Randomized controlled trial of electro-stimulation therapies to modulate retinal blood flow and visual function in retinitis pigmentosa

Abstract

Purpose: We examined changes in visual function and ocular and retinal blood flow (RBF) among retinitis pigmentosa (RP) participants in a randomized controlled trial of electro-stimulation therapies.

Methods: Twenty-one RP participants were randomized (1:1:1) to transcorneal electrical stimulation (TES) at 6 weekly half-hour sessions, electro-acupuncture or inactive laser acupuncture (sham control) at 10 half-hour sessions over 2 weeks. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA), quick contrast sensitivity function, Goldmann visual fields, AdaptDx scotopic sensitivity, spectral flow and colour Doppler imaging of the central retinal artery (CRA), and RBF in macular capillaries were measured twice pre-treatment, after 2 TES sessions, within a week and a month after intervention completion.

Results: We measured a significant improvement in retrobulbar CRA mean flow velocity for both the TES (p = 0.038) and electro-acupuncture groups (p = 0.001) on average after 2 weeks of treatment when compared to sham controls. Transcorneal electrical simulation (TES) and electro-acupuncture subjects had significant 55% and 34% greater increases, respectively, in RBF in the macular vessels when compared to sham controls (p < 0.001; p = 0.008) within a week of completing six TES sessions or a month after electro-acupuncture. There was a significant difference in the proportion of eyes that had improved visual function when comparing the three intervention groups (p = 0.038): four of seven TES subjects (57%), two of seven electro-acupuncture subjects (29%) and none of the seven control subjects (0%) had a significant visual improvement outside of typical test-retest variability at two consecutive post-treatment visits.

Conclusion: Increased blood flow following electro-stimulation therapies is an objective, physiological change that occurred in addition to visual function improvements in some RP patients.

Keywords: acupuncture; retinal blood flow; retinitis pigmentosa; transcorneal electrical stimulation.

Conflict of interest statement

The study team has no potential conflicts of interest to disclose, including financial interests, activities, relationships, and affiliations.

© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Figures

Figure 1

A chart of the flow of participants, randomization to each group, interventions, timing, and study visits at which the baseline and follow-up outcome measures were obtained.

Figure 2

Panel A shows the TrioStim microcurrent stimulator unit used for TES. Panel B displays the electrodes attached to the acupuncture needles above the eyes during electro-acupuncture.

Figure 3

Box plot of changes from mean baseline for MFV, mean log PSV and mean EDV in the CRA of each eye according to intervention group after 2 TES sessions or within a week of completing the acupuncture intervention for the electro-acupuncture subjects or laser acupuncture (i.e., placebo sham controls). The bottom and top of the box are the 25th and 75th percentile (i.e., the upper and lower quartiles, respectively), and the band near the middle of the box is the 50th percentile (i.e., the median). The ends of the whiskers represent the lowest datum within 1.5 times the interquartile range of the lower quartile, and the highest datum still within 1.5 times the interquartile range of the upper quartile. Any data not included between the whiskers is plotted as an outlier indicated by a dot.

Figure 4

Box plot of percent changes in MFV for RBF in the macular vessels according to intervention group within a week of completing six TES sessions and a month after completing electro-acupuncture compared to baseline. Dots: data not included between the whiskers and regarded as outliers.

Figure 5

Box plot of changes in logMAR VA according to intervention group within a week and a month after completing each intervention compared to baseline. Dots: data not included between the whiskers and regarded as outliers.

Figure 6

Box plot of changes in GVF log retinal area with the III4e test target according to intervention group within a week and a month of completing each intervention compared to baseline. Dots: data not included between the whiskers and regarded as outliers.

Figure 7

Mean CSFs at baseline in blue and post-treatment in red for two TES subjects and one electro-acupuncture subject with high ROC values indicating significantly improved CSFs post-treatment.

Figure 8

Changes in mean cone-mediated scotopic sensitivity at nasal and superior locations tested with the AdaptDx in one eye of an electro-acupuncture subject.