Metabolic Long-Term Monitoring of Transcorneal Electrical Stimulation in Retinitis Pigmentosa.

INTRODUCTION: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyze oxygen saturation in retinal vessels and has shown promising short-term results as a therapy monitoring tool for TES. The aim of our study was to measure the long-term effects of TES on RO parameters over a period of 3 years (3Y). METHODS: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic-disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V SO2) were measured and their difference (A-V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were employed for statistical analysis using SPSS®. RESULTS: After 3Y of TES treatment both the mean A-SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A-V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D-A and D-V (p > 0.05). CONCLUSION: Our long-term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow-up study and to confirm this trend reflecting a possible benefit of TES for RP.

Optical coherence tomography angiography findings in patients undergoing transcorneal electrical stimulation for treating retinitis pigmentosa.

PURPOSE: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment. METHODS: A total of 73 eyes were included: 43 eyes of 22 subjects (11 ♀, 11 ♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week (1W), and 6 months (6M) after treatment initiation and were compared with 30 control eyes of 15 subjects (8 ♀, 7 ♂). TES was performed simultaneously on both eyes for 30 min weekly. OCTA scans of 9 × 15 mm were recorded with a PLEX Elite 9000 swept-source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics such as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardised extended early treatment diabetic retinopathy study (ETDRS) grids centred around the fovea. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA-based linear mixed-effects models were calculated with SPSS®. RESULTS: Throughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance, also when analysed separately in the SCP and DCP (p > 0.08). In analogy, the average CPD and CFI also presented with a slight decrement (p > 0.20). However, when compared with controls, most OCTA parameters showed a significant decrement (p < 0.05). When analysed systematically in all subsections of the extended ETDRS grid, the temporal macular subsections within the outer ring (radius 1.5-3 mm) and also of the peripheral C1, C2, and C3 rings (radius 3-7.5 mm) showed lower VD and PD values when compared with the other subsections (p < 0.05). CONCLUSION: Vascular density metrics in the macular region and the peripapillary microvasculature appear to remain unaffected by continuous TES treatment within a period of 6 months.

Metabolic monitoring of transcorneal electrical stimulation in retinitis pigmentosa.

PURPOSE: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). With progression of RP, loss of photoreceptors leads to less oxygen consumption and lower demand in the retina. Retinal oximetry (RO), as a non-invasive method to analyse oxygen saturation in retinal vessels, promises to be a useful therapy monitoring tool. The aim of our study was to observe changes in RO that would be attributed to therapeutic intervention. METHODS: A total of 43 eyes of 22 subjects (11♀ 11♂) suffering from RP were examined at baseline, after the first stimulation, 1 week and 6 months after TES (OkuStim®). Stimulation was performed for 30 min weekly at 200% of the individual phosphene threshold, simultaneously on both eyes. The oxygen saturation was examined at baseline and following TES stimulation with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0-1.5 optic disc diameters from the disc margin, in retinal arterioles (A-SO2) and venules (V-SO2) were estimated and their difference (A-V SO2) was calculated. In addition, we evaluated the diameters (in µm) in the corresponding arterioles (D-A) and venules (D-V). ANOVA-based linear mixed-effects models were calculated with SPSS®. RESULTS: Six months after TES treatment, the mean A-SO2 increased (from 96.48 ± 12.27 to 100.15 ± 5.56%, p = 0.09), while the V-SO2 decreased (from 61.61 ± 12.78 to 59.79 ± 11.15%, p = 0.48). The A-V SO2, which represents the oxygen consumption of the retina, showed a statistically significant increase from 34.87 ± 9.38% at baseline to 41.36 ± 9.18% after 6 months (p = 0.02). TES had no influence on the D-A and D-V (p > 0.6). CONCLUSION: These data indicate that TES therapy in RP leads to an increased oxygen consumption of the retina. RO may thus serve as a sensitive monitoring method for TES therapy in RP.