Steven L. Mansberger

Primary Open-Angle Glaucoma Preferred Practice Pattern® Guidelines

UNLABELLED PRIMARY OPEN-ANGLE GLAUCOMA PREFERRED PRACTICE PATTERN® GUIDELINES Evidence-based update of the Primary Open-Angle Glaucoma Preferred Practice Pattern® (PPP) guidelines, describing the diagnosis and management of patients with primary open-angle glaucoma with an algorithm for patient management and detailed recommendations for evaluation and treatment options.

Psychophysical investigation of ganglion cell loss in early glaucoma.

Purpose:To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to identify optimal perimetric technique(s) for detection of early glaucomatous visual function loss. Methods:Five perimetric tests, short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency doubling technology perimetry (FDT), detection acuity perimetry (DAP), and resolution acuity perimetry (RAP) were compared in their ability to discriminate between normal individuals and patients with early glaucoma or glaucoma suspects. Comparisons were also made by their ability to produce repeatable defects. The tests examined different visual functions that are likely to be mediated by different retinal ganglion cell subpopulations, thereby permitting examination of hypotheses of ganglion cell death in early glaucoma. Results:All visual field tests demonstrated high performance in separating glaucoma patients from normal individuals. SWAP, TMP, FDT, and DAP provided the greatest discrimination between normal individuals and high- and low-risk glaucoma suspects. However, SWAP, TMP, and FDT obtained better consistency across the various analysis approaches (global indices and pointwise) than DAP and RAP. Of all the test types, FDT exhibited the highest proportion of repeatable abnormal test locations, with poor confirmation rates achieved by DAP and RAP. Conclusion:The performance of SWAP, FDT, and TMP suggests that these test types may all be suitable for detection of early loss of visual function in glaucoma. Ganglion cell subpopulations with lower levels of redundancy and/or those with larger cell sizes offer the most parsimonious explanation for earliest ganglion cell losses occurring in glaucoma.

Assessment of the Reliability of Standard Automated Perimetry in Regions of Glaucomatous Damage

PURPOSE Visual field testing uses high-contrast stimuli in areas of severe visual field loss. However, retinal ganglion cells saturate with high-contrast stimuli, suggesting that the probability of detecting perimetric stimuli may not increase indefinitely as contrast increases. Driven by this concept, this study examines the lower limit of perimetric sensitivity for reliable testing by standard automated perimetry. DESIGN Evaluation of a diagnostic test. PARTICIPANTS A total of 34 participants with moderate to severe glaucoma; mean deviation at their last clinic visit averaged -10.90 dB (range, -20.94 to -3.38 dB). A total of 75 of the 136 locations tested had a perimetric sensitivity of ≤ 19 dB. METHODS Frequency-of-seeing curves were constructed at 4 nonadjacent visual field locations by the Method of Constant Stimuli (MOCS), using 35 stimulus presentations at each of 7 contrasts. Locations were chosen a priori and included at least 2 with glaucomatous damage but a sensitivity of ≥ 6 dB. Cumulative Gaussian curves were fit to the data, first assuming a 5% false-negative rate and subsequently allowing the asymptotic maximum response probability to be a free parameter. MAIN OUTCOME MEASURES The strength of the relation (R(2)) between perimetric sensitivity (mean of last 2 clinic visits) and MOCS sensitivity (from the experiment) for all locations with perimetric sensitivity within ± 4 dB of each selected value, at 0.5 dB intervals. RESULTS Bins centered at sensitivities ≥ 19 dB always had R(2) >0.1. All bins centered at sensitivities ≤ 15 dB had R(2) <0.1, an indication that sensitivities are unreliable. No consistent conclusions could be drawn between 15 and 19 dB. At 57 of the 81 locations with perimetric sensitivity <19 dB, including 49 of the 63 locations ≤ 15 dB, the fitted asymptotic maximum response probability was <80%, consistent with the hypothesis of response saturation. At 29 of these locations the asymptotic maximum was <50%, and so contrast sensitivity (50% response rate) is undefined. CONCLUSIONS Clinical visual field testing may be unreliable when visual field locations have sensitivity below approximately 15 to 19 dB because of a reduction in the asymptotic maximum response probability. Researchers and clinicians may have difficulty detecting worsening sensitivity in these visual field locations, and this difficulty may occur commonly in patients with glaucoma with moderate to severe glaucomatous visual field loss.

Determinants of medication adherence to topical glaucoma therapy.

Introduction/PurposeTo determine the associations between medical, demographic, socioeconomic, and ocular factors and adherence to topical glaucoma ocular hypotensive therapy. MethodsOne hundred sixteen patients with ocular hypertension or open-angle glaucoma from 2 tertiary glaucoma services participated in this prospective study. Adherence to ocular hypotensive therapy was measured using an electronic dose monitor (Travatan Dosing Aid, Alcon Laboratories Inc., Fort Worth, TX) and collected data at 3 months after enrollment. We used 3 different definitions of adherence: 1) Definition 1: the proportion of days taking the prescribed number of drops within 3 hours of the prescribed dosing time; 2) Definition 2: the proportion of days taking any drops within 3 hours of the prescribed dosing time; and 3) Definition 3: the proportion of days taking any drops within 6 hours of the prescribed dosing time. Univariate and multivariate models were used to determine the association between the 3 adherence definitions, medical, demographic, socioeconomic, and ocular factors at 3-month follow-up. The main outcome measures for this study were risk factors for poor objective medication adherence. ResultsAdherence, using Definition 1, Definition 2, and Definition 3, was 64%, 75%, and 80%, respectively. Age, total number of other eye diseases, and race were significantly associated with full treatment adherence (Definition 1), with race alone significantly predicting 11% of full treatment adherence. For Definition 2, age, income, level of education, and total number of eye diseases were significantly associated with partial adherence (3 h), again race alone significantly predicted 15% of partial adherence (any drops within 3 h). For Definition 3, race, income, level of education, and total number of other eye diseases significantly predicted partial adherence (any drops within 6 h), both race and income predicted 19% of partial treatment adherence. Significant differences for adherence rates between patients of European descent and those of African descent were found for all 3 definitions with those who were less adherent more likely to be of African descent. ConclusionsElectronic dose monitors provide important information regarding adherence to topical ocular hypotensive medications in glaucoma patients. Electronic dose monitors show low adherence in a significant number of participants. Future studies are needed to determine the reasons for these differences in health behaviors related to glaucoma treatment, which should guide treatment of poor adherence with glaucoma therapy.

Understanding the importance of IOP variables in glaucoma: a systematic review.

Glaucoma is one of the leading causes of visual impairment and blindness. Lowering intraocular pressure (IOP) is the only proven means to slow or halt disease progression among those at higher risk of developing glaucoma and those with early to moderate or more advanced glaucoma. Recent publications have highlighted the potential for increased rates or likelihood of worsening glaucoma among those with larger IOP swings within defined time periods. The purpose of this systematic, comprehensive review and analysis of the literature was to assess the state of knowledge in the area of IOP changes over time and the potential impact of such changes on treatment. Current literature indicates that a random IOP measurement is a poor surrogate for IOP levels throughout the day and across visits. We address several key questions: 1) What is the best way to measure IOP? 2) Should multiple IOP measurements be performed in a day in the office (short-term IOP fluctuation)? 3) Is measurement at night required? 4) Should clinicians begin to assess long-term IOP fluctuation in patients under stable treatment (across days or visits)? and 5) Should therapy choices be influenced by properties of different treatment options relative to short- or long-term IOP fluctuation?

Long-term Comparative Effectiveness of Telemedicine in Providing Diabetic Retinopathy Screening Examinations A Randomized Clinical Trial

IMPORTANCE Minimal information exists regarding the long-term comparative effectiveness of telemedicine to provide diabetic retinopathy screening examinations. OBJECTIVE To compare telemedicine to traditional eye examinations in their ability to provide diabetic retinopathy screening examinations. DESIGN, SETTING, AND PARTICIPANTS From August 1, 2006, through September 31, 2009, 567 participants with diabetes were randomized and followed up to 5 years of follow-up (last date of patient follow-up occurred on August 6, 2012) as part of a multicenter randomized clinical trial with an intent to treat analysis. We assigned participants to telemedicine with a nonmydriatic camera in a primary care medical clinic (n = 296) or traditional surveillance with an eye care professional (n = 271). Two years after enrollment, we offered telemedicine to all participants. MAIN OUTCOMES AND MEASURES Percentage of participants receiving annual diabetic retinopathy screening examinations, percentage of eyes with worsening diabetic retinopathy during the follow-up period using a validated scale from stage 0 (none) to stage 4 (proliferative diabetic retinopathy), and percentage of telemedicine participants who would require referral to an eye care professional for follow-up care using a cutoff of moderate diabetic retinopathy or worse, the presence of macular edema, or an unable-to-determine result for retinopathy or macular edema. RESULTS The telemedicine group was more likely to receive a diabetic retinopathy screening examination when compared with the traditional surveillance group during the 6-month or less (94.6% [280/296] vs 43.9% [119/271]; 95% CI, 46.6%-54.8%; P < .001) and greater than 6-month through 18-month (53.0% [157/296] vs 33.2% [90/271]; 95% CI, 16.5%-23.1%; P < .001) time bins. After we offered telemedicine to both groups, we could not identify a difference between the groups in the percentage of diabetic retinopathy screening examinations. Diabetic retinopathy worsened by 2 stages or more in 35 (8.6%) of 409 participants (95% CI, 5.8%-11.2%) and improved by 2 stages or more in 5 (1.2%) of 409 participants (95% CI, 0.1%-2.3%) during the 4-year period. The percent of telemedicine participants requiring referral ranged from 19.2% (52/271) to 27.9% (58/208). CONCLUSIONS AND RELEVANCE Telemedicine increased the percentage of diabetic retinopathy screening examinations, most participants did not require referral to an eye care professional, and diabetic retinopathy levels were generally stable during the study period. This finding suggests that primary care clinics can use telemedicine to screen for diabetic retinopathy and monitor for disease worsening over a long period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01364129.

Glaucomatous Progression in Series of Stereoscopic Photographs and Heidelberg Retina Tomograph Images

OBJECTIVE To compare optic disc changes using automated analysis of Heidelberg retina tomograph (HRT) images with assessments, by glaucoma specialists, of change in stereoscopic photographs. METHODS Baseline and follow-up stereophotographs and corresponding HRT I series of 91 eyes from 56 patients were selected. The selection criteria were sufficiently long, good-quality HRT series (7 visits in > or =70 months of follow-up) and follow-up photographs contemporaneous with the final HRT image. Topographic change analysis (TCA), statistic image mapping (SIM), and linear regression of rim area (RALR) across time were applied to HRT series. Glaucomatous change determined from stereophotographs by expert observers was used as the reference standard. RESULTS Expert observers identified 33 eyes (36%) as exhibiting glaucomatous change. Altering HRT progression criteria such that 36% of eyes progressed according to each method resulted in concordance between HRT methods and stereophotograph assessment of 54% for TCA, 65% for SIM, and 67% for RALR (Cohen kappa = 0.05, 0.23, and 0.30, respectively). Receiver operating characteristic curves of the HRT analyses revealed poor precision of HRT analyses to predict stereophotograph-assessed change: areas under the curve were 0.61 for TCA, 0.62 for SIM, and 0.66 for RALR. CONCLUSIONS Statistical methods for detecting structural changes in HRT images exhibit only moderate agreement with each other and have poor agreement with expert-assessed change in optic disc stereophotographs.

Primary Angle Closure Preferred Practice Pattern(®) Guidelines.

UNLABELLED PRIMARY ANGLE CLOSURE PREFERRED PRACTICE PATTERN® GUIDELINES Evidence-based update of the Primary Angle Closure Preferred Practice Pattern® (PPP) guidelines, describing the diagnosis and management of patients with primary angle closure with detailed recommendations for evaluation and treatment options.

Predictive value of frequency doubling technology perimetry for detecting glaucoma in a developing country.

Purpose:To determine the feasibility and diagnostic precision of Frequency Doubling Technology (FDT) perimetry as a method to detect glaucoma in rural villages of a developing country. Design:Cross-sectional study. Methods:Testing included FDT perimetry (C-20-5 screening protocol), tonometry, anterior segment biomicroscopy, and dilated ophthalmoscopy in 296 rural, non-English speaking residents of Southern India over 35 years old. Participants repeated the FDT if they had a location with reduced sensitivity or an unreliable result. We defined an abnormal FDT as one location of reduced sensitivity present on both the initial and repeat examination. We determined the diagnostic precision of FDT separately for a glaucomatous optic disc, a cup to disc ratio (C/D) ≥ 0.7, and a C/D ≥ 0.8. Results:Ninety-three percent of subjects were able to complete the test satisfactorily. With repeat FDT testing, 37% of eyes with abnormal FDT results subsequently converted to normal and 67% of eyes with unreliable results subsequently became reliable. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for a glaucomatous optic disc were 7%, 87%, 13%, 76%, and 69%, respectively; for a C/D ≥ 0.7, they were 0%, 87%, 0%, 91%, and 81%, respectively; and for a C/D ≥ 0.8, they were 0%, 87%, 0%, 99%, and 87%, respectively. Conclusion:Clinicians can use FDT perimetry to rapidly screen for glaucoma in rural villages of a developing country. FDT testing had high specificity and negative predictive value, but low sensitivity and positive predictive value. The low sensitivity suggests that FDT has limited applicability as the sole test for glaucoma screening in this population. Repeat testing of FDT results that are unreliable or suspected of being abnormal is beneficial for this screening procedure.

A risk calculator to determine the probability of glaucoma.

The 21 century may be an enlightening time for glaucoma management. Investigators have published the results of The Ocular Hypertensive Treatment Study (OHTS), the Early Manifest Glaucoma Treatment Study, the Advanced Glaucoma Intervention Study, and the Collaborative Interventional Glaucoma Treatment Study. These studies answer important questions: will ocular hypotensive treatment delay visual field loss in early glaucoma and ocular hypertensive patients? What treatment is best for advanced open angle glaucoma? How should providers initially treat patients with early open angle glaucoma? So far, the benefit to patients and providers is murky. Consider this vignette: