The specific objectives of this report are as follows:
- To identify the optimal OCT measurement for central macular thickening in DME
- To identify roles for paracentral and global macular OCT measurements and explore correlations between these measurements and their changes in DME and treatments for DME
- To identify limitations and advantages in three methods 87 of analysis of OCT measurement changes
- Absolute change in thickness
- Relative change in thickness
- Relative change in thickening
Data reported derive from two studies performed by the Diabetic Retinopathy Clinical Research Network (DRCR.net): a randomized trial comparing modified ETDRS style focal laser photocoagulation to mild macular grid laser photocoagulation for DME (mETDRS vs MMG trial),12
and an observational study of diurnal variation in DME (diurnal variation study)2
. In each study, various OCT measurements were endpoints for analysis. Experience in analyzing OCT data in these studies led to preferred variables and methods of analysis with associated rationales for the preferences resulting from exploratory and comparative analyses. We report the current Network preferences with examples from our data sets which motivated the preferred choices and provide plausibility.
The preponderance (>99%) of data collected in DRCR.net studies has been from the Zeiss OCT3 machine. Although the data can be displayed in either 3.45 mm or 6.0 mm formats, by convention all OCT tests for DRCR.net protocols have used the 6.0 mm format. OCT tests were analyzed at the reading center of the University of Wisconsin, Madison. For OCT tests requiring manual grading, central subfield macular thickness (CSMT) was imputed from the manually graded center point thickness (CPT) by using a regression equation CSMT = CPT*0.84 + 63.6.12
Because of the variable terminology in OCT studies, we define several terms. (available at http://aaojournal.org
) cross references these terms to synonyms in the literature.
Synonymous Terms in the Optical Coherence Tomography Literature
the value in microns of the distance between the OCT layers assumed to be the retinal pigment epithelium and the internal limiting membrane. This ignores artifactitious designation of the outer segment inner segment junction as the retinal pigment epithelium in scans obtained with the OCT3.9
the calculated value equal to the thickness minus the population mean for the variable under consideration (either CPT or CSMT). The normative value chosen should be specified as these values differ according to source.13–15
Center Point (CP)
the intersection of the six radial scans of the fast macular thickness protocol of the OCT.
Center Point Thickness (CPT)
the average of the thickness values for the 6 radial scans at their point of intersection.
Central Subfield (CS)
the circular area of diameter 1 mm centered around the center point; 128 thickness measurements are made in this circular area in the fast mac protocol.
Central Subfield Mean Thickness (CSMT)
the mean value of the 128 thickness values obtained in the central subfield.
Absolute Change in Thickness
the difference in the thickness between two measurements made at different times. For example, if measurements M1 and M2 are made at two different times, then the absolute change in thickness equals M2-M1. The absolute change in thickness is equal to the absolute change in thickening, which is the first of three methods of analyzing OCT changes listed above.
Relative Change in Thickness
the absolute change in thickness divided by the baseline thickness. Using the symbols introduced previously, relative thickness equals [(M2-M1)/M1]·100%, which is the second of three methods of analyzing OCT changes.
Relative Change in Thickening
the absolute change in thickness (or thickening) divided by the baseline thickening. Using the symbols introduced previously, relative change in thickening equals [(M2-M1)/(M1-normative mean)]·100%, which is the third of three methods of analyzing OCT changes.
In comparing the methods of data analysis for change in OCT measurements, three approaches were used. The first was to visually inspect the distribution of the OCT measurement changes recorded using the three different methods to ascertain normality and the extent of outliers. This approach was used for the data sets from both studies. The second was to perform parallel analyses of the eye and subject specific factors associated with OCT measurement changes recorded under the three methodologies to determine concordance or discordance of the predictive factors of the three methods. The third was to determine whether statistical comparisons of treatment group outcomes gave meaningfully different results according to which of the three methods was used. The second and third approaches could be applied only to the mETDRS vs. MMG trial. We used the entire dataset from the mETDRS vs. MMG trial for the second and third approaches, and did not exclude the eyes with CSMT <250 microns as was done in an earlier publication from this trial.12