Gut Medications Affect Dry Eye Risk in COVID Survivors — Vasoactive Intestinal Peptide May Be the Link | Research

The takeaway

Among 1,165 hospitalized COVID-19 patients, GI medications strongly predicted dry eye development — metoclopramide increased risk 13-fold while omeprazole reduced it by 67% — with vasoactive intestinal peptide (VIP) proposed as the gut-eye connection.

13-fold dry eye risk with metoclopramide
The anti-nausea drug metoclopramide was associated with a 13-fold increase in dry eye risk (OR 13.413) in COVID-19 survivors, with over 50% of affected patients having received this medication — the strongest drug-eye association found in the study.

What the researchers found

Among 1,165 SARS-CoV-2 hospitalized patients without pre-existing dry eye:

- 167 patients (14.3%) developed dry eye disease within 6 months of discharge

- Metoclopramide: strongest association, OR 13.413 (p<0.001), >50% incidence in affected patients

- Laxatives: lactulose OR 1.939 (p=0.016), polyethylene glycol OR 2.094 (p=0.015)

- Omeprazole: protective, OR 0.332 (p<0.001) — 67% risk reduction

- Polypharmacy increased dry eye odds: OR 1.629 (p=0.015)

- Age, gender, and vaccination status were not significant

Vasoactive intestinal peptide (VIP) is proposed as the pathophysiological link between gut and lacrimal gland function, connecting GI medication effects to dry eye outcomes.

Why it matters

Dry eye disease affects hundreds of millions of people worldwide and is particularly common after COVID-19. Understanding that gut medications can significantly influence dry eye risk — and that VIP may be the connecting mechanism — opens new avenues for prevention and treatment. If VIP-based therapies can protect the tear glands, it could benefit both COVID survivors and the broader dry eye population.

How the study worked

Retrospective cohort study using electronic medical records from patients hospitalized for SARS-CoV-2 between April 2020 and December 2023. Patients were aged 18+ without pre-existing dry eye. Exclusions: ICU admissions, malignancies, recent ocular interventions, chronic dry-eye-inducing medications. Logistic regression adjusted for age, gender, and vaccination status evaluated associations between GI medications and dry eye development within 6 months post-discharge.

What this study cannot tell us

This is a retrospective observational study and cannot establish causation between GI medications and dry eye. The VIP mechanism is proposed but not directly measured — no VIP levels were assessed. Confounding factors beyond age, gender, and vaccination may exist. The very high odds ratio for metoclopramide (13.4) may be influenced by confounding with disease severity. The study was limited to hospitalized patients, who may not represent all COVID-19 cases. Dry eye diagnosis methods are not detailed.

How to read the evidence

This is a retrospective cohort study with 1,165 patients. While it identifies strong statistical associations between GI medications and dry eye, it is observational and cannot prove causation. The VIP mechanism is hypothesized but not experimentally validated. The study provides moderate evidence for an intriguing clinical association.

When this study was published

Published in 2024, this study is very recent and addresses the ongoing clinical challenge of post-COVID complications, making it directly relevant to current patient care.

The bigger picture

Vasoactive intestinal peptide is a 28-amino-acid neuropeptide with wide-ranging functions — from gut motility to immune modulation to lacrimal gland stimulation. This study provides clinical evidence that the gut-eye axis, potentially mediated by VIP, has real-world health implications. As long COVID continues to affect millions, understanding these cross-organ connections could lead to preventive strategies and new therapeutic targets for post-viral complications.

Questions still open

Does metoclopramide directly affect VIP signaling or lacrimal gland function, or is it a marker for disease severity?
Could VIP supplementation or VIP receptor agonists prevent dry eye in COVID-19 survivors?
Do proton pump inhibitors protect against dry eye through VIP-mediated mechanisms, and does this extend beyond COVID patients?

Common questions

Can COVID-19 cause dry eyes?

Yes — this study found that 14.3% of hospitalized COVID-19 patients developed dry eye disease within 6 months of leaving the hospital. However, the risk varied dramatically depending on which gut medications patients received during their hospital stay. The researchers propose that vasoactive intestinal peptide (VIP) — a natural chemical that supports both gut and tear gland function — may be disrupted by COVID-19 and certain medications.

What is VIP and how does it connect the gut to the eyes?

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide found throughout the body. In the gut, it helps regulate digestion and blood flow. In the eyes, it stimulates the lacrimal (tear) glands to produce tears. Because VIP serves both systems, medications or diseases that affect VIP signaling in the gut may also impact tear production. This study proposes VIP as the biological mechanism explaining why GI medications influenced dry eye risk in COVID survivors.

Read the original research

Exploring the protective effects of vasoactive intestinal peptides on dry eye disease in SARS-CoV-2 survivors.

Molecular vision, 30, 489-496

View on PubMed ↗

Citation

Gushansky, Konstantin Y; Tuuminen, Raimo. (2024). Exploring the protective effects of vasoactive intestinal peptides on dry eye disease in SARS-CoV-2 survivors.. Molecular vision, 30, 489-496.