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# Effects of Omega-3 Fatty Acids on Eye Health

*Evidence Reports/Technology Assessments, No. 117*

Investigators: William Hodge, MD, David Barnes, MD, Howard M Schachter, PhD, Yi Pan, MSc, Elizabeth C Lowcock, BScH, Li Zhang, MLIS, Margaret Sampson, MLIS, Andra Morrison, BSc, Khai Tran, PhD, Maia Miguelez, PhD, and Gabriela Lewin, MD.

Agency for Healthcare Research and Quality (US)2005 Jul

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## Structured Abstract

#### Context:

In the United States, blindness or low vision affects 3.3                million people over the age of 40, or one in 28 people in that age group. With the                number of people aged 50 years or older expected to increase in upcoming decades,                this number is expected to increase to 5.5 million Americans or 76 million people                worldwide by the year 2020. The most important cause of low vision worldwide is                cataracts; in developed countries, age related macular degeneration is the most                common cause of low vision. The brain and eye are highly enriched with omega-3 fatty                acids, which accumulate in these tissues during late fetal and early neonatal life.                Some studies in preterm and term human infants have suggested that a dietary supply                of omega-3 fatty acids is essential for optimal visual development. Several basic                science studies support the hypothesis that omega-3 fatty acids may be useful                therapeutic agents for pathologies of the retina and lens.

#### Objectives:

The purpose of this study was to conduct a systematic                review of the scientific-medical literature to identify, appraise and synthesize the                evidence for the effects of omega-3 fatty acids on eye health. Questions assessed                the possible primary or secondary preventive influence of the intake of omega-3                fatty acids on important eye health-related outcomes. These included age-related                macular degeneration (ARMD), diabetic retinopathy, retinitis pigmentosa, cataracts,                and occlusions of either retinal veins or retinal arteries. Adverse effects                associated with omega-3 fatty acid supplementation in interventional studies of eye                health were also sought.

#### Data Sources:

A comprehensive search was undertaken in six databases                (MEDLINE®, PreMEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, CAB                Health, and Dissertation Abstracts). Searches were not restricted by language of                publication, publication type, or study design except with the MeSH® term “dietary                fats,” which was limited by study design to increase its specificity. Search terms                related to omega-3 fatty acids and eye health. Additional published or unpublished                literature was sought through manual searches of reference lists of included studies                and key review articles, and from the files of content experts.

#### Study Selection:

Studies were considered relevant if they described                live human populations of any age, involved any type of study design, and                investigated the intake of any foods or extracts, known to contain omega-3 fatty                acids, for their possible primary or secondary preventive influence on eye health.                Ineligible were studies, which included populations exclusively exhibiting a                possible or requisite subset of the symptoms or signs of eye disease/visual                impairment (e.g., blurred vision). A review-pertinent diagnosis, as well as at least                one review-relevant clinical ocular outcome, was required.

#### Data Extraction:

Two levels of screening for relevance, and two                reviewers per level, were employed (bibliographic records, then full articles).                Calibration exercises preceded each step of the screening process. Excluded studies                were noted as to the reason for their ineligibility using a modified QUOROM format.                Disagreements were resolved by forced consensus and, if necessary, third party                intervention. A Technical Expert Panel (TEP) consisting of six members was convened                to provide advisory support to the project. They contributed to refining the                questions and highlighting key variables requiring consideration in the review. Each                included study was assessed for its quality as well as its applicability to the                North American population.

#### Data Synthesis:

Sixteen studies, described in 16 published journal                articles, were found to investigate nine of 23 potential questions.                Question-specific qualitative syntheses of the evidence were derived. Greater                interpretative emphasis was placed on evidence from randomized controlled trials                (RCTs) and other designs that were both prospective and controlled. Too little, or                flawed, available evidence precluded meta-analysis for each question.

#### Conclusions:

Based on the studies identified by this review, clinical                research has only scratched the surface with respect to understanding the possible                utility of the intake of omega-3 fatty acids as a primary or secondary prevention in                eye health. Moreover, seen from the point of view of clinical research’s typical,                linear arc—which moves from basic science to observational research to RCTs, and                culminating in the systematic review/meta-analysis of the observations obtained by                these primary studies—there is a paucity of solid observational research with which                to construct an experimental framework affording the meaningful conduct of RCTs. For                example, there is little understanding of the exact sources, types and doses of                omega-3 fatty acids, or even the possible duration of their use, which might                usefully serve as definitions of a prevention-centered “intervention” for any of the                eye diseases/visual impairments examined in our review. Perhaps only with respect to                the question of preventing the development/progression of advanced ARMD is there                some suggestive evidence, which is underscored by it being a strong public health                problem, to allow researchers to consider conducting an RCT. At the same time, a                single study reporting adverse event data likely does not permit laying to rest all                possible concerns regarding the short- or long-term safety of omega-3 fatty acid                interventions. It is therefore our view that much more research will need to be                conducted before anything conclusive can be asserted with respect to the effects of                omega-3 fatty acids on eye health. It is also our understanding that sorting out the                possible benefits of the intake of omega-3 fatty acids in eye health might profit                from taking into consideration the impact of the concurrent intake of omega-6 fatty                acids and, by definition, the omega-6/omega-3 fatty acid intake ratio.

## Contents

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                        - Preface
                        - Acknowledgments
                        - 1. Introduction                           - Metabolism and Biological Effects of Essential Fatty Acids
                          - Metabolic Pathways of Omega-3 and Omega-6 Fatty Acids
                          - U.S. Population Intake of Omega-3 Fatty Acids
                          - Dietary Sources of Omega-3 Fatty Acids
                          - Eye Health: An Increasingly Important Public Health Issue
                          - Economic Burden of Visual Impairment
                          - Vascular Diseases of the Retina
                          - Degenerative Retinal Diseases
                          - Cataracts
                          - Omega-3 Fatty Acids and the Eye
                        - 2. Methods                           - Overview
                          - Key Questions Addressed In This Report
                          - Analytic Framework
                          - Study Identification
                          - Data Abstraction
                          - Summarizing the Evidence
                        - 3. Results                           - Results of Literature Search
                          - Report and Study Design Characteristics of Included Studies
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Preventing Age-related Macular Degeneration?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Slowing the Progression of Age-related Macular Degeneration?
                          - What is the Evidence that Omega-3 Fatty Acids Decrease the Rate of Progression to Advanced Forms of Age-related Macular Degeneration?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Slowing the Progression of Retinitis Pigmentosa?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Slowing the Progression of Proliferative Retinopathy in Patients with Diabetic Retinopathy?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Slowing the Progression of Clinically Significant Macular Edema in Patients with Diabetic Retinopathy?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Preventing Age-related Cataracts?
                          - What is the Evidence for Efficacy of Omega-3 Fatty Acids in Slowing the Rate of Progression of Age-related Cataracts?
                          - What is the Evidence for the Risk of Short and Longterm Adverse Events Related to the Intake of Omega-3 Fatty Acids?
                        - 4. Discussion                           - Overview
                          - Evidence Synthesis and Appraisal
                          - Clinical Implications
                          - Research Implications and Directions
                          - Limitations of the Review
                          - Conclusion
                        - Summary Matrix
                        - Summary Table
                        - Abbreviations
                        - Appendixes                           - Appendix A. Search Strategies
                          - Appendix B. Letter to Industry Representatives
                          - Appendix C. Data Assessment and Data Abstraction Forms
                          - Appendix D. Modified QUOROM Flow Chart
                          - Appendix E. Evidence Tables
                          - Appendix F. Additional Acknowledgements
                        - References and Included Studies
                        - Listing of Excluded Studies at Level 2 Screening
                        - Listing of Included Studies for Evidence Tables

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Prepared for: Agency for Healthcare Research and Quality, U.S. Department                of Health and Human Services.1                 Contract No. 290-02-0021.                Prepared by: University of Ottawa                    Evidence-based Practice Center at The University of Ottawa, Ottawa,                    Canada.

#### Suggested citation:

Hodge W, Barnes D, Schachter H, Pan Y, Lowcock E,                    Zhang L, Sampson M, Morrison A, Tran K, Miguelez M, Lewin G. Effects of Omega-3                    Fatty Acids on Eye Health. Evidence Report/Technology Assessment No. 117                    (Prepared by University of Ottawa Evidence-based Practice Center under Contract                    No. 290-02-0021.) AHRQ Publication No. 05-E008-2. Rockville, MD: Agency for                    Healthcare Research and Quality. July 2005.

This report is based on research conducted by the University of Ottawa Evidence-based                Practice Center (EPC), under contract to the Agency for Healthcare Research and                Quality (AHRQ), Rockville, MD (Contract No. 290-02-0021). The findings and                conclusions in this document are those of the authors, who are responsible for its                contents; the findings and conclusions do not necessarily represent the views of                AHRQ. Therefore, no statement in this report should be construed as an official                position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers,                patients and clinicians, health system leaders, and policymakers make well-informed                decisions and thereby improve the quality of health care services. This report is                not intended to be a substitute for the application of clinical judgment. Anyone who                makes decisions concerning the provision of clinical care should consider this                report as they would any medical reference and in conjunction with all other                pertinent information, i.e., in the context of available resources and circumstances                presented by individual patients.

This report may be used, in whole or in part, as the basis for development of                clinical practice guidelines and other quality enhancement tools, or as a basis for                reimbursement and coverage policies. Neither AHRQ’s nor the U.S. Department of                Health and Human Services' endorsement of such derivative products may be stated or                implied.

                        - 1
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540 Gaither Road, Rockville, MD 20850. www​.ahrq.gov

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Bookshelf ID: NBK37707

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