This investigation was approved by the Johns Hopkins University School of Medicine institutional review board and adhered to the tenets of the Declaration of Helsinki. All subjects provided oral informed consent before participating in the study. Eligible patients were English speaking and at least 18 years of age, with type 1 or type 2 diabetes, any level of diabetic retinopathy, and a history of intravitreal anti-VEGF treatment for DME. The presence of additional ophthalmologic disease was not an exclusion criterion provided that the study investigator's decision making regarding anti-VEGF retreatment would be based primarily on changes in DME. From July 2011 through October 2011, we enrolled a convenience sample of patients presenting for routine follow-up care with one of four study investigators (SBB, DVD, HSY, NMB) at the Retina Division of the Wilmer Eye Institute (Johns Hopkins University, Baltimore, MD). All study procedures were completed during a single visit, and all study procedures were performed in addition to, and not as a substitute for, routine ophthalmologic care. One or both eyes of each patient could be enrolled in the study. If a patient presented for more than one follow-up visit during the enrollment period, each visit was eligible for enrollment.
After obtaining oral informed consent, patients underwent routine clinical examination, TD-OCT imaging, and SD-OCT imaging during the same visit. No standardized clinical examination was required as a part of the study in order to replicate the standard care methods adopted by the individual clinical practitioners. Study investigators used various examination methods, including slit-lamp biomicroscopy and indirect binocular ophthalmoscopy, as needed and at their discretion. Time-domain OCT imaging was performed using the Stratus OCT (Carl Zeiss Meditec, Inc.). Scans included the six radial sections of the fast macular thickness scan (6-mm diameter, 128 A scans/B scan) and the vertical and horizontal cross-hairs (6-mm length, 512 A scans/B scan). Spectral-domain OCT imaging was performed on either the Cirrus HD-OCT (Carl Zeiss Meditec, Inc.) or the Spectralis SD-OCT (Heidelberg Engineering, Inc., Carlsbad, CA). On the Cirrus HD-OCT, the macular cube 512 × 128 scan (512 A scans/B scan, 128 B scans, 6 mm × 6 mm) and the vertical and horizontal high resolution line scans (6 mm, 4096 A scans/B scan) were obtained. With the Spectralis SD-OCT, a macular cube was obtained in high speed mode (768 A scans/B scan) using 49 B scans, 120 μm spacing, 20° × 20°, and mean automatic-real time score of 16. Additional vertical and horizontal high resolution line scans (20°, 1536 A scans/B scan) were obtained. All scans were centered relative to the fovea. Because each patient participated in the study during a routine follow-up visit, an OCT was ordered at the conclusion of the last nonstudy visit as part of the patient's standard care, and an OCT instrument had been specified. If the standard care OCT was on either SD-OCT machine, a second research OCT was performed on the TD-OCT. If the standard care OCT was on the TD-OCT, a second research OCT was performed on the Cirrus. In the event that the Cirrus was unavailable, the Spectralis was used. All OCTs were obtained by trained OCT technicians at the Wilmer Eye Institute in the usual manner for routine clinical imaging following pupillary dilation.
For all scans, quantitative measurements were calculated by the automated analysis software, and the center subfield (CSF) thickness, volume, and signal strength were recorded. For each TD-OCT scan, the center point thickness (CPT) and the standard deviation of the CPT were recorded as well. The quality of each OCT scan was determined to be either adequate or inadequate by a single observer (MML). An OCT scan was determined to be of inadequate quality if there were moderate or severe boundary errors, using previously described methods for grading OCT quality,
13,14 if the scan was inappropriately centered, or if an alternate scan protocol was used. All scans were used to guide the treatment decision making of the study investigators, but quantitative measurements from OCT scans of inadequate quality were excluded from summary statistics in
Table 3.
For each study eye, study investigators recorded whether treatment with additional anti-VEGF medication was recommended (yes or no) and their level of certainty in their decision (very confident: >90% confident; somewhat confident: 75%–89% confident; neither confident nor unconfident: 26%–74% confident; somewhat unconfident: 11%–25% confident; very unconfident: <10% confident), first after reviewing the patient's medical record, performing the clinical examination, and reviewing a TD-OCT, and then again after reviewing a SD-OCT. Any one-step change in this scale of certainty after viewing the SD-OCT was considered to be an increase or decrease in certainty level. Typically, the treating ophthalmologists followed the retreatment regimen used by the Diabetic Retinopathy Clinical Research Network.
4 If any additional imaging, such as fluorescein angiography or fundus photography, was performed during the study visit as a part of the patient's routine follow-up care, these images were reviewed by the study investigator prior to recording the first set of responses. There were 15 study visits during which fundus photography was performed, 41 study visits during which fundus photography and fluorescein angiography were performed, and 73 study visits during which no additional imaging was performed.
Patient characteristics, including age at time of enrollment, age at initial diagnosis of diabetes, race, gender, level of diabetic retinopathy, history of laser treatment for DME and any panretinal photocoagulation (PRP), phakic status, most recent glycated hemoglobin (HbA1c), and VA with habitual correction at the study visit and at the most recent visit prior to the study visit were recorded from the patient's medical record. Data for age at initial diagnosis of diabetes, race, gender, and most recent HbA1c were reported by the patient. Level of diabetic retinopathy was characterized as either nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) by the managing retina specialist. Visual acuity with habitual correction was determined using a standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Any fields for which data were unavailable in the patient's medical record were omitted from analyses. All calculations were performed using R statistical software v2.13.0 (The R Foundation for Statistical Computing, Vienna, Austria).