Transcutaneous Electrical Stimulation for the Prevention of Dry Eye Disease after Photorefractive Keratectomy: Randomized Controlled Trial

Abstract

Objective: To evaluate the efficacy and safety of transcutaneous electrical stimulation (TES) for the prevention of dry eye after photorefractive keratectomy (PRK).

Design: Prospective, single-center, single-blinded, parallel group, placebo-controlled, randomized clinical trial.

Participants: Between February 2020 and October 2020, patients at the Samsung Medical Center scheduled to undergo PRK to correct myopia were screened and enrolled.

Methods: The participants in the TES group were instructed to use the electrical stimulation device (Nu Eyne 01, Nu Eyne Co) at the periocular region after the operation, whereas those in the control group were to use the sham device. Dry eye symptoms were evaluated preoperatively and postoperatively at weeks 1, 4, and 12 using the Ocular Surface Disease Index (OSDI) questionnaire, the 5-Item Dry Eye Questionnaire (DEQ-5), and the Standard Patient Evaluation for Eye Dryness II (SPEED II) questionnaire. Dry eye signs were assessed using tear break-up time (TBUT), total corneal fluorescein staining (tCFS), and total conjunctival staining score according to the National Eye Institute/Industry scale. The pain intensity was evaluated using a visual analog scale.

Main outcome measures: Primary outcomes were OSDI and TBUT.

Results: Twenty-four patients were enrolled and completed follow-up until the end of the study (12 patients in the TES group, 12 patients in the control group). Refractive outcomes and visual acuity were not different between the groups. No serious adverse event was reported with regard to device use. No significant difference in OSDI and SPEED II questionnaires and the DEQ-5 was observed between the groups in the 12th week after surgery. The TBUT scores 12 weeks after the surgery were 9.28 ± 6.90 seconds in the TES group and 5.98 ± 2.55 seconds in the control group with significant difference (P = 0.042). The tCFS and total conjunctival staining score were significantly lower in the TES group than in the control group at postoperative 4 weeks. Pain intensity at the first week was significantly lower in the TES group than in the control group by 65% (P = 0.011).

Conclusion: The application of TES is safe and effective in improving dry eye disease after PRK.

Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Corneal nerve regeneration; DED, dry eye disease; DEQ-5, 5-Item Dry Eye Questionnaire; Dry eye; Electrostimulation; LLT, lipid layer thickness; NGF, nerve growth factor; OSDI, Ocular Surface Disease Index; PRK, photorefractive keratectomy; Refractive surgery; SPEED II, Standard Patient Evaluation for Eye Dryness II; TBUT, tear break-up time; TES, transcutaneous electrical stimulation; UDVA, uncorrected distant visual acuity; tCFS, total corneal fluorescein staining.

Figure 1

Flow diagram of the study.

Figure 2

A, Electrical stimulator and electrode (NuEyne 01, Nu Eyne Co). B, Examples of electrode attachment. C, Device application. D, Waveform of electrical stimulation.

Figure 3

Subjective dry eye symptom scores from study and control groups (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, ^∗∗P < 0.01, Wilcoxon signed-rank test). A, Ocular Surface Disease Index (OSDI). B, 5-Item Dry Eye Questionnaire (DEQ-5). C, Standard Patient Evaluation for Eye Dryness II (SPEED II). TES = transcutaneous electrical stimulation.

Figure 4

(A) Tear break-up time and (B) Schirmer test results before and 12 weeks after the surgery (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, Wilcoxon rank sum test). T-BUT = tear break-up time; TES = transcutaneous electrical stimulation.

Figure 5

(A) Corneal and (B) conjunctival fluorescent staining scores 1 week (1Wk), 4 weeks (4Wk), and 12 weeks (12Wk) after the surgery compared between the study and control groups. ∗P < 0.05, Wilcoxon rank sum test). TES = transcutaneous electrical stimulation.

Figure 6

A, Osmolarity test scores before and 12 weeks after the surgery compared between the test and control groups. B, Differences of osmolarity test scores between before and 12 weeks after the surgery of the study and control groups (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, Wilcoxon rank sum test). TES = transcutaneous electrical stimulation.

Figure 7

A, Lipid layer thickness (LTT) before and 12 weeks after the surgery compared between the study and control groups. B, Differences of LLT between before and 12 weeks after the surgery of the study and control groups (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, ^∗∗P < 0.01, Wilcoxon rank sum test). TES = transcutaneous electrical stimulation.

Figure 8

Concentrations of matrix metalloproteinase 9 (MMP-9) before and 12 weeks after the surgery compared between the study and control groups (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, ^∗∗P < 0.01, Wilcoxon rank sum test). TES = transcutaneous electrical stimulation.

Figure 9

Corneal sensitivity measured with a corneal aesthesiometer before and 12 weeks after the surgery to be compared between the study and control groups (Pre: screening before the surgery, 12Wk: 12 weeks after the surgery, ^∗P < 0.05, ^∗∗P < 0.01, Wilcoxon rank sum test). A, Touch: sensing level. B, Pain: pain level. C, Eye_Closed: While the eyes were closed. TES = transcutaneous electrical stimulation.

Figure 10

Pain rating score with VAS change before and after the surgery. (1Day: 1 day after, 3Day: 3 days after, 1Wk: 1 week after the surgery, ^∗P < 0.05, Wilcoxon rank sum test). TES = transcutaneous electrical stimulation; VAS = visual analog scale.