Background: Optic neuropathy occurs very commonly in multiple sclerosis (MS) patients. Optical coherence tomography (OCT) has been shown to be a sensitive, and precise method of quantifying structural retinal changes that occur in MS. It is very likely, however, that metabolic dysfunction precedes such structural changes in the retina; therefore, a method of detecting and measuring these metabolic changes (for example, retinal oxygen utilization) would result in a more sensitive visual biomarker of MS disease activity.
Objective: To measure retinal vascular oximetry (oxygen saturation [SatO2] and partial oxygen pressure [PaO2]) in MS patients using a novel technology - the Oxymap® T1 Retinal Oximeter.
Methods: We recruited 11 healthy controls, and 13 MS patients. All subjects underwent assessments with high- and low-contrast letter acuity (2.5%), and spectral-domain OCT. Further, using the Oxymap®, we measured the mean retinal vessel SatO2, and PaO2.
Results: Using a generalized estimating equation (GEE) analysis, we found that MS patients had significantly higher mean retinal SatO2 (p = 0.039), and PaO2 (p = 0.034) when compared to normal subjects. Although the mean arteriolar SatO2 was higher in MS eyes, this difference was not significant. However, MS patients had significantly higher venular SatO2 (p = 0.02) compared to healthy controls. In a patient who presented with left acute optic neuritis (AON), we found that higher retinal SatO2 and PaO2 preceded changes in OCT-derived metrics by 3 months.
Conclusions: To our knowledge, we report the first application of objective, in vivo, ascertainment of retinal oxygenation in the eyes of patients with MS, and confirm significant differentiation from measures derived from control subjects. In the single AON patient in our study, it is noteworthy that retinal oxygen utilization was altered before any structural changes were detected by OCT. We hypothesize that the pathobiological mechanisms affiliated with MS, culminate in retinal ganglion cell neuron damage and dysfunction, thereby resulting in a reduced retinal metabolic demand, and thus, decreased oxygen extraction. As such, the application of retinal oximetry may prove to be a highly sensitive biomarker of retinal metabolic activity in MS, which would begermane to the identification of novel neurotherapeutic and remyelination strategies in MS treatment trials.
Disclosure:
Shin Beh, MD: nothing to disclose
Marlen Lucero: nothing to disclose
Amy Conger, COA: nothing to disclose
Darrel Conger, CRA: nothing to disclose
Victoria Stokes, RN: nothing to disclose
Teresa Frohman, PA-C: speaker and consultant fees from Biogen Idec, Novartis and Acorda and consulting fees from Genzyme
Rob Rennaker, PhD: owner of Vulintus LLC
Peter A. Calabresi, MD: personal compensation from Vertex and Abbott; and has received research funding from Biogen-IDEC, Abbott, Vertex, Novartis, and Bayer
Laura J. Balcer, MD MSCE: honoraria from Biogen-Idec, Novartis, Acorda, Vaccinex and Bayer, is on a clinical trial advisory board for Biogen-Idec
Elliot M. Frohman, MD PhD: speaking and consulting fees from Biogen Idec, TEVA, Acorda, Novartis and consulting fees from Genzyme and Abbott
Abstract: P698
Type: Poster
Abstract Category: Neuro-ophthalmology
Background: Optic neuropathy occurs very commonly in multiple sclerosis (MS) patients. Optical coherence tomography (OCT) has been shown to be a sensitive, and precise method of quantifying structural retinal changes that occur in MS. It is very likely, however, that metabolic dysfunction precedes such structural changes in the retina; therefore, a method of detecting and measuring these metabolic changes (for example, retinal oxygen utilization) would result in a more sensitive visual biomarker of MS disease activity.
Objective: To measure retinal vascular oximetry (oxygen saturation [SatO2] and partial oxygen pressure [PaO2]) in MS patients using a novel technology - the Oxymap® T1 Retinal Oximeter.
Methods: We recruited 11 healthy controls, and 13 MS patients. All subjects underwent assessments with high- and low-contrast letter acuity (2.5%), and spectral-domain OCT. Further, using the Oxymap®, we measured the mean retinal vessel SatO2, and PaO2.
Results: Using a generalized estimating equation (GEE) analysis, we found that MS patients had significantly higher mean retinal SatO2 (p = 0.039), and PaO2 (p = 0.034) when compared to normal subjects. Although the mean arteriolar SatO2 was higher in MS eyes, this difference was not significant. However, MS patients had significantly higher venular SatO2 (p = 0.02) compared to healthy controls. In a patient who presented with left acute optic neuritis (AON), we found that higher retinal SatO2 and PaO2 preceded changes in OCT-derived metrics by 3 months.
Conclusions: To our knowledge, we report the first application of objective, in vivo, ascertainment of retinal oxygenation in the eyes of patients with MS, and confirm significant differentiation from measures derived from control subjects. In the single AON patient in our study, it is noteworthy that retinal oxygen utilization was altered before any structural changes were detected by OCT. We hypothesize that the pathobiological mechanisms affiliated with MS, culminate in retinal ganglion cell neuron damage and dysfunction, thereby resulting in a reduced retinal metabolic demand, and thus, decreased oxygen extraction. As such, the application of retinal oximetry may prove to be a highly sensitive biomarker of retinal metabolic activity in MS, which would begermane to the identification of novel neurotherapeutic and remyelination strategies in MS treatment trials.
Disclosure:
Shin Beh, MD: nothing to disclose
Marlen Lucero: nothing to disclose
Amy Conger, COA: nothing to disclose
Darrel Conger, CRA: nothing to disclose
Victoria Stokes, RN: nothing to disclose
Teresa Frohman, PA-C: speaker and consultant fees from Biogen Idec, Novartis and Acorda and consulting fees from Genzyme
Rob Rennaker, PhD: owner of Vulintus LLC
Peter A. Calabresi, MD: personal compensation from Vertex and Abbott; and has received research funding from Biogen-IDEC, Abbott, Vertex, Novartis, and Bayer
Laura J. Balcer, MD MSCE: honoraria from Biogen-Idec, Novartis, Acorda, Vaccinex and Bayer, is on a clinical trial advisory board for Biogen-Idec
Elliot M. Frohman, MD PhD: speaking and consulting fees from Biogen Idec, TEVA, Acorda, Novartis and consulting fees from Genzyme and Abbott
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