A non-invasive in vivo imaging technique using enhanced ophthalmoscopy to assess the intrinsic function of individual photoreceptor cells while maintaining high spatial resolution. This technique could be applied for both diagnostic purposes as well as the precise measurement of treatment response to both existing and experimental therapies for retinal diseases.
Functional assessments of vision, such as visual acuity, visual fields, microperimtery, and electroretingorams are critical for the diagnosis, treatment, and prognosis of retinal diseases. These techniques are sensitive only for examining the function of a large area of retina and have insufficient resolution for detecting functional changes anywhere close to the scale of individual cones. This represents a significant gap in our ophthalmic assessment capabilities, especially given that current therapeutic approaches are attempting to restore function to individual photoreceptors.
Noninvasive cellular-scale observation of the structure of human photoreceptor cells is made possible through the use of adaptive optics (AO) enhanced ophthalmoscopes, but establishing noninvasive objective measures of photoreceptor function on a similar scale has been more difficult.
The inventors have developed a technique to assess the intrinsic function of individual photoreceptor cells using AO enhanced ophthalmoscope images acquired with near-infrared light. The images have high spatial resolution (single cell level) with low signal-to-noise ratio and could be easily incorporated into, and improve upon, existing AO enhanced ophthalmoscopes using infrared illumination.
The figure shows the cone intrinsic reflectance response measured from the stimulated and control trials. (A) Repeat control trials (cool colored lines) and stimulated trials (warm colored lines) show a clear, measurable, and reliable intrinsic reflectance response. (B) All trials for a given condition were then combined using pooled standard deviation, and the stimulus-evoked intrinsic reflectance response was taken as the difference between the stimulated and control pooled standard deviations. These results strongly indicate that the absorption of light by cone photopigment initiates a reflectance response, thereby making the intrinsic reflectance response a direct, non-invasive measure of photoreceptor function.
Preliminary results demonstrate that the Reflectance response can be used to measure non-functioning photoreceptors in those suffering retinopathies.
- Use in Ophthalmology clinics as an objective assessment of cone function.
- Monitoring retinal function as a primary or secondary outcome in clinical trials of new retinal gene therapies.
- Early and accurate diagnosis and surveillance of degenerative retinal diseases in the clinic.
- Functional, rather than structural, retinal imaging
- High spatial resolution (at the single cell level)
Stage of Development:
- Human proof-of-concept studies completed
- Future experiments will further optimize image acquisition and processing and determine the mechanistic origin of the functional response
US Provisional Patent Application
Cooper et al., Biomed Opt Express, 2017, 8 (11): 5098
Docket # 18-8578