Publications by authors named "Mae O Gordon"

83 Publications

Assessment of Cumulative Incidence and Severity of Primary Open-Angle Glaucoma Among Participants in the Ocular Hypertension Treatment Study After 20 Years of Follow-up.

JAMA Ophthalmol 2021 Apr 15. Epub 2021 Apr 15.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine in St Louis, St Louis, Missouri.

Importance: Ocular hypertension is an important risk factor for the development of primary open-angle glaucoma (POAG). Data from long-term follow-up can be used to inform the management of patients with ocular hypertension.

Objective: To determine the cumulative incidence and severity of POAG after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study.

Design, Setting, And Participants: Participants in the Ocular Hypertension Treatment Study were followed up from February 1994 to December 2008 in 22 clinics. Data were collected after 20 years of follow-up (from January 2016 to April 2019) or within 2 years of death. Analyses were performed from July 2019 to December 2020.

Interventions: From February 28, 1994, to June 2, 2002 (phase 1), participants were randomized to receive either topical ocular hypotensive medication (medication group) or close observation (observation group). From June 3, 2002, to December 30, 2008 (phase 2), both randomization groups received medication. Beginning in 2009, treatment was no longer determined by study protocol. From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments.

Main Outcomes And Measures: Twenty-year cumulative incidence and severity of POAG in 1 or both eyes after adjustment for exposure time.

Results: A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group. The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively.

Conclusions And Relevance: In this study, only one-fourth of participants in the Ocular Hypertension Treatment Study developed visual field loss in either eye over long-term follow-up. This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension.

Trial Registration: ClinicalTrials.gov Identifier: NCT00000125.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0341DOI Listing
April 2021

Crowdsourced Assessment of Surgical Skill Proficiency in Cataract Surgery.

J Surg Educ 2021 Feb 25. Epub 2021 Feb 25.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, Missouri; Graduate Medical Education, University of Minnesota, Minneapolis, Minnesota; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. Electronic address:

Objective: To test whether crowdsourced lay raters can accurately assess cataract surgical skills.

Design: Two-armed study: independent cross-sectional and longitudinal cohorts.

Setting: Washington University Department of Ophthalmology.

Participants And Methods: Sixteen cataract surgeons with varying experience levels submitted cataract surgery videos to be graded by 5 experts and 300+ crowdworkers masked to surgeon experience. Cross-sectional study: 50 videos from surgeons ranging from first-year resident to attending physician, pooled by years of training. Longitudinal study: 28 videos obtained at regular intervals as residents progressed through 180 cases. Surgical skill was graded using the modified Objective Structured Assessment of Technical Skill (mOSATS). Main outcome measures were overall technical performance, reliability indices, and correlation between expert and crowd mean scores.

Results: Experts demonstrated high interrater reliability and accurately predicted training level, establishing construct validity for the modified OSATS. Crowd scores were correlated with (r = 0.865, p < 0.0001) but consistently higher than expert scores for first, second, and third-year residents (p < 0.0001, paired t-test). Longer surgery duration negatively correlated with training level (r = -0.855, p < 0.0001) and expert score (r = -0.927, p < 0.0001). The longitudinal dataset reproduced cross-sectional study findings for crowd and expert comparisons. A regression equation transforming crowd score plus video length into expert score was derived from the cross-sectional dataset (r = 0.92) and demonstrated excellent predictive modeling when applied to the independent longitudinal dataset (r = 0.80). A group of student raters who had edited the cataract videos also graded them, producing scores that more closely approximated experts than the crowd.

Conclusions: Crowdsourced rankings correlated with expert scores, but were not equivalent; crowd scores overestimated technical competency, especially for novice surgeons. A novel approach of adjusting crowd scores with surgery duration generated a more accurate predictive model for surgical skill. More studies are needed before crowdsourcing can be reliably used for assessing surgical proficiency.
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http://dx.doi.org/10.1016/j.jsurg.2021.02.004DOI Listing
February 2021

Volumetric Versus Empirical Determination of Enucleation Implant Size.

Ophthalmic Plast Reconstr Surg 2020 Nov 4. Epub 2020 Nov 4.

*John F. Hardesty MD, Department of Ophthalmology and Visual Sciences †Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, U.S.A.

Purpose: To compare the use of sizing implants versus intraoperative volume measurements for individualization of enucleation implant size, and to identify preoperative factors affecting the choice of implant.

Methods: In this retrospective observational cohort study, 2 implant sizing methods were compared using clinical records and photographs in 139 patients who underwent enucleation between 2007 and 2016.

Results: There was no difference in mean implant (p = 0.6562) or prosthetic (p = 0.1990) enophthalmos between the 2 methods, or when comparing patients with and without conjunctival-Tenons fibrosis. The incidence and severity of superior sulcus deformity was similar between the methods (p = 0.6394). Preoperative phthisis (p < 0.0001) and intraoperative conjunctival-Tenons fibrosis (p = 0.0010) were more common in the sizing implant group. Among all study patients, mean implant size was larger in males (21.3 mm, n = 80) than females (20.7 mm, n = 59) (p = 0.0027). Implants >20 mm were more frequently inserted in patients with a wider Hertel exophthalmometry base (80% of males >95 mm; 77% of females >97 mm). Approximately 21.0% of patients demonstrated ≥8 mm of implant enophthalmos, suggesting an undersized implant. The authors estimate that 11% of patients could have received a sphere larger than 22 mm.

Conclusions: Individualization of enucleation implant size can reduce the incidence of anophthalmic socket syndrome. The empirical use of sizing implants provided similar results as intraoperative volumetric measurements, when evaluated by postoperative superior sulcus depth and prosthetic or implant enophthalmos. Preoperative exophthalmometry may facilitate selection of implant size. Preexisting conjunctival-Tenon fascial fibrosis often did not limit implant size and was not associated with a higher prevalence of wound breakdown or implant exposure.
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http://dx.doi.org/10.1097/IOP.0000000000001884DOI Listing
November 2020

Anophthalmic Ptosis and the Effects of Enucleation on Upper Eyelid Function.

Ophthalmic Plast Reconstr Surg 2020 Aug 24. Epub 2020 Aug 24.

Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, U.S.A.

Purpose: To describe the incidence of anophthalmic ptosis, identify clinical factors associated with its development, and evaluate the effects of enucleation on eyelid mechanics.

Methods: In this observational cohort study, measurements and photographs were reviewed in 139 patients who underwent enucleation between 2007 and 2016. Patient demographics, pre- and postoperative eyelid measurements, and exophthalmometry were used to assess the incidence of ptosis and effects of surgery on eyelid function.

Results: Preoperative ptosis was common and more often present in patients with enophthalmos (p = 0.0305) or reactive blepharospasm (p < 0.0001). The incidence of new-onset ptosis and improvement of preexisting ptosis following enucleation were similar (40%). Surgical repair was performed in 7% of patients with ptosis. Contralateral levator function declined with age and was positively correlated with exophthalmometry (p < 0.0001). Anophthalmic levator function was greater with increased anterior projection of the implant (p < 0.0001) and prosthesis (p < 0.0001). Patients with larger implants had improved levator function, with (p = 0.0065) and without (p = 0.0007) the prosthesis. Superior sulcus deepening was associated with decreased levator activity, but not margin-reflex distance.

Conclusions: Preoperative ptosis was common, and often related to reactive blepharospasm or enophthalmos. Levator function declined with age, and correlated to greater anterior projection of the implant and prosthesis following enucleation. The surgeon can counsel patients regarding the similar likelihood (40%) of preoperative ptosis improving and new ptosis developing after enucleation. The primary factor the surgeon can modify to improve postoperative eyelid function is to maximize implant size, which is associated with greater levator activity.
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http://dx.doi.org/10.1097/IOP.0000000000001823DOI Listing
August 2020

Factors Associated with Adherence to Screening Guidelines for Diabetic Retinopathy Among Low-Income Metropolitan Patients.

Mo Med 2020 May-Jun;117(3):258-264

John F. Hardesty Department of Ophthalmology and Visual Sciences, at Washington University School of Medicine, St. Louis, Missouri.

In this retrospective analysis of patients with diabetes in an academic primary care clinic in St. Louis, attendance at ophthalmic screening appointments was recorded over a two-year observation window. Factors associated with adherence were analyzed by multivariable regression. Among 974 total patients included, only 330 (33.9%) were adherent within a two-year period. Multivariate analyses identified older age, female gender, primary language other than English, and attendance at ancillary diabetes clinic visits as factors associated with improved diabetic retinopathy screening adherence. Factors not associated with adherence included race and insurance status.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302017PMC
March 2021

Evaluation of a Primary Open-Angle Glaucoma Prediction Model Using Long-term Intraocular Pressure Variability Data: A Secondary Analysis of 2 Randomized Clinical Trials.

JAMA Ophthalmol 2020 07;138(7):780-788

Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.

Importance: The contribution of long-term intraocular pressure (IOP) variability to the development of primary open-angle glaucoma is still controversial.

Objective: To assess whether long-term IOP variability data improve a prediction model for the development of primary open-angle glaucoma (POAG) in individuals with untreated ocular hypertension.

Design, Setting, And Participants: This post hoc secondary analysis of 2 randomized clinical trials included data from 709 of 819 participants in the observation group of the Ocular Hypertension Treatment Study (OHTS) followed up from February 28, 1994, to June 1, 2002, and 397 of 500 participants in the placebo group of the European Glaucoma Prevention Study (EGPS) followed up from January 1, 1997, to September 30, 2003. Data analyses were completed between January 1, 2019, and March 15, 2020.

Exposures: The original prediction model for the development of POAG included the following baseline factors: age, IOP, central corneal thickness, vertical cup-disc ratio, and pattern SD. This analysis tested whether substitution of baseline IOP with mean follow-up IOP, SD of IOP, maximum IOP, range of IOP, or coefficient of variation IOP would improve predictive accuracy.

Main Outcomes And Measures: The C statistic was used to compare the predictive accuracy of multivariable landmark Cox proportional hazards regression models for the development of POAG.

Results: Data from the OHTS consisted of 97 POAG end points from 709 of 819 participants (416 [58.7%] women; 177 [25.0%] African American and 490 [69.1%] white; mean [SD] age, 55.7 [9.59] years; median [range] follow-up, 6.9 [0.96-8.15] years). Data from the EGPS consisted of 44 POAG end points from 397 of 500 participants in the placebo group (201 [50.1%] women; 397 [100%] white; mean [SD] age, 57.8 [9.76] years; median [range] follow-up, 4.9 [1.45-5.76] years). The C statistic for the original prediction model was 0.741. When a measure of follow-up IOP was substituted for baseline IOP in this prediction model, the C statistics were as follows: mean follow-up IOP, 0.784; maximum IOP, 0.781; SD of IOP, 0.745; range of IOP, 0.741; and coefficient of variation IOP, 0.729. The C statistics in the EGPS were similarly ordered. No measure of IOP variability, when added to the prediction model that included mean follow-up IOP, age, central corneal thickness, vertical cup-disc ratio, and pattern SD, increased the C statistic by more than 0.007 in either cohort.

Conclusions And Relevance: Evidence from the OHTS and the EGPS suggests that long-term variability does not add substantial explanatory power to the prediction model as to which individuals with untreated ocular hypertension will develop POAG.
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http://dx.doi.org/10.1001/jamaophthalmol.2020.1902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273317PMC
July 2020

Densitometric Profiles of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study.

Am J Ophthalmol 2020 09 23;217:10-19. Epub 2020 Apr 23.

Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA. Electronic address:

Purpose: The origin of blood in glaucoma-related disc hemorrhages (DH) remains unknown. A prior clinic-based study of primary open-angle glaucoma (POAG)-related DH showed that they had grayscale pixel intensities more similar to blood from retinal macroaneurysms and adjacent retinal arterioles than to blood from retinal vein occlusions or adjacent retinal venules, suggesting an arterial source. Here we assessed the densitometric profile of DH from fundus photographs in the Ocular Hypertension Treatment Study (OHTS).

Design: Retrospective cross-sectional study of prospectively collected images.

Methods: Stereo disc photographs of 161 DH events from 83 OHTS participants (mean age [standard deviation (SD)]: 65.6 [9.2] years; 46.6% female; 13.0% black race) were imported into ImageJ to measure densitometry differences (adjacent arterioles minus DH [ΔA] or venules minus DH [ΔV]). Their size as percentage of disc area, ratio of length to midpoint width, and location relative to the disc margin were also analyzed. We performed t tests to compare ΔA and ΔV, analysis of variance to compare ΔA and ΔV across DH recurrent events, and multivariable linear regression to identify determinants of ΔA and ΔV.

Results: Mean (SD) ΔA and ΔV were -2.2 (8.7) and -11.4 (9.7) pixel intensity units, respectively (P < .001). ΔA and ΔV each did not differ significantly across recurrence of DH (P ≥ .92) or between DH events with and without POAG (P ≥ .26).

Conclusions: OHTS DH had densitometric measurements more similar in magnitude to adjacent arterioles than venules, supporting an arterial origin for DH. Vascular dysregulation may contribute to disc hemorrhage formation in ocular hypertension.
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http://dx.doi.org/10.1016/j.ajo.2020.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011293PMC
September 2020

Central Corneal Thickness in the Ocular Hypertension Treatment Study (OHTS).

Ophthalmology 2020 04;127(4S):S72-S81

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.

Objective: Central corneal thickness influences intraocular pressure (IOP) measurement. We examined the central corneal thickness of subjects in the Ocular Hypertension Treatment Study (OHTS) and determined if central corneal thickness is related to race.

Design: Cross-sectional study.

Participants: One thousand three hundred one OHTS subjects with central corneal thickness measurements.

Intervention: Central corneal thickness was determined with ultrasonic pachymeters of the same make and model at all clinical sites of the OHTS.

Main Outcome Measures: Correlation of mean central corneal thickness with race, baseline IOP, refraction, age, gender, systemic hypertension, and diabetes.

Results: Mean central corneal thickness was 573.0 ± 39.0 μm. Twenty-four percent of the OHTS subjects had central corneal thickness > 600 μm. Mean central corneal thickness for African American subjects (555.7 ± 40.0 μm; n = 318) was 23 μm thinner than for white subjects (579.0 ± 37.0 μm; P < 0.0001). Other factors associated with greater mean central corneal thickness were younger age, female gender, and diabetes.

Conclusions: OHTS subjects have thicker corneas than the general population. African American subjects have thinner corneas than white subjects in the study. The effect of central corneal thickness may influence the accuracy of applanation tonometry in the diagnosis, screening, and management of patients with glaucoma and ocular hypertension.
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http://dx.doi.org/10.1016/j.ophtha.2020.01.028DOI Listing
April 2020

Accuracy of Kalman Filtering in Forecasting Visual Field and Intraocular Pressure Trajectory in Patients With Ocular Hypertension.

JAMA Ophthalmol 2019 Nov 14. Epub 2019 Nov 14.

Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor.

Importance: Techniques that properly identify patients in whom ocular hypertension (OHTN) is likely to progress to open-angle glaucoma can assist clinicians with deciding on the frequency of monitoring and the potential benefit of early treatment.

Objective: To test whether Kalman filtering (KF), a machine learning technique, can accurately forecast mean deviation (MD), pattern standard deviation, and intraocular pressure values 5 years into the future for patients with OHTN.

Design, Setting, And Participants: This cohort study was a secondary analysis of data from patients with OHTN from the Ocular Hypertension Treatment Study, performed between February 1994 and March 2009. Patients underwent tonometry and perimetry every 6 months for up to 15 years. A KF (KF-OHTN) model was trained, validated, and tested to assess how well it could forecast MD, pattern standard deviation, and intraocular pressure at up to 5 years, and the forecasts were compared with results from the actual trial. Kalman filtering for OHTN was compared with a previously developed KF for patients with high-tension glaucoma (KF-HTG) and 3 traditional forecasting algorithms. Statistical analysis for the present study was performed between May 2018 and May 2019.

Main Outcomes And Measures: Prediction error and root-mean-square error at 12, 24, 36, 48, and 60 months for MD, pattern standard deviation, and intraocular pressure.

Results: Among 1407 eligible patients (2806 eyes), 809 (57.5%) were female and the mean (SD) age at baseline was 57.5 (9.6) years. For 2124 eyes with sufficient measurements, KF-OHTN forecast MD values 60 months into the future within 0.5 dB of the actual value for 696 eyes (32.8%), 1.0 dB for 1295 eyes (61.0%), and 2.5 dB for 1980 eyes (93.2%). Among the 5 forecasting algorithms tested, KF-OHTN achieved the lowest root-mean-square error (1.72 vs 1.85-4.28) for MD values 60 months into the future. For the subset of eyes that progressed to open-angle glaucoma, KF-OHTN and KF-HTG forecast MD values 60 months into the future within 1 dB of the actual value for 30 eyes (68.2%; 95% CI, 54.4%-82.0%) and achieved the lowest root-mean-square error among all models.

Conclusions And Relevance: These findings suggest that machine learning algorithms such as KF can accurately forecast MD, pattern standard deviation, and intraocular pressure 5 years into the future for many patients with OHTN. These algorithms may aid clinicians in managing OHTN in their patients.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.4190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865321PMC
November 2019

Association of Retinopathy and Insulin Resistance: NHANES 2005-2008.

Curr Eye Res 2020 02 28;45(2):173-176. Epub 2019 Aug 28.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO, USA.

In animal models, insulin resistance without severe hyperglycemia is associated with retinopathy; however, corroborating data in humans are lacking. This study aims to investigate the prevalence of retinopathy in a population without diabetes and evaluate the association of insulin resistance and retinopathy within this group. The study population included 1914 adults age ≥40 without diabetes who were assigned to the morning, fasted group in the National Health and Nutrition Examination Survey 2005-2008, conducted by the Centers for Disease Control. Retinopathy was determined using fundus photos independently graded by a reading center and insulin resistance was determined using the homeostatic model of insulin resistance. Prevalence of retinopathy in those without diabetes was survey design adjusted 9.4% (174/1914). In multivariable analyses, retinopathy was associated with insulin resistance (HOMA-IR OR: 1.09, 95% CI: 1.03, 1.16; = .0030), male gender (OR: 1.39, 95% CI: 1.04, 1.85; = .0267), and age (OR: 1.03, 95% CI: 1.01, 1.05; = .0203). Insulin resistance in the absence of overt hyperglycemia could be an early driver of retinopathy.
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http://dx.doi.org/10.1080/02713683.2019.1659977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980426PMC
February 2020

Safety and tolerability of a one-time, in-office administration of 5% povidone-iodine in the treatment of adenoviral conjunctivitis: The Reducing Adenoviral Patient Infected Days (RAPID) study.

Ocul Surf 2019 10 8;17(4):828-832. Epub 2019 Aug 8.

Washington University in St. Louis, MO, USA.

Purpose: To report safety and tolerability of a one-time administration of ophthalmic 5% povidone-iodine (5% PVP-I) in a double-masked randomized trial for the treatment of adenoviral conjunctivitis (Ad-Cs).

Methods: Of 212 participants screened, 56 eligible participants with red eye symptoms ≤4 days and a positive adenoviral rapid immunoassay were randomized to a one-time administration of ophthalmic 5% PVP-I or preservative free artificial tears (AT). Safety was assessed by corneal fluorescein staining (baseline, immediate post-administration and Day 1) and visual acuity (VA) (baseline and Day 1). Tolerability was assessed using participant-rated overall ocular discomfort (baseline, immediately post-administration and on Day 1.

Results: In the 5% PVP-I group, corneal staining increased immediately post-administration but returned to baseline levels by Day 1. There was no change in VA between baseline and Day 1 in either 5% PVP-I or AT groups (p = 0.87). In the 5% PVP-I group, there was no change in participant-rated overall discomfort immediately post-administration (p = 0.78) or on day 1 (p = 0.10) compared to baseline. In the AT group, participant-rated overall discomfort was lower immediately post-administration but returned to baseline levels by Day 1. One adverse event was reported in the 5% PVP-I group on Day 1-2 that was classified as not related to treatment.

Conclusion: These results suggest ophthalmic 5% PVP-I used as a one-time treatment is safe and well tolerated by patients with Ad-Cs.
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http://dx.doi.org/10.1016/j.jtos.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874762PMC
October 2019

Assessment of the Impact of an Endpoint Committee in the Ocular Hypertension Treatment Study.

Am J Ophthalmol 2019 03 22;199:193-199. Epub 2018 Nov 22.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, Missouri, USA.

Purpose: To assess the impact of a masked Endpoint Committee on estimates of the incidence of primary open-angle glaucoma (POAG) treatment efficacy and statistical power of the Ocular Hypertension Treatment Study-Phase 1, 1994-2002 (OHTS-1).

Design: Retrospective interrater reliability analysis of endpoint attribution by the Endpoint Committee.

Methods: After study closeout, we recalculated estimates of endpoint incidence, treatment efficacy, and statistical power using all-cause endpoints and POAG endpoints. To avoid bias, only the first endpoint per participant is included in this report.

Results: The Endpoint Committee reviewed 267 first endpoints from 1636 participants. The Endpoint Committee attributed 58% (155 of 267) of the endpoints to POAG. The incidence of all-cause endpoints vs POAG endpoints was 19.5% and 13.2%, respectively, in the observation group and 13.1% and 5.8%, respectively, in the medication group. Treatment effect for all-cause endpoints was a 33% reduction in risk (relative risk = 0.67, 95% confidence interval [CI] of 0.54-0.84) and a 56% reduction in risk for POAG endpoints (relative risk = 0.44, 95% CI of 0.31-0.61). Post hoc statistical power for detecting treatment effect was 0.94 for all-cause endpoints and 0.99 for POAG endpoints.

Conclusion: Endpoint Committee adjudication of endpoints improved POAG incidence estimates, increased statistical power, and increased calculated treatment effect by 23%. An Endpoint Committee should be considered in therapeutic trials when common ocular and systemic comorbidities, other than the target condition, could compromise study results.
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http://dx.doi.org/10.1016/j.ajo.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382552PMC
March 2019

Identifying Incidence of and Risk Factors for Fluoroscopy-Guided Lumbar Puncture and Subsequent Persistent Low-Pressure Syndrome in Patients With Idiopathic Intracranial Hypertension.

J Neuroophthalmol 2019 06;39(2):161-164

Department of Ophthalmology and Visual Sciences (PL, JBH, MOG, GPVS), Washington University School of Medicine, St. Louis, Missouri; Mallinckrodt Institute of Radiology (MG), Washington University School of Medicine, St. Louis, Missouri; and Department of Neurology (MG, GPVS), Washington University School of Medicine, St. Louis, Missouri.

Background: To explore the incidence of and potential risk factors for developing persistent low-pressure syndrome after lumbar puncture (LP) in patients with idiopathic intracranial hypertension (IIH), as measured by use of blood patches.

Methods: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and LP, comparing them to patients with multiple sclerosis (MS) as controls who also received diagnostic LPs. Demographic, clinical, and radiological data were collected for each patient. The main outcome measure was the rate of post-LP blood patches in IIH patients compared with MS patients. Secondary outcome measures were the likelihood of undergoing an epidural blood patch related to age, body mass index, volume removed, opening pressure, the difference between opening and closing pressure, and the level of puncture within the IIH cohort.

Results: One hundred four IIH patients and 149 MS patients were included in the study. Among IIH patients, 12/104 (11.5%) underwent an epidural blood patch after LP as compared to 8/149 (5.4%) of the MS control patients (P = 0.086). Within the IIH population, none of the clinical or LP parameters were significantly correlated with increased risk of needing a blood patch.

Conclusions: The incidence of low-pressure syndrome, as measured by blood patches, is similar in IIH patients and MS controls. This suggests that having elevated intracranial pressure before an LP is not protective against developing postpuncture low-pressure syndrome, contrary to common assumptions.
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http://dx.doi.org/10.1097/WNO.0000000000000719DOI Listing
June 2019

Reply.

Am J Ophthalmol 2018 08 31;192:249. Epub 2018 May 31.

St. Louis, Missouri.

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http://dx.doi.org/10.1016/j.ajo.2018.04.019DOI Listing
August 2018

What We Have Learned From the Ocular Hypertension Treatment Study.

Am J Ophthalmol 2018 05 1;189:xxiv-xxvii. Epub 2018 Mar 1.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri. Electronic address:

Purpose: To identify results from the Ocular Hypertension Study that can aid patients and clinicians to make evidence-based decisions about the management of ocular hypertension.

Design: Perspective.

Results: At 60 months, the cumulative frequency of developing primary open-angle glaucoma (POAG) was 4.4% in the medication group and 9.5% in the observation group (hazard ratio for medication, 0.40; 95% confidence interval [CI], 0.27-0.59; P < .0001). At 13 years the cumulative proportion of participants who developed POAG was 0.22 (95% CI 0.19-0.25) in the original observation group and 0.16 (95% CI 0.13-0.19) in the original medication group (complementary log-log xP = .009). A 5-factor model (older age, higher IOP, thinner central corneal thickness, larger cup-to-disc ratio, and higher visual field pattern standard deviation) separated participants at high and low risk of developing POAG.

Conclusions: Clinicians and patients can make evidence-based decisions about the management of ocular hypertension using the risk model and considering patient age, medical status, life expectancy, and personal preference.
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http://dx.doi.org/10.1016/j.ajo.2018.02.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915899PMC
May 2018

Estimating correlation between multivariate longitudinal data in the presence of heterogeneity.

BMC Med Res Methodol 2017 Aug 17;17(1):124. Epub 2017 Aug 17.

Division of Biostatistics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO, 63110, USA.

Background: Estimating correlation coefficients among outcomes is one of the most important analytical tasks in epidemiological and clinical research. Availability of multivariate longitudinal data presents a unique opportunity to assess joint evolution of outcomes over time. Bivariate linear mixed model (BLMM) provides a versatile tool with regard to assessing correlation. However, BLMMs often assume that all individuals are drawn from a single homogenous population where the individual trajectories are distributed smoothly around population average.

Methods: Using longitudinal mean deviation (MD) and visual acuity (VA) from the Ocular Hypertension Treatment Study (OHTS), we demonstrated strategies to better understand the correlation between multivariate longitudinal data in the presence of potential heterogeneity. Conditional correlation (i.e., marginal correlation given random effects) was calculated to describe how the association between longitudinal outcomes evolved over time within specific subpopulation. The impact of heterogeneity on correlation was also assessed by simulated data.

Results: There was a significant positive correlation in both random intercepts (ρ = 0.278, 95% CI: 0.121-0.420) and random slopes (ρ = 0.579, 95% CI: 0.349-0.810) between longitudinal MD and VA, and the strength of correlation constantly increased over time. However, conditional correlation and simulation studies revealed that the correlation was induced primarily by participants with rapid deteriorating MD who only accounted for a small fraction of total samples.

Conclusion: Conditional correlation given random effects provides a robust estimate to describe the correlation between multivariate longitudinal data in the presence of unobserved heterogeneity (NCT00000125).
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http://dx.doi.org/10.1186/s12874-017-0398-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561646PMC
August 2017

Neuroimaging Features of Idiopathic Intracranial Hypertension Persist After Resolution of Papilloedema.

Neuroophthalmology 2016 Aug 27;40(4):165-170. Epub 2016 May 27.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine , St. Louis, Missouri, USA.

Papilloedema is a key clinical finding in the diagnosis of idiopathic intracranial hypertension (IIH). However, newly proposed criteria allow diagnosis without papilloedema only if certain neuroimaging features are present. It is currently unclear if these findings persist upon resolution of papilloedema and IIH. A retrospective chart review identified three groups of patients (six per group) who had received orbital imaging within 4 weeks of fundoscopic examination: (1) IIH patients without active papilloedema, (2) IIH patients with active papilloedema, and (3) patients with no history of IIH or papilloedema. All magnetic resonance imaging (MRI) scans were graded by a neuroradiologist who was blinded to clinical status. Neuroimaging features were compared by using the Kruskal-Wallis one-way analysis of variance. Measurements of sellar and optic nerve configuration showed a statistical trend with papilloedema status. For the control group versus the active papilloedema group, the values were 0.0597 and 0.0621, respectively. For the control group versus the resolved papilloedema group, the values were 0.0485 and 0.0512, respectively. However, globe and sellar values for the resolved papilloedema group versus the active papilloedema group were 1.000 and 0.6023, respectively, and not significant. Sellar and globe configuration suggest that a statistical trend for persistence after papilloedema has resolved and intracranial pressure (ICP) has normalised. Careful clinical correlation and fundus examination are essential because some of these neuroimaging features can be seen in normal patients and those with resolved IIH, and their presence on MRI may not necessarily indicate active disease or elevated ICP.
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http://dx.doi.org/10.1080/01658107.2016.1179767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123153PMC
August 2016

Glaucoma Risk Alleles in the Ocular Hypertension Treatment Study.

Ophthalmology 2016 12 1;123(12):2527-2536. Epub 2016 Oct 1.

Department Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa. Electronic address:

Purpose: Primary open-angle glaucoma (POAG) is a major cause of blindness and visual disability. Several genetic risk factors for POAG and optic nerve features have been identified. We measured the relative risk for glaucoma that these factors contribute to participants in the Ocular Hypertension Treatment Study (OHTS).

Design: Comparative series.

Participants: One thousand fifty-seven of 1636 participants (65%) of the OHTS were enrolled in this genetics ancillary study.

Methods: Samples of DNA were available from 1057 OHTS participants. Of these, 209 developed POAG (cases) and 848 did not develop glaucoma (controls) between 1994 and 2009. The frequencies of 13 risk alleles previously associated with POAG or with optic disc features in other cohorts were compared between POAG cases and controls in the OHTS cohort using analyses of variance. The 2 largest subgroups, non-Hispanic whites (n = 752; 70.7%) and blacks (n = 249, 23.7%), also were analyzed separately. The probability of glaucoma developing over the course of the OHTS was compared between participants stratified for transmembrane and coiled-coil domains 1 (TMCO1) risk alleles using Kaplan-Meier and Cox proportional hazards analyses.

Main Outcome Measures: Association of POAG with known genetic factors.

Results: No association was detected between the known POAG risk alleles when the OHTS cohort was examined as a whole. However, in the subgroup of non-Hispanic whites, allele frequencies at the TMCO1 locus were statistically different between cases and controls (P = 0.00028). By 13 years, non-Hispanic white participants with TMCO1 risk alleles had a 12% higher cumulative frequency of glaucoma developing than participants with no TMCO1 risk alleles. Moreover, the Cox proportional hazard analysis demonstrated that TMCO1 alleles increased relative risk comparable with that of some previously analyzed clinical measures (i.e., intraocular pressure).

Conclusions: The size of the OHTS cohort and its composition of 2 large racial subgroups may limit its power to detect some glaucoma risk factors. However, TMCO1 genotype was found to increase the risk of glaucoma developing among non-Hispanic whites, the largest racial subgroup in the OHTS cohort, at a magnitude similar to clinical predictors of disease that long have been associated with glaucoma.
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http://dx.doi.org/10.1016/j.ophtha.2016.08.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121091PMC
December 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

Physician-Industry Interactions and Anti-Vascular Endothelial Growth Factor Use Among US Ophthalmologists.

JAMA Ophthalmol 2016 08;134(8):897-903

Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, Missouri.

Importance: The publication of the US Physician Payments Sunshine Act provides insight into the financial relationship between physicians and the pharmaceutical industry. This added transparency creates new opportunities of using objective data to better understand prior research that implicates pharmaceutical promotions as an important factor in a physician's decision-making process.

Objective: To assess the association between reported industry payments and physician-prescribing habits by comparing the use of anti-vascular endothelial growth factor (VEGF) intravitreal injections by US ophthalmologists to the industry payments these same physicians received.

Design, Setting, Participants: This study reviews data from the Centers for Medicare & Medicaid Services (CMS) 2013 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File and the CMS-sponsored August through December 2013 Open Payments program (Physician Payments Sunshine Act). Ophthalmologists who prescribe anti-VEGF injections for all indications were analyzed.

Main Outcomes And Measures: Association between industry payments reportedly received and the number and type of anti-VEGF injections administered.

Results: A total of 3011 US ophthalmologists were reimbursed by CMS for 2.2 million anti-VEGF injections in 2013. Of these physicians, 38.0% reportedly received $1.3 million in industry payments for ranibizumab and aflibercept. Analysis revealed positive associations between increasing numbers of reported industry payments and total injection use (r = 0.24; 95% CI, 0.22-0.26; P < .001), aflibercept and ranibizumab injection use (r = 0.32; 95% CI, 0.29-0.34; P < .001), and percentage of injections per physician that were aflibercept or ranibizumab (r = 0.27; 95% CI, 0.25-0.29; P < .001). A smaller association was noted between greater number of industry payments and bevacizumab injection use (r = 0.07; 95% CI, 0.04-0.09; P < .001). Similar associations were found between the total dollars of reported industry payments received to injection use. Subgroup analysis further revealed that physicians receiving $1 to $25 in reported industry benefits were more likely than those not receiving industry payments to perform a greater percentage of their injections with aflibercept and ranibizumab.

Conclusions And Relevance: Among ophthalmologists who prescribe anti-VEGF medications, there is a positive association between reported pharmaceutical payments and increased use of aflibercept and ranibizumab injections. As is inherent to the design of correlation studies, this analysis cannot determine whether the payments reported caused the increased use, are a result of the increased use, or are merely associated with some other factor that causes the increased use.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.1678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231579PMC
August 2016

Predicting Clinical Binary Outcome Using Multivariate Longitudinal Data: Application to Patients with Newly Diagnosed Primary Open-Angle Glaucoma.

J Biom Biostat 2015 Oct 26;6(4). Epub 2015 Oct 26.

Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA; Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.

Primary open angle glaucoma (POAG) is a chronic, progressive, irreversible, and potentially blinding optic neuropathy. The risk of blindness due to progressive visual field (VF) loss varies substantially from patient to patient. Early identification of those patients destined to rapid progressive visual loss is crucial to prevent further damage. In this article, a latent class growth model (LCGM) was developed to predict the binary outcome of VF progression using longitudinal mean deviation (MD) and pattern standard deviation (PSD). Specifically, the trajectories of MD and PSD were summarized by a functional principal component (FPC) analysis, and the estimated FPC scores were used to identify subgroups (latent classes) of individuals with distinct patterns of MD and PSD trajectories. Probability of VF progression for an individual was then estimated as weighted average across latent classes, weighted by posterior probability of class membership given baseline covariates and longitudinal MD/PSD series. The model was applied to the participants with newly diagnosed POAG from the Ocular Hypertension Treatment Study (OHTS), and the OHTS data was best fit by a model with 4 latent classes. Using the resultant optimal LCGM, the OHTS participants with and without VF progression could be accurately differentiated by incorporating longitudinal MD and PSD.
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http://dx.doi.org/10.4172/2155-6180.1000254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760987PMC
October 2015

Stereo Photo Measured ONH Shape Predicts Development of POAG in Subjects With Ocular Hypertension.

Invest Ophthalmol Vis Sci 2015 Jul;56(8):4470-9

Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, United States 2Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States 4Department of Ophthalmology and Visual Sciences, University of Iow.

Purpose: To identify objective, quantitative optic nerve head (ONH) structural features and model the contributions of glaucoma.

Methods: Baseline stereoscopic optic disc images of 1635 glaucoma-free participants at risk for developing primary open-angle glaucoma (POAG) were collected as part of the Ocular Hypertension Treatment Study. A stereo correspondence algorithm designed for fundus images was applied to extract the three-dimensional (3D) information about the ONH. Principal component analysis was used to identify ONH 3D structural features and the contributions of demographic features, clinical variables, and disease were modeled using linear regression and linear component analysis. The computationally identified features were evaluated based on associations with glaucoma and ability to predict which participants would develop POAG.

Results: The computationally identified features were significantly associated with future POAG, POAG-related demographics (age, ethnicity), and clinical measurements (horizontal and vertical cup-to-disc ratio, central corneal thickness, and refraction). Models predicting future POAG development using the OHTS baseline data and STEP features achieved an AUC of 0.722 in cross-validation testing. This was a significant improvement over using only demographics (age, sex, and ethnicity), which had an AUC of 0.599.

Conclusions: Methods for identifying objective, quantitative measurements of 3D ONH structure were developed using a large dataset. The identified features were significantly associated with POAG and POAG-related variables. Further, these features increased predictive model accuracy in predicting future POAG. The results indicate that the computationally identified features might be useful in POAG early screening programs or as endophenotypes to investigate POAG genetics.
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http://dx.doi.org/10.1167/iovs.14-16142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509059PMC
July 2015

Silent cerebral infarction, income, and grade retention among students with sickle cell anemia.

Am J Hematol 2014 Oct 4;89(10):E188-92. Epub 2014 Aug 4.

Program in Occupational Therapy and Department of Pediatrics, Hematology/Oncology, Washington University School of Medicine, St. Louis, Missouri.

Children with sickle cell anemia have a higher-than-expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross-sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5-15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia.
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http://dx.doi.org/10.1002/ajh.23805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4261188PMC
October 2014

Correlation between papilledema grade and diffusion-weighted magnetic resonance imaging in idiopathic intracranial hypertension.

J Neuroophthalmol 2014 Dec;34(4):331-5

Department of Ophthalmology and Visual Sciences (DMS, JBH, MOG, GPVS), Washington University, Saint Louis, Missouri; Department of Ophthalmology and Visual Sciences (LVP), Washington University, Saint Louis, Missouri; Department of Radiology (RV, AS), Mallinckrodt Institute of Radiology, Washington University School, Saint Louis, Missouri; and Department of Neurology (GPVS), Washington University, Saint Louis, Missouri.

Background: To explore the relationship between diffusion-weighted magnetic resonance imaging (DWI) hyperintensity of the optic nerve head (ONH) and papilledema grade in patients with idiopathic intracranial hypertension (IIH).

Methods: A retrospective chart review was conducted of patients with definitively diagnosed IIH by clinical examination and visual field (VF) analysis who underwent orbital magnetic resonance imaging (MRI) within 4 weeks of diagnosis. A neuroradiologist masked to the diagnosis assessed the results of DWI for each eye independently and graded the signal intensity of the ONH into none, mild, and prominent categories. DWI grading was compared with papilledema grade and visual field mean deviation (VFMD) by Spearman rank correlation analysis and t-tests.

Results: Forty-two patients were included in the study. A statistically significant difference (P = 0.0195) was found between papilledema grade and patients with prominent DWI findings (n = 16; mean papilledema grade 3.75 ± 1.25) vs mild or no ONH hyperintensity (n = 26; mean papilledema grade 2.79 ± 1.24) at the time of initial diagnosis. DWI hyperintensity of the ONH at diagnosis was also found to be significantly correlated with the degree of papilledema at follow-up (ρ = 0.39, P = 0.0183) but not with VFMD.

Conclusions: We found a significant correlation between the severity of papilledema and ONH hyperintensity on DWI in patients with IIH but not with VF loss or other visual parameters. These findings may offer insight into the pathophysiology of papilledema in IIH and provide a surrogate marker for the presence and severity of papilledema.
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http://dx.doi.org/10.1097/WNO.0000000000000150DOI Listing
December 2014

Reproducibility of detecting silent cerebral infarcts in pediatric sickle cell anemia.

J Child Neurol 2014 Dec 5;29(12):1685-91. Epub 2013 Dec 5.

Vanderbilt Meharry Center of Excellence in Sickle Cell Disease, Division of Pediatric Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

Detecting silent cerebral infarcts on magnetic resonance images (MRIs) in children with sickle cell anemia is challenging, yet reproducibility of readings has not been examined in this population. We evaluated consensus rating, inter-, and intra-grader agreement associated with detecting silent cerebral infarct on screening MRI in the Silent Infarct Transfusion Trial. Three neuroradiologists provided consensus decisions for 1073 MRIs. A random sample of 53 scans was reanalyzed in blinded fashion. Agreement between first and second consensus ratings was substantial (κ = 0.70, P < .0001), as was overall intergrader agreement (κ = 0.76, P < .0001). In the test-retest sample, intragrader agreement ranged from κ of 0.57 to 0.76. Consensus decisions were more concordant when MRIs contained more than one larger lesions. Routine use of MRI to screen for silent cerebral infarcts in the research setting is reproducible in sickle cell anemia and agreement among neuroradiologists is sufficient.
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http://dx.doi.org/10.1177/0883073813506491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096057PMC
December 2014

Association between visual parameters and neuroimaging features of idiopathic intracranial hypertension.

J Neurol Sci 2013 Sep 11;332(1-2):80-5. Epub 2013 Jul 11.

School of Medicine, Washington University in St. Louis, MO 63108, United States.

Background/aims: Papilledema refers to optic disc swelling resulting from high intracranial pressure (ICP). The precise mechanism by which papilledema occurs remains uncertain. Although orbital neuroimaging features associated with papilledema are well-described, it is unclear whether these findings correlate with visual function. Idiopathic Intracranial Hypertension (IIH) is a condition in which the intracranial pressure is elevated with no obvious cause, causing papilledema and visual loss. The utility of papilledema and IIH neuroimaging findings as a surrogate marker for visual loss, or a predictor of visual loss, is understudied. This retrospective cross-sectional review aims to correlate parameters of visual function with orbital magnetic resonance imaging (MRI) findings.

Methods: Patients meeting criteria for IIH who had received orbital imaging within 4 weeks of examination were included. Visual parameters of papilledema grade, visual field mean deviation, and visual acuity were correlated with neuroimaging features, including optic nerve thickness, and optic nerve sheath thickness, among others. All MRI scans were reviewed by a neuroradiologist blinded to clinical status. Spearman rank correlations and t-tests were generated with SAS (v9.2).

Results: Thirty five patients were included. No significant relationships were found between the main visual parameters of papilledema grade and visual field mean deviation, and MRI findings.

Conclusions: We found no significant correlation between visual parameters and imaging features of papilledema. This might indicate that MRI features may provide insight into the structural changes that occur in papilledema, but may not be helpful when making clinical management decisions for patients with IIH in particular, and papilledema in general.
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http://dx.doi.org/10.1016/j.jns.2013.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354812PMC
September 2013

The rate of structural change: the confocal scanning laser ophthalmoscopy ancillary study to the ocular hypertension treatment study.

Am J Ophthalmol 2013 Jun 14;155(6):971-82. Epub 2013 Mar 14.

Hamilton Glaucoma Center, Department of Ophthalmology, University of California, San Diego, La Jolla, California 92093-0946, USA.

Purpose: To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change.

Design: Longitudinal, randomized clinical trial.

Methods: Four hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models.

Results: In both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, -0.0131 mm(2)/year and -0.0026 mm(2)/year, respectively). The significantly faster rate of rim area loss in black persons found in the univariate analysis did not remain significant when baseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint.

Conclusions: The rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods.
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http://dx.doi.org/10.1016/j.ajo.2013.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310682PMC
June 2013

Seasonal changes in visual field sensitivity and intraocular pressure in the ocular hypertension treatment study.

Ophthalmology 2013 Apr 26;120(4):724-30. Epub 2013 Jan 26.

Discoveries in Sight Laboratories, Devers Eye Institute, Legacy Research Institute, Legacy Health, Portland, Oregon 97232, USA.

Purpose: Longitudinal testing plays a key role in glaucoma management. Variability between visits hampers the ability to monitor progression. It has previously been shown that average intraocular pressure (IOP) exhibits seasonal fluctuations. This study examines whether visual field sensitivity also exhibits seasonal fluctuations and seeks to determine whether such fluctuations are correlated to seasonal IOP effects.

Design: Comparative case series.

Participants: A total of 33 873 visits by 1636 participants enrolled in the Ocular Hypertension Treatment Study. Participants were split into 6 geographic zones according to the prevailing climate in their location.

Testing: At each visit, standard automated perimetry was conducted on each eye, and IOP was measured.

Main Outcome Measures: Mixed effects regression models were formed to look for sinusoidal periodic effects on the change in perimetric mean deviation since the last visit (ΔMD) and on IOP, both overall and within each zone.

Results: When all the data were included, a significant seasonal effect on ΔMD was found with magnitude 0.06 dB, peaking in February (P < 0.001). Five of the 6 geographic zones exhibited significant seasonal effects on ΔMD, peaking between January and April, with magnitudes ranging from 0.04 dB (P = 0.049) to 0.21 dB (P < 0.001). Zones with greater climactic variation showed larger seasonal effects on ΔMD. All 6 zones exhibited a seasonal effect on IOP, peaking in January or February, with magnitudes ranging from 0.14 to 0.39 mmHg (P ≤ 0.02 in all cases). However, there was no evidence of a significant association between the magnitudes or dates of peaks of the 2 seasonal effects.

Conclusions: The mean deviation was significantly higher in winter than in summer. There is no evidence of an association with seasonal IOP fluctuations. The cause of the seasonal effect on visual field sensitivity is unknown. These findings may help shed light on the glaucomatous disease process and aid efforts to reduce test-retest variability.
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http://dx.doi.org/10.1016/j.ophtha.2012.09.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618610PMC
April 2013

Series length used during trend analysis affects sensitivity to changes in progression rate in the ocular hypertension treatment study.

Invest Ophthalmol Vis Sci 2013 Feb 15;54(2):1252-9. Epub 2013 Feb 15.

Devers Eye Institute, Legacy Health, Portland, OR 97232, USA.

Purpose: Trend analysis techniques to detect glaucomatous progression typically assume a constant rate of change. This study uses data from the Ocular Hypertension Treatment Study to assess whether this assumption decreases sensitivity to changes in progression rate, by including earlier periods of stability.

Methods: Series of visual fields (mean 24 per eye) completed at 6-month intervals from participants randomized initially to observation were split into subseries before and after the initiation of treatment (the "split-point"). The mean deviation rate of change (MDR) was derived using these entire subseries, and using only the window length (W) tests nearest the split-point, for different window lengths of W tests. A generalized estimating equation model was used to detect changes in MDR occurring at the split-point.

Results: Using shortened subseries with W = 7 tests, the MDR slowed by 0.142 dB/y upon initiation of treatment (P < 0.001), and the proportion of eyes showing "rapid deterioration" (MDR <-0.5 dB/y with P < 5%) decreased from 11.8% to 6.5% (P < 0.001). Using the entire sequence, no significant change in MDR was detected (P = 0.796), and there was no change in the proportion of eyes progressing (P = 0.084). Window lengths 6 ≤ W ≤ 9 produced similar benefits.

Conclusions: Event analysis revealed a beneficial treatment effect in this dataset. This effect was not detected by linear trend analysis applied to entire series, but was detected when using shorter subseries of length between six and nine fields. Using linear trend analysis on the entire field sequence may not be optimal for detecting and monitoring progression. Nonlinear analyses may be needed for long series of fields. (ClinicalTrials.gov number, NCT00000125.).
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http://dx.doi.org/10.1167/iovs.12-10218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597197PMC
February 2013

Rate of visual field progression in eyes with optic disc hemorrhages in the ocular hypertension treatment study.

Arch Ophthalmol 2012 Dec;130(12):1541-6

Objective: To compare rates of visual field (VF) change in ocular hypertensive eyes with and without optic dischemorrhage (DH).

Methods: Ocular Hypertension Treatment Study subjects(minimum 10 reliable VF tests, followed up 5 years) were included. Trend analyses of VF sequences over time of DH and non-DH eyes were assessed by regression of mean deviation (MDR) and pointwise linear regression (PLR). The main outcome measures were rates of VF change in DH and non-DH eyes.

Results: Two thousand six hundred seven eyes (1378 participants) were included. The mean (SD) number of VF tests per eye was 23.7 (4.9) spanning a mean (SD) of 12.2 (2.0) years. At least 1 DH was detected in 187 eyes(7.2%), of which 52 eyes had recurrent DH. Mean deviation rate of change was significantly worse in DH compared with non-DH eyes (mean [SD], −0.17 [0.27] vs−0.07 [0.19] dB/y; P<.01). Significant PLR progression occurred more frequently in eyes with DH (odds ratio,3.6; P<.01), which increased when 2 or more DHs were present (odds ratio, 4.2; P=.01). Eyes initially randomized to treatment were less likely to have a DH during follow-up.

Conclusions: Eyes with DH had more rapid VF deterioration when assessed by global (MDR) or local (PLR)trend analysis than eyes without DH. Eyes with recurrent DH had similar rates of global VF change (MDR)when compared with eyes with a single DH but reached criteria for rapid PLR change more often. Intraocular pressure reduction in ocular hypertension reduces the risk of developing a DH. Ocular hypertensive eyes with DH should be monitored closely and may need more aggressive therapy.

Trial Registration: clinicaltrials.gov Identifier: NCT00000125
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http://dx.doi.org/10.1001/jamaophthalmol.2013.1137DOI Listing
December 2012