JAMA Ophthalmology Journal Club Slides: Vision Restoration Training for Glaucoma

1. JAMA Ophthalmology Journal Club Slides:Vision Restoration Training for Glaucoma Sabel BA, Gudlin J. Vision restoration training for glaucoma: a randomized clinical trial. JAMA Ophthalmol. Published online February 6, 2014. doi:10.1001/jamaophthalmol.2013.7963.

2. Introduction • Vision loss in glaucoma was considered irreversible. • However, the brain, which processes vision, is modifiable even in adulthood and old age, able to adapt to change. • Evidence for this neuroplasticity includes the following: • In adult visual cortex, receptive fields can change in size and location after retinal injury. • Training eccentric (peripheral) viewing in macular degeneration activates cortical regions normally representing central visual areas. • Visual training can improve visual fields in hemianopia, optic nerve damage, and amblyopia. • Noninvasive transorbital alternating current stimulation can improve visual fields in optic neuropathy.

3. Introduction Pilot study patient, age 56 years, chronic open-angle glaucoma, right eye • Motivation to initiate study: pilot trial results showing that vision restoration training for glaucoma (gVRT) improved detection accuracy in 4 of 5 patients with glaucoma. Before After 3 months of gVRT • Study Objective: To evaluate efficacy of gVRT.

4. Methods Study Design • Prospective, double-blind, randomized, placebo-controlled clinical trial. • Blinding procedure: neither the patient nor the outcome assessor was aware of the patient’s group identity. Intervention • Computer-based vision training with gVRT designed to preferentially present visual stimuli in areas of residual vision (ARVs) to activate them (n=15) or • Visual discrimination placebo training where visual stimuli are presented only in the intact visual field (n=15). • Training in both groups lasted 6 days a week for 3 months (for 30 min twice daily) on a home PC with adaptive parameter adjustments online.

5. ARVs: Shades of Gray Hemianopia visual field Fully input 5 Full damage Partial damage Glaucoma visual field Vision intact ARV Blind The extent of vision loss (detection ability) is a function of neuronal loss: the greater the cell loss is, the greater the field defect in different regions of the visual field. ARVs can be found in all kinds of visual field defects such as after stroke (hemianopia) or retinal damage (glaucoma). Sabel et al., Progr Brain Res, 2011

6. Methods Data Analysis • Statistical comparisons: pretreatment vs posttreatment within and between groups. • Primary outcome measure: • Detection accuracy in high-resolution perimetry (HRP) visual fields. • Secondary outcome measures: • White-on-white and blue-on-yellow near-threshold perimetry. • Reaction time in HRP. • Eye movement (eye tracker), fixation reliability. • Vision-related quality of life as assessed with the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). Limitations • 30-minute training creates fatigue in some patients (pauses required). • Training discipline needed for 3 months of daily training.

7. Results • Single patient example of HRP detection chart before vs after gVRT.

8. Results • Within-group analysis of detection performance. HRP detection rate in the gVRT group increased significantly compared with placebo.

9. Results •  Comparison of detection accuracy changes. • Between-group analysis: pre-post detection improvements greater with gVRT than placebo, but results are variable.

10. Results Further Observations • HRP reaction time was significantly faster after gVRT than after placebo. • Visual improvements were located mainly in ARVs. Vision-Related Quality of Life Measured by NEI-VFQ-25 • The gVRT group but not the placebo group significantly improved on the mental health subscale and reported subjective visual improvements due to training. • Both groups reported a high level of satisfaction with the vision training, which confirms successful blinding on the group identities. Eye Movements and Fixation Performance • No change in either group.

11. Comment • Compared with placebo, gVRT significantly improves vision in glaucoma in the following: • Detection accuracy in HRP and in white-on-white and blue-on-yellow near-threshold perimetry. • Faster reaction times compared with placebo. • Improved general health and subjective training effects. • Changes cannot be explained by natural fluctuationsor eye movements. • Results confirm the following: • Previous pilot study in glaucoma. • Controlled trials of vision restoration training in hemianopia and optic nerve damage. • Variability of response in prior studies: • Approximately one-third were nonresponders, one-third had moderate response, and one-third were substantial responders.

12. Comment • Possible mechanism(s) why gVRT works: • Plasticity in the retina. • Changes of receptive fields at higher processing levels (lateral geniculate or visual cortex). • Improved visual attention. • Enhance synchronization of brain wave activity. • However, further studies are needed using electroencephalography or magnetic resonance imaging to clarify mechanisms.

13. Comment • General take-home messages: • Visual system neuroplasticity is maintained into adulthood and even old age, despite widespread visual system degeneration. • Vision loss in glaucoma must not be permanent; it is partially reversible. • Vision restoration is subjectively notable and clinically useful. • The findings confirm the theory of activating residual vision after retinal or brain damage through brain plasticity (Sabel BA, Henrich-Noack P, Fedorov A, Gall C. Vision restoration after brain and retina damage: the “residual vision activation theory.” Prog Brain Res. 2011;192:199-262).

14. Contact Information • If you have questions, please contact the corresponding author: • Bernhard A. Sabel, PhD, Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke University of Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany (imp@med.ovgu.de). Funding/Support • This work was supported by NovaVision Inc (Dr Sabel), by Braingames Online GmbH (Dr Sabel), and by a predoctoral fellowship under the LOM program of the University of Magdeburg (Dr Gudlin). Conflict of Interest Disclosures • None reported.