Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial

Trials · 9 authors, 2 centres

AI SUMMARY

FIDELITY 100%

POPULATIONRP patients aged 18-80 years with BCVA ≥35 letters (20/200) and VF radius >5° in at least one eye

INTERVENTIONTranspalpebral electrical stimulation (TpES) applied to both eyelids twice daily for 5 minutes, with current intensity 0-800 μA and frequencies 292 Hz, 30 Hz, 9.1 Hz, and 0.3 Hz

COMPARISONSham stimulation (device applied but no electrical stimulation)

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TL;DR

This study protocol describes the first prospective randomized trial evaluating transpalpebral electrical stimulation (TpES) for retinitis pigmentosa (RP). Using an N-of-1 single-blind crossover design with 12 participants, the primary outcome is visual field changes over 48 weeks. The trial aims to provide high-quality evidence on the safety and efficacy of TpES for RP, a rare inherited retinal disease.

Full summary

2,944 CHARS

**Background:** Retinitis pigmentosa (RP) is an inherited retinal disease causing progressive photoreceptor loss and blindness, affecting about 1.5 million people worldwide. No prospective clinical studies have documented interventions that reverse or reduce RP progression. Electrical stimulation (ES) has shown neuroprotective effects in animal models and small clinical studies for glaucoma, age-related macular degeneration, and RP, but large randomized trials are lacking. This protocol describes the first prospective randomized study evaluating transpalpebral electrical stimulation (TpES) for RP.

**Methods:** This is a prospective, comparative, single-blind N-of-1 trial with 3 crossover comparisons. Each comparison includes an 8-week treatment period (TpES) and an 8-week control period (sham), randomly arranged. Twelve participants will be recruited from the Eye Hospital, China Academy of Chinese Medical Sciences. Inclusion criteria: RP diagnosis, age 18-80 years, best corrected visual acuity (BCVA) ≥35 letters (20/200) on ETDRS chart, visual field (VF) radius >5°, and informed consent. Exclusion criteria include adverse reactions to ES, other eye diseases, unreliable VF results, mental illness, pacemakers, pregnancy, and recent participation in other trials. The TpES device delivers biphasic pulses at frequencies of 292 Hz (30 s), 30 Hz (30 s), 9.1 Hz (2 min), and 0.3 Hz (2 min), with current intensity 0-800 μA, applied twice daily for 5 minutes. The control period uses the same device without stimulation. The primary outcome is VF (mean defect [MD], mean sensitivity [MS], square root of loss variance [sLV]) measured by OCTOPUS perimetry at baseline and weeks 8, 16, 24, 32, 40, and 48. Secondary outcomes include BCVA, optical coherence tomography (OCT), fundus autofluorescence (FAF), electroretinogram (ERG), and NEI VFQ-25 questionnaire. Sample size calculation based on Sun et al. (MD change 2.06±1.73 for treatment vs 0.73±1.93 for control, difference 1.43, SD 1.93) with 80% power and 5% significance yielded 10 cases, increased to 12 to account for 20% dropout. Statistical analysis uses paired t-tests or Wilcoxon rank sum tests for within-group effects, and repeatability measure ANOVA or linear mixed-effects models for between-group effects, with P<0.05 considered significant.

**Key Results:** This is a study protocol; no results are reported. The trial is registered (ChiCTR2300067357) and recruitment started January 2023, expected to finish March 2024.

**Clinical Implications:** If TpES proves effective, it could offer a non-invasive, patient-administered therapy for RP, a rare disease with limited treatment options. The N-of-1 design addresses heterogeneity in RP and allows individualized assessment. Potential limitations include the long trial duration (48 weeks) and lack of long-term follow-up. The study may provide high-quality evidence for TpES as a neuroprotective therapy for RP.

PICO

PPOPULATION

RP patients aged 18-80 years with BCVA ≥35 letters (20/200) and VF radius >5° in at least one eye

IINTERVENTION

Transpalpebral electrical stimulation (TpES) applied to both eyelids twice daily for 5 minutes, with current intensity 0-800 μA and frequencies 292 Hz, 30 Hz, 9.1 Hz, and 0.3 Hz

OOUTCOME

Primary: visual field (MD, MS, sLV); Secondary: BCVA, OCT, FAF, ERG, NEI VFQ-25

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10821291

Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial

Trials

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ABSTRACT

Abstract Background Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP. Methods Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF). Discussion The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial. Trial registration Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635 . Registered on 5 January 2023 Supplementary Information The online version contains supplementary material available at 10.1186/s13063-024-07933-0. Keywords: Transpalpebral electrical stimulation, Microcurrent stimulation, Retinitis pigmentosa, N-of-1 trial

CITATION EXPORT

Wei Zhou, Ziyang Huang, Kai Xu et al.. Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial. Trials. (2024). https://doi.org/10.1186/s13063-024-07933-0

AUTHORS

9 · 2 CENTRES

Wei Zhou, Ziyang Huang, Kai Xu, Yamin Li, Xiaoyu Li, Jiaxian Li, Yu Jin, Torkel Snellingen, Lina Liang

1Department of Eye Function Laboratory, Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China
2Beijing Research Institute of Vision Science & Sekwa Eye Hospital, Beijing, China