Assessment of chamber anglepigmentation during longtermlatanoprost treatment foropen-angle glaucoma

Yuko Nakamura, Yoshimi Nakamura, Sayo Morine-Shinjo,

Hiroshi Sakai and Shoichi Sawaguchi

Department of Ophthalmology, Ryukyu University, Faculty of Medicine, Okinawa,

Japan

ABSTRACT.

Purpose: This study aimed to determine whether the longterm use of latanoprost

is associated with an increase in trabecular pigmentation, especially in subjects in

whom iris pigmentation has increased.

Methods: We enrolled 50 subjects for whom treatment was to start for ocular

hypertension, primary open-angle glaucoma or normal tension glaucoma. All

subjects received latanoprost 0.005% daily. Trabecular pigmentation was docu-

mented using gonioscopic photography of the inferior quadrant at baseline, every

3months for the first year and every 6months for the second and third years.

Three glaucoma specialists evaluated the series of gonioscopic photographs for

each eye of each subject in a masked fashion. The intraocular pressure (IOP) was

also recorded at each visit.

Results: A total of 41 subjects (79 eyes) completed 3 years of follow-up, and

none showed any increase in the grade of trabecular pigmentation, including 10

subjects (20 eyes) in whom the iridial pigment increased.

Conclusion: Although latanoprost increased iridial pigmentation in some sub-

jects, we found no evidence of an increase in trabecular pigmentation over the

3 years of follow-up.

Key words: latanoprost – chamber angle pigmentation – open-angle glaucoma

Acta Ophthalmol. Scand. 2004: 82: 158–160Copyright # Acta Ophthalmol Scand 2004.

doi: 10.1111/j.1600-0420.2004.00243.x

Introduction

Latanoprost is a selective FP receptor(prostaglandin F2-alpha receptor) ago-nist which lowers intraocular pressure(IOP) in various types of glaucoma byenhancing uveoscleral outflow (Camraset al. 1996; Watson 1998; Mastropasquaet al. 1999; Aung et al. 2000). It is effec-tive and is well tolerated in glaucoma

patients and has a long duration ofaction and no known systemic side-effects. However, its longterm use doeslead to increased iridial pigmentationin some patients (Alm & Stjernschantz1995; Camras et al. 1996; Wistrandet al. 1997; Brown 1998; Watson 1998;Mastropasqua et al. 1999; Aung et al.2000).

The trabecular meshwork plays animportant role in aqueous outflow.Increasing outflow resistance in themeshwork results in elevated IOP inprimary open-angle glaucoma (Segawa1979; Rohen 1983; Knepper et al.1996). Increased trabecular meshworkpigmentation occurs in two types ofsecondary glaucoma, pigmentary glau-coma and pseudoexfoliation glaucoma(Kupfer et al. 1975; Richardson et al.1977), and is thought to contribute toincreased outflow resistance.

We used goniophotography to followthe degree of trabecular meshworkpigmentation and monitored the IOPcontrol of subjects put on latanoprostand followed for 3 years.

Material and Methods

All patients with primary open-angle glau-coma (POAG), normal tension glaucoma(NTG) or ocular hypertension (OH), whoneeded therapy or additional therapy andwho were seen in the Glaucoma Clinic ofthe Ryukyu University, Hospital wereasked to participate in this study. Thepatients were recruited from the Glau-coma Clinic at the Ryukyu UniversityHospital between November 1999 andApril 2000. The patients included wereJapanese in ethnic origin and all hadbrown eyes. Patients were excluded if theyhad angle closure glaucoma, ocular tra-uma or inflammation, dry eye syndrome,

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were contact lens wearers, or had a historyof intraocular surgery or argon lasertrabeculoplasty. The study was approvedby the Human Studies Committee andcomplied with the Declaration of Helsinkiguidelines. Informed consentwas obtainedfrom all subjects after discussion of thebenefits and risks of using latanoprost,including the possibility of developingincreased iris pigmentation. A total of 41of the 50 subjects recruited completed the3years of follow-up, including 30 withPOAG, five with OH and six with NTG.The average age at initiation of therapywas 57.5� 13.3years. Previously, 20subjects had been untreated, 14 had beentreated with a beta-blocker, six with abeta-blocker and dorzolamide, and onewith pilocarpine.

Intraocular pressure wasmeasuredwithGoldmann applanation tonometry on themorning of the subjects’ visits. The trabe-cular meshwork pigmentation in the infer-ior quadrant was recorded through a two-mirror gonioscopic lens using slit-lamp(Topcon Co, Tokyo, Japan) video photo-graphy (3CCD video system, Sony DXC970MD Power Head). The imagesacquired at baseline, and every 3monthsfor the first year and every 6months forthe second and third years, were reviewedindependently by three glaucoma specia-lists in a masked fashion. The first andfinal images were also graded accordingto the classification system described byScheie (1957). Iris pigmentation was alsorecorded using slit-lamp video photo-graphy at baseline, and every 6monthsfor 3years. In addition, three glaucomaspecialists evaluated all the baselinephotographs together.

Results

Of the 50 subjects who were startedon latanoprost, one was withdrawnbecause of inadequate IOP control, onewas withdrawn due to conjunctival hyper-aemia, and seven subjects dropped out,preferring to be followed locally aftertheir pressure was brought under control.No adverse systemic effects of latanoprosttreatment were observed.

In the remaining 41 subjects (79 eyes),IOP fell significantly from an average of20.3� 3.3mmHg to 16.5� 3.3mmHg at3months, a reduction of 3.8� 2.9mmHg(p< 0.001), and no upward drift wasnoted during the 3-year follow-up(Fig. 1). The percentage IOP reductionaveraged 20% for those with POAG aswell as for those with OH, and 19% forthose with NTG.

Initially, Scheie grade 0 pigmentationwas found in two subjects, grade 1 in15 subjects, grade 2 in 21 subjectsand grade 3 in three subjects, withnone having grade 4 pigmentation. Nochange in trabecular pigmentationwas detected for any of the eyes at3 years (Fig. 2), even in the 20 eyes of10 subjects in which an increase in irispigmentation was observed.

Discussion

In this study, no changes in trabecularpigmentation were detected, even in theeyes in which the iridial pigmentationincreased.

The increase in iris pigmentation in eyestreated with latanoprost has been attri-

buted to increased melanogenesis in iridialmelanocytes and not to cellular prolifera-tion (Alm& Stjernschantz 1995;Wistrandet al. 1997). Indeed, iridectomy specimenssubjected to light and electron micro-scopy do not demonstrate eithermelanocyte proliferation or atypical fea-tures (Grierson et al. 1999). In addition,the in vitro cell culture of dermal anduveal melanocytes exposed to latano-prost does not demonstrate any increasein cell proliferation (Imesh et al. 1997).

Nevertheless, there is concern that theincreased iridial pigmentation mightlead to an increased release of melano-somes from the iris and their accumula-tion in the trabecular meshwork, with aconsequent increase in outflow resis-tance (Wistrand et al. 1997). Excessiverelease of melanosomes does occur fromthe posterior iris chafing on the zonularfibres in pigment dispersion syndromeand in pigmentary glaucoma. However,in general, significant natural irispigmentation is not associated with apathological increase in trabecularpigmentation.

Previous studies that have lookedfor a possible increase in trabecularmeshwork pigmentation during latano-prost treatment produced negativeresults, but were limited to 12monthsor fewer of follow-up (Watson &Stjernschantz 1996; Mastropasquaet al. 1999; Hara 2000), or involved asmall number of subjects with a longerfollow-up. The study by Watson &Stjernschantz (1996) followed 61 subjectsfor 1 year and 13 for 2years. The study byMastropasqua et al. (1999) was of parti-cular interest as it was conducted with

IOP(mmhg)

25

21

19

1715

13

11

9

75

3 6 9 12 18 24 30 36 M

23

IOP: mean±SD

P < 0.001(Student t-test)

Fig. 1. Time course of IOP with latanoprost. Intraocular pressures were continuously and significantly (p< 0.001) reduced for 3 years without upward

drift.

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patients who already had pigmentaryglaucoma.

In our study, no increase in trabe-cular pigmentation was observed dur-ing latanoprost treatment in 41 subjects(79 eyes) followed for 3 years. Never-theless, glaucoma is usually present formany years, and longer follow-up maybe required to confirm our findings.

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Received on February 18th, 2003.

Accepted on December 4th, 2003.

Correspondence:

Yuko Nakamura

Department of Ophthalmology

Ryukyu University Faculty of Medicine

207 Uehara Nishihara-cho

Okinawa 903-0125

Japan

Tel:þ 81 098 895 3331

Fax:þ 81 098 895 1427

Email: dr-ganka@med.u-ryukyu.ac.jp

A

B

C

D

Fig. 2. Chamber angle pigmentation at (A) pre-latanoprost treatment; (B) 6months into treatment; (C) 1 year into treatment, and (D) 3 years into

latanoprost treatment. Chamber angle pigmentation grade 3 in a 40-year-old male POAG patient. Note that no significant change is evident in any of

the gonioscopic photographs.

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