Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.
- 1Department of Ophthalmology, Dankook University Hospital, Cheonan, 31116, Republic of Korea.
- 2Technical R&D Center, Kitto Life Co., Ltd., Pyeongtaek, Republic of Korea.
- 3Department of Ophthalmology, Dankook University Hospital, Cheonan, 31116, Republic of Korea. [email protected].
Abstract
Introduction
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.Methods
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).Results
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.Conclusion
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.Trial registration
Clinical Research Information Service (CRIS; https://cris.nih.go.kr ), KCT0012279, registered on 14 July 2026; retrospectively registered.
Related
- Efficacy and Safety of Vitex Extract on Menopausal Symptoms and Quality of Life in Postmenopausal Women: A Randomized Placebo-Controlled Trial
- Thymus serpyllum Extract Improves Gastrointestinal Symptoms and Modulates Fecal Gut Microbiome Composition in a Multicenter, Randomized, Placebo-Controlled Clinical Trial.
- A Kampo medicine, kamishoyosan, ameliorates menstruation-associated symptoms in patients with premenstrual syndrome: An exploratory open-label, randomized controlled trial
- Fronto-temporal transcranial direct current stimulation reduces symptoms in treatment-resistant schizophrenia: a randomized sham-controlled trial
- A Randomized Clinical Trial of a Standardized Pumpkin-Seed-Derived Peptide Extract: Body Composition Outcomes and Exploratory Analysis by Baseline Adiposity in Overweight Adults
BibTeX
@article{kim2026effects,
title = {{Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.}},
author = {Hoon Kim and Hyun Pil Yang and Yuli Park and Kyongjin Cho},
journal = {Ophthalmology and therapy},
year = {2026},
month = oct,
doi = {10.1007/s40123-026-01509-8},
url = {https://europepmc.org/article/MED/42832166},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.
AU - Hoon Kim
AU - Hyun Pil Yang
AU - Yuli Park
AU - Kyongjin Cho
PY - 2026
DA - 2026/10/05
JO - Ophthalmology and therapy
DO - 10.1007/s40123-026-01509-8
UR - https://europepmc.org/article/MED/42832166
AB - Introduction 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.Methods 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).Results 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.Conclusion 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.Trial registration Clinical Research Information Service (CRIS; https://cris.nih.go.kr ), KCT0012279, registered on 14 July 2026; retrospectively registered.
SN - 2193-8245
SN - 2193-6528
ER -