It is not time to abandon radiotherapy for neovascular age-related macular degeneration.
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Biomedical subjects
Publications and source records attributed to M G Maguire.
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The impact of pill organizers on pill taking was determined in the Trial of Antioxidant Vitamins C and E (TRACE) Study, a factorial trial of vitamin C and vitamin E supplementation in 184 individuals. Participants were recruited in 1996-1997 and randomized to one of two groups (pill organizer or no organizer) and to one of four supplement groups for 2 months. The pill count (observed/expected X 100%) distribution was similar in the organizer and no organizer group for both vitamins. Mean differences in changes in serum vitamin levels between active and placebo groups did not differ by pill organizer use. The impact of pill organizers and blister packs was compared in another trial, the Vitamins, Teachers, and Longevity (VITAL) Study, in 297 individuals randomized in 1993-1994 to receive study pills either in blister packs or in pill organizers and to take one of two supplements. Among those with lower adherence, the pill count distribution in the blister-pack group exceeded that in the organizer group. Mean differences in serum vitamin E levels between active and placebo groups did not differ by types of pill packaging. In summary, use of blister packs, but not pill organizers, improved adherence as measured by pill counts among those with lower adherence. Neither pill delivery system improved adherence as measured by serum vitamin levels.
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PURPOSE: To describe the clinical features and complications of diabetic retinopathy, visual acuity, and number of repeat treatments after panretinal photocoagulation for proliferative diabetic retinopathy in a tertiary care center. METHODS: A cohort study was conducted with data collection from medical records of patients undergoing panretinal photocoagulation between 1985 and 1995 at the Scheie Eye Institute; 297 eyes of 186 patients were eligible for study. RESULTS: The presence of neovascularization of the disk at baseline, an earlier onset of diabetes, and a shorter duration of disease before panretinal photocoagulation were the strongest risk factors for needing an additional panretinal photocoagulation treatment. Sixty-two percent of eyes with poor visual acuity (< or =20/200) at baseline still had poor visual acuity at 1 year, and 76% with good visual acuity (> or =20/40) at baseline maintained good visual acuity at 1 year. Poor vision at baseline was the only risk factor for having poor vision at 1 year. Vitreous hemorrhage was present in 44% of eyes at baseline. New vitreous hemorrhage developed in 37% of eyes during the first year after panretinal photocoagulation. A traction retinal detachment was present in 4% of eyes at baseline and newly developed in 6% of eyes during follow-up. A repeat panretinal photocoagulation treatment was performed in 39% of eyes after initial treatment. A vitrectomy was performed in 10% of eyes from baseline through the 1-year follow-up visit. CONCLUSIONS: The data from this study are useful for counseling patients with respect to likely visual outcome, possibility of major complications from proliferative diabetic retinopathy, and the chance of undergoing additional laser treatment after panretinal photocoagulation.
OBJECTIVE: To investigate the ability of a portable, personal computer-driven, pupillometer to record the pupillary response curve during the swinging flashlight test. Also, to determine whether these response curves can be used to identify and quantify relative asymmetry in the pupillary light reflex between eyes in healthy volunteers with simulated afferent pupil defects (APDs) and patients with optic neuropathies. DESIGN: Comparative, observational case series and instrument validation. PARTICIPANTS: Healthy volunteers with no known ocular disease and patients (n = 20) with various optic neuropathies noted to have relative APDs on examination. METHODS: Pupillary response curves of the right eye were recorded with a portable, electronic, infrared pupillometer from healthy volunteers (with and without simulated APDs) and patients with APDs while the light stimulus alternated between eyes, simulating the swinging flashlight test. Simulated APDs in healthy volunteers were created with increasingly dense neutral density filters in front of the left eye. MAIN OUTCOME MEASURES: Differences in constriction amplitude, latency, and constriction velocity of the pupillary response with right eye stimulation versus left eye stimulation in both groups of subjects. RESULTS: A significant correlation between neutral density filter strength and intereye differences was seen for all measurement parameters in volunteers with simulated APDs. Depending on the measurement parameter and stimulus intensity, simulated APDs of 0.6 log units or more could be distinguished from normal responses. Clinically graded true APDs had intereye differences similar to simulated APDs of the same density. Those with real and simulated APDs of 0.9 log units or more could be distinguished from healthy volunteers with 80% sensitivity and 92% specificity. Responses from those with real and simulated small APDs of 0.3 to 0.6 log units could not be distinguished reliably. CONCLUSIONS: Portable, personal-computer driven, electronic, infrared pupillography can record the swinging flashlight test accurately and identify large afferent pupillary defects. An affordable, portable, reliable device for identifying relative APDs would be useful in the identification and follow-up of patients with neurogenic vision loss.
The quantitative assessment of visual function in multiple sclerosis (MS) clinical trials has been limited to Snellen visual acuity. The purpose of this study was to examine the inter-rater reliability and test characteristics of a new visual outcome measure, the Low-Contrast Sloan Letter Charts, in patients with MS and visually-asymptomatic volunteers. Contrast letter acuity scores (letter scores) were measured at each of four contrast levels (100, 5, 1.25 and 0.6%) by two independent raters. Inter-rater agreement was described with the intraclass correlation coefficient (ICC) and comparison of mean scores. Excellent inter-rater agreement (ICC=0.86 - 0.95) was demonstrated at each contrast level among MS patients (n=100) and visually-asymptomatic volunteers (n=33). Average letter scores at the lowest contrast level (0.6%) were highly variable in the MS group, even among patients with visual acuities of 20/20 or better, and among those who required no assistance for ambulation. Low-Contrast Sloan Letter Chart testing is a highly reliable method of visual assessment, and provides information on an aspect of neurologic impairment in MS which is not captured by Snellen visual acuity or ambulation status. This new method demonstrates excellent potential as a visual function outcome measure for future MS clinical trials.
Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported visual dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon beta-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n= 118). These differences were observed despite a relatively younger age and tighter distribution of binocular visual acuities in the MS cohort Patients with MS in this study thus demonstrated a greater degree of self-reported visual dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.
PURPOSE: To determine whether there is rod system dysfunction in the central retina of patients with age-related macular degeneration (AMD). METHODS: Dark-adapted sensitivity (500-nm stimulus) and light-adapted sensitivity (600 nm) were measured psychophysically at 52 loci in the central 38 degrees (diameter) of retina in 80 patients with AMD, and results were compared with those from older adult normal controls. All dark-adapted data were corrected for preretinal absorption. RESULTS: Mean field dark-adapted sensitivity was significantly lower in AMD patients as a group than in normal subjects. Within the AMD group were subsets of patients with normal mean dark- and light-adapted sensitivities; reduced dark-adapted sensitivities without detectable light-adapted losses; both types of losses; and, least commonly, only light-adapted losses. Regional retinal analyses of the dark-adapted deficit indicated the greatest severity was 2 degrees to 4 degrees or approximately 1 mm from the fovea, and the deficit decreased with increasing eccentricity. CONCLUSIONS: These psychophysical results are consistent with histopathologic findings of a selective vulnerability for parafoveal rod photoreceptors in AMD. The different patterns of rod and cone system losses among patients at similar clinical stages reinforces the notion that AMD is a group of disorders with underlying heterogeneity of mechanism of visual loss. Dark-adapted macula-wide testing may be a useful complement to the more traditional outcome measures of fundus pathology and foveal cone-based psychophysics in future AMD trials.
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The relation between obesity and age in children with idiopathic intracranial hypertension (pseudotumor cerebri) has remained uncertain. The authors reviewed the records of 45 consecutive children with newly diagnosed idiopathic intracranial hypertension seen at two medical centers. Forty-three percent of patients aged 3 to 11 years were obese, whereas 81% of those in the 12- to 14-year age group and 91% of those in the 15- to 17-year age group met criteria for obesity (p = 0.01). Younger children with idiopathic intracranial hypertension are less likely to be obese than are older children or adults.
PURPOSE: To investigate optic nerve head blood flow in patients with glaucoma and to assess the effect of systemic hypertension. METHODS: This study included 24 eyes of 24 patients with primary open-angle glaucoma. Eleven of these patients had a history of systemic hypertension. Results in patients with glaucoma were compared with those of 13 eyes of 13 age-matched normal controls. Determinations of relative optic nerve head blood velocity, volume, and flow were obtained with laser Doppler flowmetry in the superotemporal and inferotemporal neuroretinal rim and also in the cup. Means of the velocity, volume, and flow of these three measurement sites were calculated for each subject. RESULTS: Mean overall optic nerve head blood flow was 29% lower in glaucoma patients than in normal controls (t test, P < .001). This decrease in flow was mainly caused by a decrease of 23% in mean blood velocity (P < .001). Mean flow in glaucoma patients without systemic hypertension was 26% lower than that of glaucoma patients with hypertension (Tukey honest significant difference test, P = .05). A significant direct correlation was observed between mean flow and mean blood pressure (R = 0.51, P < .02). CONCLUSIONS: Optic nerve blood flow is reduced in glaucoma patients. Glaucoma patients without systemic hypertension have lower optic nerve blood flow than those with hypertension. Our results raise concerns that treatment of systemic hypertension may further decrease optic nerve blood flow in glaucoma patients.
OBJECTIVE: To describe the relationship of laser-induced drusen reduction to change in visual function at 1 year among patients enrolled in the Choroidal Neovascularization Prevention Trial (CNVPT). DESIGN: Comparison of groups with and without drusen reduction; follow-up of a randomized controlled trial. PARTICIPANTS: Evaluations of drusen and visual acuity at baseline and at 1 year were performed for 351 eyes of the 432 eyes enrolled in the CNVPT Bilateral Drusen Study and Fellow Eye Study (81%). One hundred eighty-four eyes were assigned to observation, and 167 eyes were assigned to laser treatment. Eyes with conditions that precluded an analysis of drusen reduction, such as those that developed choroidal neovascularization (CNV) within the first year, are excluded from this analysis. METHODS: Change in macular drusen between initial visit and after 1 year was assessed by side-by-side grading by evaluators masked to information on visual function. Visual acuity, contrast threshold, and critical print size were measured by certified visual function examiners. MAIN OUTCOME MEASURES: Change in visual acuity is the primary outcome. Change in contrast threshold and change in critical print size are secondary outcome measures. RESULTS: Laser-treated eyes with 50% or more drusen reduction at 1 year had more 1- and 2-line increases in visual acuity and less losses in visual acuity compared with laser-treated eyes with less drusen reduction or with observed eyes (P = 0.001). Similar improvements were noted for contrast threshold but not critical print size at 1 year. CONCLUSIONS: Laser-induced drusen reduction is associated with improved visual acuity and contrast sensitivity in eyes at 1 year. Longer term effects of laser-induced drusen reduction on visual function require additional observation. The overall potential value of laser treatment in eyes with high-risk drusen requires consideration of not only short-term effects on vision but also the effects of CNV and atrophy on vision.
BACKGROUND: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. OBJECTIVE: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. DESIGN: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 64 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. RESULTS: In multivariable linear regression and generalized linear models, there was an independent, inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03). In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of 1n tHcy with dietary protein and coffee persisted. CONCLUSIONS: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes.
PURPOSE: To determine if any relationship exists between the amount of adjustment using this surgical technique and resulting changes in the strabismic deviation. METHODS: A prospective database obtained between the years 1991 and 1996 was used to obtain retrospective clinical information and data for this study. We found in the database 172 postoperatively adjusted muscles in 159 patients who could be included in this study. All patients had their muscles adjusted postoperatively within the first 24 hours after surgery. Information retrieved specific to this study included the post-surgical, pre-adjustment strabismic deviation, the amount and direction of the adjustment and the resulting deviation immediately after this postoperative adjustment. Statistical analysis was performed on the total and individual muscles, as well as the direction of adjustment, comparing pre- to post-adjustment binocular deviations. RESULTS: There was a significant overall relationship between the millimeters of postoperative adjustment and the amount of change in the binocular deviation (p<.0001). This relationship was more linear under 3.0 mm of postoperative adjustment. The effect of the amount of postop' adjustment when advancing the muscle was significantly greater than when recessing the muscle (p<.0001). There was more effect per mm of postop' adjustment of horizontal muscles than vertical muscles (p=.004). CONCLUSIONS: There is a linear correlation of postoperative extraocular muscle adjustment when advancing an adjustable muscle but this correlation is more variable for adjustments over 3.0 mm. The effect of adjustment per mm is greater when adjusting horizontal than vertical muscles. There is a poor correlation for further recession. Prediction Equations are provided to enhance clinical results of this technique.
OBJECTIVE: To describe the comparative impact of current and preventive treatments on incidence of choroidal neovascularization (CNV) and severe vision loss in patients with bilateral soft drusen (BSD). DESIGN: Stochastic model. SETTING: US population. PATIENTS: Prevalence cohort of white patients 43 years or older with BSD. INTERVENTIONS: Application of prophylaxis of 10% to 50% efficacy to 1 or both eyes of patients with BSD, application of laser photocoagulation to eligible CNV lesions, or both. MAIN OUTCOME MEASURES: Proportion of patients with BSD after 10 years with unilateral and bilateral CNV and resultant unilateral and bilateral vision loss to visual acuity of 20/200 or worse. RESULTS: The natural history of patients with BSD generated by the model shows that 12.40% of these patients develop either unilateral or bilateral CNV within 10 years of their entry into the BSD prevalence cohort. Bilateral disease occurs in 3.86% of patients with BSD within 10 years. The proportion of patients with BSD becoming legally blind from CNV within 10 years is 2.54% if no treatment is performed. Current laser treatment for CNV decreases the proportion with legal blindness within 10 years to 2.24%. The addition of a preventive treatment of 10% efficacy applied bilaterally to the current laser treatment regimen decreases the proportion with legal blindness to 1.86%; a 25% effective preventive treatment decreases it to 1.34%. Comparatively, preventive treatment of 10% and 25% efficacy given to the fellow eye only after the first eye has developed CNV decreases the proportion of legally blind patients at 10 years only to 2.06% and 1.77%, respectively. All outcomes vary with sex and age at entry into the BSD cohort. CONCLUSIONS: Patients with BSD face a 12.40% risk of developing CNV within 10 years. The addition of even a modest (10% effective) bilateral preventive treatment to the current regimen for CNV would more than double the prevention of legal blindness in the BSD population relative to current laser treatment; a preventive treatment of 33% efficacy more than halves the rate of legal blindness caused by CNV. Preventive treatment given to the fellow eye only after the first develops CNV has substantially less impact.
PURPOSE: To compare measurements of the foveolar choroidal blood circulation in subjects with nonexudative, age-related macular degeneration (AMD) with those of control subjects. METHODS: Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the center of the fovea. Measurements were obtained in 20 eyes of 20 subjects with 10 or more large drusen, visual acuity of 20/32 or better, and no evidence of choroidal neovascularization. Findings obtained in these subjects were compared with those of 10 eyes of 10 age- and blood pressure-matched control subjects with no large drusen. Foveolar choroidal blood flow measurements were obtained by asking the study participants to fixate on a probing laser beam. RESULTS: No significant differences in average age, blood pressure, or intraocular pressure were observed between subjects with AMD and control subjects. In subjects with AMD, average ChBVol was 0.24 +/- 0.08 (+/- 1 SD) arbitrary units (AU); this value was 33% lower than that of control subjects (0.36 +/- 0.11 AU; two-tailed, independent Student's t-test, P = 0.005). Average ChBVel, conversely, was not significantly different from normal (0.44 +/- 0.07 AU) in subjects with AMD (0.44 +/- 0.10 AU). Average ChBFlow in subjects with AMD (8.7 +/- 3.1 AU) was 37% lower than that of control subjects (13.7 +/- 3.5 AU) (P = 0.0005). Average blood flow pulsatility was 6% higher in subjects with AMD (0.71 +/- 0.15) than in control subjects (0.66 +/- 0.14), but this difference was not statistically significant (P = 0.42). CONCLUSIONS: Average ChBFlow in the nonexudative stages of AMD is lower than that of age-matched controls, and the effect is caused mainly by a decrease in ChBVol. Further studies are needed to elucidate whether decreased ChBFlow plays a role in the development of choroidal neovascularization, and whether ChBFlow measurements may help identify subjects with AMD at risk for developing choroidal neovascularization.
This study was conducted to test whether cortical activation varies across successive epoques during functional magnetic resonance imaging (fMRI) studies. Ten normal adult volunteers were studied with a 1.5-T MR scanner. Pseudocoronal study planes were chosen perpendicular to the tentorium cerebelli, at two thirds the distance from the posterior edge of the splenium of the corpus callosum to the transverse sinuses. Functional images were acquired with a T2*-weighted spoiled gradient echo sequence. The visual cortex was stimulated by goggles flashing at 8 Hz. Each study consisted of 82 sequential scans, lasting 15 seconds each for a total of 20.5 minutes. Two scans without stimulation were alternated with two scans of visual stimulation. Scans 3 through 83 were divided into five sequences of 16 scans. For each sequence, the number of pixels within a predefined rectangular region of interest that showed increased activity during stimulation were counted. Least squares regression models of straight lines were fit to the data. The initial level of visual cortex activation in the region of interest, as measured by the y-intercept, varied substantially from subject to subject (range: 4-68, p < 0.001). There was sufficient evidence of systematic change with time to reject the hypothesis of constant activation with the same stimulus over time (p=0.02). The observed visual cortex activation with single-plane fMRI varied both with time over successive epoques and among subjects. Possible factors responsible for the variation may include head movement, eyelid position, attention, and physiologic fatigue. These factors must be accounted for in experimental design and in data analysis and interpretation.
OBJECTIVE: To describe the interval between first appearance of mild nonproliferative diabetic retinopathy (NPDR) and first appearance of neovascularization (NV) in type I diabetes. SETTING: A longitudinal study of 269 patients followed up annually. PARTICIPANTS: Participants had insulin-dependent diabetes and were free of proliferative diabetic retinopathy in both eyes at the baseline visit. MAIN OUTCOME MEASURE: Stereoscopic color fundus photographs of each eye at each study visit, graded for features of retinopathy. RESULTS: Among the 305 eyes for which the duration of diabetes at the first appearance of mild NPDR could be determined, NV developed in 28 by the end of the study. Survival analysis showed that the later the onset of mild NPDR was, the shorter the time from onset of mild NPDR to onset of NV (relative hazard for each additional year to onset of mild NPDR, 1.22; 95% confidence interval, 1.10-1.35). Adjustment for systolic and diastolic blood pressure, proteinuria, and glycosylated hemoglobin (Hgb A10) levels did not change the relative hazard estimate for onset of mild NPDR. Higher levels of Hgb A10 were associated with a shorter time from onset of mild NPDR to onset of NV (relative hazard, 1.26; 95% confidence interval, 1.05-1.51 [after adjusting for time at onset of mild NPDR]), as were higher levels of diastolic blood pressure, although not significantly (relative hazard for 10-mm Hg increase in diastolic blood pressure, 1.52; 95% confidence interval, 0.82-2.83 [adjusting for onset of mild NPDR, Hgb A10 level, systolic blood pressure, and proteinuria]). Neither proteinuria nor systolic blood pressure had an effect on time from onset of mild NPDR to onset of NV, after adjustment for time at onset of mild NPDR, Hgb A10 level, and diastolic blood pressure. CONCLUSION: Later onset of mild NPDR is not necessarily associated with delayed development of NV in patients with type I diabetes. Caution must therefore be used in assessing the value of interventions that delay the onset of mild NPDR without evidence of delayed onset of NV.