Macular Degeneration: Browning DJ

Browning DJ, Altaweel MM, Bressler NM, Bressler SB, Scott IU, Anonymous00050. · Jaeb Center for Health Research, Tampa, FL 33647, USA. · Am J Ophthalmol. · Pubmed #18774122 No free full text.

Abstract: PURPOSE: To review the available information on classification of diabetic macular edema (DME) as focal or diffuse. DESIGN: Interpretive essay. METHODS: Literature review and interpretation. RESULTS: The terms focal diabetic macular edema and diffuse diabetic macular edema frequently are used without clear definitions. Published definitions often use different examination methods and often are inconsistent. Evaluating published information on the prevalence of focal and diffuse DME, the responses of focal and diffuse DME to treatments, and the importance of focal and diffuse DME in assessing prognosis is hindered because the terms are used inconsistently. A newer vocabulary may be more constructive, one that describes discrete components of the concepts such as extent and location of macular thickening, involvement of the center of the macula, quantity and pattern of lipid exudates, source of fluorescein leakage, and regional variation in macular thickening and that distinguishes these terms from the use of the term focal when describing one type of photocoagulation technique. Developing methods for assessing component variables that can be used in clinical practice and establishing reproducibility of the methods are important tasks. CONCLUSIONS: Little evidence exists that characteristics of DME described by the terms focal and diffuse help to explain variation in visual acuity or response to treatment. It is unresolved whether a concept of focal and diffuse DME will prove clinically useful despite frequent use of the terms when describing management of DME. Further studies to address the issues are needed.

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.

Do DV, Nguyen QD, Shah SM, Browning DJ, Haller JA, Chu K, Yang K, Cedarbaum JM, Vitti RL, Ingerman A, Campochiaro PA. · The Wilmer Eye Institute, 600 North Wolfe Street, Maumenee #719, Baltimore, MD 21287, USA. · Br J Ophthalmol. · Pubmed #19174400 No free full text.

Abstract: AIM: The aim of the study was to assess the safety and bioactivity of a single intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye in subjects with diabetic macular oedema (DMO). METHODS: Five subjects with DMO, foveal thickness > or =250 microm measured by optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) between 20/40 and 20/320, were enrolled. Each participant received a single intravitreal injection of 4.0 mg of VEGF Trap-Eye followed by a 6-week observation period. Outcome measures included safety and biological activity, including changes in BCVA and excess retinal thickness assessed by OCT. RESULTS: Injections of VEGF Trap-Eye were well tolerated with no ocular toxicity. One patient had an unrelated serious adverse event: hospitalisation for cellulitis of the left foot 27 days after injection of VEGF Trap-Eye. Median baseline BCVA was 36 ETDRS letters read at 4 m (not ETDRS visual acuity score; Snellen equivalent: 20/50) and median baseline excess central 1 mm foveal thickness (FTH) was 108 microm. At 4 weeks after injection, the median excess FTH was 59 microm and the median improvement in BCVA was nine letters. At 6 weeks after injection, four of the five patients showed improvement in excess FTH (median 74 microm; 31% reduction from baseline, p = 0.0625) and four of the five showed improvement in BCVA (median improvement of three letters). CONCLUSIONS: A single intravitreal injection of 4.0 mg of VEGF Trap-Eye was well tolerated and preliminary evidence of bioactivity was detected. These findings support additional studies investigating multiple injections of VEGF Trap-Eye in patients with DMO.

Scott IU, Bressler NM, Bressler SB, Browning DJ, Chan CK, Danis RP, Davis MD, Kollman C, Qin H, Anonymous00398. · Pennsylvania State University College of Medicine, Hershey, PA, USA. · Retina. · Pubmed #18185135 links to  free full text

Abstract: PURPOSE: To evaluate agreement in diabetic retinopathy severity classification by retina specialists performing ophthalmoscopy versus reading center (RC) grading of seven-field stereoscopic fundus photographs in a phase 2 clinical trial of intravitreal bevacizumab for center-involved diabetic macular edema. METHODS: Clinicians' grading scale used four levels: microaneurysms only, mild/moderate nonproliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR) or prior panretinal photocoagulation (PRP) or both. The RC scale used eight levels: microaneurysms only, mild NPDR, moderate NPDR, moderately severe NPDR, severe NPDR, mild PDR, moderate PDR, and high-risk PDR. Percent agreement and kappa statistic were defined by collapsing RC categories to match those used by clinicians. RESULTS: There was agreement in 89/118 eyes (75%) with kappa = 0.55 (95% confidence interval [0.41, 0.68]). In six eyes, disagreements were of potential substantial clinical importance: five eyes with subtle retinal neovascularization and one with a small preretinal hemorrhage identified only in photographs. CONCLUSIONS: Clinician grading of retinopathy severity had moderate agreement with RC grading and might be useful for placing eyes into broad baseline categories.

Scott IU, Danis RP, Bressler SB, Bressler NM, Browning DJ, Qin H, Anonymous00054. · Department of Ophthalmology and Public Health Sciences, Penn State Hershey Eye Center, Penn State College of Medicine, Hershey, Pennsylvania, USA. · Retina. · Pubmed #19373126 No free full text.

Abstract: PURPOSE: To report visual acuity and anatomic changes from baseline to 12 months after modified Early Treatment Diabetic Retinopathy Study (ETDRS)-style (focal/grid) photocoagulation in eyes with non-center-involved (non-CI) clinically significant macular edema. METHODS: Visual acuity, optical coherence tomography, fluorescein angiography, and fundus photography data were analyzed from eyes with non-CI clinically significant macular edema treated with modified ETDRS-style (focal/grid) photocoagulation in a Diabetic Retinopathy Clinical Research Network trial. RESULTS: Among the 22 eyes (of 22 patients) with 12-month follow-up, median visual acuity letter score remained within 1 letter of baseline over 12 months. The median central subfield retinal thickness decreased by 10 mum, median total macular volume decreased by 0.2 mm, and median fluorescein leakage area within the grid decreased by 0.7 disk areas. CONCLUSION: We are unaware of any other systematic evaluation of eyes with non-CI clinically significant macular edema since the ETDRS. Focal/grid laser in these non-CI eyes was associated with relatively stable visual acuity and retinal thickness measurements, and decreased fluorescein leakage area at 1 year. One-year visual acuity results are consistent with those published by the ETDRS, despite the intervening significant differences in the management of diabetes. Although this was a small study without a concurrent control group, the ETDRS recommendation to consider focal/grid laser in eyes with non-CI clinically significant macular edema still seems appropriate.

Browning DJ, Apte RS, Bressler SB, Chalam KV, Danis RP, Davis MD, Kollman C, Qin H, Sadda S, Scott IU, Anonymous00031. · Charlotte Eye Ear Nose and Throat Assoc, PA, Charlotte, North Carolina, USA. · Retina. · Pubmed #19174719 No free full text.

Abstract: PURPOSE: To determine whether the extensiveness of diabetic macular edema using a 10-step scale based on optical coherence tomography explains pretreatment variation in visual acuity and predicts change in macular thickness or visual acuity after laser photocoagulation. METHODS: Three hundred twenty-three eyes from a randomized clinical trial of two methods of laser photocoagulation for diabetic macular edema were studied. Baseline number of thickened optical coherence tomography subfields was used to characterize diabetic macular edema on a 10-step scale from 0 to 9. Associations were explored between baseline number of thickened subfields and baseline fundus photographic variables, visual acuity, central subfield mean thickness (CSMT), and total macular volume. Associations were also examined between baseline number of thickened subfields and changes in visual acuity, CSMT, and total macular volume at 3.5 and 12 months after laser photocoagulation. RESULTS: For baseline visual acuity, the number of thickened subfields explained no more variation than did CSMT, age and fluorescein leakage. A greater number of thickened subfields was associated with a greater baseline CSMT, total macular volume, area of retinal thickening, and degree of thickening at the center of the macula (r = 0.64, 0.77, 0.61-0.63, and 0.45, respectively) and with a lower baseline visual acuity (r = 0.38). Baseline number of thickened subfields showed no association with change in visual acuity (r < or = 0.01-0.08) and weak associations with change in CSMT and total macular volume (r from 0.11 to 0.35). CONCLUSION: This optical coherence tomography based assessment of the extensiveness of diabetic macular edema did not explain additional variation in baseline visual acuity above that explained by other known important variables nor predict changes in macular thickness or visual acuity after laser photocoagulation.

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.

Browning DJ, Fraser CM, Propst BW. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. · Am J Ophthalmol. · Pubmed #18329622 No free full text.

Abstract: PURPOSE: To determine the variation in optical coherence tomography (OCT)-measured macular thickness in diabetic eyes without clinical edema and to investigate factors that might influence variation in macular thickness. DESIGN: Retrospective, observational case series from a clinical practice. METHODS: Review of clinical charts and longitudinal OCT measurements of a consecutive series of 56 eyes of 56 patients with diabetes but no clinical macular edema. Measured variables include OCT central subfield mean thickness (CSMT), total macular volume (TMV), and logarithm of the minimum angle of resolution (logMAR) visual acuity. RESULTS: Over a median follow-up of 17 months, interquartile range (IQR) (9, 23), the median variation in CSMT was 18 microns, IQR (11, 31), and the median variation in TMV was 0.09 mm(3), IQR (0.06, 0.16). Variation in CSMT did not change significantly with increasing CSMT. Absolute, but not relative, variation in TMV increased with increasing baseline values (P = .0127 and P = .1538 for absolute variation and relative variation in TMV, respectively). The variation in CSMT and TMV did not vary with follow-up time and did not vary with age, gender, race, hypertension status, glycosylated hemoglobin, or retinopathy level. CONCLUSIONS: Variation in CSMT and TMV in diabetic eyes without DME over intervals up to 17 months is no greater than OCT measurement variability in eyes without and with DME. A change in the OCT-measured macular thickness greater than 10% of the baseline thickness is likely to represent a true change in the macular thickness and not OCT measurement variability, diurnal variation, or variability occurring over longer time scales.

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.

Browning DJ, Fraser CM, Clark S. · Charlotte Eye, Ear, Nose, and Throat Associates, PA, Charlotte, North Carolina, USA. · Ophthalmology. · Pubmed #18067962 No free full text.

Abstract: PURPOSE: To examine the relationship of optical coherence tomography (OCT) measured macular thickness to retinopathy severity in patients with diabetes and no clinically detectable macular edema. DESIGN: Retrospective observational case series. PARTICIPANTS: Three hundred eighty-three eyes of 383 patients of a private retina practice; including 100 normal eyes of patients without diabetes, 100 eyes of diabetics without retinopathy, 100 eyes of diabetics with mild to moderate retinopathy, 35 eyes of diabetics with severe nonproliferative or proliferative retinopathy, and 48 eyes of diabetics with regressed proliferative retinopathy. METHODS: Review of clinical charts and optical coherence tomography measurements. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT), inner and outer zone measurements, and total macular volume. RESULTS: Central subfield mean thicknesses (mean +/- standard deviation) were 208+/-22, 198+/-25, 204+/-26, 224+/-38, and 205+/-27 microm for normals, eyes of diabetics without retinopathy, eyes with mild to moderate nonproliferative retinopathy, eyes with severe nonproliferative to proliferative retinopathy, and eyes with regressed proliferative retinopathy, respectively. For all groups, mean CSMT was larger in males than in females. Statistically significant differences by gender were observed for normals, diabetics without retinopathy, and diabetics with mild to moderate nonproliferative retinopathy (mean differences, 12, 14, and 18 microm, respectively; Ps = 0.0057, 0.0057, and 0.0002). For increasing retinopathy severity, the probability of macular thickening detected by OCT but not detected by clinical examination increased. Fifteen percent of eyes with severe nonproliferative or proliferative retinopathy and no clinically detected edema had OCT-measured macular thickening. CONCLUSIONS: Because OCT measurements are gender dependent, gender balance or statistical adjustment for gender imbalances of compared groups in OCT studies of diabetic macular edema is important. As retinopathy severity increases, the probability of subclinical edema rises. Except for an individual baseline measurement possibly useful for longitudinal comparison, the data suggest that there is little reason routinely to obtain OCT in eyes with diabetes and no retinopathy or mild to moderate diabetic retinopathy when clinical examination fails to show macular edema.

Browning DJ, Fraser CM. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. · Am J Ophthalmol. · Pubmed #17997393 No free full text.

Abstract: PURPOSE: To define the course of subclinical diabetic macular edema (DME) and identify any predictors of progression to clinically significant DME. DESIGN: Retrospective, observational case series. METHOD: Setting: Private retina practice. Patient population: One hundred and fifty-three eyes of 153 patients with diabetic retinopathy and subclinical DME. Observation procedures: Clinical charts review and longitudinal optical coherence tomography (OCT) measurements. Main outcome measures: Change in OCT values and time to eventual treatment for clinically significant DME. RESULTS: Over a median follow-up of 14 months (interquartile range, seven to 25 months), 48 of 153 eyes (31.4%) progressed to clinically significant DME. The numbers (%) of eyes showing decreased, unchanged, and increased central subfield mean thickness were 16 (10.5%), 117 (76.5%), and 20 (13.1%), respectively. None of the patients or eye variables typically assessed in clinical practice was predictive of progression from subclinical DME to clinically significant DME. CONCLUSIONS: Progression from subclinical DME to clinically significant DME may be detected by serial clinical and OCT assessment. Subclinical DME does not inexorably progress over time scales of one to two years, and a substantial fraction of eyes spontaneously improve. Follow-up intervals of four to six months allowed detection of progression to clinically significant DME. In this sample of patients, OCT did not help in predicting which eyes with subclinical DME would progress to clinically significant DME.

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.

Browning DJ, Fraser CM, Powers ME. · Charlotte Eye, Ear, Nose, and Throat Associates, PA, Charlotte, North Carolina, USA. · Ophthalmic Surg Lasers Imaging. · Pubmed #17017466 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: To provide a tool for analyzing optical coherence tomography data in patients with diabetic macular edema. PATIENTS AND METHODS: Retrospective series of 206 patients with diabetic macular edema involving at least one eye and receiving focal laser photocoagulation, intravitreal triamcinolone acetonide injection, or vitrectomy, membrane peeling, and intravitreal triamcinolone acetonide injection, and of untreated fellow eyes without diabetic macular edema. Main outcome measures included foveal subfield mean thickness and thickening relative to normal (microns), total macular volume and its increase relative to normal (mm3), visual acuity (Snellen decimal), and intraocular pressure (mm Hg). RESULTS: The authors demonstrate a graphical display of data based on a spreadsheet template for the longitudinal management of diabetic macular edema. Complex relationships of ocular response and interventions are concisely displayed. CONCLUSION: A graphical display of optical coherence tomography, visual acuity, and intraocular pressure data is a practical aid in the management of diabetic macular edema.

Browning DJ, Fraser CM, Powers ME. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. · Ophthalmology. · Pubmed #16889833 No free full text.

Abstract: PURPOSE: To determine estimates of the magnitude and time course of macular thinning induced by three interventions for diabetic macular edema (DME). DESIGN: Retrospective observational case series. PARTICIPANTS: Two hundred eleven eyes of 133 patients of a private retina practice, each diagnosed with DME in > or =1 eye. METHODS: Review of clinical charts and optical coherence tomography measurements of eyes receiving focal laser photocoagulation, intravitreal triamcinolone injection (IVTA), or vitrectomy compared to untreated fellow eyes without DME. MAIN OUTCOME MEASURES: Central subfield mean thickness (CSMT; in micrometers), total macular volume (cubic millimeters), visual acuity, and rates of increased macular thickening at follow-up. RESULTS: At 6 months follow-up, predicted change in CSMT is 0 mum for untreated fellow eyes without DME, -28 mum for eyes receiving focal laser, -83 mum for eyes receiving triamcinolone, and -92 mum for eyes receiving vitrectomy. The predicted change in Early Treatment Diabetic Retinopathy Study letters read at 6 months is 0 for untreated fellow eyes without DME, 0 for eyes receiving focal laser, +3 for eyes receiving IVTA, and -1 for eyes receiving vitrectomy. Increased thickening of the macula after interventions designed to thin it were 25.4% for focal laser, 3.8% for IVTA, and 19.0% for vitrectomy. CONCLUSIONS: Interventions for DME differ in effect size, durability of effects, and potential for subsequent increases in macular thickness. A prospective study to elucidate a preferred sequence of interventions in DME may be worthwhile.

Browning DJ, Fraser CM. · Charlotte Eye, Ear, Nose, and Throat Associates, North Carolina, USA. · Am J Ophthalmol. · Pubmed #15953575 No free full text.

Abstract: PURPOSE: To define regional patterns of macular thickening in diabetic macular edema (DME). DESIGN: Retrospective case series. METHODS: SETTING: Retina practice. PATIENT POPULATION: Fifty-two normal eyes of 48 patients and 100 eyes of 80 patients with DME. EXPERIMENTAL PROCEDURE: We measured retinal thickness for nine zones and total macular volume using the 3.5-mm display of an optical coherence tomograph (OCT). We determined the normal ranges of values for zones, and then normal ranges of values for the difference in thickness between each pair of zones, termed comparisons. main outcome measures: Frequencies of increased zonal thickness, increased total macular volume, and abnormalities in zonal comparisons. RESULTS: We found the following abnormalities: increased total macular volume 49% (49/100), increased foveal zone thickness 46% (46/100), increased inner parafoveal zone thickness (average 42.2% for the four zones), and increased outer zone thickness (average 34.3% for the four zones). Abnormal two-zone comparisons were found in 1027 of the 7200 possible comparisons (14.3%). Of these abnormal comparisons, the fovea was thicker relative to another zone in 26%; the four inner parafoveal zones were thicker relative to other zones in 8.7% to 15.2% (average 13.0%); and the four outer zones were thicker relative to other zones in 3.9% to 7.6% (average 6%). Eighty-eight percent (88/100) of the eyes chosen on clinical grounds as needing focal laser photocoagulation were detected. CONCLUSION: A broader concept of OCT abnormality, which includes abnormalities in zonal relationships, may improve automated detection of DME compared with clinical judgment.

Browning DJ, Fraser CM. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina, USA. · Ophthalmology. · Pubmed #15882903 No free full text.

Abstract: OBJECTIVE: To determine frequency and outcomes of conditions with peripapillary subretinal neovascular membranes (PSRNVMs). DESIGN: Retrospective observational case series. PARTICIPANTS: All patients from a private community-based retina practice diagnosed with a PSRNVM. METHODS: Review of clinical charts, photographs, and fluorescein angiograms of 115 eyes of 96 patients, accrued over 18 years. MAIN OUTCOME MEASURES: Demographics, visual acuity (VA), laterality, neovascular membrane type and recurrence status over treatment course, and associated ocular conditions. RESULTS: Prevalences of reported associations were 52 (45.2%), age-related maculopathy (ARM); 45 (39.1%), idiopathic; 5 (4.3%), multifocal choroiditis; 3 (2.6%), angioid streaks; 2 (1.7%), histoplasmosis; 2 (1.7%), choroidal osteoma; 1 (0.9%), optic disc drusen; and 1 (0.9%), congenital disc anomaly. Newly recognized associations include pattern dystrophy (3 [2.6%]) and peripapillary pseudopodal pigment epithelial and choroidal atrophy (1 [0.9%]). Second-eye involvement was observed in 19.8% of patients over a median follow-up of 2 years. Median initial VAs were 20/40 for ARM-associated eyes and 20/30 for idiopathic eyes (P = 0.0230). Median final VAs were 20/70 for ARM-associated eyes and 20/32 for idiopathic eyes (P = 0.0261). The VA changes in the ARM-associated and idiopathic groups did not differ significantly (P = 0.1453). Recurrence of PSRNVMs after laser ablation was seen in 14 of 73 eyes (19.2%). A case of a PSRNVM as a cause of pseudopapilledema leading to unnecessary neurological imaging is reported. CONCLUSIONS: Close inspection of fellow eyes at the time of first eye diagnosis and regular follow-up afterward are indicated, given the high rate of eventual bilateral involvement regardless of associated condition. Laser ablation of PSRNVMs with broad treatment margins reduces recurrence rates relative to earlier series. The differential diagnosis of disc edema should include PSRNVMs. Pattern dystrophy can be associated with PSRNVMs.

Browning DJ. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210, USA. · Am J Ophthalmol. · Pubmed #15183798 No free full text.

Abstract: PURPOSE: To assess the interobserver variability of optical coherence tomography (OCT) measurements in patients with macular edema. DESIGN: Noninterventional case series using a diagnostic instrument. METHODS: Ordinary least products analysis of OCT data obtained by two masked observers from a set of 20 eyes from 10 patients. SETTING: Private retina practice. RESULTS: Foveal zone thickness measurements were operator dependent. Fixed and proportional bias was found between the two observers. Total macular volume measurements were independent of observers. CONCLUSION: Foveal zone thickness measurements are not directly comparable across different observers, but total macular volume measurements are directly comparable. Multicenter studies involving OCT measurements and clinical users of OCT data will need to factor interobserver variability into conclusions drawn from pooled OCT foveal zone thickness measurements.

Browning DJ, Fraser CM. · Charlotte Eye, Ear, Nose, and Throat Associates, 6035 Fairview Road, Charlotte, NC 28210, USA. · Am J Ophthalmol. · Pubmed #15126175 No free full text.

Abstract: PURPOSE: To propose the use of optical coherence tomography as an effective diagnostic tool for identifying macular edema in patients with asteroid hyalosis obscuring the fundus view. DESIGN: Case report. METHODS: Review of clinical chart and images. SETTING: Private retina practice. PATIENT: One patient diagnosed with diabetic retinopathy and asteroid hyalosis, who was experiencing decreased visual acuity and whose fundus view was inadequate for diagnosis using customary techniques. RESULTS: Usual methods of diagnosis were ineffective until OCT obtained a clear image of the fundus and subsequent macular thickening with vitreomacular adhesion. CONCLUSIONS: Optical coherence tomography is an effective diagnostic tool for discovering macular edema in cases of dense asteroid hyalosis where traditional methods fail to obtain a clear image of the fundus.

Browning DJ, McOwen MD, Bowen RM, O'Marah TL. · Charlotte Eye, Ear, Nose, and Throat Associates, 6035 Fairview Road, Charlotte, NC 28210, USA. · Ophthalmology. · Pubmed #15051203 No free full text.

Abstract: PURPOSE: To compare the diagnosis of diabetic macular edema (DME) by stereoscopic slit-lamp biomicroscopic examination of the fundus with a 78-diopter noncontact lens with diagnosis by optical coherence tomography (OCT). DESIGN: Prospective, double-masked, noninterventional diagnostic study. METHODS: Analysis of slit-lamp biomicroscopic findings compared with OCT measurements. PARTICIPANTS: Patients with DME from a private retina practice. MAIN OUTCOME MEASURES: Presence or absence of macular thickening. RESULTS: The reference range for this clinic was comparable to reference ranges published from other clinics. The clinical detection of DME was less than detection by OCT. Chance-corrected agreements (kappa statistic) of the 2 methods were 0.63 for the foveal zone and 0.36 to 0.42 for the 4 parafoveal zones. The errors committed in clinical examination were primarily of the type in which clinical examination did not detect DME but OCT did (58%-90%) for the 5 zones analyzed. CONCLUSIONS: Reference ranges for OCT seem to be similar for different clinical settings, suggesting the usefulness of OCT in multicenter studies. The current standard of care for DME detection, stereoscopic slit-lamp examination of the fundus, is less sensitive than OCT for detection of DME. Because the principal therapy for DME, focal laser photocoagulation, is mainly sight preserving and not sight restoring, the wider use of OCT may beneficially impact visual disability from DME.

Browning DJ. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210, USA. · Am J Ophthalmol. · Pubmed #14700665 No free full text.

Abstract: PURPOSE: To report a positioning method for macular laser photocoagulation in obese or large-breasted patients. DESIGN: Report of a laser technique. METHODS: Review of clinical experience. SETTING: Private retina practice. RESULTS: Standing the patient up, leaning forward, and using the examination chair as buttocks support allows easier positioning of the obese or large-breasted patient in the slit lamp. The laser surgeon's hand manipulating the slit-lamp joystick does not fatigue, which allows more careful examination and treatment in these delicate cases. CONCLUSIONS: The technique described may allow more thorough diagnostic evaluation and focal laser treatment of obese and large-breasted patients with macular diseases.

Browning DJ. · Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina 28210, USA. · Am J Ophthalmol. · Pubmed #12967819 No free full text.

Abstract: PURPOSE: To describe potential pitfalls in the use of optical coherence tomography for management of diabetic macular edema. DESIGN: Prospective, noninterventional case series. METHODS: Review of optical coherence tomographs in 13 eyes with clinically significant diabetic macular edema from 11 consecutive patients in a private retina practice. RESULTS: Optical coherence tomography displays are based on 3.5-mm or 6-mm diameter circular grids that look very similar and have identical sector names but schematize different areas of the macula. The numeric outputs for the identically named sectors in the two displays do not differ significantly for retinal thickness but differ significantly in all sectors except the fovea for retinal volume because of the different areas represented by the sectors. CONCLUSIONS: Failure to explicitly note the scale of the optical coherence tomography display can potentially misdirect planned focal and grid laser treatment for diabetic macular edema. Failure to explicitly verify identical optical coherence tomography display scales in longitudinal studies of laser treatment for diabetic macular edema can potentially lead to errors in interpreting treatment efficacy.

Browning DJ. · No affiliation provided · Retina. · Pubmed #18667948 No free full text.

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