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A Standardized Method for Reporting Changes in Macular Thickening Using Optical Coherence Tomography
Annie Chan, BS;
Jay S. Duker, MD
Arch Ophthalmol. 2005;123:939-943.
ABSTRACT
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Objective To describe a standardized method for reporting quantitative changes in macular thickening using optical coherence tomography (OCT).
Methods The proposed method consists of calculating the actual change in central foveal thickening (the initial pretreatment thickness minus the posttreatment thickness) using OCT and dividing that value by the potential change (the initial pretreatment thickness minus the normal thickness based on normative data) to provide the total improvement in macular edema as a percentage. We refer to this method as the standardized change in macular thickening (SCMT). To illustrate the effectiveness of this method, we performed a retrospective review of 2 studies that evaluated different strategies for treating refractory macular edema.
Results Patients treated with intravitreal triamcinolone acetonide for refractory diabetic macular edema had an overall SCMT of approximately 75%, 78%, and 55% at the 1-, 3-, and 6-month follow-up visits, respectively. More than half of the patients in the study cohort (9 of 16 patients) experienced greater than 80% SCMT at the last follow-up visit. Patients who underwent vitrectomy for a taut, thickened posterior hyaloid on OCT responded with an SCMT of approximately 78% at the 3-month follow-up visit and 87% at the final follow-up visit (mean, 19 months). Patients who underwent vitrectomy for diabetic macular edema unresponsive to laser photocoagulation but with no evidence of vitreomacular traction experienced an SCMT of 37% at the 3-month follow-up visit and 20% at the final follow-up visit (mean, 17 months).
Conclusion The proposed method offers an objective and intuitive basis for evaluating and comparing the efficacy of different therapeutic modalities.
INTRODUCTION
Optical coherence tomography (OCT) has become a valuable imaging modality in the evaluation and management of various macular diseases, particularly with regard to diseases that result in abnormal macular thickness, such as macular edema. Traditionally, physicians rely mainly on fluorescein angiography to assess the integrity of the blood-retinal barrier and on stereoscopic fundus photography to qualitatively detect changes in retinal thickness. Recently, OCT was found to be in good agreement with the clinical gold standard (slitlamp examination through a dilated pupil with a contact lens) for detecting the presence or absence of macular edema and was found to be potentially more sensitive in cases of mild foveal thickening.1 The Early Treatment Diabetic Retinopathy Study used slitlamp biomicroscopy and/or stereoscopic fundus photography to diagnose diabetic macular edema and to evaluate the role of laser photocoagulation.2 The conventional methods are able to detect approximately 80% of local areas of retinal thickening but are relatively insensitive to small changes in thickness or diffuse areas of thickening.3 Since the accumulation of fluid can be due to the breakdown of the blood-retinal barrier, fluorescein angiography is routinely performed to detect areas of leakage. However, evidence exists that the amount of leakage does not correlate with the degree of thickening.4 In response, several instruments have been developed to quantitatively assess macular thickness. Optical coherence tomography has emerged as a useful tool for quantitatively measuring foveal thickness in a reliable and reproducible manner.5-10
Currently, in the literature and in clinical practice, no uniform method exists for reporting changes in macular thickness. Some articles report the absolute values of macular thickness before and after treatment (eg, 450 µm pretreatment and 300 µm posttreatment). Other articles report the percentage change in macular thickness (eg, a decline from 450 to 300 µm equals a 33.3% reduction). Given that the baseline for normal macular thickness is not zero (instead it ranges from 133 to 182 µm, depending on the OCT unit),5-8,11-15 it is difficult for physicians to objectively compare the different therapies that are available. Rather than reporting percentage changes from baseline or the actual values of central macular thickness before and after treatment, we propose a standardized method for reporting changes in macular thickness as a percentage of total possible change based on normative OCT data. To illustrate the facility of this clinical method, we reviewed and compared 2 studies that evaluated different strategies for treating diffuse macular edema refractory to standard laser photocoagulation. In the first study, Martidis et al16 evaluated intravitreal triamcinolone acetonide as a treatment for refractory macular edema. In the second study, Massin et al17 used OCT to evaluate diabetic macular edema before and after vitrectomy for 2 groups of patients. In group 1, vitrectomy was performed because vitreomacular traction was seen on biomicroscopy or OCT. In group 2, vitrectomy was performed for diabetic macular edema unresponsive to laser photocoagulation, with no vitreomacular traction noted during biomicroscopy or OCT examination. Our article describes a standardized method for reporting changes in macular thickening and compares the 2 clinical studies that used this method to demonstrate its usefulness.
METHODS
After reviewing the literature, 2 studies that used different strategies to treat refractory macular edema were selected for further review. A method for reporting changes in macular thickening was designed and used for all the patients in the studies. We refer to this method as the standardized change in macular thickening (SCMT). The SCMT reflects the total percentage improvement observed in the patient. First, we calculated the actual change in central foveal thickness by subtracting the posttreatment central foveal thickness from the initial pretreatment central foveal thickness. The central foveal thickness is defined as the mean thickness at the point of intersection of 6 radial scans. We used this value in our calculations because this was the value used in both studies for tracking the change in macular edema. (Alternatively, we could have used the foveal thickness, the mean thickness in the central 1000-µm-diameter area, shown as the central area in the Figure.) Second, we divided this number by the potential change, which is determined by subtracting the normal central foveal thickness (151 µm for the prototype OCT,5-6,11 148 µm for the commercial OCT,7-8,12-15 and 182 µm for the Stratus OCT [OCT3; Carl Zeiss Meditec, Dublin, Calif]16) from the initial pretreatment central foveal thickness. Because both studies used either the prototype OCT system or a commercially available machine based on the prototype (OCT1), normative central foveal thickness values were based on those systems. If complete resolution of macular edema occurred, this method would produce an SCMT of 100%.
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Figure. Normative macular thickness measurements (in micrometers) on the Stratus OCT (OCT3; Carl Zeiss Meditec, Dublin, Calif) in a healthy population. Mean ± SD central foveal thickness (mean thickness at the point of intersection of 6 radial scans) equals 182 ± 23 µm.18
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RESULTS
For case 1 in the first study, the investigators reported central foveal thickness using the prototype OCT to be 378, 214, and 236 µm at 1-, 3-, and 6-month follow-up intervals, respectively (Table 1). The initial central foveal thickness was 612 µm before intravitreal triamcinolone injection. The formula for determining the SCMT is as follows:
SCMT = [actual change] / [potential change] = [initial thickness – final thickness] / [initial thickness – 151 µm]
The formulas for determining the SCMT at the follow-up visits are as follows:
At 1-month follow-up:
([actual change] / [potential change] = [612 µm – 378 µm] / [612 µm – 151 µm]) x 100 = 51% improvement
At 3-month follow-up:
([612 µm – 214 µm] / [612 µm – 151 µm]) x 100 = 86% improvement
At 6-month follow-up:
([612 µm – 236 µm] / [612 µm – 151 µm]) x 100 = 82% improvement
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Table 1. Results of Intravitreal Triamcinolone Injection on Refractory Diabetic Macular Edema
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We performed the same calculations for all 16 patients in the first study and all 15 patients in the second study. The results are given in Table 1 and Table 2. A comparison of the 2 studies is given in Table 3.
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Table 2. Results of Vitrectomy for Diabetic Macular Edema With or Without Vitreomacular Traction
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Table 3. Comparison of Different Treatments for Diffuse Macular Edema Using Optical Coherence Tomography
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In the first study by Martidis et al,16 the overall improvements in macular edema, represented as the SCMT, at the 1-, 3-, and 6-month follow-up visits were determined to be 75%, 78%, and 55%, respectively. One patient (case 5) initially responded with an SCMT of nearly 100% at the 1-month follow-up visit, but at the final visit, macular edema returned and central foveal thickness was even thicker than the baseline. In 15 (94%) of the 16 patients who responded positively to the corticosteroid injection, the mean SCMT was 70% at the final follow-up visit. More than half of the patients in the study cohort (9 of 16 patients) experienced an SCMT greater than 80% at the last follow-up visit.
According to the data in the second study led by Massin et al,17 the first group (those who underwent vitrectomy for a taut, thickened posterior hyaloid on OCT) responded with a postoperative SCMT of approximately 78% at the 3-month follow-up visit and 87% at the final follow-up visit (mean, 19 months). The second group (those who underwent vitrectomy for diabetic macular edema unresponsive to laser photocoagulation but with no evidence of vitreomacular traction) experienced a slight SCMT of approximately 37% at the 3-month follow-up visit and 20% at the final follow-up visit (mean, 17 months). In 5 (63%) of the 8 patients who responded positively to vitrectomy in the second group, the overall SCMT was 42% at the final follow-up visit. The other 3 patients had worsening macular edema, corresponding to an SCMT of –18%. Therefore, in the presence of vitreomacular traction on biomicroscopy or OCT in patients with diabetic macular edema, vitrectomy led to a much higher percentage of improvement that was sustained at the last follow-up.
COMMENT
Currently in the literature and in clinical practice, it is difficult to objectively assess and compare different therapies for macular edema because there is no uniform method for reporting changes in macular thickness. In addition, pharmaceutical companies are increasingly using OCT retinal thickness measurements as a primary or secondary end point for clinical trials of therapeutic agents for macular edema.10 In response, we propose a standardized method for reporting changes in macular thickening as a percentage of total possible change based on normative data on OCT. We believe that this method is a simple and intuitive way to compare different therapies. For example, in the first study, case 1 and case 16 had similar absolute changes in central foveal thickness at the 1-month follow-up visit (234 and 219 µm, respectively). However, the SCMT was determined to be 51% for case 1 vs 88% for case 16. Therefore, treatment was much more effective for case 16 than case 1, despite similar decreases in actual macular thickness. An SCMT of greater than 100% may suggest that the macula has actually become thinner than the baseline thickness. It is possible that long-standing macular edema may lead to tissue damage and loss. This finding may help explain poor vision despite improvement in macular edema. A negative SCMT represents a worsening in macular edema and therefore a failure of therapy. By using this method as a framework for reporting treatment outcomes, OCT can be used to compare the efficacy of current and emerging therapies, as well as monitor the progression of disease in patients.
Until recently, the literature lacked normative data, including macular thickness, for the latest commercially available OCT system, the Stratus OCT (OCT3). Frank et al19 compared measurements acquired from 8 patients with macular edema using OCT1 and OCT3 and found that the measurements from the 2 instruments were statistically different. Consequently, normative data for the OCT3 are critical. Recently, Chan et al18 used the OCT3 to determine mean ± SD foveal thickness (mean thickness in the central 1000-µm-diameter area) in 37 healthy eyes to be 212 ± 20 µm, approximately 38 to 62 µm thicker than previously reported values from earlier versions of the instrument. The mean ± SD central foveal thickness (mean thickness at the point of intersection of 6 radial scans) was also determined in healthy eyes to be 182 ± 23 µm, approximately 20 to 49 µm thicker than previously published values18 (Figure).
Foveal thickness was found to be potentially more reliable for tracking changes in the macula than central foveal thickness for several reasons. Foveal thickness is determined from many more data points than central foveal thickness. For example, each radial scan on the OCT3 is composed of a sequence of 512 A-scans. The macular thickness map scan protocol uses 6 radial scans per individual. Within the central 1000-µm-diameter area, foveal thickness is determined from 512 data points, whereas central foveal thickness is determined from only 6 data points. In addition, Chan et al18 compared manually acquired measurements of the central foveal thickness from the raw data with the automated measurements of the computer and found mean ± SD central foveal thickness to be 170 ± 18 µm, approximately 12 µm less than the value automatically obtained from the OCT3 software. This may be a reflection of the difference in approach between the manual method and the automatic method of the OCT3 mapping software. The software automatically determined the mean ± SD thickness for the center point where all 6 scans intersected, whereas the manual method located the minimum point on each separate radial scan and averaged those values. If the OCTs were not perfectly centered on the patient’s fixation for all 6 scans, the point of intersection of the radial macular scans would not correspond to the center exactly, thereby giving falsely elevated values. In a fast macular scan protocol, all 6 radial scans are acquired simultaneously, and the central foveal thickness measurement would theoretically provide a more accurate reading for that central point. Fixation loss would be less of a concern, but image resolution would be compromised in a fast macular scan protocol compared with a slow protocol. In a slow macular scan protocol, the 6 radial scans are acquired sequentially to provide more data points and may be more indicative of changes in the macula. Furthermore, the central point used to measure central foveal thickness may be difficult, if not impossible, to identify in abnormal eyes with macula edema. Foveal thickness measurements allow us to quantify the area of clinical interest in a reliable manner. Consequently, future OCT studies should report foveal thickness and use these values for determining the SCMT in evaluation of the efficacy of different therapies for macular edema. We believe that standardizing reported changes in macular thickening will help physicians and their patients better evaluate the efficacy of therapeutic intervention, as well as improve our ability to compare various treatment strategies.
AUTHOR INFORMATION
Correspondence: Jay S. Duker, MD, Tufts–New England Medical Center, New England Eye Center, 750 Washington St, Box 450, Boston, MA 02111-1533.
Submitted for Publication: May 20, 2004; final revision received October 19, 2004; accepted October 19, 2004.
Financial Disclosure: None.
Author Affiliations: New England Eye Center, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Mass.
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