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THE NATURAL HISTORY OF FULL-FIELD STIMULUS THRESHOLD DECLINE IN CHOROIDEREMIA

Dimopoulos, Ioannis S., MD, MSc; Freund, Paul R., MD, MSc; Knowles, JACOB A., BSc; MacDonald, Ian M., MD CM, MSc

doi: 10.1097/IAE.0000000000001764
Original Study

Purpose: To evaluate full-field sensitivity thresholds (FSTs) across a wide range of choroideremia (CHM) disease stages and to determine their applicability as functional endpoints for CHM clinical trials.

Methods: Thirty CHM subjects (60 eyes) and 50 healthy controls (50 eyes) underwent FST testing under dark-adapted conditions to determine rod- and cone-mediated FSTs. Central retinal structure and function were assessed using fundus autofluorescence and microperimetry. Correlation and regression analyses were performed to compare FST responses with the residual area of retinal pigment epithelium in the peri- and parafoveal regions, as well as the mean and highest macular microperimetry sensitivity.

Results: All patients with CHM had a baseline of 18 dB elevation in dark-adapted rod FSTs, including the least affected individuals. Further FST sensitivity loss was exponentially associated with decrease in the area of residual peri- and parafoveal retinal pigment epithelium, with precipitous loss of sensitivity noted for fundus autofluorescence areas less than 5 mm2. Cone FSTs were comparable with controls, except for advanced stages of CHM. Full-field sensitivity threshold responses showed high correlation with both mean and highest macular microperimetry thresholds (P < 0.001). In some cases of absent macular fundus autofluorescence, the peripheral retina could contribute to detectable rod FST responses but with severely diminished cone-driven responses.

Conclusion: Full-field sensitivity threshold testing demonstrated a baseline level of rod dysfunction in CHM present in all rod photoreceptors. Further decline in FST responses correlated strongly with the extent of central retina structural and functional loss. Full-field sensitivity threshold allowed quantification of residual rod function in peripheral islands of vision, which cannot be reliably achieved with other conventional tests. As such, the FST can serve as a complimentary tool to guide patient selection and expand the eligibility criteria for current and future CHM clinical trials.

In choroideremia, full-field stimulus threshold (FST) testing shows high correlation with measures of central retinal structure and function, in addition to allowing quantification of peripheral islands of vision. Full-field stimulus threshold can serve as a complimentary tool to expand patient selection for current and future choroideremia clinical trials.

Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Alberta, Canada.

Reprint requests: Ioannis S. Dimopoulos, MD, Department of Ophthalmology and Visual Sciences, 7-030 Katz Building, University of Alberta, Edmonton, AB T6G 2E1, Canada; e-mail: dimopoul@ualberta.ca

Grants: Canadian Institutes of Health Research (CIHR) grant (119190); Alberta Innovates - Health Solutions (AIHS) grant 201201139, and Canadian Foundation for Innovation Grant 28916.

None of the authors has any conflicting interests to disclose.

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© 2018 by Ophthalmic Communications Society, Inc.