I thank Dr Gosala for his letter. He first suggests that differences in iris stroma between angle-closure and other eyes might be an effect of acute high intraocular pressure (IOP) leading to “damage to the stroma” rather than a pre-existing risk factor. This is not compatible with our findings, since most of the angle-closure eyes in which we found lower iris volume loss with pupil dilation had never had an acute attack. The general level of IOP in the angle-closure eyes was similar to the open-angle glaucoma eyes in our studies—including adjustment for other features such as medical eyedrop treatment, length of disease, and surgery. To show that the feature of lower iris volume loss is truly predictive (hence, “causative”), we and others are carrying out prospective studies of angle-closure suspects.

Second, Dr Gosala stated: “the irideal stroma as a percentage of iris tissue is negligible compared to other constituents, like the iris vasculature.” This is incorrect, as shown by quantitative histologic measurements in which iris blood vessels make up only a small fraction of total iris volume. Retention or even expansion of iris blood volume on dilation can play a possible role in changes in iris volume. Up to 5% of eyes actually gain iris volume on pupil dilation, and it may be that expansion of the vascular volume contributes somewhat to this phenomenon. However, given the small proportion of the iris tissue that is made up of vessels, a 50% loss of volume on dilation cannot be explained as solely a vascular change. Nor is the likely direction of change “reduction of vascular resistance” as stated by Dr Gosala—rather, intravascular volume would expand by increased venous resistance.

Third, the proposals I have made regarding choroidal expansion as contributing to angle closure are more likely to be attributable to abnormal vascular permeability, not, as suggested by Gosala, from “unstable vasomotor tone.” As demonstrated by imaging studies in angle-closure eyes, it is the extravascular choroidal space that expands, contributing to angle closure and malignant glaucoma.