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Background <p>To compare the therapeutic effects of omega-3 polyunsaturated fatty acids (PUFAs) supplements across different formulations and dry eye disease (DED) etiologies.</p> Methods <p>Studies were systematically searched in six databases without language restrictions. Dry eye symptom scores, tear break-up time (TBUT), Schirmer test, corneal fluorescein staining (CFS), and meibomian gland dysfunction (MGD) scores were extracted as outcomes. Meta-regression, sensitivity and subgroup analyses were implemented to investigate significant heterogeneity.</p> Results <p>Twenty-seven randomized controlled trials (RCTs) were included. Systemic omega-3 supplementation appeared to improve all assessed outcomes in the overall pooled analysis; however, subgroup analyses revealed formulation- and etiology-dependent effects. Among systemic long-chain omega-3 formulations, efficacy was etiology-dependent: no significant benefits were observed in MGD-associated dry eye or in cases of unspecified etiology, whereas significant improvements were found in video display terminal-related dry eye and contact lens-associated dry eye. Given the limited evidence, findings were synthesized qualitatively: omega-3 supplements demonstrated beneficial effects in rosacea-associated and Sjögren’s syndrome-related dry eye, whereas no clinically meaningful improvement was observed in LASIK-induced dry eye. In contrast, neither systemic short-chain fatty acids nor the combination of long- and short-chain omega-3 PUFAs achieved statistical significance. Furthermore, topical omega-3 delivery failed to demonstrate significant benefits compared with artificial tears. Meta-regression analysis revealed a significant association between omega-3 supplementation and several external factors, including mean age, geographic location, assessment methodologies, omega-3 dose, and publication year.</p> Conclusions <p>Our research suggests that omega-3 supplements in different forms fail to demonstrate consistent effectiveness for DED of various etiological origins. Therefore, personalized guidance from healthcare providers regarding the application of omega-3 PUFAs for the management of ocular surface disorders is warranted.</p> PROSPERO Registration <p>CRD42024623916.</p>

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The effects of different forms of omega-3 polyunsaturated fatty acids on dry eye disease resulting from various etiologies: a meta-analysis and systematic review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • Guozhen Chen,
  • Xinlin Yan,
  • Shumei Yang,
  • Xuan Li

摘要

Background

To compare the therapeutic effects of omega-3 polyunsaturated fatty acids (PUFAs) supplements across different formulations and dry eye disease (DED) etiologies.

Methods

Studies were systematically searched in six databases without language restrictions. Dry eye symptom scores, tear break-up time (TBUT), Schirmer test, corneal fluorescein staining (CFS), and meibomian gland dysfunction (MGD) scores were extracted as outcomes. Meta-regression, sensitivity and subgroup analyses were implemented to investigate significant heterogeneity.

Results

Twenty-seven randomized controlled trials (RCTs) were included. Systemic omega-3 supplementation appeared to improve all assessed outcomes in the overall pooled analysis; however, subgroup analyses revealed formulation- and etiology-dependent effects. Among systemic long-chain omega-3 formulations, efficacy was etiology-dependent: no significant benefits were observed in MGD-associated dry eye or in cases of unspecified etiology, whereas significant improvements were found in video display terminal-related dry eye and contact lens-associated dry eye. Given the limited evidence, findings were synthesized qualitatively: omega-3 supplements demonstrated beneficial effects in rosacea-associated and Sjögren’s syndrome-related dry eye, whereas no clinically meaningful improvement was observed in LASIK-induced dry eye. In contrast, neither systemic short-chain fatty acids nor the combination of long- and short-chain omega-3 PUFAs achieved statistical significance. Furthermore, topical omega-3 delivery failed to demonstrate significant benefits compared with artificial tears. Meta-regression analysis revealed a significant association between omega-3 supplementation and several external factors, including mean age, geographic location, assessment methodologies, omega-3 dose, and publication year.

Conclusions

Our research suggests that omega-3 supplements in different forms fail to demonstrate consistent effectiveness for DED of various etiological origins. Therefore, personalized guidance from healthcare providers regarding the application of omega-3 PUFAs for the management of ocular surface disorders is warranted.

PROSPERO Registration

CRD42024623916.