Latanoprost does not cause ocular pathology by inducing ultrastructural iris changes, says study

Cheryl Guttman
in Mainz

Norbert Pfeiffer

TREATMENT with latanoprost (Xalatan) for six months does not effect early ultrastructural changes in the iris which could cause ocular pathology, according to the results of a study published recently.

Researchers in the Mainz II study group used masked light and electron microscopy to assess peripheral iris specimens obtained from 17 patients scheduled to undergo sequential bilateral trabeculectomy for the treatment of open-angle or pseudoexfoliation glaucoma.

The patients underwent surgery in the worse eye first, and during the usual six-month interval between bilateral procedures, used latanoprost once nightly contralaterally.

Specimens were available from 17 untreated control eyes and 14 latanoprost-treated eyes, of which one showed a marked colour change.

The analyses found no evidence of stromal inflammation, alterations in the structure of stromal blood vessels, or degeneration of iris stroma or posterior epithelial cells in any specimens.
Positive results included the presence of free melanin granules in the stroma, melanin turnover, abundance of stromal clump cells, melanocytic cellular atypia and prominence of the anterior border layer.

However, those five features could not be used to accurately discriminate between the treated and fellow control eyes.
Iris darkening is well described as an ocular side-effect of topical latanoprost treatment, but there is not much known about the morphological and ultrastructural effects of this prostaglandin on the iris or the mechanism for the eye colour change.
The findings of this study are consistent with a previous investigation by the Mainz researchers, which found no evidence of iris tissue alteration.

“The current study has the strengths of evaluating fellow eye specimens after a two-fold longer treatment period and using more sensitive techniques for structural analysis.
“Against that background, it is reassuring to find that the ultrastructure of latanoprost-treated eyes conformed to published standards for normal tissue,” Norbert Pfeiffer MD said.

The specimens studied to identify ultrastructural alteration of iris tissue were all graded by Ian Grierson PhD at ophthalmology unit of the University of Liverpool, UK, using a five-point scoring system which ranged from marked (+++) to absent (-).

In the masked evaluation, clump cells were noted to be marked in 10 specimens, a prominent anterior border layer (greater than two or three cell layers and up to five) was present (+) in about half, and extracellular melanin granules were identified as present (+) in only two specimens.

The examiner noted both intraspecimen and interspecimen variation in the incidence of melanin granules in the anterior border melanocytes. Nuclear atypia was noted as present (+) in about half of the specimens and was marginal (+/-) or absent (-) in the rest.

Based on the scoring of the features of each specimen, the masked investigators attempted to predict whether it was derived from a latanoprost-treated eye or control.
Only five (36%) of the 14 latanoprost-treated eyes were correctly identified. Only seven (44%) of the 16 evaluable control specimens were picked accurately. The treated and control iris specimens were also compared to see if the five features showing morphological variation were present consistently more often in the latanoprost-treated eyes, but no such pattern was found.

Melanin turnover in melanocytes from the stroma and the anterior border layer was assessed by examination of the specimens for the presence of premelanosomes, immature melanosomes, and incomplete melanisation of melanin granules, along with evidence of giant melanosome formation and melanin clumping.
Based on those features, only four specimens were identified as having obvious melanin turnover and six showed no evidence of turnover.

“Notably, there was no clear relationship between those changes and latanoprost treatment, nor was the eye with a colour change distinguished from the rest of the group in terms of fine structural evidence of melanin turnover,” Dr Pfeiffer said.

Eye colour among the 17 patients was about equally distributed between brown, hazel and blue/green/gray. Eye colour changed during latanoprost treatment in two patients, but one declined trabeculectomy because the medical treatment resulted in IOP control. Both patients were categorised as having brown eyes initially with some green-brown colouration.

“Further quantitative analysis will investigate whether latanoprost increased the incidence of melanin granules in the melanocytes, especially in the patient with colour change, but there is no evidence of that yet from the available morphological assessment,” Dr Pfeiffer said.

The study appears in the Archives of Ophthalmology (Pfeiffer et al; 2003;121:23-31).

Norbert Pfeiffer MD
Johannes Gutenberg-Universitat, Mainz, Germany
Email: Pfeiffer@augen.klinik.uni-mainz.de

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