Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.

Authors

Hoon Kim, Hyun Pil Yang, Yuli Park, Kyongjin Cho

Published in

Ophthalmology and therapy. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

Dry eye disease impairs visual function and quality of life. This trial evaluated the efficacy and safety of grape skin enzyme fermentation extract (KL-GEFE; Nunaezone, Kitto Life Co., Ltd., Pyeongtaek, Republic of Korea), a grape skin enzyme fermentation extract, in adults with ocular fatigue and dry-eye-related symptoms.
In this 12-week, randomized, double-blind, placebo-controlled trial at Dankook University Hospital, 68 adults were allocated 1:1 to KL-GEFE (400 mg/day) or placebo. The study protocol specified the Schirmer I test, adapted Eye Strain Questionnaire (ESQ), noninvasive break-up time (NIBUT), fluorescein tear break-up time (TBUT), ocular-surface staining, critical flicker fusion frequency (CFF), and Ocular Surface Disease Index (OSDI) as efficacy outcomes but did not assign them a formal hierarchy. The protocol-specified efficacy analysis used baseline-adjusted analysis of covariance (ANCOVA) in the per-protocol set (PPS; n = 65), with supportive analysis in the full analysis set (FAS; n = 68) using last observation carried forward (LOCF).
At week 12, the adjusted KL-GEFE-minus-placebo difference was 4.46 mm for the Schirmer I test (95% CI 2.96-5.95; P < 0.001) and -4.29 points for the adapted ESQ total score (95% CI -8.39 to -0.19; P = 0.041). The corresponding FAS-LOCF estimates were 4.36 mm (95% CI 2.92-5.80; P < 0.001) and -4.56 points (95% CI -8.57 to -0.56; P = 0.026), respectively. The week 12 OSDI difference was not statistically significant, and no statistically significant week 12 between-group differences were observed for NIBUT, fluorescein TBUT, CFF, or ocular-surface staining. Two mild adverse events unrelated to the study product occurred; no serious adverse events occurred.
KL-GEFE supplementation was associated with week 12 between-group differences in Schirmer I test values and adapted ESQ total scores, whereas no statistically significant week 12 between-group differences were observed for the other efficacy outcomes. Given the absence of a prospectively defined outcome hierarchy and multiplicity-control framework, these findings should be considered exploratory and require confirmation in prospectively designed trials.
Clinical Research Information Service (CRIS; https://cris.nih.go.kr ), KCT0012279, registered on 14 July 2026; retrospectively registered.

PMID:
42832166
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

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