Abstract
Purpose :
Leber hereditary optic neuropathy (LHON) is one of the most common inherited optic neuropathies, which is due to point mutations in mitochondrial DNA. The disease affects the metabolism of retinal ganglion cells, with early involvement of the papillomacular bundle. Building on our success developing a phase Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) and detecting inflammatory cells in Multiple Sclerosis patients, we now propose to examine the retinal ganglion cells layer in LHON patients to extract cellular biomarkers of inflammation and neurodegeneration and perform cell quantification to gather new information on the pathological mechanism of this disease. In addition, we contribute to monitoring the effectiveness of novel gene therapy (GenSight) designed to restore function of the ND4 gene by injecting a viral vector carrying a normal gene into participants' eyes which is currently being used in a subset of these patients.
Methods :
We acquired retinal images at 4° Temporal and Nasal with our phase contrast AOSLO on a cohort of 38 LHON patients, of which 15 have received the gene therapy. A total of 65 eyes were imaged, of which 31 eyes received treatment and 13 of these eyes were imaged before that treatment. Image sequences were registered and confocal and phase contrast images generated. Some patients made several visits over months and timelapse videos have been generated. Finally, we computed quantitative biomarkers such as cell density and cell size.
Results :
We detected numerous inflammatory cells, with diameters ranging from 9 µm to 20 µm. From the 34 non treated eyes analyzed, 13 eyes displayed these cells. In patients receiving the gene therapy, we identified inflammatory cells: 1) in 21 treated eyes; 2) in 10 treated eyes before treatment; in 4 non treated eyes from patients where the other eye was injected, out of 4 eyes analyzed.
Conclusions :
Phase contrast AOSLO may reveal many biomarkers detectable in LHON patients, including inflammatory cells specifically in the ganglion cells layer. We detected the presence of immune cells in this non inflammatory disease. This imaging technique may also evaluate the response to gene therapy, where inflammation is one of the main safety related concerns. Finally, phase contrast may in future enable detection of these cellular biomarkers in healthy carriers, who have not yet shown any symptoms.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.