Morphometric effects of long-term exposure to latanoprost

Purpose: To investigate the morphological and melanin granule changes in irides after variable-term exposure to latanoprost, where the latanoprost-induced iris darkening (LIID) side effect has been identified and photographically recorded. Design: Experimental study. Participants: Fifteen LIID cases and 15 untreated controls. Methods: Iridectomy specimens from LIID cases were collected from patients undergoing trabeculectomy, whereas before surgery they had been on topical latanoprost and there was clear evidence of iris color change from the treating ophthalmologist, which was recorded photographically. A control series of peripheral iridectomies were obtained from blue, heterogeneous, and brown irides. All the specimens were visualized by light and electron microscopy. Masked assessment was made of stromal cell number, cell atypia, anterior border thickness, presence of free stromal melanin, melanin proximity to blood vessels, and change in stromal melanocyte melanin granule numbers and size. For the melanin granule analysis, electron micrographs were subjected to detailed image analysis to quantify the number of melanin granules, size of the granules, and overall percentage filling of the iris stromal melanocytes with melanin. Main Outcome Measures: Iris morphology and melanin granule changes. Results: There was no evident difference in stromal cellularity or anterior border thickness. Atypia, free stromal melanin, and melanin adjacent to blood vessel lumina were identified, but there was no difference between LIIDs and controls. Within stromal melanocytes, we found no change in the total number of melanin granules of the LIID cases, as compared with the brown and heterogeneously colored normals. However, melanin granules in the anterior border melanocytes; of the LIID eyes were significantly larger than those in the controls. A trend towards bigger melanin granules was apparent in the deep stroma, but this difference did not reach significance. Conclusions: In the LIID cases that we examined, the darkening side effect does not seem to be associated with either proliferative or generative iris changes, nor with increases in number of granules. Instead, it appears to be due to small increases in the size of mature melanin granules, particularly in the anterior border region.