John Paul SanGiovanni

Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review

BACKGROUND Biologically active neural tissue is rich in docosahexaenoic acid (DHA), an omega-3 long-chain polyunsaturated fatty acid (LCPUFA). We conducted a systematic review to examine the nature of discordant results from studies designed to test the hypothesis that dietary DHA leads to better performance on visually-based tasks in healthy, fullterm infants. We also conducted a meta-analysis to derive combined estimates of behavioral- and electrophysiologic-based visual resolution acuity differences and sample sizes that would be useful in planning future research. STUDY DESIGN AND METHODS Twelve empirical studies on LCPUFA intake during infancy and visual resolution acuity were identified through bibliographic searches, examination of monograph and review article reference lists, and written requests to researchers in the field. Works were reviewed for quality and completeness of information. Study design and conduct information was extracted with a standardized protocol. Acuity differences between groups consuming a source of DHA and groups consuming DHA-free diets were calculated as a common outcome from individual studies; this difference score was evaluated against a null value of zero and then used, with the method of DerSimonian and Laird (Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188), to derive combined estimates of visual resolution acuity differences within seven age categories. RESULTS OF RANDOMIZED COMPARISONS: The combined visual resolution acuity difference measured with behaviorally based methods between DHA-supplemented formula fed groups and DHA-free formula fed groups is 0.32+/-0.09 octaves (combined difference+/-S.E.M., P=0.0003) at 2 months of age. The direction of this value indicates higher acuity in DHA-fed groups. RESULTS OF NON-RANDOMIZED STUDY DESIGNS: The combined visual resolution acuity difference measured with behaviorally based methods between human milk fed groups and DHA-free formula fed groups is 0.49+/-0.09 octaves (P< or =0.000001) at 2 months of age and 0.18+/-0.08 octaves (P=0.04) at 4 months of age. Acuity differences for electrophysiologic-based measures are also greater than zero at 4 months (0.37+/-0.16 octaves, P=0.02). CONCLUSION Some aspect of dietary n-3 intake is associated with performance on visual resolution acuity tasks at 2, and possibly, 4 months of age in healthy fullterm infants. Whether n-3 intake confers lasting advantage in the development of visually based processes is still in question.

THE RELATIONSHIP OF DIETARY OMEGA-3 LONG-CHAIN POLYUNSATURATED FATTY ACID INTAKE WITH INCIDENT AGE-RELATED MACULAR DEGENERATION: AREDS REPORT NO. 23

OBJECTIVE To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). METHODS Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. RESULTS After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. CONCLUSIONS Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA.

Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case–control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10−64) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10−60) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 × 10−15), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10−4), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case–control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.

Omega-3 long-chain polyunsaturated fatty acid intake is inversely associated with 12-year progression to advanced AMD

To the Editor: Age-related macular degeneration (AMD) is a leading cause of vision loss. Age-related Eye Disease Study (AREDS) participants reporting highest intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) were approximately half as likely as their peers reporting lowest intake of these nutrients to have neovascular (NV) AMD1 at baseline or to progress across a six year period from bilateral drusen to central geographic atrophy (CGA).2 AREDS provides data that represent, to our knowledge, the largest longitudinal sample collected and classified with standardized methods as part of a natural history study on AMD. We now report that our baseline and six-year findings persisted in 12-year AMD incidence models. These results are consistent with existing data.3,7

Anatomical and visual results of vitreoretinal surgery for stage 5 retinopathy of prematurity.

Purpose: To provide a historical perspective on outcomes of surgery for infants with stage 5 retinopathy of prematurity (ROP) as perfomed by a single surgeon over a 24-year period. Design: Retrospective observational cohort study. Methods: Setting: Clinical practice of the Charles Retina Institute. Patients: The 601 infants with stage 5 ROP in at least one eye who were referred for surgery between 1977 and 2001. Charts were reviewed for demographic data and postoperative anatomical and visual acuity outcomes in eyes that underwent surgery. Main Outcome Measures: The postoperative anatomical status of the retina and visual function were assessed after surgery. Anatomical outcome was categorized as success (macula attached), partial success (macula detached), failure (total retinal detachment), or lost eye (opaque cornea, secluded pupil, or phthisis). Visual function was classified as>20/200, 20/200 – 5/200, hand movement, light perception, or no light perception. Multivariable logistic regression was used to explore relationships between outcomes and baseline characteristics. Results: Only a minority of eyes had prior cryotherapy (15%) or laser photocoagulation (7%) therapy. The mean follow-up was 44 months for the 956 eyes treated surgically. The 608 eyes with available follow-up data were classified as follows: 28% success, 5% partial success, 55% failure, and 11% lost eye. Visual function of light perception or better was achieved in 74% of the 183 eyes with data on visual acuity. Controlling for other baseline factors, early postpartum age at the time of surgery was a statistically significant predictor of failure/lost eye (OR = 2.08, 95% CI 1.09-3.97) and no light perception (OR = 5.13, 95% CI 1.45-18.14). Surgery for stage 5 ROP on the fellow eye was also a predictor of failure/lost eye (OR = 2.38, 95% CI 1.39-4.08). Conclusions: Surgery resulted in anatomical success for approximately one third of infant eyes with stage 5 ROP, and only a minority of eyes (8 of 183) achieved visual acuity better than 5/200. However, some initially successfully attached retinas redetached. Although this study is limited by follow-up and may represent a group of patients with a more vascularly active disease state due to the low proportion of patients with prior peripheral ablation, this cohort of infants provides results against which future interventions may be compared.