ON-OFF Perimetry

Background:

Perimetry is a systematic measure of visual field function, i.e., the area where stimuli can be seen in peripheral vision while the eye is fixed on a central point. In clinical settings, e.g. neurology, optometry, and ophthalmology, perimetry testing is commonly used to detect and map declines in peripheral vision for diagnostic purposes.
Currently, standard automated perimetry (aka static automated perimetry or "white-on-white perimetry") is the most commonly used form of visual field testing. In this form of perimetry, threshold values are determined by projecting white stimuli on a white background. It is now known that the visual cortex processes visual information stemming from two parallel pathways, the ON-pathway, which signals light increments or light stimuli, and the OFF-pathway, which signals light decrements or dark stimuli. The ON-pathway and OFF-pathway first combine in the primary visual cortex, at which point cortical neurons receive input from both pathways. Prior to arrival in the visual cortex, the ON-pathway and OFF-pathway are segregated in the thalamus. Research has shown that cortical responses to dark stimuli are stronger, faster, have better spatial and temporal resolution. Such responses are more linearly related to luminance contrast and are driven by a larger number of cortical neurons as compared to responses to light stimuli.
Moreover, dark targets are detected faster and more accurately on noisy backgrounds, and dark pixels are more important in judging texture variance. Given the importance of the ON-OFF pathways, a better understanding of a patients' eye health is possible. Unfortunately, traditional white-on-white perimetry has shortcomings which limit its ability to exploit this new understanding of eye physiology. 
Although white-on-white perimetry is well-suited to measure ON-pathway cortical responses, it is unable to measure deficits in the OFF-pathway function. In addition, the test must be administered at specialized eye clinics. Taken together, these limitations greatly constrain the efficacy and utility of the white-on-white visual field test and reduce the ability of different patient populations to take advantage of the technology. 
It is particularly problematic because deficits in OFF-pathway function are important in monitoring the progression, and treatment, of diseases, such as glaucoma; a group of eye conditions where damage to the optic nerve causes irreparable vision loss. Therefore, new technological advancements and new methods are needed to address the shortcomings in the currently used methods for measuring visual deficits both in the OFF and ON-pathways.

Technology Overview:

Glaucoma is best known as a leading cause of blindness for people over the age of 60 but can occur in individuals at any age. Often times, glaucoma presents without warning signs and with effects so gradual that a change in vision may not become noticeable until the disease is advanced. Experiments in animal models of glaucoma suggest that the OFF pathway may be affected sometimes earlier than the ON-pathway in the retina. However, white-on-white perimetry is not optimized for detecting early stage glaucoma deficits in OFF-pathway function.  Researchers of the College of Optometry of the State University of New York have developed an innovative method to measure and characterize visual deficits in the ON-pathway and OFF-pathway in diseases affecting the retina, visual cortex, and other components of the visual pathway.
This method involves performing an ON-OFF perimetry visual field test using a head-mounted display. The patient is directed to focus on a fixation point at the center of the visual field, which is divided into a right side and left side, and to detect a dark or light target stimulus when it appears in the visual field. When a stimulus detected, the patient presses the button in the hand corresponding to the side of the visual field where the stimulus was detected.
This ON-OFF perimetry test has multiple tracking components for eye position, head position, blinks, and pupil diameter. The patient's ability to correctly detect light and dark stimulus or inability to detect the light and dark stimulus is used to identify deficits in ON-pathway and OFF-pathway and subsequent progression of certain eye diseases. The innovation uses a proprietary computer-implemented analysis algorithm to process the data and measure deficits in the ON-OFF pathway. This novel perimetry test approach can be implemented to measure scotomas, as well as slow-moving stimuli, and increasing stimulus size to make it more reliable in its ability to become a valuable diagnostic tool in the eye clinic. Similar to glaucoma, amblyopia affects both ON and OFF visual pathways.
Amblyopia, also known as lazy eye, is a vision development disorder common in children where one eye fails to achieve normal visual acuity. In amblyopia patients, the nerve pathways between a thin layer of tissue (retina) at the back of the eye and the brain are disrupted or changed leading to weakening of visual acuity in one eye. Eventually, the eyes' ability to work together decreases, the brain suppresses or ignores input from the weaker eye and relies only on the stronger eye. Unlike traditional white-on white perimetry, the innovation described herein, can be administered in homes allowing it to be administered to poorly mobile populations in regions with poor access to medical resources. 
Furthermore, based on the European Glaucoma Society (EGS) guidelines and statistical modeling of visual-field data, newly diagnosed glaucoma patients should undergo perimetry testing three times per year in the first 2 years after initial diagnosis. This new visual field-testing approach allows patients more easily adhere to these EGS guidelines. Further Details:

1. Pons C, Jin J, Mazade R, Dul M, Zaidi Q, Alonso JM. (2019) Amblyopia affects the ON visual pathway more than the OFF. The Journal of Neuroscience : J. NEUROSCIENCE (39) 6276-6290.
2. Mazade R, Jin J, Pons C, Alonso JM. (2019) Functional Specialization of ON and OFF Cortical Pathways for Global-Slow and Local-Fast Vision. Cell Reports. (27) 2881-2894.
3. Jansen M, Jin J, Li X, Lashgari R, Kremkow J, Bereshpolova Y, Swadlow HA, Zaidi Q, Alonso JM. (2019) Cortical Balance Between ON and OFF Visual Responses Is Modulated by the Spatial Properties of the Visual Stimulus. Cerebral Cortex (29), Issue 1, January, Pages 336-355,
4. Zhao L, Sendek C, Davoodnia V, Lashgari R, Dul MW, Zaidi Q, Alonso JM. (2015) Effect of Age and Glaucoma on the Detection of Darks and Lights. Investigative Ophthalmology & Visual Science. (56): 7000-6.
5. Jens Kremkow, Jianzhong Jin, Stanley J. Komban, Yushi Wang, Reza Lashgari, Xiaobing Li, Michael Jansen, Qasim Zaidi, and Jose-Manuel Alonso (2014) Neuronal nonlinearity explains greater visual spatial resolution for darks than lights PNAS February (8) 3170-3175
6. Stanley Jose Komban , Jens Kremkow , Jianzhong Jin , Yushi Wang, Reza Lashgari, Xiaobing Li, Qasim Zaidi, Jose-Manuel Alonso (2014) Neuronal and perceptual differences in the temporal processing of darks and lights. Neuron 82(1): 224-234.
7. Erin Koch Jianzhong Jin, Jose M. Alonso, Qasim Zaidi (2016) Functional implications of orientation maps in primary visual cortex. Nature Communications (7), Article number: 13529.
8. Rahimi-Nasrabadi H, Jin J, Mazade R, Pons C, Najafian S, Alonso JM. (2021) Image luminance changes contrast sensitivity in visual cortex. Cell Reports. 34: 108692.
9. Kremkow, J., Jin, J., Wang, Y., and Alonso, J.M. (2016). Principles underlying sensory map topography in primary visual cortex. Nature 533, 52-57.
10. Kremkow, J., and Alonso, J.M. (2018). Thalamocortical Circuits and Functional Architecture. Annu Rev Vis Sci 4, 263-285. 11. Najafian, S., Jin, J., and Alonso, J.M. (2019). Diversity of Ocular Dominance Patterns in Visual Cortex Originates from Variations in Local Cortical Retinotopy. J Neurosci 39, 9145-9163.
    
    
    
    

    Advantages:

    This visual field innovation offers several distinct advantages over competing technologies that are currently used to detect and monitor eye health:
    • Ability to measure both ON and OFF pathways simultaneously and therefore improve the detection and monitoring of eye disease such as glaucoma.
    • The test does not require specialized eye clinics and can be administered in homes and therefore can allow testing of poorly mobile populations such as the elderly as well as permit testing in regions with poor medical resources.
    • Permits easier adherence to the European Glaucoma Society (EGS) guidelines for newly diagnosed glaucoma patients which recommends that patients undergo frequent perimetry testing.

      Intellectual Property Summary:

      Provisional patent, Patent application submitted

      Stage of Development:

      The innovation is the subject of a Provisional Patent entitled On-OFF Perimetry
      

      Licensing Status:

      This technology is available for licensing.

      Licensing Potential:

      Licensing, Commercial partner, Development partner