Solve Your Patient’s Visual Acuity Complaints by Prescribing NeuroVision Technology

1. Solve Your Patient’s Visual Acuity Complaints by Prescribing NeuroVision Technology Peter Shaw-McMinn, OD Assistant Professor Southern California College of Optometry

2. One of the advantages of our profession is we have the opportunity to improve the quality of our patient’s life on a daily basis.

3. We have the opportunity to improve the quality of life of: • Patients • Staff • Ourselves • Our professions • The Eyecare Industry • Society

4. Today’s Objectives You will be able to: • Explain what limits visual acuity • Describe the brain processes that allow us to see clearly • Understand how the NeuroVisiontechnology works • Recognize how the NeuroVision program can benefit patients

5. What Determines Our Visual Acuity?

6. Retinal image + Neural Processing

7. Visual system

8. Cells in the retina

9. Neuronal morphology • Dendrites: shaft, spines, specialized synaptic structures • Extensions of cell body, with same membrane & organelles • Shape and number characteristic of each type of neuron; shape determines number of synaptic sites, physiological properties

10. Light hits photoreceptor

11. The initial step in the translation of light information from a spot of light into an electric signal propagating to the visual cortex takes place in the photoreceptors in a process known as transduction. This consists of the cis-trans isomerization of the carotenoidchromophore, which leads to a transient change in the membrane potential of the cell. The result consists of a graded response, seen as a hyperpolarization of the photoreceptor, and an electrotonic current linking the outer and inner segments. A photoreceptor is capable of transducing the energy of a single photon (about 4×10-12erg) into a pulsed reduction of axial current of about 1 pA lasting about 1 s with an energy equivalent of 2×10-7erg (Levick and Dvorak, 1986). Thus, a photoreceptor serves as a photomultiplier with an energy gain of some 105 times.

12. Chemical reaction releases glutamate

13. How we see - at the Retinal Level Photoreceptors use a biochemical process to convert light in electrical signals that are transmitted via bipolar cells to ganglion cells. The axons of the ganglion cells form the optic nerve that connects the retina with visual centers of the brain. This vertical signal transduction is mediated by the excitatory neurotransmitter glutamate, and is modulated laterally by horizontal and amacrine cells that use the inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine. This horizontal inhibition causes a negative feed-back for the vertical excitatory signal pathway. This feed-back increases the signal to noise ratio of the light signal, regulates the light sensitivity of the retina (adaptation), causes selectivity in ganglion cell responses for the orientation of objects and the direction of their movements, and is important for the generation of receptive fields.

15. Receptive field Hartline introduced the concept of 'receptive field' to describe the spatial properties of retinal ganglion cells. He used 'spot mapping' to define such fields. Cells were found to respond to relatively dim spots when the stimulus was positioned in the 'center' of the receptive field but brighter stimuli were required as the spots were moved away from this region. Hartline concluded that ganglion cell receptive fields were fixed in space and immobile, typically did not extend beyond 1 mm in diameter, and were graded in sensitivity over this region. Receptive fields were much larger than expected of individual photoreceptors, suggesting signal processing and integration through retinal circuitry.

16. Receptive Fields and Contrast Sensitivity • The characteristic 'spatial tuning' of ganglion cell receptive fields is reflected in peaked contrast sensitivity functions • This tuning reflects in part the variable dendritic span in ganglion cells. • Dendritic span is one of the factors allowing ganglion cells to collect visual signals over a broad reach of visual space. • But dendritic field span in itself does not provide for a decline in sensitivity as stimulus sizes become large. Surrounds are required.

17. Contrast sensitivity is one measure of size selectivity in ganglion cells. Another measure is 'hyperacuity'. This is the ability to detect movements within the ganglion cell receptive field. Examples are:

18. Lateral Geniculate Body

19. LGN has six layers of cells

20. 1 .3 million neurons same as number of ganglion cells • The mangocellular layers process visual information concerned with low spatial frequencies, high temporal frequencies, low contrast and luminance. (Peripheral retina) • The parvocellular layers process visual information concerned with high spatial frequencies, low temporal frequencies, high contrast and color. (Central retina)

21. Sharpest vision at fovea The specialized cone pathways of the central fovea of human and monkey retinas are designed to have the least convergence and the greatest resolution capabilities of the visual system. This is accomplished by making the connections as "private" as possible and narrowing them to a one to one relationship in the so-called midget pathways.

22. The midget pathways consist of midget bipolar cells and midget ganglion cells, the latter of which project to individual parvocellular layer cells of the lateral geniculate nucleus in the brain. Because of the need for the high acuity midget pathways also to be organized into ON- and OFF-center channels like the diffuse cone pathways for maximization of contrast, it means that every cone of the fovea will have dual midget pathways. The two midget bipolars will be an ON-center type and an OFF-center type and will connect with ON-center and OFF-center midget ganglion cells respectively. This improves contrast sensitivity for high spatial frequencies.

24. Striate Cortex

25. Striate Cortex has 6 layers • 1.3 million ganglion and LGN cells diverge to 260 million neurons in the visual cortex • Layers 5 and 6 project back to the LGN • Layer 4 goes on to higher cortical layers • Cells are arranged retinotopically as in the LGN, so cells located next to one another in the cortex process information from areas of the visual field located next to one another. • More cortical cells are devoted to processing macular information than peripheral information. 50% of the striate cortex is devoted to processing information from the central 10 degrees of visual field. Borish.

26. Visual Cortical Cells • In 1959 Hubel and Wiesal discovered that cortical cells responded to certain orientation of bar targets. All cells within a column through the 6 cortical layers have roughly the same orientation preference.

27. Receptive fields in V1 of visual cortex Recall that the receptive fields of both ganglion cells and LGN neurons were center-surround, and that they responded optimally to points of light. Neurons in the cortex, however, respond very poorly to points of light. The optimal stimulus for most cortical neurons turns out to be a bar of light, in a very specific orientation. How did this come about?

29. How we see Light strikes our retinal photoreceptors which converts chemicals into energy releasing electrical stimulation to the bipolar cells with lateral interactions modulated by the horizontal cells which releases energy to ganglion cells whose lateral interactions are modulated by amacrine cells. The 1.3 million ganglion cells compose the optic nerve which goes to the lateral geniculate nucleus and organized into 6 layers where lateral interactions occur between on/off midget cells. From there 1.3 million cells terminate in the striate cortex where lateral interactions occur in 260 million cells which further process the image allowing us to see.

31. What happens when something goes wrong with this? AMBLYOPIA

32. Amblyopia • In amblyopia radiographic visual evoked response studies show that cells in the LGN and visual cortex are smaller and have fewer connections. • Electrophysiologically, Amblyopic cells have decreased CSF with higher spatial frequencies. • Temporal timing functions are also reduced, meaning they can detect slower moving targets versus faster moving targets.

33. Amblyopia • Biochemically, autoradiographic analysis of enzymes used in transporting information show less energy production so there is less activity among neural connections. Less lateral interactions.

34. How does Patching work? • Patching results in increased cell size and more connections by making pathway function more efficiently improving the response. • It is important that the amblyopic eye looks at targets which stress the eye at the limit of it’s ability.

35. How does loss of the good eye affect the amblyopic eye? When good eye is lost, connections which were turned off by interactions with good eye are now allowed to turn on. The inhibiting connections from the good eye are gone, unmasking the good connections already present. The more connections, the better the acuity.

36. So, who is amblyopic? • Could a 20/20 eye be amblyopic? • During our developmental years, the visual pathway efficiency depends upon a sharp image on the retina. No sharp image, less cell interactions and decreased v.a. • How many of us have sharp images on our retina during our formative years?

37. Refractive error and age

38. Lack of sharp image on retina • Most kids are hyperopic, going into and out of focus. • Many have uncorrected astigmatism. At age 4 2/3 have astigmatism. Borish • Many have higher order aberrations. (20% of blur in average person.) Only a few of us have our visual pathways developed for maximal v.a. (Think Ted Williams)

39. What if we could improve the visual pathway efficiency in the adult? What if we could increase the cell size and number of connections throughout the visual pathway in adults?

41. Scientific Basic Principles • Enhance neuronal Lateral Interactions • Neuronal Plasticity • Perceptual Learning

42. Neuronal Network of Lateral Interactions Target excites cortical cells Area of lateral excitation provided by interaction of similar orientations Area of lateral inhibition (orientation of little relevance)

43. The Visual Cortex • Cortical cells (neurons) are highly specialized and optimized image analyzers • They respond only to a limited range of parameters (filters) of the visual image

44. The VisualCortex (cont) • Individual neurons respond to • Precise location • Specific orientation • Specific spatial frequency Adapted from: Hubel & Wiesel (1959). Receptive fields of singleneurons in the cat’s striatecortex. J Physiol (Lond) 148:574-591

45. The Visual Cortex (cont) • To characterize an image, visual processing involves the cooperative activity of many neurons, these neuronal interactions are contributing both excitation and inhibition.

46. Gabor Patch “Gabor Patches” 1 are widely used in the field of visual neuroscience. Having been shown to efficiently describe the shape of receptive fields of neurons in the primary visual cortex they thus represent the most effective stimulation.2 • Gabor (1946), Theory of Communication. Journal of the Institute of Electrical Engineers, London, 93, 429-457). • Daugman. Two-dimensional spectral analysis of cortical receptive field profiles. Vision Res 1980; 20:847-56.

47. Precise Control of Variables Spatial Frequency Local Orientation Contrast Global Orientation Target-Flankers Separation Target Displacement

48. Excitation from outside the CRF Adapted from: Polat U., Mizobe, K., Kasamatsu, T., Norcia A.M. (1998). Collinear stimuliregulate visual responsesdepending on Cell's contrastthreshold.Nature, 391, 580-584 Contrast response of a single neuron can be modulated by activity of neighboring neurons (single-unit recordings in cats and monkeys1) • Chen, Kasamatsu, Polat, & Norcia, 2001; • Kapadia, Ito, Gilbert, & Westheimer, 1995; • Levitt & Lund, 1997; • Mizobe, Polat, Pettet, & Kasamatsu, 2001; • Polat, Mizobe, Pettet, Kasamatsu, & Norcia, 1998; • Sillito, Grieve, Jones, Cudeiro, & Davis, 1995

49. Neural Plasticity • Neural plasticity - relates to the ability of the nervous system to adapt to changed conditions, in acquiring new skills. The new required skills are retained for years • Evidence for Neural plasticity - Visual acuity improvement in adults with amblyopia has been reported afterprolonged patching1 or when the better eye’s vision has been lost2 or degraded, by age related macular degeneration3, cataract4 or trauma5 • Birnbaum MH, Koslowe K, Sanet R. (1977) • Vereecken EP, Brabant P. (1984) • El Mallah MK, Chakravarthy U, Hart PM. (2000) • Wilson ME. (1992) • Rabin J. (1984)

50. Perceptual Learning & Neural Plasticity • The phenomenon - Perception can be modified by experience. Visual performance improves with practice • The technique - Repetitive performance of controlled and specific visual tasks • Perceptual learning has been evidenced in a variety of visual tasks and was found to persist for years without further practice1 • Clinical observations2 and experimental evidence3 indicate the presence of residual neural plasticity well after the critical period. • Gilbert, 1998; Sagi & Tanne, 1994). • Moseley, Fielder (2001) • Polat, Sagi(1994); Levi, Polat (1996);Levi, Polat, Hu (1997)