{
  "abstract": "Introduction\n\nDry 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\n\nIn 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\n\nAt 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\n\nKL-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\n\nClinical Research Information Service (CRIS; https://cris.nih.go.kr ), KCT0012279, registered on 14 July 2026; retrospectively registered.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, Dankook University Hospital, Cheonan, 31116, Republic of Korea.",
    "Technical R&D Center, Kitto Life Co., Ltd., Pyeongtaek, Republic of Korea.",
    "Department of Ophthalmology, Dankook University Hospital, Cheonan, 31116, Republic of Korea. perfectcurekj@gmail.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hoon Kim"
    },
    {
      "affs": [
        1
      ],
      "name": "Hyun Pil Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuli Park"
    },
    {
      "affs": [
        2
      ],
      "name": "Kyongjin Cho",
      "orcid": "0000-0003-1468-467X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9tf6g1sv4md69.bib",
  "cited_by": 0,
  "doi": "10.1007/s40123-026-01509-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13694643",
  "id": "9tf6g1sv4md69",
  "issns": [
    "2193-8245",
    "2193-6528"
  ],
  "landing_url": "https://europepmc.org/article/MED/42832166",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RE1-994"
    ],
    [
      "openalex",
      "2739|Ocular Surface and Contact Lens"
    ]
  ],
  "openalex": "W7220370210",
  "pdf_url": "https://europepmc.org/articles/PMC13694643?pdf=render",
  "pmcid": "PMC13694643",
  "pmid": "42832166",
  "published": "2026-10-05",
  "publisher": "Adis, Springer Healthcare",
  "ris": "https://research.draconitic.com/paper/9tf6g1sv4md69.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42832166",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42832166"
    },
    {
      "first_seen": "2026-10-30T13:45:41Z",
      "native_id": "03243df013cb4555aa7e84aff7aeab3e",
      "source": "doaj",
      "url": "https://doi.org/10.1007/s40123-026-01509-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Ocular Surface and Contact Lens",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.",
  "title_text": "Effects and Safety of Grape Skin Enzyme Fermentation Extract for Eye Fatigue and Dry Eye Symptoms: An Exploratory Randomized Controlled Trial.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:20:41Z",
  "url": "https://research.draconitic.com/paper/9tf6g1sv4md69",
  "venue": "Ophthalmology and therapy",
  "versions": []
}