravitreous injections are associated with a small but statistically significant decrease in IOP over time. A proportion of patients, on average 2.6%, experienced a sustained clinically significant IOP rise with these drugs overall compared with 1.5% in the fellow untreated eyes. However, such an increase was not seen with aflibercept.

Trends in Use of Ambulatory Surgery Centers for Cataract Surgery in the United States, 2001-2014.

Importance: Cataract surgery is commonly performed at ambulatory surgery centers (ASCs) and hospital outpatient departments (HOPDs). These venues differ in many ways, including surgical efficiency, patient throughput, patient safety, and costs per surgery. Objective: To determine trends in use of ASCs and HOPDs for cataract surgery from 2001 to 2014 and factors affecting the site of surgery. Design, Setting, and Participants: This retrospective longitudinal cohort analysis involved individuals 40 years and older who underwent cataract surgery between January 2001 and December 2014 from a nationwide US managed care network. Data were analyzed from February 2016 to February 2017. Main Outcomes and Measures: We identified all enrollees who underwent cataract surgery and determined whether the surgery was performed at an ASC or HOPD. We calculated the proportion of surgeries performed at each site each year from 2001 to 2014. Multivariable logistic regression identified characteristics of enrollees who had cataract surgery at an ASC vs a HOPD. We also assessed geographic variation in the proportion of cataract surgeries performed at ASCs in 306 communities throughout the United States. Results: Of the 369 320 enrollees included in this study, 208 319 (56.4%) were female, and the mean (SD) age was 66.3 (10.4) years. All enrollees underwent cataract surgery (531 325 surgeries) from 2001 to 2014. Of these, 237 046 (64.2%) underwent cataract surgery at an ASC. The proportion of cataract surgeries performed at ASCs increased from 43.6% in 2001 to 73.0% in 2014. Compared with enrollees with incomes less than $40 000, those with incomes greater than $100 000 were 20% more likely to undergo cataract surgery at an ASC (odds ratio, 1.20; 95% CI, 1.12-1.29). Enrollees with better overall health were no more likely to undergo cataract surgery at an ASC (odds ratio, 1.00; 95% CI, 0.99-1.00) than at an HOPD. Enrollees who lived in communities without certificate of need laws were more than twice as likely to have surgery at an ASC (odds ratio, 2.49; 95% CI, 2.35-2.63). The proportion of cataract surgeries performed at ASCs from 2012 to 2014 varied considerably, from 1.6% in La Crosse, Wisconsin, to 98.8% in Pueblo, Colorado. Conclusions and Relevance: We observed a large shift in the site of cataract surgery from HOPDs to ASCs from 2001 to 2014. Future research is needed to assess the effect of this transition in site of surgical care on patient access to surgery, surgical outcomes, patient safety, and societal costs.

Two-Year COMPASS Trial Results: Supraciliary Microstenting with Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts.

PURPOSE: We evaluated 2-year safety and efficacy of supraciliary microstenting (CyPass Micro-Stent; Transcend Medical, Inc., Menlo Park, CA) for treating mild-to-moderate primary open-angle glaucoma (POAG) in patients undergoing cataract surgery. DESIGN: Multicenter (24 US sites), interventional randomized clinical trial (RCT) (ClinicalTrials.gov identifier, NCT01085357). PARTICIPANTS: Subjects were enrolled beginning July 2011, with study completion in March 2015. Subjects had POAG with mean diurnal unmedicated intraocular pressure (IOP) 21-33 mmHg and were undergoing phacoemulsification cataract surgery. METHODS: After completing cataract surgery, subjects were intraoperatively randomized to phacoemulsification only (control) or supraciliary microstenting with phacoemulsification (microstent) groups (1:3 ratio). Microstent implantation via an ab interno approach to the supraciliary space allowed concomitant cataract and glaucoma surgery. MAIN OUTCOME MEASURES: Outcome measures included percentage of subjects achieving ≥20% unmedicated diurnal IOP lowering versus baseline, mean IOP change and glaucoma medication use, and ocular adverse event (AE) incidence through 24 months. RESULTS: Of 505 subjects, 131 were randomized to the control group and 374 were randomized to the microstent group. Baseline mean IOPs in the control and microstent groups were similar: 24.5±3.0 and 24.4±2.8 mmHg, respectively (P > 0.05); mean medications were 1.3±1.0 and 1.4±0.9, respectively (P > 0.05). There was early and sustained IOP reduction, with 60% of controls versus 77% of microstent subjects achieving ≥20% unmedicated IOP lowering versus baseline at 24 months (P = 0.001; per-protocol analysis). Mean IOP reduction was ↓7.4 mmHg for the microstent group versus ↓5.4 mmHg in controls (P < 0.001), with 85% of microstent subjects not requiring IOP medications at 24 months. Mean 24-month medication use was 67% lower in microstent subjects (P < 0.001); 59% of control versus 85% of microstent subjects were medication free. Mean medication use in controls decreased from 1.3±1.0 drugs at baseline to 0.7±0.9 and 0.6±0.8 drugs at 12 and 24 months, respectively, and in the microstent group from 1.4±0.9 to 0.2±0.6 drugs at both 12 and 24 months (P < 0.001 for reductions in both groups at both follow-ups vs. baseline). No vision-threatening microstent-related AEs occurred. Visual acuity was high in both groups through 24 months; >98% of all subjects achieved 20/40 best-corrected visual acuity or better. CONCLUSIONS: This RCT demonstrated safe and sustained 2-year reduction in IOP and glaucoma medication use after microinterventional surgical treatment for mild-to-moderate POAG.

American Glaucoma Society position statement: glaucoma surgery by surgeons.

POSITION STATEMENT: The American Glaucoma Society seeks to ensure the highest quality care for patients with glaucoma. The surgical care of the glaucoma patient requires the skills and judgment of physicians who have graduated from the rigorous training and hands-on experience provided by a complete curriculum in allopathic or osteopathic medicine with subsequent subspecialty training in Ophthalmology. Surgery for glaucoma includes the use of laser, incisional surgery with and without devices, injections into or around the eye, and should be performed only by physicians who have been licensed and credentialed in allopathic (MD) or osteopathic (DO) medicine.

Evaluating objective and subjective quantitative parameters at the initial visit to predict future glaucomatous visual field progression.

BACKGROUND AND OBJECTIVE: To evaluate the ability of structural assessment to predict glaucomatous visual field progression. PATIENTS AND METHODS: A total of 119 healthy eyes with suspected glaucoma and glaucomatous eyes with 5 or more optic nerve stereophotographs, optical coherence tomography (OCT), and confocal scanning laser ophthalmoscopy (CSLO) all acquired within 6 months of each other were enrolled. Odds ratios to predict progression were determined by generalized estimating equation models. RESULTS: Median follow-up was 4.0 years (range: 1.5 to 5.7 years). Fifteen eyes progressed by glaucoma progression analysis, 20 by visual field index, and 10 by both. Baseline parameters from stereophotographs (vertical cup-to-disc ratio and Disc Damage Likelihood Scale), OCT (global, superior quadrant, and inferior quadrant retinal nerve fiber layer thickness), and CSLO (cup shape measure and mean cup depth) were significant predictors of progression. Comparing the single best parameter from all models, only the OCT superior quadrant RNFL predicted progression. CONCLUSION: Baseline stereophotographs, OCT, and CSLO measurements may be clinically useful to predict glaucomatous visual field progression.

A prospective study of diabetes, lifestyle factors, and glaucoma among African-American women.

PURPOSE: To evaluate the association of self-reported type 2 diabetes, anthropometric factors, alcohol consumption, and cigarette smoking with risk of primary open-angle glaucoma (POAG) in a prospective cohort study of African-American women. METHODS: From 1995 through 2007, 32,570 Black Women's Health Study participants aged 21 to 69 years at baseline were followed for incident POAG. Questionnaires were mailed biennially to update exposures and identify incident cases of POAG. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were derived from Cox regression models. RESULTS: During 416,171 person-years of follow-up, 366 incident POAG cases were confirmed by physician report. After adjustment for potential confounders, the IRR comparing women with and without type 2 diabetes was 1.58 (95% CI, 1.17-2.13), and the IRR comparing current with never alcohol consumers was 1.35 (95% CI, 1.05-1.73). Among women younger than 50, associations with diabetes and alcohol consumption were stronger, and POAG was significantly associated with body mass index, waist circumference, waist-to-hip ratio, and both long-duration and high-intensity current smoking. CONCLUSIONS: These results suggest that type 2 diabetes and current alcohol consumption are independent risk factors for POAG among African-American women, and that in addition to those factors, overall and central adiposity and smoking may be associated with increased risk of early-onset POAG.

Macular changes detected by Fourier-domain optical coherence tomography in patients with hypotony without clinical maculopathy.

PURPOSE: To investigate macular changes in eyes with postoperative hypotony without clinical maculopathy using high-resolution Fourier-domain optical coherence tomography (FD-OCT). METHODS: Fourteen eyes of 12 patients with postoperative intraocular pressure (IOP) ï¿¡ 6 mmHg for at least 4 weeks but with no detectable clinical features associated with hypotony maculopathy were imaged by FD-OCT prospectively. Images were analysed by two retina specialists masked to clinical findings. RESULTS: Most patients were female (83%) and myopic (75%) with a mean age of 65 ± 17 [standard deviation (SD)] years (range 2­86 years). Mean central corneal thickness was 519 ± 34 lm [95% confidence interval (CI) 502­537] and mean IOP before surgery was 20 ± 8 mmHg (95% CI 15­24). During the period of hypotony (mean 15 ± 6 weeks), the average mean IOP was 4 ± 1 mmHg (95% CI 3­5). Abnormal FD-OCT findings (retinal folds and / or intraretinal fluid) were present in eight eyes. These patients had a higher rate of visual symptoms (75% versus 17%), visual acuity loss (‡ 2 lines; 63% versus 17%) and increased mean foveal thickness (250 ± 26 versus 210 ± 12 lm; p < 0.01, Mann­Whitney U-test) compared with those with normal FD-OCT. CONCLUSION: FD-OCT identified subclinical macular abnormalities in over half of the eyes with postoperative hypotony. These findings were accompanied by visual disturbances and central macular thickening. FD-OCT can be an important diagnostic tool for this disorder when clinical features are absent.

Clinical assessment of mirror artifacts in spectral-domain optical coherence tomography.

PURPOSE. To investigate the characteristics of a spectral-domain optical coherence tomography (SD-OCT) image phenomenon known as the mirror artifact, calculate its prevalence, analyze potential risk factors, measure severity, and correlate it to spherical equivalent and central visual acuity (VA). METHODS. OCT macular cube 512 x 128 scans taken between January 2008 and February 2009 at the New England Eye Center were analyzed for the presence of mirror artifacts. Artifact severity was determined by the degree of segmentation breakdown that it caused on the macular map. A retrospective review was conducted of the medical records of patients with artifacts and of a random control group without artifacts. RESULTS. Of 1592 patients, 9.3% (148 patients, 200 eyes) had scans that contained mirror artifacts. A significantly more myopic spherical equivalent (P < 0.001), worse VA (P < 0.001), longer axial lengths (P = 0.004), and higher proportions of moderate to high myopia (P < 0.001) were found in patients with mirror artifacts than in patients without artifacts. Worse VA was associated with increased artifact severity (P = 0.04). CONCLUSIONS. In all scans analyzed, a high prevalence of mirror artifacts was found. This image artifact was often associated with patients with moderate to high myopia. Improvements in instrumentation may be necessary to resolve this problem in moderately and highly myopic eyes. Operators should be advised to properly position the retina when scanning eyes. In cases in which peripheral abnormalities in topographic measurements of retinal thickness are found, corresponding OCT scans should be examined for the presence of mirror artifacts.

Matrix metalloproteinase gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs.

The goal of glaucoma filtering surgery is to create a low resistance pathway for aqueous outflow. The result is a blister or 'bleb' on the conjunctiva, from which fluid drains into the vasculature. Filtering surgery results may be compromised if blebs develop leaks, a problem that surfaces more frequently when antimetabolites are used to control the wound healing response. We investigated the role of tissue remodelling enzymes of the Matrix metalloproteinase (MMP) family in the development of bleb leaks. Our design was a case series. We enrolled glaucoma patients with leaking blebs, glaucoma patients with overhanging blebs and normal eyes. Leaking bleb tissues (n=11) and bleb leak fluid were collected from patients undergoing bleb revision surgery. Overhanging bleb tissues (from non-leaking blebs, n=3), normal conjunctiva (n=8), and aqueous humour (n=4) were collected for comparison. Samples were analysed for MMP content and proteinase activity by the methods of zymography, western blotting, immunohistochemistry, and in situ zymography. Our main outcome measures were presence and activity of MMP in sample. Zymography revealed the presence of a high molecular weight caseinase and a 92-kDa gelatinase of a size appropriate for the proenzyme form of gelatinase B (gelB; MMP-9), in extracts from leaking bleb tissue, but not in bleb leak fluid or aqueous humour samples. In contrast, a 65-kDa gelatinase of a size appropriate for gelatinase A (MMP-2) proenzyme was observed in all samples. All proteinases disappeared when 10mm EDTA was added to the development buffer, consistent with their identity as MMPs. Western blotting and immunohistochemical analyses confirmed the identity of the 92kDa proteinase as gelB, and further revealed its absence from extracts of overhanging bleb tissue and normal conjunctiva. In situ zymography demonstrated strong gelatinolytic activity in leaking bleb tissue, but not overhanging bleb tissue or normal conjunctiva. MMP-g may be involved in the mechanism of formation of bleb leaks. Precise description of the cascade of events leading to bleb leakage may allow the design of therapeutic interventions to prevent, stabilize or reverse bleb leakage.

Optical coherence tomography longitudinal evaluation of retinal nerve fiber layer thickness in glaucoma.

OBJECTIVES: To longitudinally evaluate optical coherence tomography (OCT) peripapillary retinal nerve fiber layer thickness measurements and to compare these measurements across time with clinical status and automated perimetry. METHODS: Retrospective evaluation of 64 eyes (37 patients) of glaucoma suspects or patients with glaucoma participating in a prospective longitudinal study. All participants underwent comprehensive clinical assessment, visual field (VF) testing, and OCT every 6 months. Field progression was defined as a reproducible decline of at least 2 dB in VF mean deviation from baseline. Progression of OCT was defined as reproducible mean retinal nerve fiber layer thinning of at least 20 mum. RESULTS: Each patient had a median of 5 usable OCT scans at median follow-up of 4.7 years. The difference in the linear regression slopes of retinal nerve fiber layer thickness between glaucoma suspects and patients with glaucoma was nonsignificant for all variables; however, Kaplan-Meier survival curve analysis demonstrated a higher progression rate by OCT vs VF. Sixty-six percent of eyes were stable throughout follow-up, whereas 22% progressed by OCT alone, 9% by VF mean deviation alone, and 3% by VF and OCT. CONCLUSIONS: A greater likelihood of glaucomatous progression was identified by OCT vs automated perimetry. This might reflect OCT hypersensitivity or true damage identified by OCT before detection by conventional methods.

Ultrahigh-resolution optical coherence tomography in glaucoma.

OBJECTIVE: Optical coherence tomography (OCT) has been shown to be a valuable tool in glaucoma assessment. We investigated a new ultrahigh-resolution OCT (UHR-OCT) imaging system in glaucoma patients and compared the findings with those obtained by conventional-resolution OCT. DESIGN: Retrospective comparative case series. PARTICIPANTS: A normal subject and 4 glaucoma patients representing various stages of glaucomatous damage. TESTING: All participants were scanned with StratusOCT (axial resolution of approximately 10 mum) and UHR-OCT (axial resolution of approximately 3 microm) at the same visit. MAIN OUTCOME MEASURE: Comparison of OCT findings detected with StratusOCT and UHR-OCT. RESULTS: Ultrahigh-resolution OCT provides a detailed cross-sectional view of the scanned retinal area that allows differentiation between retinal layers. These UHR images were markedly better than those obtained by the conventional-resolution OCT. CONCLUSIONS: Ultrahigh-resolution OCT provides high-resolution images of the ocular posterior segment, which improves the ability to detect retinal abnormalities due to glaucoma.

Ocular hypotensive efficacy of bimatoprost when used as a replacement for latanoprost in the treatment of glaucoma and ocular hypertension.

PURPOSE: To evaluate the clinical effectiveness of bimatoprost (Lumigan, Allergan, Inc.) when used as a replacement for latanoprost (Xalatan, Pharmacia) in the treatment of glaucoma and ocular hypertension. METHODS: This was a community-based, two-month, open-label, multicenter, trial. Patients with glaucoma or ocular hypertension who needed additional IOP lowering or who were intolerant of other glaucoma medications were placed on bimatoprost therapy (alone or in combination with other drugs at the physician's discretion). RESULTS: This first report of the data from this study focuses on those patients for whom the physician chose to replace latanoprost therapy with bimatoprost therapy (n = 1283). After 2 months of bimatoprost therapy, the mean decrease in IOP was 3.4 mm Hg and many more patients had achieved low target pressures. The percentage of patients achieving a target pressure of < or =18 mm Hg doubled from 33% to 66% (P <.001). The percentage of patients achieving target pressures of < or =15 mm Hg and < or =14 mm Hg was approximately 3 to 4 times greater at the end of the study than the beginning; increasing from 11% to 36% and from 6% to 26%, respectively (P <.001). A subgroup analysis showed comparable improvements in IOP-control regardless of the previous treatment regimen or whether bimatoprost was used alone or in combination with other medications. The most commonly reported adverse event was conjunctival hyperemia (3.7%; 47/1283). CONCLUSION: Bimatoprost therapy is well-tolerated and helps many more patients reach low target pressures when used as a replacement for latanoprost in a variety of treatment regimens.