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Editors Selection IGR 15-4

Risk factors: Low-fat diet and incidence of POAG

Comment by Vivek Gupta & Tanuj Dada on:

106412 Effect of Low-Fat Dietary Modification on Incident Open-Angle Glaucoma, Mehta R; Ray RM; Tussing-Humphreys LM et al., Ophthalmology, 2023; 130: 565-574

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Mehta et al. report on the effects of a dietary modification (DM) intervention on incidence of primary open-angle glaucoma (POAG) in a secondary analysis of data from post-menopausal women enrolled in the Women's Health Initiative (WHI) DM trial in USA between 1993-1998. The hypothesis was that low-fat, high-grain diet with fruits and vegetables could be protective against glaucoma. The intervention consisted of group sessions including information and activities targeting 20% energy from fats per day, and ≥ five servings per day of fruits and vegetable, and ≥ six servings per day of grains consumption, and ended September 2004. The intervention was based on the US Department of Agriculture's 1977 Dietary Guidelines for Americans (DGA), recommending reductions in dietary, especially saturated, fat intake.

POAG outcomes were ascertained from linked Medicare data based on ICD codes during 1993-2018. Of the 48,835 women enrolled in the trial, 23,776 were enrolled in Medicare Part B, which covers outpatient care including glaucoma. After excluding 559 prevalent cases, there were 23,217 women at risk of POAG, with mean age, 64.4 years. Among them, 3001 incident cases are identified over a median follow-up of 12.4 years. There was no benefit of DM in reducing incident POAG (Hazard Ratio, 1.04; 95% CI, 0.96-1.12). The lack of benefit persisted after adjusting for age, race or ethnicity, body mass index, hypertension, diabetes, and statin use.

The risk of POAG within lowest quartile group for percentage calories (kilocalories) from total fat (< 33.8%) was increased in the intervention group (HR, 1.22; 95% CI, 1.05-1.41) compared to controls. This is the only statically significant result obtained. However, the lower confidence interval is bordering on non-significance, and given the extensive number of analyses performed, there is a possibility that this result was a false positive (type 1 error), also noted as a limitation by the authors.

While the rationale that oxidative stress may predispose to glaucoma is sound, it is quite likely that the design of WHI DM is not appropriate

While the rationale that oxidative stress may predispose to glaucoma is sound, it is quite likely that the design of WHI DM is not appropriate. While the food frequency questionnaire based assessment of nutritional intake was done in a one-third sub-sample every year from years 2 onwards, the authors have just used FFQ results from end of year 1 of trial. At the end of year 1, there are statistically significant reductions in dietary total fat, energy, and increase in fruit vegetable and while grain intakes. However, the dietary goals of the trial was not achieved.¹ The vegetable cups equivalent are only marginally more in intervention group, and the statistical significance observed in Table 3 may be due to large sample size. Authors note that participants in whom POAG developed showed a statistically significantly higher fruit intake, vitamin C levels, and b-carotene levels at baseline compared with participants who did not. However, no results have been presented to support these statements.

The diagnosis of glaucoma is based on ICD codes and not on standardized clinical assessments and there is a likelihood of change in diagnostic standards over the long follow-up period, which emphasize shifting away from IOP to perimetry and other assessments. There have also been concerns that the very low fat diet target in the WHI-DM study may expose individuals to coronary heart disease risk.²

Based on the data from WHI DM Trial, a change in dietary pattern to a low-fat diet with increased vegetables fruits, and grains intake did not alter the risk of POAG developing in post- menopausal women

In conclusion, based on the data from WHI DM Trial, a change in dietary pattern to a low-fat diet with increased vegetables fruits, and grains intake did not alter the risk of POAG developing in post- menopausal women.

Future studies may look at objective quantification of serum lipid profile with dietary modifications and change in biomarkers levels of oxidative stress with improved fruit and vegetable intakes, and evaluate the risk of POAG.

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