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Watanabe et al (p. 2103) investigated the effect of corneal guttae severity on the quality of vision in patients with mild Fuchs’ corneal dystrophy. They found that corneal guttae—even without edema seen on slit-lamp examination—have a negative impact on patients’ quality of vision, and that intraocular forward light scatter caused by the guttae may result in visual disturbances. This cross-sectional study included 23 eyes of 14 patients who had Fuchs’ dystrophy but no evident edema. The researchers evaluated the area ratio of the guttae and correlated that with corrected distance visual acuity (CDVA), letter contrast sensitivity (LCS), and intraocular straylight.

We agree with Dr Odaibo that small sample sizes in subgroups and data-derived biases are problematic in assessing the subgroup analysis conducted by Awh et al.1 The small sample size means that, at best, the conclusions of the subgroup analysis are useful for hypothesis development. The biases, inherent in data-derived analyses, make it even more important that there are replicate analyses before accepting the associations in the Awh et al analysis, as suggested by Dr Odaibo. The replicate analysis of the independent “residual cohort” provides no indication that the genotypes complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) have any influence on the response to treatment with Age-Related Eye Disease Study (AREDS) supplements (combination of antioxidants and zinc).

There has been intriguing and protracted controversy over what conclusions and treatment recommendations can be drawn from the Age-Related Eye Disease Study (AREDS) experiment. Based on data from this one experiment, the AREDS study group and Awh et al have come away with very different conclusions.1–3 On the one hand, the AREDS Study group recommends that the AREDS formulation is beneficial to individuals with intermediate macular degeneration.2,4 On the other hand, based on genetic subanalysis of the AREDS data, Awh et al suggest that, for patients with certain combinations of CFH (rs412852 and rs3766405) and ARMS2 (c.372_815del443ins54) risk alleles, the AREDS formulation may actually worsen outcomes.

We appreciate that Drs Awh and Zanke are concerned our findings differ from theirs on the need for genetic testing when using the Age-Related Eye Disease Study (AREDS) supplement.1 Fortunately, there have recently been several independent reviews of this issue that have all provided thoughtful insight and all conclude that genetic testing is not recommended for determining treatment with AREDS supplement at this time.