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Pilot Study To Evaluate The Efficacy of Neural Vision Correction™ (NVC™) Technology For Vision Improvement in Low Myopia Donald Tan 1,2,3, Bill Chan 1, Frederick Tey 4, Lionel Lee 4 Singapore Eye Research Institute Singapore National Eye Centre 5 Defence Medical & Environmental Research Institute , Singapore. -----------------Introduction-----------------NeuroVision’s NVC vision correction technology is a non-invasive, patient-specific treatment based on visual stimulation and facilitation of neural connections responsible for vision. The technology involves the use of an internet-based computer generated visual training exercise regime using sets of patient specific stimuli based on Gabor patches, to sharpen contrast sensitivity and visual acuity. 2; Department of Ophthalmology, Faculty of Medicine, National University of Singapore The results shown in Figures 3,4 are derived from subjects (adults), who were exposed to psychophysical tasks using the “Lateral Masking” technique. Figure 3: When subjects are practicing contrast modulation under a very precise and subject-specific stimuli regimen, a dramatic improvement in contrast sensitivity is achieved We evaluated the efficacy of NVC treatment in the enhancement of unaided visual acuity (UAVA) and contrast sensitivity function (CSF) in low myopes. -----------------Scientific Background-----------------Cortical neurons in the visual cortex function as highly specialized image analyzers or filters, responding only to specific parameters of a visual image, such as orientation and spatial frequency, and visual processing involves the integrated activity of many neurons, with interneural interactions effecting both excitation and inhibition1. Visual contrast activates neurons involved in vision processing, and neural interactions determine the sensitivity for visual contrast at each spatial frequency, and the combination of neural activities set Contrast Sensitivity Function (CSF)1,2. The relationship between neuronal responses and perception are mainly determined by the signal-to-noise ratio (S/N ratio) of neuronal activity, and the brain pools responses across many neurons to average out noisy activity of single cells, thus improving S/N ratio, leading to improved visual performance and acuity3. Studies have shown that the noise of individual neurons can be brought under experimental control by appropriate choice of stimulus conditions, and contrast sensitivity at low levels can be increased dramatically through control of stimulus parameters4-8. This precise control of stimulus conditions leading to increased neuronal efficiency is fundamental in initiating the neural modifications that are the basis for brain plasticity9,10. Brain plasticity (the ability to adapt to changed conditions in acquiring new skills) has been demonstrated in many basic tasks, with evidence pointing to physical modifications in the adult cortex during repetitive performance11-12. NeuroVision’s technology probes specific neuronal interactions, using a set of patientspecific stimuli that improve neuronal efficiency6,13 and induce improvement of CSF due to a reduction of noise and increase in signal strength. As visual perception quality depends both on the input received through the eye and the processing in the visual cortex, NeuroVision’s technology compensates for blurred (myopic) inputs, coming from the retina, by enhancing neural processing. ------------------Technology Implementation ------------------The building block of these visual stimulations is the Gabor patch (Figure 1), which efficiently activates and matches the shape of receptive field in the Visual Cortex. The fundamental stimulation-control technique is called “Lateral Masking”, where collinearly oriented flanking Gabors are displayed in addition to the target Gabor image. The patient is exposed to two short displays in succession, in a random order; the patient identifies which display contains the target Gabor image (Figure 2). The system provides the patient with audio feedback when provided with an incorrect response. The task is repeated and a staircase is applied until the patient reaches their visual threshold level. First Display Q uickTim e™ and a G r aphics decom pr essor ar e needed t o see t his pict ur e. Figure 2: Lateral Masking images Figure 1: The Gabor Patch Second Display • Mean UAVA improvement was 2.1 lines (from 0.315 to 0.105) (Fig. 6) • Maximum UAVA improvement was 5 lines of logMAR (n=2) - Figure 4: Effect of Lateral Masking -----------------NeuroVision Treatment System-----------------The NeuroVision Treatment System is a software-based, interactive system tailored and continuously adaptive to the individual visual abilities. In the first stage, the subject is exposed to a set of visual perception tasks, aimed to analyze and identify each subject’s neural inefficiencies or deficiencies. Based on this analysis, a treatment plan is initialized, and subject specificity is achieved by administering patient-specific stimuli in a controlled environment. 3; -------------------- Pilot Study Results Cont’d-------------------- -------------Technology Implementation Cont’d----------------- 34 eyes who had baseline of 20/25 or worse improved in average 2.3 lines from a mean of 0.36 (20/45) to 0.13(20/25) 26 eyes who had baseline of 20/30 or worse improved in average 2.6 lines from a mean of 0.42 (20/50) to 0.16 (20/25) 22 eyes who had baseline of 20/40 or worse improved in average 2.8 lines from a mean of 0.46 (20/60) to 0.18 (20/30) • Mean CSF improved at all spatial frequencies to within the normal range (Fig 8). • Vision improvement appears to be retained for at least 6 months (Fig. 9) • No side-effects were encountered during treatment Figure 8: Figure 6: Mean Improvement in logMAR lines 0.4 Normalisation of Contrast Sensitivity Function at Treatment End Q uickTim e™ and a G r aphics decom pr essor ar e needed t o see t his pict ur e. 0.3 0.2 0.1 Each session is designed to train, directly and selectively, those functions in the visual cortex, which were diagnosed to be further enhanced. At each session an algorithm analyzes the patient's responses and accordingly adjusts the level of visual difficulty to the range most effective for further improvement. Between sessions, the progress of the patient is taken into account by the algorithm for the next session generation. Thus, for each subject an individual training schedule is designed based on the initial state of visual performance, severity of dysfunction and progress in course of treatment. The treatment is applied in successive 30-minute sessions, administered 2-3 times a week, a total of approximately 30 sessions. Every 5 sessions, subject’s visual acuity is tested in order to continuously monitor subject’s progress. The average entire treatment duration is around 3 months. 0 Figure 9: 0 2 4 6 8 10 Most Current Post-Treatment Improved vision retained at 6 months Pre-Treatment Figure 7: Pre-Tx UCVA change - EXIT Visit Post-Tx 35 Change in UAVA at Treatment End Mean Vision Improvement Retention 10 Patients 10 Patients that completed 6 of Months Examined 6 months Post Treatment 30 0.4 0.4 25 Percentage 1; 20 0.3 0.3 15 0.2 0.2 10 0.1 0.1 -----------Singapore Pilot Study on Low Myopia------------Twenty (20) adult patients with low myopia (mean cycloplegic spherical equivalent of –1.09D (range –0.25 to –1.75)) were recruited in a prospective pilot study of NVC treatment. Study subjects comprised 10 male and 10 female Asian volunteers with a mean age of 32 years (range 19 to 53 years). Patients underwent clinic-based (n=11) or home-based (n=9) treatment sessions on an alternate day basis until no further improvement occurred (mean treatment period = 3.2 months). Investigations included manifest and cycloplegic refraction, LogMAR unaided acuity (UAVA), aided acuity (BCVA) and contrast sensitivity (CSF). All will be followed up for 12 months after completion of treatment. Currently, all patients have completed treatment and 10 patients have reached 6 months follow-up. 5 0.00 0 -0.1 • Improvement in UAVA of 1 logMAR line or more occurred in 32 out of 40 eyes (80%) at treatment end • Improvement in UAVA of 2 logMAR lines or more occurred in 21 out of 40 eyes (53%) at treatment end Figure 5: Individual Eye Improvement at treatment end 1.0 0.8 0.6 0.4 0.2 0.1 0.2 0.3 0.4 0.5 0.6 0.7 UCVA (logMAR) Treatment 1 Start Treatment End 2 3 Months Post 3 Treatment Early results of this pilot study suggest that NVC treatment is able to improve visual acuity and contrast sensitivity in adults with low myopia. This improvement appears to be retained for at least 6 months after treatment. Patients will continue to be followed up for another 6 months. A large-scale, placebo-controlled randomized clinical trial is currently being planned. -----------------References-----------------1. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. (Lond.) 160, 106-154 (1962). 2. Polat, U. Functional architecture of long-range perceptual interactions. Spat Vis 12, 143-62 (1999). 3. Geisler, W. S. & Albrecht, D. G. Visual cortex neurons in monkeys and cats: detection, discrimination, and identification. Vis Neurosci 14, 897-919 (1997). 4. Kasamatsu, T., Polat, U., Pettet, M. W. & Norcia, A. M. Colinear facilitation promotes reliability of single-cell responses in cat striate cortex. Exp Brain Res 138, 163-72. (2001). 5. Polat, U., Mizobe, K., Pettet, M. W., Kasamatsu, T. & Norcia, A. M. Collinear stimuli regulate visual responses depending on cell's contrast threshold. Nature 391, 580-4 (1998). 6. Polat, U. & Sagi, D. Spatial interactions in human vision: from near to far via experience- dependent cascades of connections. Proc Natl Acad Sci U S A 91, 1206-9 (1994). 7. Polat, U. & Sagi, D. Lateral interactions between spatial channels: suppression and facilitation revealed by lateral masking experiments. Vision Res 33, 993-9 (1993). 8. Polat, U. & Sagi, D. The architecture of perceptual spatial interactions. Vision Res 34, 73-8 (1994). 9. Dosher, B. A. & Lu, Z. L. Perceptual learning reflects external noise filtering and internal noise reduction through channel reweighting. Proc Natl Acad Sci U S A 95, 13988-93. (1998). 10. Dosher, B. A. & Lu, Z. L. Mechanisms of perceptual learning. Vision Res 39, 3197-221. (1999). 0.0 11. Sagi, D. & Tanne, D. Perceptual learning: learning to see. Curr Opin Neurobiol 4, 195-9 (1994). 12. Gilbert, C. D. Adult Cortical Dynamics. Physiological Reviews 78, 467-485 (1998). -0.2 6 Months Post 4 Treatment -----------------Conclusions------------------ ----------------------- Pilot Study Results---------------------Individual Vision Improvement 0 13. Polat, U. & Sagi, D. in Maturational Windows and Adult Cortical Plasticity (eds. Julesz, B. & Kovâcs, I.) 1-15 (Addison-Wesley, 1995).