Table 2.
TES: Clinical Studies
| Reference | Disease | Experimental population; stimulation location | Control group | ES parameters | Evaluation method | Results |
|---|---|---|---|---|---|---|
| Schatz et al, 201136 | RP | 24 patients; cornea; both eyes | Sham | Intensity 66% and 150% of EPT, 20 Hz, 5-millisecond biphasic pulses, 30 minutes per week, for 6 weeks | VA; VF; ERG recordings; color discrimination; EPTs; blood tests | TES improved VF; all functional parameters were improved or remained constant in 150% group; TES led to decreased desaturated color discrimination and VF mean sensitivity; no marked tendency was observed in 66% group |
| Fujikado et al, 200737 | Normal-sighted | Eight patients | — | 25–250 μA, biphasic pulses at 5–50 Hz, 20 pulses of 10-millisecond duration | Measurement of PR | TES with a frequency of 20 Hz yielded the maximum PR; biphasic pulses with duration of 0.5–1.0 millisecond and a frequency of 20–50 Hz were highly efficient for evoking phosphene |
| Fujikado et al, 200638 | NAION; TON | Eight patients; NAION (n = 3); TON (n = 5); cornea; one eye | Fellow eyes | 300–800 μA, 20 Hz, 10 milliseconds, 30 minutes, one session | EEPR; BCVA; VF | The VA increased in two subjects with NAION and in four subjects with TON |
| Inomata et al, 200739 | RAO | Three patients, two with central and one with branch RAO, cornea; one eye | Fellow eyes | 0–1100 μA until evoking phosphene, 20 Hz, 30-minute duration, once per month for up to 3 months | VA; VF; mfERGs | Improved function of retina in eyes with long-standing RAOs; the VA and mfERGs improved in two cases, and VF was improved in all three cases |
| Kurimoto et al, 201040 | Normal-sighted | 10 patients; cornea; both eyes | Fellow eyes; sham | Up to 150 μA, 20 Hz, 30 minutes, one session | LSFG; SBR; IOP; measurement of blood pressure and pulse rate | Increased the chorioretinal blood flow in normal patients with mild effects on the systemic blood circulation and IOP |
| Morimoto et al, 200641 | RP; CRD | 20 patients; RP (n = 16); CRD (n = 4); cornea | Eight healthy patients | 50 μA–2 mA, biphasic pulses at 20 Hz, 20 pulses of 10-millisecond duration; three electrical current thresholds: T1, T2, and P | EEPR; BCVA; VF; phosphene thresholds | All thresholds significantly higher in patients compared to healthy subjects; T1 and T2 were not correlated with VA, but related to the area and location of the remaining VF; T1 and T2 in RP eyes with EEPR was lower compared to RP eyes without an EEPR |
| Naycheva et al, 201242 | RP; STG; RAO; NAION; POAG | RP (n = 30); STG (n = 14); RAO (n = 20); NAION (n = 16); POAG (n = 17); cornea | 20 Healthy patients | 1 μA–10 mA, 3, 6, 9, 20, 40, and 80 Hz with 10-millisecond biphasic current pulses; 5 millisecond positive, thereafter 5 millisecond negative; periodically switching of the light, every 60–90 seconds | VA; VF; electrophysiology; slit-lamp biomicroscopy; fundus examination; tonometry | EPTs differed between the disease groups; in all groups, EPTs were lowest at 20 Hz; subjects with retinal diseases and across all frequencies exhibited higher EPTs than healthy patients, except in STG at 20 Hz |
| Naycheva et al, 201343 | Central and branch RAO | 13 patients; 12 with central, 1 with branch RAO | Three patients; sham | 5-Milliseconds positive, thereafter 5-milliseconds negative biphasic pulses at 20 Hz, 30 minutes once a week for 6 days, intensity 66% and 150% of EPT | Kinetic and static VFs; VA; full-field and mfERG | The scotopic a-wave slopes increased in 150% treatment group; other parameters in all other groups were unchanged |
| Oono et al, 201144 | Branch RAO | Five patients; two fresh and three long-standing cases; cornea; both eyes | — | 500–900-μA, biphasic pulses at 20 Hz, duration 30 minutes | BCVA; mfERGs; automated static perimetry with HFA | TES reforms the visual function in patients with branch RAO, primarily in long-standing cases |
| Ozeki et al, 201345 | BVMD | One patient; cornea; right eye | — | First treatment: 250 μA/170 μA, 20 Hz, 10 milliseconds/phase, 30-minute duration, two sessions with interval of 1 month; second treatment 2 years later: 160 μA, 20 Hz, 10 milliseconds, 30-minute duration, two sessions with interval of 1 month | BCVA; VF; mfERG | BCVA improved from 20/40–20/30 after 1 month, and from 20/40–20/25 after 6 months; slight improvements for VFs and mfERGs; BCVA decreased to 20/70 after 2 years; second treatment: BCVA improved to 20/30 after 1 month; no improvements in VFs and mfERGs |
| Xie et al, 201146 | Normal-sighted | Six patients; cornea; right eye | — | DTL-Plus corneal electrode and ERG-Jet contact lens electrode; 1.5× EPT current amplitude, 30-minute duration, 2 Hz, 2-millisecond pulse width; after every 5 minutes of continuous TES, stimulation turned off for 30 seconds | PET imaging; FDG activity | The results with both corneal electrodes demonstrated activation of areas in visual cortex that were related to the reported phosphene percept; ERG-Jet was able to generate brighter phosphene percept compared to DTL-Plus; the use of ERG-Jet led to activation of retinotopically mapped primary visual cortex |
| Xie et al, 201247 | RD | Five patients; cornea; right eye | Five healthy patients | First, 30 minutes dark adaptation; 1.5× EPT current amplitude, 2-millisecond pulses, 2 Hz with interpulse of 996 milliseconds, 30-minute duration; after every 5 minutes of continuous TES, stimulation turned off for 30 seconds | PET imaging; FDG activity | EPT current was higher in RD patients compared with control; in both groups, TES and light stimulation resulted in activation of retinotopically mapped primary visual cortex |
BCVA, best-corrected visual acuity; BVMD, best vitelliform macular dystrophy; CRD, cone-rod dystrophy; DTL, Dawson-Trick-Litzkow; EEPR, electrically evoked pupillary response; EPT, electrical phosphene threshold; ERG, electroretinogram; ES, electrical stimulation; FDG, 18F-fluorodeoxyglucose; HFA, Humphrey field analyzer; IOP, intraocular pressure; LSFG, laser speckle flowgraphy; mfERG, multifocal electroretinogram; NAION, nonarteritic ischemic optic neuropathy; PET, positron emission tomography; POAG, primary open-angle glaucoma; PR, pupillary reflex; RAO, retinal artery occlusion, RD, retinal degeneration; RP, retinitis pigmentosa; SBR, square blur rate; STG, Stargardt disease; TES, transcorneal electrical stimulation; TON, traumatic optic neuropathy; VA, visual acuity; VF, visual field; –, not reported.