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EW GLAUCOMA 98 March 2016 by Matt Young and Gloria Gamat EyeWorld Contributing Writers are potentially poor candidates for visual field tests—the very young, the elderly, and those with poor vision," he added. However, Dr. Lee noted, de- spite these technological advance- ments, clinicians should not lose sight of their patients' welfare. Life expectancy, IOP levels, co-existing ocular conditions, the diagnostic findings—and the benefit of earlier treatment—should all be taken into account. Furthermore, emphasized Dr. Lee, more accurate tracking of progression (via the loss in both the NFL and GCC) can help in making decisions to treat patients earlier with the knowledge that structural loss can precede functional loss by up to 5 years. "However, this can incur a heavy cost burden on younger pa- tients, who have a longer life expec- tancy, with the potential for loss to follow-up and non-compliance due to the longer treatment duration," he warned. Whether starting therapy early or not, each case should be thor- oughly discussed with the patient, Dr. Lee said. "On the flip side, studying the corresponding GCC and NFL for loss can help a clinician determine if the VFD is an artifact and hence avoid starting patients on a costly thera- py," he concluded. EW References 1. Zhang X, et al; Advanced Imaging for Glau- coma Study Group. Predicting development of glaucomatous visual field conversion using baseline Fourier-domain optical coherence tomography. Am J Ophthalmol. 2015 Nov 25. 2. Loewen NA, et al; Advanced Imaging for Glaucoma Study Group. Combining mea- surements from three anatomical areas for glaucoma diagnosis using Fourier-domain optical coherence tomography. Br J Ophthalmol. 2015;99(9):1224–1229. Editors' note: Drs. Zhang and Lee have no financial interests related to their comments. Contact information Lee: kelvinlee@eagleeyecentre.com.sg Zhang: zhangxin@ohsu.edu "With this imaging procedure [FD-OCT], clinicians can now track NFL and GCC loss even before glau- comatous visual defect occurs," Dr. Lee said. "All of the potential covariates were evaluated to build an optimal multivariate Cox regression model through a combination of manual elimination and automatic stepwise selection processes," Zhang and colleagues reported. "Since clinical glaucoma management is based on using all available diagnostic information, we combined the available demograph- ic, clinical, and FD-OCT continuous variables together to construct the glaucoma composite conversion index (GCCI). When the optimal combination of the covariates was determined, the linear form was transformed through a logistic function. The resulting value, which ranged from 0 to 1, was defined as the glaucoma composite conversion index." According to the researchers, values closer to 1 implied a higher risk of conversion. "To avoid overestimate predic- tion accuracy of the GCCI, leave-one -out cross validation was used to calculate the AUC for GCCI," they added. "FD-OCT variables are useful to assess the risk of conversion to PG," concluded Zhang and colleagues. "Individuals who have abnormal or borderline OCT parameters, especial- ly those affecting the macula, may require closer follow-up and initia- tion of treatment to avoid the vision loss. Combining anatomic and VF variables appears to be synergistic in the assessment of glaucoma conver- sion risk," they said. "With the FD-OCT's ability to track and detect NFL and GCC loss accurately, clinicians can have an additional modality to diagnose glaucoma and monitor progression of glaucoma that does not rely on one's subjective responses, like the visual field test," Dr. Lee said. "We can use it to diagnose glau- coma and monitor progression in patients with distorted discs, for ex- ample, tilted discs in highly myopic patients, and also in patients who Medicine, Zhang and colleagues emphasized that due to the objec- tive and automated nature of digital imaging, variables derived from them may provide greater accuracy in predicting glaucoma conversion. "All FD-OCT variables were significant predictive factors except horizontal CDR, and among disc variables, vertical CDR had the highest predictive value by AUC, while among NFL variables, overall average, global loss volume (GLV), and focal loss volume (FLV) were the strongest predictors," reported Xinbo Zhang, PhD, research assis- tant professor, Casey Eye Institute, Oregon Health & Science Universi- ty, Portland, Ore., the study's lead investigator. "All GCC variables were strong predictors except the superior hemispheric average. The strongest single predictive variable was the GCC-FLV," he added. "These are exciting times as we are at a stage of technological advancement where even the indi- vidual ganglion cells themselves can be potentially mapped and tracked for loss/death over time; this is something to look forward to," said Kelvin Lee, MD, senior consultant ophthalmologist, and director of glaucoma services, Eagle Eye Centre, Singapore. Glaucoma, emphasized Dr. Lee, affects the inner retinal layers comprised of the axons, cell bodies, and dendrites of the ganglion cell complex. "Variations to the thickness of NFL and GCC can be accurately detected by FD-OCT imaging," Dr. Lee said. In fact, a related study by the same research group, which com- bined the values of NFL and GCC, as well as the vertical cup-to-disc ratio (CDR), showed improved specificity and sensitivity in the diagnosis of glaucoma. "Combining structural mea- surements of GCC, NFL and disc variables from FD-OCT created a glaucoma structural diagnostic index (GSDI) that improved the accuracy for glaucoma diagnosis," report- ed Loewen and colleagues in the September 2015 issue of the British Journal of Ophthalmology. Prevention is better than needing a cure, and it just got a whole lot more sophisticated E xperts in all medical special- ties aspire to catch a disease at its earliest stage before the onset of any consider- able damage. The earlier any treatment can commence, the better patient outcomes tend to be. This has led to the evolution of advanced diagnostic procedures and risk calculators capable of predicting disease progression. In glaucoma, the basic challenge among clinicians is how to accurate- ly estimate the progression risks in glaucoma suspects and the ability to intervene with treatment before significant visual damage occurs. While numerous studies in glau- coma have attempted to combine anatomic, visual field, and epidemi- ological variables to come up with risk calculators, the initial presenta- tion of risk factors can vary tremen- dously from patient to patient. For example, in the Ocular Hypertension Treatment Study (OHTS) and in subsequent OHTS validation studies conducted, researchers developed a formula that predicts the onset of primary open-angle glaucoma (POAG) using different standard glaucoma param- eters, including intraocular pressure (IOP), central corneal thickness (CCT), cup-disc ratio (CDR), and visual field (VF) indices. However, the downside is accuracy, being limited by the variability of the parameters used (i.e., IOP, VF, and CDR derived from subjective clinical assessments). Using Fourier-domain optical coherence tomography (FD-OCT), the Advanced Imaging for Glaucoma Study Group in the U.S. was able to predict when glaucomatous VF loss arises in glaucoma suspects and preperimetric glaucoma patients by measuring reductions in the peri- papillary retinal nerve fiber layer (NFL), as well as macular ganglion cell complex (GCC) thickness. Reporting in the October 2015 issue of Science Translational Predicting glaucoma using FD-OCT

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