Author: Alfred Stett (Germany)
Co-authors: Andreas Schatz, Florian Gekeler, Jeremy Franklin
Purpose
After the onset of retinitis pigmentosa (RP), progressive visual field loss follows an exponentially decreasing course, leading to legal blindness in most cases. Any therapy, which is given or started at any stage of the disease, should stop, or at least significantly slow down the further decrease. So far, a dose-response relationship for the therapeutic effect of transcorneal electrical stimulation (TcES) on annual decline rate of the visual field is missing. To test whether TcES has a current-dependent effect on progressive visual field loss, we conducted an a posteriori analysis of raw data and a reappraisal of the outcome of a closed clinical trial.
Setting/Venue
We analysed raw data from 52 adult patients with RP who participated in an interventional, randomized, single-masked study at the University Eye Hospital Tübingen (EST2 trial, clinicaltrials.gov: NCT01837901). At that time, patients were randomly assigned to TcES with 0 mA (sham stimulation), 150% or 200% of their individual threshold current for phosphene perception. Over the period of 52 weeks, TcES was applied monocularly once per week for 30 min with biphasic current pulses (OkuStim, 5 ms each phase, 20 Hz). The visual field areas (VFA) were repeatedly assessed in both eyes (Octopus 900).
Methods
In contrast to the group-based statistics of the VFA of the stimulated eyes in the previous analysis (Schatz et al., IOVS, 2017, 58:1), we now determined the individual percentage reductions of the VFA in the stimulated (R1) and non-stimulated fellow eyes (R0) and analyzed the dependency of the reductions and the differences D = R1 - R0 on the individual current strengths. Mean current strength over 52 weeks stimulation was analyzed as a continuous variable (linear regression). We focused on the data obtained with Goldman target V4e.
Results
In the sham group (n=20), the mean percentage reduction of VFA was 7% in both eyes, as expected for the natural course of RP. A different picture emerged in the stimulated patients. The mean reduction R1 and R0 in the stimulated and non-stimulated fellow eyes (both n=32) was 4.5% ± 15.4%, and 8.1%±16.6% (mean ± SD), respectively. The two distributions were statistically significant different (p = 0,031, Wilcoxon signed rank test). As a result, TcES with current amplitudes from 0.2 to 1.0 mA led to an overall deceleration D/R0 of 44% in annual VFA decline compared with non-stimulated eyes. There was a significant linear relationship (p = 0.049, F test) between the difference D and the current strength. As the current strength increased, the VFA decreased more slowly. The effect was particularly pronounced in the subgroup of patients stimulated with the highest current amplitude from 0.8 mA to 1.0 mA (n=9). While in this subgroup R0 was 8.6% ± 9.0%, R1 was reduced to 0.8% ± 7.1% (difference between both eyes: p = 0.098). Thus, TcES with high current amplitudes resulted in a mean deceleration of annual VFA decline by 90%.
Conlusions
For the first time, a dose-response relationship for the effect of TcES on the progression of the visual field area has been created from the data from a clinical trial with RP patients. Depending on the current strength, TcES slowed down the annual decline rate of the VFA to less than 1%. The results provide clinical evidence that TES significantly has a therapeutic effect and is an efficient method to delay or stop the disease progression in RP.
Financial Disclosure
A. Stett is CEO and Employee of Okuvision. Institute of Medical Statistics and Computational Biology (J. Franklin) received financial support from Okuvision. A. Schatz and F. Gekeler have no specific financial relations. Okuvision GmbH sponsored the EST2 clinical trial and commercializes the OkuStim therapy.
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