Predicting Progression of Glaucoma from Rates of Frequency Doubling Technology Perimetry Change Daniel Meira-Freitas, MD, PhD, 1,2 Andrew J. Tatham, FRCOphth, 1 Renato Lisboa, MD, 1,2 Tung-Mei Kuang, MD, MPH, 1,3,4 Linda M. Zangwill, PhD, 1 Robert N. Weinreb, MD, 1 Christopher A. Girkin, MD, MSPH, 5 Jeffrey M. Liebmann, MD, 6 Felipe A. Medeiros, MD, PhD 1 Purpose: To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the devel- opment of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. Design: Prospective, observational cohort study. Participants: The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.71.9 FDT tests during a mean follow-up time of 73.128.0 months. Methods: Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). Main Outcome Measures: The R 2 index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. Results: Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04e1.18; P ¼ 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08e17.96; P ¼ 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R 2 of 82% (95% CI, 74e89) versus 11% (95% CI, 2e24), respectively. Conclusions: Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma. Ophthalmology 2014;121:498-507 ª 2014 by the American Academy of Ophthalmology. Glaucoma is an optic neuropathy characterized by pro- gressive loss of retinal ganglion cells, which ultimately can lead to functional loss, visual disability, and blindness. 1 Standard automated perimetry (SAP) using a white stimulus on a white background is the most commonly used method for detection of glaucomatous functional damage. However, histologic and clinical studies have shown that visual field defects on SAP often are detectable only after a substantial number of ganglion cells have been lost. 2,3 Frequency doubling technology (FDT) perimetry has been proposed as a test for the early detection of glaucom- atous functional damage. 4,5 Testing involves presentation of a frequency-doubling stimulus, and the contrast sensitivity of the stimulus is adjusted to determine the limit of detec- tion. Several independent studies have shown that FDT has high sensitivity and specificity for discriminating glau- comatous and healthy subjects. 4,6e12 The 24-2 Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) has been shown to be significantly better than SAP at distinguishing eyes with early glaucoma from healthy eyes and offers shorter test duration and less variability in areas of low sensitivity than SAP. 8,10,13,14 Baseline functional abnormalities detected by FDT perimetry have been shown to be predictive of future onset and location of SAP visual field loss among glaucoma suspects. 15e17 However, the predictive ability of infor- mation obtained from only the baseline visit is relatively weak. 16 Predictive models that take into account longitudinal information as it becomes available during follow-up could perform better than those using only baseline information. To the best of our knowledge, no study has yet evaluated the ability of longitudinal FDT data in predicting the development of visual field loss in glaucoma. 498 Ó 2014 by the American Academy of Ophthalmology ISSN 0161-6420/14/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ophtha.2013.09.016