Macular Degeneration: Glassman AR

Anonymous00148, Brucker AJ, Qin H, Antoszyk AN, Beck RW, Bressler NM, Browning DJ, Elman MJ, Glassman AR, Gross JG, Kollman C, Wells JA. · No affiliation provided · Arch Ophthalmol. · Pubmed #19204228 No free full text.

Abstract: OBJECTIVE: To compare the effects of single-sitting vs 4-sitting panretinal photocoagulation (PRP) on macular edema in subjects with severe nonproliferative or early proliferative diabetic retinopathy with relatively good visual acuity and no or mild center-involved macular edema. METHODS: Subjects were treated with 1 sitting or 4 sittings of PRP in a nonrandomized, prospective, multicentered clinical trial. Main Outcome Measure Central subfield thickness on optical coherence tomography (OCT). RESULTS: Central subfield thickness was slightly greater in the 1-sitting group (n = 84) than in the 4-sitting group (n = 71) at the 3-day (P = .01) and 4-week visits (P = .003). At the 34-week primary outcome visit, the slight differences had reversed, with the thickness being slightly greater in the 4-sitting group than in the 1-sitting group (P = .06). Visual acuity differences paralleled OCT differences. CONCLUSIONS: Our results suggest that clinically meaningful differences are unlikely in OCT thickness or visual acuity following application of PRP in 1 sitting compared with 4 sittings in subjects in this cohort. More definitive results would require a large randomized trial. Application to Clinical Practice These results suggest PRP costs to some patients in terms of travel and lost productivity as well as to eye care providers could be reduced. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00687154.

Anonymous00065, Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. · No affiliation provided · Arch Ophthalmol. · Pubmed #19273785 No free full text.

Abstract: OBJECTIVE: To report 3-year outcomes of patients who participated in a randomized trial evaluating 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone compared with focal/grid photocoagulation for treatment of diabetic macular edema. METHODS: Eyes with diabetic macular edema and visual acuities of 20/40 to 20/320 were randomly assigned to focal/grid photocoagulation or 1 mg or 4 mg of triamcinolone. At the conclusion of the trial, 3-year follow-up data were available in 306 eyes. RESULTS: Between 2 years (time of the primary outcome) and 3 years, more eyes improved than worsened in all 3 treatment groups. Change in visual acuity letter score from baseline to 3 years was +5 in the laser group and 0 in each triamcinolone group. The cumulative probability of cataract surgery by 3 years was 31%, 46%, and 83% in the laser and 1-mg and 4-mg triamcinolone groups, respectively. Intraocular pressure increased by more than 10 mm Hg at any visit in 4%, 18%, and 33% of eyes, respectively. CONCLUSIONS: Results in a subset of randomized subjects who completed the 3-year follow-up are consistent with previously published 2-year results and do not indicate a long-term benefit of intravitreal triamcinolone relative to focal/grid photocoagulation in patients with diabetic macular edema similar to those studied in this clinical trial. Most eyes receiving 4 mg of triamcinolone as given in this study are likely to require cataract surgery. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00367133.

Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, Davis MD, Ferris FL, Huang SS, Kaiser PK, Kollman C, Sadda S, Scott IU, Qin H, Anonymous00193. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #18675696 No free full text.

Abstract: OBJECTIVE: To evaluate optical coherence tomography (OCT) measurements and methods of analysis of OCT data in studies of diabetic macular edema (DME). DESIGN: Associations of pairs of OCT variables and results of 3 analysis methods using data from 2 studies of DME. PARTICIPANTS: Two hundred sixty-three subjects from a study of modified Early Treatment of Diabetic Retinopathy Study (mETDRS) versus modified macular grid (MMG) photocoagulation for DME and 96 subjects from a study of diurnal variation of DME. METHODS: Correlations were calculated for pairs of OCT variables at baseline and for changes in the variables over time. Distribution of OCT measurement changes, predictive factors for OCT measurement changes, and treatment group outcomes were compared when 3 measures of change in macular thickness were analyzed: absolute change in retinal thickness, relative change in retinal thickness, and relative change in retinal thickening. MAIN OUTCOME MEASURES: Concordance of results using different OCT variables and analysis methods. RESULTS: Center point thickness correlated highly with central subfield mean thickness (CSMT) at baseline (0.98-0.99). The distributions of changes in CSMT were approximately normally distributed for absolute change in retinal thickness and relative change in retinal thickness, but not for relative change in retinal thickening. Macular thinning in the mETDRS group was significantly greater than in the MMG group when absolute change in retinal thickness was used, but not when relative change in thickness and relative change in thickening were used. Relative change in macular thickening provides unstable data in eyes with mild degrees of baseline thickening, unlike the situation with absolute or relative change in retinal thickness. CONCLUSIONS: Central subfield mean thickness is the preferred OCT measurement for the central macula because of its higher reproducibility and correlation with other measurements of the central macula. Total macular volume may be preferred when the central macula is less important. Absolute change in retinal thickness is the preferred analysis method in studies involving eyes with mild macular thickening. Relative change in thickening may be preferable when retinal thickening is more severe.

Glassman AR, Beck RW, Browning DJ, Danis RP, Kollman C, Anonymous00143. · Jaeb Center for Health Research, Tampa, Florida 33647, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18566462 No free full text.

Abstract: PURPOSE: To analyze the value of reading center error correction in automated optical coherence tomography (OCT; Stratus; Carl Zeiss Meditec, Inc., Dublin, CA) retinal thickness measurements in eyes with diabetic macular edema (DME). METHODS: OCT scans (n=6522) obtained in seven Diabetic Retinopathy Clinical Research Network (DRCR.net) studies were analyzed. The reading center evaluated whether the automated center point measurement appeared correct, and when it did not, measured it manually with calipers. Center point standard deviation (SD) as a percentage of thickness, center point thickness, signal strength, and analysis confidence were evaluated for their association with an automated measurement error (manual measurement needed and exceeded 12% of automated thickness). Curves were constructed for each factor by plotting the error rate against the proportion of scans sent to the reading center. The impact of measurement error on interpretation of clinical trial results and statistical power was also assessed. RESULTS: SD was the best predictor of an automated measurement error. The other three variables did not augment the ability to predict an error using SD alone. Based on SD, an error rate of 5% or less could be achieved by sending only 33% of scans to the reading center (those with an SD >or= 5%). Correcting automated errors had no appreciable effect on the interpretation of results from a completed randomized trial and had little impact on a trial's statistical power. CONCLUSIONS: In DME clinical trials, the error involved with using automated Stratus OCT center point measurements is sufficiently small that results are not likely to be affected if scans are not routinely sent to a reading center, provided adequate quality control measures are in place.

Davis MD, Bressler SB, Aiello LP, Bressler NM, Browning DJ, Flaxel CJ, Fong DS, Foster WJ, Glassman AR, Hartnett ME, Kollman C, Li HK, Qin H, Scott IU, Anonymous00289. · Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18316700 links to  free full text

Abstract: PURPOSE: To explore the correlation between optical coherence tomography (OCT) and stereoscopic fundus photographs (FP) for the assessment of retinal thickening (RT) in diabetic macular edema (DME) within a clinical trial. METHODS: OCT, FP, and best corrected visual acuity (VA) measurements were obtained in both eyes of 263 participants in a trial comparing two photocoagulation techniques for DME. Correlation coefficients (r) were calculated comparing RT measured by OCT, RT estimated from FP, and VA. Principal variables were central subfield retinal thickness (CSRT) obtained from the OCT fast macular map and DME severity assessed by a reading center using a seven-step photographic scale combining the area of thickened retina within 1 disc diameter of the foveal center and thickening at the center. RESULTS: Medians (quartiles) for retinal thickness within the center subfield by OCT at baseline increased from 236 (214, 264) microm in the lowest level of the photographic scale to 517 (455, 598) microm in the highest level (r = 0.67). However, CSRT interquartile ranges were broad and overlapping between FP scale levels, and there were many outliers. Correlations between either modality and VA were weaker (r = 0.57 for CSRT, and r = 0.47 for the FP scale). OCT appeared to be more reproducible and more sensitive to change in RT between baseline and 1 year than was FP. CONCLUSIONS: There was a moderate correlation between OCT and FP assessments of RT in patients with DME and slightly less correlation of either measure with VA. OCT and FP provide complementary information but neither is a reliable surrogate for VA.

Anonymous00133, Fong DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, Davis MD, Feman SS, Ferris F, Friedman SM, Garcia CA, Glassman AR, Han DP, Le D, Kollman C, Lauer AK, Recchia FM, Solomon SD. · No affiliation provided · Arch Ophthalmol. · Pubmed #17420366 links to  free full text

Abstract: OBJECTIVE: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present. METHODS: Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted. MAIN OUTCOME MEASURE: Change in optical coherence tomography measurements at 12-month follow-up. RESULTS: Among eyes with a baseline central subfield thickness of 250 microm or greater, central subfield thickening decreased by an average of 88 microm in the modified ETDRS group and by 49 microm in the MMG group at 12-month follow-up (adjusted mean difference, 33 microm; 95% confidence interval, 5-61 microm; P = .02). Weighted inner zone thickening by optical coherence tomography decreased by 42 microm in the modified ETDRS group and by 28 microm in the MMG group (adjusted mean difference, 14 microm; 95% confidence interval, 1-27 microm; P = .04); maximum retinal thickening (maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 microm, respectively (adjusted mean difference, 27 microm; 95% confidence interval, 6-47 microm; P = .01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference, 0.3 mm3; 95% confidence interval, 0.02-0.53 mm3; P = .03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P = .10). CONCLUSIONS: At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified. APPLICATION TO CLINICAL PRACTICE: Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00071773.

Anonymous00153, Krzystolik MG, Strauber SF, Aiello LP, Beck RW, Berger BB, Bressler NM, Browning DJ, Chambers RB, Danis RP, Davis MD, Glassman AR, Gonzalez VH, Greenberg PB, Gross JG, Kim JE, Kollman C. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #17353052 links to  free full text

Abstract: PURPOSE: To evaluate optical coherence tomography (OCT) reproducibility in patients with diabetic macular edema (DME). DESIGN: Prospective 1-day observational study. PARTICIPANTS: Two hundred twelve eyes of 107 patients with DME involving the macular center by clinical examination and OCT central subfield thickness of > or =225 microm. METHODS: Retinal thickness was measured with the OCT3 system, and scans were evaluated by a reading center. Reproducibility of retinal thickness measurements was assessed, and 95% confidence intervals (CIs) for a change in thickness were estimated. MAIN OUTCOME MEASURES: Reproducibility of OCT-measured central subfield thickness. RESULTS: Reproducibility was better for central subfield thickness than for center point thickness (half-width of the 95% CI for absolute change, 38 microm vs. 50 microm, and for relative change, 11% vs. 17%, respectively; P<0.001). The median absolute difference between replicate measurements of the central subfield was 7 microm (2%). Half-widths of the 95% CI for a change in central subfield thickness were 22, 23, 33, and 56 microm for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. When expressed as percentage differences between 2 measurements, half-widths of the 95% CI for a change in central subfield thickness were 10%, 10%, 10%, and 13% for scans with central subfield thicknesses of <200, 200 to <250, 250 to <400, and > or =400 microm, respectively. We were unable to identify an effect on reproducibility of central subfield measurements with respect to the presence of cystoid abnormalities, subretinal fluid, vitreomacular traction, or reduced visual acuity. Reproducibility was better when both scans had a standard deviation (SD) of the center point of <10.0% (half-width of the 95% CI for change, 33 microm vs. 56 microm; P<0.001). CONCLUSIONS: Reproducibility is better for central subfield thickness measurements than for center point measurements, and variability is less with retinal thickness when expressed as a percent change than when expressed as an absolute change. A change in central subfield thickness exceeding 11% is likely to be real. Scans with an SD of the center point of > or =10.0% are less reproducible and should be viewed with caution when assessing the validity of an observed change in retinal thickness in patients with DME.

Anonymous00159, Danis RP, Glassman AR, Aiello LP, Antoszyk AN, Beck RW, Browning DJ, Ciardella AP, Kinyoun JL, Murtha TJ, Topping TM, Shami M, Sharuk GS, Wells JA. · Jaeb Center for Health Research, Tampa, FL 33647, USA. · Arch Ophthalmol. · Pubmed #17159029 links to  free full text

Abstract: OBJECTIVE: To evaluate diurnal variation in retinal thickness measured with optical coherence tomography (OCT) in patients with center-involved diabetic macular edema. METHODS: Serial OCT3 measurements were performed in 156 eyes of 96 subjects with clinically diagnosed diabetic macular edema and OCT central subfield retinal thickness of 225 microm or greater at 8 am. Central subfield thickness was measured from OCT3 retinal thickness maps at 6 points over a single day between 8 am and 4 pm. A change in central subfield thickening (observed thickness minus mean normal thickness) of at least 25% and of at least 50 microm at 2 consecutive points or between 8 am and 4 pm was considered to have met the composite outcome threshold. RESULTS: At 8 am, the mean central subfield thickness was 368 microm and the mean visual acuity was 66 letters (approximately 20/50). The mean change in relative central subfield retinal thickening between 8 am and 4 pm was a decrease of 6% (95% confidence interval, -9% to -3%) and the mean absolute change was a decrease of 13 microm (95% CI, -17 to -8). The absolute change was significantly greater in retinas that were thicker at 8 am (P<.001) but the relative change was not (P = .14). The composite threshold of reduction in central subfield thickening (as defined above) was observed in 5 eyes of 4 subjects (3% of eyes; 95% CI, 1% to 8%) while 2 eyes of 2 subjects (1%; 95% CI, 0% to 5%) had an increase in central subfield thickening of this same magnitude. The maximum decrease was observed at 4 pm in all 5 eyes. CONCLUSION: Although on average there are slight decreases in retinal thickening during the day, most eyes with diabetic macular edema have little meaningful change in OCT central subfield thickening between 8 am and 4 pm.

Anonymous00052, Browning DJ, Glassman AR, Aiello LP, Beck RW, Brown DM, Fong DS, Bressler NM, Danis RP, Kinyoun JL, Nguyen QD, Bhavsar AR, Gottlieb J, Pieramici DJ, Rauser ME, Apte RS, Lim JI, Miskala PH. · Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. · Ophthalmology. · Pubmed #17123615 links to  free full text

Abstract: OBJECTIVE: To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: Two hundred ten patients (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. METHODS: Retinal thickness was measured with OCT and visual acuity was measured with the electronic Early Treatment of Diabetic Retinopathy procedure. MAIN OUTCOME MEASURES: Optical coherence tomography-measured center point thickness and visual acuity. RESULTS: The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months after laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% confidence interval, 3.5-5.3) of better of visual acuity for every 100-mum decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44, with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7%-17% at the 3 time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%-26% at the 3 time points). CONCLUSIONS: There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity after focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema. Thus, although OCT measurements of retinal thickness represent an important tool in clinical evaluation, they cannot substitute reliably as a surrogate for visual acuity at a given point in time. This study does not address whether short-term changes on OCT are predictive of long-term effects on visual acuity.