Publications by authors named "Kuldev Singh"

139 Publications

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract.

Ophthalmology 2020 Nov 6. Epub 2020 Nov 6.

Stanford University School of Medicine, Byers Eye Institute, Palo Alto, California.

Purpose: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone.

Design: Multicenter randomized clinical trial.

Participants: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery.

Methods: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years.

Main Outcome Measures: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts.

Results: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group.

Conclusions: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.
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http://dx.doi.org/10.1016/j.ophtha.2020.11.004DOI Listing
November 2020

Trabeculectomy Must Survive!

Ophthalmol Glaucoma 2021 Jan-Feb;4(1):1-2. Epub 2020 Oct 29.

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http://dx.doi.org/10.1016/j.ogla.2020.08.009DOI Listing
October 2020

Effect of general anaesthesia on intraocular pressure in paediatric patients: a systematic review.

Eye (Lond) 2020 Jul 20. Epub 2020 Jul 20.

Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.

Objectives: Assessment of the impact of general anaesthetic agents on intraocular pressure (IOP) in children via systematic review.

Methods: Pubmed, Embase, and CENTRAL databases were systematically searched to identify randomised controlled trials, prospective, and interventional studies. The search included all studies through October 5, 2018 with no date or language restrictions. A linear mixed-effects regression analysis was performed to study the change in IOP after general anaesthesia (GA).

Results: The strategy identified 518 studies that met search criteria. Six studies (531 eyes) were included for quantitative synthesis. Seven categories of mixed and non-mixed induction and maintenance agents were compared. When assessing all agents utilising a model of mean IOP as a function of time, IOP decreased after induction phase at a rate of -0.59 ± 0.19 mmHg/min (P value = 0.006).

Conclusions: This systematic review showed that most anaesthetic agents significantly decrease IOP over time after the induction phase of general anaesthesia in children. An understanding of the effects of GA on IOP is critical for those performing paediatric ophthalmic examinations under anaesthesia.
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http://dx.doi.org/10.1038/s41433-020-1093-8DOI Listing
July 2020

Comparing Treatment Outcomes from the Tube Versus Trabeculectomy and Primary Tube Versus Trabeculectomy Studies.

Ophthalmology 2021 Feb 2;128(2):324-326. Epub 2020 Jul 2.

Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota.

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http://dx.doi.org/10.1016/j.ophtha.2020.06.059DOI Listing
February 2021

Comparison of 1-Year Effectiveness of Trabecular Microbypass Stent implantation (iStent) in Conjunction With Phacoemulsification Among Mild, Moderate, and Severe Primary Open-angle Glaucoma Patients.

J Glaucoma 2020 07;29(7):542-549

Department of Ophthalmology, Stanford University, Palo Alto, CA.

Precis: The study compared 1-year effectiveness of single trabecular microbypass stent (iStent) implantation with phacoemulsification among glaucoma severities in primary open-angle glaucoma. The study found that mild glaucoma had greater success rate and lower number of medications compared with moderate and severe glaucoma.

Purpose: To evaluate the effectiveness of iStent implantation in combination with cataract surgery in moderate to severe glaucoma compared with mild glaucoma.

Methods: Medical charts of primary open-angle glaucoma subjects undergoing 1 iStent implantation were retrospectively reviewed. Glaucoma was classified on the basis of mean deviation (MD) of the preoperative standard automated perimetry into mild (MD>-6 dB), moderate (MD -6 to -12 dB), and severe (MD<-12 dB). Mixed effect regression models were performed to determine the effect of iStent at 1 year. The outcomes included as follows: (1) intraocular pressure (IOP) and the number of medications, (2) eyes with IOP ≤ severity-based target (18 mm Hg for mild, 15 mm Hg for moderate, 12 mm Hg for severe) (2A) without medication, and (2B) with medication reduction.

Results: In total, 104 eyes from 89 subjects were analyzed. Cataract combined with iStent surgery significantly lowered the number of medications in all groups and significantly decreased IOP in moderate and severe glaucoma (P<0.05). There was significantly higher number of medications in moderate (β: 0.58, P=0.002) and severe (β: 1.20, P<0.001) compared with mild glaucoma. Eyes with moderate glaucoma had significantly lower rate of success (criterion 2A) compared with mild glaucoma [odds ratio (OR): 0.008, P=0.047]. Eyes with moderate and severe glaucoma had significantly lower rates of success (criterion 2B) (moderate vs. mild OR: 0.002, P=0.028; severe vs. mild OR: 0.026, P=0.026).

Conclusions: Combined phacoemulsification with iStent seems to have a better IOP-lowering and medication-lowering effect in mild glaucoma cases versus those with moderate and severe glaucoma. This difference was found in real-world data over one-year follow-up period. Long-term studies with defined IOP goals and medication removal protocols are warranted.
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http://dx.doi.org/10.1097/IJG.0000000000001542DOI Listing
July 2020

Management of the glaucoma patient progressing at low normal intraocular pressure.

Curr Opin Ophthalmol 2020 Mar;31(2):107-113

Department of Ophthalmology, Stanford University, Byers Eye Institute, Palo Alto, California, USA.

Purpose Of Review: Patients with glaucoma with disease progression despite low or normal intraocular pressure (IOP) present special challenges to the treating clinician. Treatment goals may depend on whether patients have apparent low IOP with concurrent treatment or have low IOP at baseline without treatment. We review the diagnostic and therapeutic approaches to these patients.

Recent Findings: Apparent progression at low IOP should start with confirmation of IOP, made easier by devices enabling patient home self-tonometry. Suspected visual field progression should be confirmed by repeat testing prior to advancement of therapy. Trabeculectomy remains the most effective surgical method of achieving long-term success, particularly when there is a low starting IOP. Drainage tube implantation or the use of novel micro-incisional non-bleb-forming procedures are less likely to be successful in achieving low IOP goals.

Summary: Diagnostic testing is important in confirming progressive glaucomatous disease at low IOP levels. The most effective way of slowing the progression of glaucoma in a patient with low IOP is to lower the IOP further, sometimes to single digit levels, which is most often achievable with trabeculectomy.
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http://dx.doi.org/10.1097/ICU.0000000000000640DOI Listing
March 2020

Patient-reported outcomes measures and patient preferences for minimally invasive glaucoma surgical devices.

Eye (Lond) 2020 01 26;34(1):205-210. Epub 2019 Nov 26.

Stanford University School of Medicine, Stanford, CA, USA.

Background: Many therapeutic options are available to glaucoma patients. One recent therapeutic option is minimally invasive glaucoma surgical (MIGS) devices. It is unclear how patients view different treatments and which patient-reported outcomes would be most relevant in patients with mild to moderate glaucoma. We developed a questionnaire for patients eligible for MIGS devices and a patient preference study to examine the value patients place on certain outcomes associated with glaucoma and its therapies.

Objectives: To summarize the progress to date.

Methods: Questionnaire development: We drafted the questionnaire items based on input from one physician and four patient focus groups, and a review of the literature. We tested item clarity with six cognitive interviews. These items were further refined. Patient preference study: We identified important benefit and risk outcomes qualitatively using semi-structured, one-on-one interviews with patients who were eligible for MIGS devices. We then prioritized these outcomes quantitatively using best-worst scaling methods.

Results: Questionnaire testing: Three concepts were deemed relevant for the questionnaire: functional limitations, symptoms, and psychosocial factors. We will evaluate the reliability and validity of the 52-item draft questionnaire in an upcoming field test. Patient preference study: We identified 13 outcomes that participants perceived as important. Outcomes with the largest relative importance weights were "adequate IOP control" and "drive a car during the day."

Conclusions: Patients have the potential to steer clinical research towards outcomes that are important to them. Incorporating patients' perspectives into the MIGS device development and evaluation process may expedite innovation and availability of these devices.
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http://dx.doi.org/10.1038/s41433-019-0676-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002517PMC
January 2020

The Patient Perspective: Putting the Patient at the Center of the Translational Innovation Process.

Clin Pharmacol Ther 2020 01 23;107(1):82-84. Epub 2019 Nov 23.

Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA.

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http://dx.doi.org/10.1002/cpt.1686DOI Listing
January 2020

Association of a Primary Open-Angle Glaucoma Genetic Risk Score With Earlier Age at Diagnosis.

JAMA Ophthalmol 2019 Aug 22. Epub 2019 Aug 22.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston.

Importance: Genetic variants associated with primary open-angle glaucoma (POAG) are known to influence disease risk. However, the clinical effect of associated variants individually or in aggregate is not known. Genetic risk scores (GRS) examine the cumulative genetic load by combining individual genetic variants into a single measure, which is assumed to have a larger effect and increased power to detect relevant disease-related associations.

Objective: To investigate if a GRS that comprised 12 POAG genetic risk variants is associated with age at disease diagnosis.

Design, Setting, And Participants: A cross-sectional study included individuals with POAG and controls from the Glaucoma Genes and Environment (GLAUGEN) study and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) study. A GRS was formulated using 12 variants known to be associated with POAG, and the alleles associated with increasing risk of POAG were aligned in the case-control sets. In case-only analyses, the association of the GRS with age at diagnosis was analyzed as an estimate of disease onset. Results from cohort-specific analyses were combined with meta-analysis. Data collection started in August 2012 for the NEIGHBOR cohort and in July 2008 for the GLAUGEN cohort and were analyzed starting in March 2018.

Main Outcomes And Measures: Association of a 12 single-nucleotide polymorphism POAG GRS with age at diagnosis in individuals with POAG using linear regression.

Results: The GLAUGEN study included 976 individuals with POAG and 1140 controls. The NEIGHBOR study included 2132 individuals with POAG and 2290 controls. For individuals with POAG, the mean (SD) age at diagnosis was 63.6 (9.8) years in the GLAUGEN cohort and 66.0 (13.7) years in the NEIGHBOR cohort. For controls, the mean (SD) age at enrollment was 65.5 (9.2) years in the GLAUGEN cohort and 68.9 (11.4) years in the NEIGHBOR cohort. All study participants were European white. The GRS was strongly associated with POAG risk in case-control analysis (odds ratio per 1-point increase in score = 1.24; 95% CI, 1.21-1.27; P = 3.4 × 10-66). In case-only analyses, each higher GRS unit was associated with a 0.36-year earlier age at diagnosis (β = -0.36; 95% CI, -0.56 to -0.16; P = 4.0 × 10-4). Individuals in the top 5% of the GRS had a mean (SD) age at diagnosis of 5.2 (12.8) years earlier than those in the bottom 5% GRS (61.4 [12.7] vs 66.6 [12.9] years; P = 5.0 × 10-4).

Conclusions And Relevance: A higher dose of POAG risk alleles was associated with an earlier age at glaucoma diagnosis. On average, individuals with POAG with the highest GRS had 5.2-year earlier age at diagnosis of disease. These results suggest that a GRS that comprised genetic variants associated with POAG could help identify patients with risk of earlier disease onset impacting screening and therapeutic strategies.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.3109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707005PMC
August 2019

Characteristics of cataract surgery patients influencing patient satisfaction scores.

J Cataract Refract Surg 2019 04 27;45(4):437-442. Epub 2019 Feb 27.

Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California, USA. Electronic address:

Purpose: To determine factors that influence patient satisfaction scores in individuals who have recently had cataract surgery.

Setting: Byers Eye Institute, Palo Alto, California, USA.

Design: Prospective case series.

Methods: Selected questions from the Press Ganey survey and the National Eye Institute Visual Function Questionnaire-25 were administered to each patient immediately after completion of a clinic visit. The correlation between patient-specific variables and the answer to the survey question "likelihood of recommending our practice to others," a surrogate for overall patient satisfaction, was assessed using the Student t test. A logistical regression model was used to adjust for potentially confounding variables.

Results: One hundred forty-three patients were recruited from 4 providers; 57 (39.8%) were men, and the mean age was 70.0 years ± 11.6 (SD). The main outcome was the proportion of scores less than 5, or "very good," for the likelihood of recommending the practice to others. There was a statistically significant association between a non-5 patient satisfaction score and self-reported ethnicity of Asian or Pacific Islander compared with other ethnicities (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.1; P = .049); other possible correlates were not statistically significant. The relationship persisted after adjustment for potential confounding variables (OR, 2.6; 95% CI, 1.1-6.3; P = .027).

Conclusion: In postoperative cataract patients, Asian or Pacific Islander ethnicity, a factor out of the control of the provider and clinic staff, was associated with a lower overall Press Ganey patient satisfaction score compared with patients of all other ethnicities.
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http://dx.doi.org/10.1016/j.jcrs.2018.11.031DOI Listing
April 2019

Corneal Biomechanics Using a Scheimpflug-Based Noncontact Device in Normal-Tension Glaucoma and Healthy Controls.

Asia Pac J Ophthalmol (Phila) 2019 Jan-Feb;8(1):22-29. Epub 2019 Feb 18.

Stanford University School of Medicine, Palo Alto, CA, United States.

Purpose: To determine if a novel biomechanical parameter, corneal applanation velocity, as measured by the Corvis ST, is associated with a diagnosis of normal-tension glaucoma (NTG).

Design: Prospective, cross-sectional study.

Methods: Study and control subjects were recruited from the ophthalmology clinic of a university teaching hospital in Hong Kong over an 8-week period in 2013. A total of 80 eyes with NTG diagnosis and 155 healthy eyes randomly selected to be in the control group were included in the final analysis. All subjects underwent corneal biomechanical testing with the Oculus Corvis ST non-contact tonometer. Logistic regression analysis adjusted for age and central corneal thickness was conducted to assess the relationship between inward and outward applanation velocity and the risk of NTG. Secondary outcome variables included corneal applanation time, length, amplitude, and highest concavity.

Results: Inward applanation velocity was faster in the NTG eyes (0.15 ± 0.02 m/s) than in the control eyes (0.14 ± 0.02 m/s) ( = 0.016). The odds ratio for a 0.01 m/s increase in inward applanation velocity when comparing NTG eyes with control eyes adjusted for age and central corneal thickness was 1.15 (95% confidence interval, 1.03-1.30) ( = 0.016). There was no evidence that outward applanation velocity or any secondary corneal biomechanical variable differed between the NTG and control eyes.

Conclusions: Normal-tension glaucoma eyes demonstrated a small, statistically significant faster corneal inward applanation velocity than normal control eyes.
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http://dx.doi.org/10.22608/APO.2018334DOI Listing
March 2019

Relationship of lifestyle, exercise, and nutrition with glaucoma.

Curr Opin Ophthalmol 2019 Mar;30(2):82-88

Glaucoma Center of San Francisco, San Francisco, California, USA.

Purpose Of Review: Although reducing the intraocular pressure (IOP) through medications, laser or surgery remains the primary means of glaucoma treatment, there is increasing evidence during the last decade that environmentally modifiable factors may help to prevent glaucoma or its progression through different mechanisms that may or may not involve lowering IOP. Additionally, patients are increasingly interested in maintaining a healthy lifestyle and taking an active role in the management of their disease. Therefore, the aim of this review is to summarize the current evidence regarding environmentally modifiable factors such as lifestyle, exercise, and nutrition in the pathogenesis of glaucoma.

Recent Findings: In the last decade, large population-based studies have helped to identify possible environmentally modifiable protective and risk factors with regard to glaucomatous disease. Smoking cessation; moderate aerobic exercise; recommended weight; and a balanced diet including green leafy vegetables, omega fatty-acids, and moderate intake of hot tea and coffee have been reported to be possibly protective against developing glaucoma or its progression.

Summary: Modifiable environmental factors such as lifestyle, exercise, and nutrition may play a role in glaucoma pathogenesis. Large prospective studies with long-term follow-up should be encouraged to corroborate these findings, which may guide future treatments for our patients, some of which may not be limited to IOP reduction.
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http://dx.doi.org/10.1097/ICU.0000000000000553DOI Listing
March 2019

Ocular Antihypertensive Medication Use After iStent Implantation Concurrent With Cataract Surgery vs Cataract Surgery Alone in a Large US Health Care Claims Database.

JAMA Ophthalmol 2019 01;137(1):21-27

Byers Eye Institute, Stanford University, Palo Alto, California.

Importance: The iStent Trabecular Micro-Bypass (Glaukos Corporation) is a minimally invasive glaucoma implant used in conjunction with cataract surgery to lower intraocular pressure.

Objective: To determine whether implantation of the iStent concurrent with cataract surgery is associated with reduced use of ocular antihypertensive medications in a US health care claims database.

Design, Setting, And Participants: Retrospective, observational longitudinal cohort study of individuals enrolled in a US managed care network who underwent iStent implantation with cataract surgery (iStent/CEIOL) from 2012 to 2016 (n = 1509 bilateral and n = 1462 unilateral surgery). A control group of individuals who underwent bilateral cataract surgery only (CEIOL) were matched 1:1 to patients undergoing bilateral iStent/CEIOL on baseline demographic and clinical factors. Data were analyzed between November 1, 2017, and January 31, 2018.

Main Outcomes And Measures: The number of topical ocular antihypertensive agents used postoperatively by patients undergoing iStent/CEIOL compared with baseline and with matched CEIOL control individuals, and hazard ratios with 95% confidence intervals for sustained reduced use of at least 1 topical ocular antihypertensive agent postoperatively.

Results: Of the 2971 eligible enrollees, mean age at first surgery was 74.3 years, and 1659 (55.8%) were women. Patients undergoing iStent/CEIOL had diagnoses that included primary open-angle glaucoma (n = 2329; 78.4%), narrow angles (n = 381; 12.8%), and secondary glaucomas (n = 261; 8.8%). At baseline, 1223 (41.2%) were receiving no topical glaucoma agents; 876 (29.5%), 437 (14.7%), and 435 (14.6%) were receiving 1, 2, or at least 3 agents, respectively. Although only 678 persons (22.8%) completed at least 2 years of postoperative follow-up, the proportion of patients receiving no drops increased postoperatively (64.7%, 20-24 months, P < .001, χ2). Patients receiving at least 1 topical agent at baseline had mean reduction of 1.01 and 0.61 medications used at 20 to 24 months with bilateral or unilateral surgery, respectively (both P < .001, paired t). Sustained reduction in glaucoma medication use was more likely in patients receiving at least 3 vs 1 medication at baseline (hazard ratio, 1.68; 95% CI, 1.36-2.09). Compared with matched control individuals undergoing CEIOL, patients undergoing bilateral iStent/CEIOL had a greater mean reduction in drops used (0.99 vs 0.49; postoperative month 20-24; P < .001; paired t) and a higher proportion receiving no drops postoperatively (73.5% vs 55.3%, postoperative month 20-24; P < .001; χ2).

Conclusions And Relevance: Implantation of the iStent trabecular micro-bypass stent concurrent with cataract surgery was associated with moderately reduced use of topical ocular antihypertensive medication. Reduction in the use of glaucoma medications may lessen the burden of medication adverse effects and promote better adherence.
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http://dx.doi.org/10.1001/jamaophthalmol.2018.4461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439782PMC
January 2019

Orbital, eyelid, and nasopharyngeal silicone oil granuloma presenting as ptosis & pseudo-xanthelasma.

Am J Ophthalmol Case Rep 2018 Sep 14;11:45-48. Epub 2018 May 14.

Department of Ophthalmology, Byers Eye Institute at Stanford University, 2452 Watson Court, Palo Alto, CA, United States.

Purpose: To highlight the presentation and management of a patient with eyelid, orbital and nasopharyngeal silicone oil migration through a glaucoma drainage implant presenting as pseudo-xanthelasma and ptosis.

Observations: A 68-year male presented with unilateral ptosis and presumed xanthelasma. He had a history of glaucoma drainage implant surgery, pseudophakia, and multiple retinal detachment repairs with silicone oil. During ptosis repair it was discovered that his presumed xanthelasma was in fact an eyelid silicone granuloma. Additional work up revealed silicone infiltration of the eyelids, orbits, and nasopharynx, resulting from emulsified silicone oil leakage through his glaucoma valve implant.

Conclusions And Importance: Silicone oil may emulsify with time, with potential egress via a glaucoma filtration device. Clinicians should be alert for eyelid, orbital and sinonasal findings that may indicate occult migration.
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http://dx.doi.org/10.1016/j.ajoc.2018.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026769PMC
September 2018

A Schlemm Canal Microstent for Intraocular Pressure Reduction in Primary Open-Angle Glaucoma and Cataract: The HORIZON Study.

Ophthalmology 2019 01 23;126(1):29-37. Epub 2018 Jun 23.

Stanford University, Stanford, California.

Objective: To compare cataract surgery with implantation of a Schlemm canal microstent with cataract surgery alone for the reduction of intraocular pressure (IOP) and medication use after 24 months.

Design: Prospective, multicenter, single-masked, randomized controlled trial.

Participants: Subjects with concomitant primary open-angle glaucoma (POAG), visually significant cataract, and washed-out modified diurnal IOP (MDIOP) between 22 and 34 mmHg.

Methods: Subjects were randomized 2:1 to receive a single Hydrus Microstent (Ivantis, Inc, Irvine, CA) in the Schlemm canal or no stent after uncomplicated phacoemulsification. Comprehensive eye examinations were conducted 1 day, 1 week, and 1, 3, 6, 12, 18, and 24 months postoperatively. Medication washout and MDIOP measurement were repeated at 12 and 24 months.

Main Outcome Measures: The primary and secondary effectiveness end points were the proportion of subjects demonstrating a 20% or greater reduction in unmedicated MDIOP and change in mean MDIOP from baseline at 24 months, respectively. Hypotensive medication use was tracked throughout the course of follow-up. Safety measures included the frequency of surgical complications and adverse events.

Results: A total of 369 eyes were randomized after phacoemulsification to Hydrus Microstent (HMS) and 187 to no microstent (NMS). At 24 months, unmedicated MDIOP was reduced by ≥20% in 77.3% of HMS group eyes and in 57.8% of NMS group eyes (difference = 19.5%, 95% confidence interval [CI] 11.2%-27.8%, P < 0.001). The mean reduction in 24-month unmedicated MDIOP was -7.6±4.1 mmHg (mean ± standard deviation) in the HMS group and -5.3±3.9 mmHg in the NMS group (difference = -2.3 mmHg; 95% CI, -3.0 to -1.6; P < 0.001). The mean number of medications was reduced from 1.7±0.9 at baseline to 0.3±0.8 at 24 months in the HMS group and from 1.7±0.9 to 0.7±0.9 in the NMS group (difference = -0.4 medications; P < 0.001). There were no serious ocular adverse events related to the microstent, and no significant differences in safety parameters between the 2 groups.

Conclusions: This 24-month multicenter randomized controlled trial demonstrated superior reduction in MDIOP and medication use among subjects with mild-to-moderate POAG who received a Schlemm canal microstent combined with phacoemulsification compared with phacoemulsification alone.
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http://dx.doi.org/10.1016/j.ophtha.2018.05.012DOI Listing
January 2019

Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.

Invest Ophthalmol Vis Sci 2018 02;59(2):629-636

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.

Purpose: Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk.

Methods: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]).

Results: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations.

Conclusions: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.
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http://dx.doi.org/10.1167/iovs.17-22708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795896PMC
February 2018

The Association Between Body Mass Index and Open-angle Glaucoma in a South Korean Population-based Sample.

J Glaucoma 2018 03;27(3):239-245

Department of Ophthalmology, University of California San Francisco, San Francisco.

Purpose: The purpose of this article is to investigate the association between body mass index (BMI) and open-angle glaucoma (OAG) in a sample of the South Korean population.

Materials And Methods: The sample consisted of a cross-sectional, population-based sample of 10,978 participants, 40 years of age and older, enrolled in the 2008 to 2011 Korean National Health and Nutrition Examination Survey. All participants had measured intraocular pressure <22 mm Hg and open anterior chamber angles. OAG was defined using disc and visual field criteria established by the International Society for Geographical and Epidemiological Ophthalmology. Multivariable analyses were performed to determine the association between BMI and OAG. These analyses were also performed in a sex-stratified and age-stratified manner.

Results: After adjusting for potential confounding variables, lower BMI (<19 kg/m) was associated with greater risk of OAG compared with normal BMI (19 to 24.9 kg/m) [odds ratio (OR), 2.28; 95% confidence interval (CI), 1.22-4.26]. In sex-stratified analyses, low BMI remained adversely related to glaucoma in women (OR, 3.45; 95% CI, 1.42-8.38) but not in men (OR, 1.72; 95% CI, 0.71-4.20). In age-stratified analyses, lower BMI was adversely related to glaucoma among subjects 40- to 49-year old (OR, 5.16; 95% CI, 1.86-14.36) but differences in glaucoma prevalence were not statistically significant between those with low versus normal BMI in other age strata.

Conclusions: Lower BMI was associated with increased odds of OAG in a sample of the South Korean population. Multivariate analysis revealed the association to be statistically significant in women and those in the youngest age stratum.
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http://dx.doi.org/10.1097/IJG.0000000000000867DOI Listing
March 2018

The Primary Tube Versus Trabeculectomy Study: Methodology of a Multicenter Randomized Clinical Trial Comparing Tube Shunt Surgery and Trabeculectomy with Mitomycin C.

Ophthalmology 2018 05 18;125(5):774-781. Epub 2017 Dec 18.

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.

Purpose: To describe the methodology of the Primary Tube Versus Trabeculectomy (PTVT) Study.

Design: Multicenter randomized clinical trial.

Participants: Patients with medically uncontrolled glaucoma and no prior incisional ocular surgery.

Methods: Patients are being enrolled at 16 clinical centers and randomly assigned to treatment with a tube shunt (350-mm Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (0.4 mg/ml for 2 minutes).

Main Outcome Measures: The primary outcome measure is the rate of surgical failure, defined as intraocular pressure (IOP) more than 21 mmHg or reduced by less than 20% from baseline, IOP of 5 mmHg or less, reoperation for glaucoma, or loss of light perception vision. Secondary outcome measures include IOP, glaucoma medical therapy, visual acuity, visual fields, and surgical complications.

Conclusions: Practice patterns vary in the surgical management of glaucoma, and opinions differ among surgeons regarding the preferred primary operation for glaucoma. The PTVT Study will provide valuable information comparing the 2 most commonly performed glaucoma surgical procedures.
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http://dx.doi.org/10.1016/j.ophtha.2017.10.037DOI Listing
May 2018

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

Eur J Hum Genet 2017 11 30;25(11):1261-1267. Epub 2017 Aug 30.

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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) 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); 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.
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http://dx.doi.org/10.1038/ejhg.2017.136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643970PMC
November 2017

Use of phosphodiesterase inhibitors and prevalence of self-reported glaucoma in the United States.

PLoS One 2017 17;12(8):e0183388. Epub 2017 Aug 17.

Department of Ophthalmology, University of California San Francisco, San Francisco, California, United States of America.

Objective: While decreased ocular blood flow is thought to be a possible contributor to glaucoma pathogenesis, it is unclear what role systemic phosphodiesterase inhibitors (PDEi) play. We performed a cross-sectional study of a nationally representative sample of the U.S. population to investigate the relationship between the most commonly used PDEi, sildenafil and theophylline, and self-reported glaucoma.

Methods: We used the National Health and Nutrition Examination Survey 2005-2008 cycles for this observational study. 7,042 participants, aged 40 years and over, responded to a survey item on glaucoma status and were included in the analysis. Multivariable logistic regression models were constructed to evaluate the association between at least 1 year of self-reported PDEi use and prevalent glaucoma. Regressions were adjusted for potential confounding variables, including demographics, socioeconomic status, and general health conditions, and accounted for the complex design of the survey. Sample weights were constructed and used to ensure the generalizability of results.

Results: 482 respondents self-reported a diagnosis of glaucoma, of which 11 used sildenafil and 20 used theophylline for at least 1 year. Covariates significantly associated with higher odds of glaucoma prevalence in univariable analyses included older age, black race, former smoking status, diabetes, hyperlipidemia, myocardial infarction, and stroke. Conversely, higher education and income were significantly associated with lower odds of glaucoma prevalence. In regression analyses adjusted for demographic and socioeconomic variables, sildenafil (OR = 4.90, CI: 1.24-19.27, p = 0.025) and theophylline (OR = 3.15, CI: 1.46-6.80, p = 0.005) were significantly associated with higher odds of self-reported glaucoma. These associations held after further adjustment with general health behaviors and conditions for both sildenafil and theophylline.

Conclusions: Use of sildenafil and theophylline for one or more years was associated with greater prevalence of self-reported glaucoma, a finding which requires further prospective study to assess causality and possible mechanisms of action.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183388PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560666PMC
October 2017

Disinfection of Tonometers: A Report by the American Academy of Ophthalmology.

Ophthalmology 2017 12 11;124(12):1867-1875. Epub 2017 Jul 11.

Harvard Medical School, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Glaucoma Service, Boston, Massachusetts.

Objective: To examine the efficacy of various disinfection methods for reusable tonometer prisms in eye care and to highlight how disinfectants can damage tonometer tips and cause subsequent patient harm.

Methods: Literature searches were conducted last in October 2016 in the PubMed and the Cochrane Library databases for original research investigations. Reviews, non-English language articles, nonophthalmology articles, surveys, and case reports were excluded.

Results: The searches initially yielded 64 unique citations. After exclusion criteria were applied, 10 laboratory studies remained for this review. Nine of the 10 studies used tonometer prisms and 1 used steel discs. The infectious agents covered in this assessment include adenovirus 8 and 19, herpes simplex virus (HSV) 1 and 2, human immunodeficiency virus 1, hepatitis C virus, enterovirus 70, and variant Creutzfeldt-Jakob disease. All 4 studies of adenovirus 8 concluded that after sodium hypochlorite (dilute bleach) disinfection, the virus was undetectable, but only 2 of the 4 studies found that 70% isopropyl alcohol (e.g., alcohol wipes or soaks) eradicated all viable virus. All 3 HSV studies concluded that both sodium hypochlorite and 70% isopropyl alcohol eliminated HSV. Ethanol, 70% isopropyl alcohol, dilute bleach, and mechanical cleaning all lack the ability to remove cellular debris completely, which is necessary to prevent prion transmission. Therefore, single-use tonometer tips or disposable tonometer covers should be considered when treating patients with suspected prion disease. Damage to tonometer prisms can be caused by sodium hypochlorite, 70% isopropyl alcohol, 3% hydrogen peroxide, ethyl alcohol, water immersion, ultraviolet light, and heat exposure. Disinfectants can cause tonometer tips to swell and crack by dissolving the glue that holds the hollow tip together. The tonometer tip cracks can irritate the cornea, harbor microbes, or allow disinfectants to enter the interior of the tonometer tip.

Conclusions: Sodium hypochlorite (dilute bleach) offers effective disinfection against adenovirus and HSV, the viruses commonly associated with nosocomial outbreaks in eye care. Tonometer prisms should be examined regularly for signs of damage.
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http://dx.doi.org/10.1016/j.ophtha.2017.05.033DOI Listing
December 2017

The relation between exercise and glaucoma in a South Korean population-based sample.

PLoS One 2017 10;12(2):e0171441. Epub 2017 Feb 10.

Department of Ophthalmology; University of California San Francisco; San Francisco, California, United States of America.

Purpose: To investigate the association between exercise and glaucoma in a South Korean population-based sample.

Design: Population-based, cross-sectional study.

Participants: A total of 11,246 subjects, 40 years and older who underwent health care assessment as part of the 2008-2011 Korean National Health and Nutrition Examination Survey.

Methods: Variables regarding the duration (total minutes per week), frequency (days per week), and intensity of exercise (vigorous, moderate exercise and walking) as well as glaucoma prevalence were ascertained for 11,246 survey participants. Demographic, comorbidity, and health-related behavior information was obtained via interview. Multivariable logistic regression analyses were performed to determine the association between the exercise-related parameters and odds of a glaucoma diagnosis.

Main Outcome Measure(s): Glaucoma defined by International Society for Geographical and Epidemiological Ophthalmology criteria.

Results: Overall, 336 (2.7%) subjects met diagnostic criteria for glaucomatous disease. After adjustment for potential confounding variables, subjects engaged in vigorous exercise 7 days per week had higher odds of having glaucoma compared with those exercising 3 days per week (Odds Ratio [OR] 3.33, 95% confidence interval [CI] 1.16-9.54). High intensity of exercise, as categorized by the guidelines of the American College of Sports Medicine (ACSM), was also associated with greater glaucoma prevalence compared with moderate intensity of exercise (OR 1.55, 95% CI 1.03-2.33). There was no association between other exercise parameters including frequency of moderate exercise, walking, muscle strength exercise, flexibility training, or total minutes of exercise per week, and the prevalence of glaucoma. In sub-analyses stratifying by gender, the association between frequency of vigorous exercise 7 days per week and glaucoma diagnosis remained significant in men (OR 6.05, 95% CI 1.67-21.94) but not in women (OR 0.96 95% CI: 0.23-3.97). A U-shaped association between exercise intensity and glaucoma prevalence was noted in men (OR 1.71, 95% CI 1.09-2.69 for low intensity versus moderate intensity; OR 2.19, 95% CI 1.25-3.85 for high intensity versus moderate intensity).

Conclusion: In a South Korean population sample, daily vigorous exercise was associated with higher glaucoma prevalence. In addition, the intensity of exercise was positively associated with glaucoma diagnosis in men but not women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171441PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302806PMC
August 2017

Age at natural menopause genetic risk score in relation to age at natural menopause and primary open-angle glaucoma in a US-based sample.

Menopause 2017 02;24(2):150-156

1Department of Ophthalmology, Massachusetts Eye and Ear Infirmary 2Channing Division of Network Medicine, Brigham and Women's Hospital 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard Medical School, Boston, MA 4Department of Epidemiology and Biostatistics 5Institute of Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH 6Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 7Department of Ophthalmology 8Department of Medicine, Duke University, Duke University Medical Center, Durham, NC 9Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 10Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 11Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI 12Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh, Pittsburgh, PA 13Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, IO 14Department of Ophthalmology, University of North Carolina, Chapel Hill, NC 15Department of Ophthalmology, WVU Eye Institute, Morgantown, WV 16Scripps Genome Center, University of California at San Diego, San Diego, CA 17Emmes Corporation, Chevy Chase, MD 18Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 19Department of Ophthalmology, Stanford University, Palo Alto, CA 20Department of Ophthalmology, Mayo Clinic, Rochester, MN 21Wills Eye Institute, Philadelphia, PA 22Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, NY 23Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH 24Department of Ophthalmology & Visual Sciences, University of Nebraska Medical Center, Omaha, NE 25Department of Genetics; Stanford University, Palo Alto, CA 26Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, MD 27Department of Ophthalmology, Hamilton Eye Center; University of California at San Diego, San Diego, CA 28Department of Cellular Biology & Anatomy, Augusta University, Augusta, GA.

Objective: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG.

Methods: Using data from the Nurses' Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method.

Results: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10 percentile or highest 90 percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively).

Conclusions: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.
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http://dx.doi.org/10.1097/GME.0000000000000741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5266624PMC
February 2017

Outcomes of Wound Dehiscence After Penetrating Keratoplasty.

Cornea 2016 12;35(12):e42

Byers Eye Institute, Stanford University, Palo Alto, CA.

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http://dx.doi.org/10.1097/ICO.0000000000001060DOI Listing
December 2016

Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses.

Invest Ophthalmol Vis Sci 2016 Sep;57(11):5046-5052

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States.

Purpose: Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins.

Methods: We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure.

Results: We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010).

Conclusions: We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important.
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http://dx.doi.org/10.1167/iovs.16-20017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040191PMC
September 2016

A Common Variant in MIR182 Is Associated With Primary Open-Angle Glaucoma in the NEIGHBORHOOD Consortium.

Invest Ophthalmol Vis Sci 2016 08;57(10):4528-4535

Department of Ophthalmology, Mass Eye & Ear, Boston, Massachusetts, United States.

Purpose: Noncoding microRNAs (miRNAs) have been implicated in the pathogenesis of glaucoma. We aimed to identify common variants in miRNA coding genes (MIR) associated with primary open-angle glaucoma (POAG).

Methods: Using the NEIGHBORHOOD data set (3853 cases/33,480 controls with European ancestry), we first assessed the relation between 85 variants in 76 MIR genes and overall POAG. Subtype-specific analyses were performed in high-tension glaucoma (HTG) and normal-tension glaucoma subsets. Second, we examined the expression of miR-182, which was associated with POAG, in postmortem human ocular tissues (ciliary body, cornea, retina, and trabecular meshwork [TM]), using miRNA sequencing (miRNA-Seq) and droplet digital PCR (ddPCR). Third, miR-182 expression was also examined in human aqueous humor (AH) by using miRNA-Seq. Fourth, exosomes secreted from primary human TM cells were examined for miR-182 expression by using miRNA-Seq. Fifth, using ddPCR we compared miR-182 expression in AH between five HTG cases and five controls.

Results: Only rs76481776 in MIR182 gene was associated with POAG after adjustment for multiple comparisons (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.11-1.42, P = 0.0002). Subtype analysis indicated that the association was primarily in the HTG subset (OR = 1.26, 95% CI: 1.08-1.47, P = 0.004). The risk allele T has been associated with elevated miR-182 expression in vitro. Data from ddPCR and miRNA-Seq confirmed miR-182 expression in all examined ocular tissues and TM-derived exosomes. Interestingly, miR-182 expression in AH was 2-fold higher in HTG patients than nonglaucoma controls (P = 0.03) without controlling for medication treatment.

Conclusions: Our integrative study is the first to associate rs76481776 with POAG via elevated miR-182 expression.
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http://dx.doi.org/10.1167/iovs.16-19688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991020PMC
August 2016

Association between self-reported bupropion use and glaucoma: a population-based study.

Br J Ophthalmol 2017 04 28;101(4):525-529. Epub 2016 Jun 28.

University of California San Francisco, San Francisco, California, USA.

Purpose: To investigate the relationship between self-reported bupropion use and self-reported glaucoma in a nationally representative sample of the US population.

Methods: This cross-sectional study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, age ≥40 years, who responded to a question regarding their glaucoma status. Participants were interviewed regarding the use of prescription medications, and those ascertained as having used bupropion were further divided into groups based on duration of usage. Other relevant information, including demographics, comorbidities and health-related behaviours, was obtained via interview. Multivariate logistic regression was performed to determine the OR and 95% CIs for association between bupropion use and prevalent glaucoma. Covariates in the final multivariate model included parameters associated with glaucoma at p<0.1: age, gender, ethnicity and annual income.

Results: 453 participants self-reported a diagnosis of glaucoma, and 108 reported bupropion medication use. Participants who reported using bupropion for more than 1 year had decreased odds of self-reporting a diagnosis of glaucoma (unadjusted OR=0.5, 95% CI 0.01 to 0.52; adjusted OR=0.1, 95% CI 0.01 to 0.81) compared with those not using bupropion or using it for less than a year.

Conclusions: Bupropion use, particularly for an extended period of time, may be associated with a reduced risk of glaucomatous disease.
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http://dx.doi.org/10.1136/bjophthalmol-2016-308846DOI Listing
April 2017

Oral Contraceptive Use and Prevalence of Self-Reported Glaucoma or Ocular Hypertension in the United States.

Ophthalmology 2016 Apr 11;123(4):729-36. Epub 2016 Feb 11.

Department of Ophthalmology, University of California, San Francisco, California. Electronic address:

Purpose: To investigate the association between oral contraceptive (OC) use and glaucoma prevalence in the United States.

Design: Cross-sectional study.

Participants: A total of 3406 female participants, aged 40 years or older, from the 2005 to 2008 National Health and Nutrition Examination Survey, who reported a presence or absence of glaucoma or ocular hypertension completed both the vision and the reproductive health questionnaires and underwent eye examinations.

Methods: Multivariate regression analysis was used to assess the correlation between OC use and self-reported glaucoma or ocular hypertension (n = 231 cases), controlling for potential confounders, including age, ethnicity, systemic comorbidities such as hypertension and stroke, ocular diseases such as cataract and diabetic retinopathy, and reproductive health factors, including age at menopause, age at menarche, history of hormone replacement therapy, and gynecological surgical history.

Main Outcome Measures: The outcome variable was self-reported glaucoma or ocular hypertension.

Results: After adjusting for confounders, those with ≥3 years of OC use had greater odds (odds ratio, 1.94; 95% confidence interval, 1.22-3.07) of self-reported glaucoma or ocular hypertension. Other factors associated with higher glaucoma or ocular hypertension prevalence included older age, African American race, and later age at menarche.

Conclusions: Oral contraceptive use may be associated with increased risk of self-reported glaucoma or ocular hypertension.
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http://dx.doi.org/10.1016/j.ophtha.2015.11.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857187PMC
April 2016

Refractive Error and the Risk of Age-Related Macular Degeneration in the South Korean Population.

Asia Pac J Ophthalmol (Phila) 2016 Mar-Apr;5(2):115-21

From the *Department of Ophthalmology, University of California, San Francisco, San Francisco, CA; †National Yang-Ming University, Taipei, Taiwan; and ‡Department of Ophthalmology, Stanford University, Stanford, CA.

Purpose: We investigated the association between refractive error and the prevalence of age-related macular degeneration (AMD) in a population-based study.

Design: This was a cross-sectional study.

Methods: Right eyes were included from 14,067 participants aged 40 years and older with gradable fundus photographs and refraction data from the fourth and the fifth Korea National Health and Nutrition Examination Survey 2008 to 2011. Early and late AMD was graded based on the International Age-Related Maculopathy Epidemiological Study Group grading system. Autorefraction data were collected to calculate spherical equivalent refraction in diopters (D) and classified into 4 groups: hyperopia (≥1.0 D), emmetropia (-0.99 to 0.99 D), mild myopia (-1.0 to -2.99 D), and moderate to high myopia (≤-3.0 D).

Results: After adjustment for potential confounders, each diopter increase in spherical equivalent was associated with a 16% [odds ratio (OR), 1.16; 95% confidence interval (CI), 1.08-1.25] and 18% (OR, 1.18; 95% CI, 1.10-1.27) increased risk of any (early + late) and early AMD, respectively. Mild and moderate to high myopia were associated with lower odds of any and early AMD compared with hyperopia (any AMD: OR, 0.62; 95% CI, 0.4-0.95 for mild myopia; OR, 0.41; 95% CI, 0.21-0.81 for moderate to high myopia; early AMD: OR, 0.63; 95% CI, 0.4-0.99 for mild myopia; OR, 0.36; 95% CI, 0.16-0.77 for moderate to high myopia group). There was no association between refractive status and the likelihood of late AMD (P = 0.91).

Conclusions: Myopia is associated with lower odds of any and early AMD, but not with late AMD in the South Korean population.
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http://dx.doi.org/10.1097/APO.0000000000000169DOI Listing
November 2016