We appreciate the opportunity to further discuss our recent report on central macular splaying and outer retinal thinning in asymptomatic sickle cell patients, in particular, to respond to the interest and letter from Minnal and associates, who had concerns about the methodology of the study.

Minnal and associates point out that inclusion of patients with varying stages of sickle cell retinopathy (including 6 eyes from 4 patients with no retinopathy) introduces a level of variability to the study. Among our experimental group, 2 subjects had unilateral sickle cell retinopathy with no retinopathy noted in the contralateral eye. Inclusion of these patients, if anything, would have decreased the significance in terms of difference between experimental and control groups. Additionally, there may be tendencies to miss arteriolar occlusions in the far periphery, so the distinction between stage 0 and stage 1 may not be consistent among other graders of retinopathy. Therefore, we felt it was prudent to be inclusive. Again, inclusion of these patients in the experimental group would have decreased the significance in terms of difference between the 2 groups. Additionally, 2 other subjects had sickle cell retinopathy in neither eye, which represents only 5% of the eyes, and thus removing them is not expected to significantly change our findings.

Minnal and associates also point out that both the control and study groups had central macular total thicknesses that fall within the reported standard error mean of reported normative data in the Spectralis instrument. Retinal thickness was measured in both groups of subjects by our image analysis algorithm, and therefore the statistical comparison of the results is valid. These results cannot be compared to the database of the Spectralis instrument, since a different algorithm was used for generating the data. A review of literature clearly documents differences in thickness measurements between different instruments, stemming from the depth location of the chorioretinal interface. For these reasons, in fact, comparison of our measurements to the instrument database as suggested would be flawed.

It was also astutely pointed out that central subfield analysis would be useful and clinically meaningful. More extensive work on this topic exploring focal retinal thinning in ETDRS-like macular subfields or more temporal watershed region by SD-OCT, with frequency of focal retinal thinning stratified by stage of retinopathy as well as sickle cell genotype, is currently in submission.