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Melanie R Lalonde, Ange-Lynca Kantungane, Alfredo A Sadun, Stuart G Coupland, Rustum Karanjia; Photopic Negative Response as an Objective Outcome Measure in Mitochondrial Disease. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5029.
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© ARVO (1962-2015); The Authors (2016-present)
Standard clinical assessment of optic nerve function is heavily dependent on subjective measures such as visual fields and visual acuity. However, these metrics can be difficult to assess in patients with optic neuropathies and severe vision loss due to a floor effect which limits their utility. Measuring the retinal ganglion cell (RGC) layer by optical coherence tomography (OCT) analysis provides an in-vivo objective measure of anatomical change and axon loss but does not provide a functional metric.The photopic negative response (PhNR) recorded via the electroretinogram (ERG) is a signal known to originate from RGCs. The objective of this study is to quantify and validate PhNR as a biomarker of ophthalmic function in patients with profound and mild vision loss from hereditary optic neuropathies including Leber’s hereditary optic neuropathy (LHON) and Kjer’s dominant optic atrophy (DOA). We correlated functional PhNR and structural OCT in these patients.
Objective OCT and PhNR data were collected from patients with confirmed primary mitochondrial diseases (MDs) seen at uOttawa Eye Institute. Ganglion cell complex (GCC) analysis was performed on Cirrus HD-OCT (Carl Zeiss Meditec) and PhNR data recorded on Espion E3 (Diagnosys LLC, Lowell, MA). Briefly, full field PhNRs were recorded using red (640 nm) flashes on blue (470 nm) rod saturating background.
In affected LHON and DOA (n=12), GCC analysis demonstrated abnormally reduced thickness in all 6 sectors. The circumpapillary retinal nerve fiber layer (cpRNFL) showed abnormally reduced thickness with the exception of the nasal quadrant; not surprising since the papillomacular bundle is most susceptible in these patients. PhNR amplitude was reduced but peak implicit time (IT) was normal. Both GCC and cpRNFL were normal in LHON carriers (n=4). PhNRs were normal in amplitude and peak IT.
We were able to record PhNR in patients with primary MDs. Our findings show that PhNR amplitude is abnormally reduced in LHON affected and DOA patients but normal in LHON carriers. These findings correlate with GCC analysis.Accurate objective structural and functional measures of RGCs provide quantifiable metrics, which could be useful to understand disease progression and evaluate the effects of therapy. Further studies looking at inter test variability and correlation with disease severity is required to make PhNR a viable functional biomarker.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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