Elsevier

Ophthalmology

Volume 115, Issue 1, January 2008, Pages 109-115
Ophthalmology

Original article
The Ocular Surface of Glaucoma Patients Treated over the Long Term Expresses Inflammatory Markers Related to Both T-Helper 1 and T-Helper 2 Pathways

Presented in part at: American Academy of Ophthalmology Annual Meeting, October 2005, Chicago, Illinois.
https://doi.org/10.1016/j.ophtha.2007.01.036Get rights and content

Purpose

To investigate the expression of CCR5 and CCR4, two chemokine receptors, as markers of the T helper (Th) 1 and Th2 pathways, respectively, and class II antigen HLA-DR as a hallmark of inflammation on conjunctival cells obtained from patients receiving long-term glaucoma treatment.

Design

Case–control study.

Participants

A total of 18 normal subjects and 70 glaucoma patients treated with topical antiglaucoma drugs for more than 1 year: 14 receiving a β-blocker as monotherapy, 38 treated with a prostaglandin analog alone (19 with latanoprost, 6 with travoprost, 13 with bimatoprost), and 18 receiving multiple treatments.

Methods

Impression cytologic specimens (ICSs) were obtained from 1 eye of the patients and processed for flow cytometry. Conjunctival cells were extracted and incubated with monoclonal antibodies against CCR4, CCR5, HLA-DR, or their specific controls to measure, in a masked manner, the percentages of conjunctival cells positive for the 3 markers.

Main Outcome Measures

HLA-DR and chemokine receptors (CCR4 and CCR5) in ICSs.

Results

Compared with all other groups, HLA-DR expression was raised significantly in the multitreatment group, whereas all monotherapies showed slight and nonsignificant increases. Both CCR4 and CCR5 were increased significantly in all 5 glaucoma groups compared with normal subjects, with no between-group differences.

Conclusions

This study demonstrates the overexpression of 2 chemokine receptors in the conjunctival epithelium of glaucoma patients treated over the long term. These results show the simultaneous overexpression of CCR4 and CCR5, suggesting that the chronic use of topical treatments may stimulate both the Th1 and Th2 systems simultaneously. These results also suggest that inflammatory mechanisms combining allergy with toxicity are at work and illustrate the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.

Section snippets

Patients

A series of 70 patients with chronic primary open-angle glaucoma using the conjunctival impression cytologic technique was compared with a group of normal eyes, using the technique previously developed in the authors’ laboratory (Table 1).19 Glaucoma patients had been treated for at least 1 year with the same treatment when examined. Patients evidencing allergic phenomena or with symptoms or signs of poor tolerance to their eye drops at presentation were excluded: repeated stinging or ocular

Results

The mean percentage of HLA-DR–positive conjunctival cells in the multitreatment group was at the highest level (mean±standard error, 67.1±5.1%), significantly higher than in the control (22.1±4.6%), latanoprost (35.2±6.5%), travoprost (29.5±6.2%), and bimatoprost (23.8±5.1%) groups (P<0.001 compared with the control and 3 prostaglandin groups; Fig 1). Although β-blockers showed a lower percentage of HLA-DR–positive cells (47.5±8.6%) compared with the multitreatment group, the difference was not

Discussion

Flow cytometry in impression cytologic analysis is a reliable technique for assessing inflammatory changes in ocular surface cells. It is minimally invasive and can be performed routinely for OSDs and evaluations of topical drug effects on the eye surface, because the technique of cell collection is the same as that used in standard impression cytologic analysis. The authors’ group has developed this technique and has found a wide variety of applications, such as examining inflammation in dry

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    Manuscript no. 2006-949.

    Supported by unrestricted grants from Institut National de la Santé et de la Recherche Médicale, Paris, France, and Quinze-Vingts National Ophthalmology Hospital, Paris, France.

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