Leslie Hyman

Early manifest glaucoma trial: Design and baseline data

OBJECTIVES The Early Manifest Glaucoma Trial (EMGT) will evaluate the effectiveness of reducing intraocular pressure (IOP) in early, previously untreated open-angle glaucoma. Its secondary aims are to explore factors related to glaucoma progression and to study the natural history of the disease. This article describes the EMGT design and presents baseline data. DESIGN Randomized, clinical trial. PARTICIPANTS Newly diagnosed patients 50 to 80 years of age with early glaucomatous visual field defects were mainly identified from a population-based screening of more than 44,000 residents of Malmö and Helsingborg, Sweden. Exclusion criteria were advanced visual field loss; mean IOP greater than 30 mmHg or any IOP greater than 35 mmHg; visual acuity less than 0.5; and inability to complete follow-up protocols. INTERVENTIONS After informed consent, patients were randomized to treatment or no initial treatment with close follow-up. Treated patients had laser trabeculoplasty and started receiving topical betaxolol twice daily in eligible eyes. Follow-up visits include computerized perimetry and tonometry every 3 months and fundus photography every 6 months. Decisions to change or begin treatment are made jointly with the patient when EMGT progression occurs and also later if clinically needed. MAIN OUTCOME MEASURES The EMGT progression is defined by sustained increases of visual field loss in three consecutive C30-2 Humphrey tests, as determined from computer-based analyses, or by optic disc changes, as determined from flicker chronoscopy and side-by-side comparisons of fundus photographs performed by masked, independent graders. RESULTS A total of 255 patients were randomized between 1993 and 1997 and will be followed for at least 4 years. All had generally good health status; mean age was 68.1 years, and 66% were women. At baseline, mean IOP was 20.6 mmHg and 80% of eyes had IOP less than 25 mmHg. CONCLUSIONS The Early Manifest Glaucoma Trial is the first large randomized, clinical trial to evaluate the role of immediate pressure reduction, as compared to no initial reduction, in patients with early glaucoma and normal or moderately elevated IOP. Its results will have implications for: (1) the clinical management of glaucoma; (2) understanding the role of IOP and the natural history of glaucoma; and (3) evaluating the rationale for glaucoma screening.

Study and treatment of post Lyme disease (STOP-LD): A randomized double masked clinical trial

Objective: To determine whether post Lyme syndrome (PLS) is antibiotic responsive. Methods: The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit. Results: Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization. Conclusions: Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.

Natural History of Open-Angle Glaucoma

OBJECTIVE This article, based on the Early Manifest Glaucoma Trial (EMGT), provides prospective natural history data on progression of glaucomatous field defects in 3 of the most common glaucoma types. DESIGN Cohort of EMGT patients randomized to the untreated control group and followed up to the time of progression, when treatment could be initiated. PARTICIPANTS We evaluated 118 control patients: 46 with high-tension glaucoma (HTG), 57 with normal-tension glaucoma (NTG), and 15 with pseudoexfoliation glaucoma (PEXG). METHODS Visual fields were tested every 3 months with the Humphrey 30-2 Full Threshold test program. MAIN OUTCOME MEASURES Linear regression analyses of the perimetric mean deviation (MD) values were performed, and the rate of progression was defined as the regression coefficient in decibels per year. Percentages of progressed eyes and time to progression were determined using EMGT event-based predetermined progression criteria derived from Glaucoma Change Probability Maps. RESULTS The median and interquartile rates of visual function loss were -0.40 (1.05) dB/year overall and -0.46 (1.61) in HTG, -0.22 (0.65) in NTG, and -1.13 (6.13) in PEXG. Thus, interpatient variability was large. Mean rates were considerably higher than medians: -1.08 dB/year overall, -1.31 in HTG, -0.36 in NTG, and -3.13 in PEXG. Differences in median visual function progression rates among groups were statistically significant (NTG vs. HTG, P = 0.003; PEXG vs. non-PEXG, P<0.001). Progression was considerably and significantly faster in older than in younger patients (P = 0.002). By 6 years, 68% of patients had progressed overall, 74% of those with HTG, 56% of those with NTG, and 93% of those with PEXG (P = 0.012). Median time to progression also differed considerably among groups: 19.5 months in PEXG, 44.8 months in HTG, and particularly 61.1 months in NTG (P<0.0001). CONCLUSIONS In this 6-year follow-up study, the median untreated rate of progression corresponded to advancing from normal visual function to blindness in approximately 70 years, whereas on the basis of the mean rate, visual function would show the same deterioration in approximately 25 years. Large differences existed among patients and different glaucoma types, with PEXG progressing considerably faster than HTG, and NTG progressing at the lowest rate.

Prevalence and causes of visual impairment in the Barbados eye study

OBJECTIVE To determine the prevalence and causes of low vision and blindness in a predominantly black population. DESIGN Population-based prevalence study of a simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS Four thousand seven hundred nine persons (84% participation). METHODS The standardized protocol included best-corrected visual acuity (with a Ferris-Bailey chart), automated perimetry, lens gradings (LOCS II), and an interview. Participants with visual acuity of worse than 20/30, other positive findings, and a 10% sample also had an ophthalmologic examination that evaluated the cause and extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES Low vision and blindness were defined as visual acuity in the better eye between 6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health Organization [WHO] criteria). RESULTS Of the 4631 participants with complete examinations, 4314 (93%) reported their race as black, 184 (4%) reported their race as mixed (black and white), and 133 (3%) reported their race as white or other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of white or other participants. Bilateral blindness was similar for black and mixed race participants (1.7% and 1.6%, respectively) and was not found in whites. Among black and mixed participants, the prevalence of low vision increased with age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of blindness was higher (P < 0.001) for men than women at each age group (0.5% versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty percent of blindness was due to open-angle glaucoma and age-related cataract, each accounting for more than one fourth of cases. Other major causes were optic atrophy or neuropathy and macular and other retinal diseases. Few cases of blindness were due to diabetic retinopathy (1.4%), and none were due to age-related macular degeneration. CONCLUSIONS Using the WHO criteria, prevalence of visual impairment was high in this African-origin population, particularly at older ages. Most blindness was due to open-angle glaucoma and cataract, with open-angle glaucoma causing a higher proportion of blindness than previously reported. The increased prevalence of blindness in men may be due to the increased male prevalence of glaucoma in this population and warrants further investigation. Results underline the need for blindness prevention programs, with emphasis on effective treatment of age-related cataract and enhancing strategies for early detection and treatment of open-angle glaucoma.

Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial.

Purpose of review This review summarizes factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of treatment. EMGT randomized patients with early glaucoma either to argon laser trabeculoplasty plus betaxolol (n = 129) or to no immediate treatment (n = 126) and followed them every 3 months. Recent findings Treated patients had delayed progression, as compared with controls. In Cox regression, EMGT treatment halved the risk of progression (hazard ratio = 0.50; 95% confidence interval: 0.35, 0.71). Risk decreased about 10% with each millimeter mercury of intraocular pressure (IOP) reduction from baseline; the higher (or lower) the IOP at follow-up, the higher (or lower) the risk. Baseline factors increasing progression were higher IOP, exfoliation, bilateral disease, worse perimetric mean deviation and older age; frequent disc hemorrhages at follow-up also increased risk. Summary EMGT treatment reduced progression risk in half, demonstrating the value of IOP lowering in early glaucoma. Age and indicators of disease severity also predicted progression.

Frequency of Convergence Insufficiency Among Fifth and Sixth Graders

PURPOSE To estimate the frequency of convergence insufficiency (CI) and its related clinical characteristics among 9- to 13-year-old children. METHODS Fifth and sixth graders were screened in school settings at three different study sites. Eligible children with 20/30 or better visual acuity, minimal refractive error, no strabismus, and exophoria at near were evaluated according to a standardized protocol to determine the presence and severity of CI. These children were classified according to the presence and number of the following clinical signs: (1) exophoria at near > or =4delta than far, (2) insufficient fusional convergence, and (3) receded nearpoint of convergence. Also, children were classified as accommodative insufficient (AI) if they failed Hofstetters minimum amplitude formula or had greater than a + 1.00 D lag on Monocular Estimate Method retinoscopy. RESULTS Of 684 children screened, 468 (68%) were eligible for further evaluation. Of these, 453 had complete data on CI measurements and were classified as: no CI (nonexophoric at near or exophoric at near and < 4delta difference between near and far) (78.6%); low suspect CI (exophoric at near and one clinical sign: exophoria at near > or =4delta than far) (8.4%); high suspect CI (exophoric at near and two clinical signs) (8.8%); and definite CI (exophoric at near and three clinical signs) (4.2%). CI status varied according to ethnicity and study site (p < 0.0005), but not gender. The frequency of AI increased with the number of CI-related signs. For CI children with three signs, 78.9% were classified as also having AI. CONCLUSIONS These findings suggest that CI (defined as high suspect and definite) is frequent (13%) among fifth and sixth grade children. In addition, there is a high percentage of CI children with an associated AI.

The effect of nonsurgical periodontal therapy on hemoglobin a1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial

IMPORTANCE Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00997178.

Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados Eye Study

OBJECTIVE The increased cataract prevalence of black populations, especially of cortical cataract, remains unexplained. The authors evaluate the relationships of diabetes, hypertension, and obesity patterns to lens opacities, by age, among 4314 black participants in the Barbados Eye Study. DESIGN AND PARTICIPANTS Prevalence study of a random sample of the Barbados population, ages 40 to 84 years (84% participation). MAIN OUTCOME MEASURES Associations with age-related lens changes (grade > or = 2 in the Lens Opacities Classification System II at the slit lamp) were evaluated in logistic regression analyses by age (persons < 60 years and > or = 60 years). Results are presented as odds ratios (OR) with 95% confidence intervals. RESULTS Of the 1800 participants with lens changes, most had cortical opacities. Diabetes history (18% prevalence) was related to all lens changes, especially at younger ages (age < 60 years: OR = 2.23 [1.63, 3.04]; age > or = 60 years: OR = 1.63 [1.22, 2.17]). Diabetes also increased the risk of cortical opacities (age < 60 years: OR = 2.30 [1.63, 3.24]; age > or = 60 years: OR = 1.42 [1.03, 1.96]); additional risk factors were high diastolic blood pressure (age < 60 years: OR = 1.49 [1.00, 2.23]) and higher waist/hip ratio (all ages: OR = 1.36 [1.00, 1.84]). Diabetes was also related to posterior subcapsular opacities. Glycated hemoglobin levels were positively associated with cortical and posterior subcapsular opacities. Overall, 14% of the prevalence of lens changes could be attributed to diabetes. CONCLUSIONS The high prevalence of cortical opacities was related to diabetes, hypertension, and abdominal obesity, which also are common in this and other black populations. Interventions to modify these risk factors, especially in populations in which they are highly prevalent, may have implications to control visual loss from cataract, which is the first cause of blindness worldwide.

A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients

PURPOSE Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. DESIGN Longitudinal, comparative study of diagnostic criteria. PARTICIPANTS AND CONTROLS Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). METHODS Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensitivity, specificity, time to progression, and sustainability were calculated. MAIN OUTCOME MEASURES Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. RESULTS Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogressing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P<0.001), and pairwise (P<0.01). The specificity for EMGT criteria was 89%, lower (P<0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30-36 months) than with AGIS (66 months; 95% CI, 57-78 months) and CIGTS (55 months; 95% CI, 48-66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. CONCLUSIONS The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression.

Frequency of convergence insufficiency in optometry clinic settings

Purpose. To estimate the frequency of convergence insufficiency (CI) and its related characteristics among 8- to 12-year-old children randomly selected from 2 optometry clinic populations. Methods. Clinic records of 620 children were randomly selected and reviewed according to a standard protocol, using a systematic sampling method based on the total number of 8- to 12-year-old children seen over a 1-year period at 2 optometry clinics. Records were reviewed for demographic and clinical data. Data on CI-related symptoms were obtained at one of the sites. Records that met the eligibility criteria of: good visual acuity (20/30 or better in both eyes); minimal refractive error (–0.50 to +1.00 D and ≤1.00 D of astigmatism in either eye, and ≤1.00 D of anisometropia); and no strabismus were evaluated for Cl-related characteristics. Eligible children were classified according to the direction of their near heterophoria and the number of the following clinical signs present: (1) exophoria at near ≥4δ than at far; (2) insufficient fusional convergence [i.e., failing Sheards criterion or minimum normative positive fusional vergence (PFV) of 12 A base-out (BO) blur/15 A BO break]; and (3) receded nearpoint of convergence (NPC) of ≥7.5 cm break or ≥10.5 cm recovery. Children were then classified as: no Cl (nonexophoric at near or <4 δ difference between far and near); low suspect (exophoric at near and 1 sign); high suspect (exophoric at near and 2 signs); or definite Cl (exophoric at near and 3 signs). Results. Sixty-seven percent (415/620) of the records met the eligibility criteria and had complete data on phoria, NPC, and PFV. The age (mean ±SD) of the study population was 10.2 ±1.2 years. Ethnicity data were available for 85% of those eligible; the ethnic distribution was 36% African American, 29% Caucasian, 19% Hispanic, and 1% Asian. About one-half of the 415 children were classified as either low suspect (33%); high suspect (12%); or definite Cl (6%). Clinically significant Cl (high suspect and definite categories) was identified in 17.6% of the children. The percentage of children rated as symptomatic increased with the number of Cl-related clinical signs present. Conclusions. These findings suggest a high frequency of Cl in optometry clinic populations and a potential correlation between patient symptoms and the number of Cl signs present. (Optom Vis Sci 1998;75:88-96)