מגוון רחב של גידולים ותהליכים דמויי גידול פסאודו-טומורים יכולים להתפתח בארובה.

מחקרים

van Leeuwen R, Tomany SC, Wang JJ, Klein R, Mitchell P, Hofman A, Klein BEK, Vingerling JR, Cumming RG, de Jong PTVM: Is medication use associated with the incidence of early age-related maculopathy? Pooled findings from 3 continents

Ophthalmology 2004;111:1169-1175

1 Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands

2 Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands

3 Department of Ophthalmology & Visual Science, University of WisconsinMadison, Madison, Wisconsin, USA

4 Department of Ophthalmology, University of Sydney, Sydney, Australia

5 Department of Public Health and Community Medicine, University of Sydney, Sydney, Australia

6 Netherlands Ophthalmic Research Institute, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

7 Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands Received 21 May 2003; accepted 13 October 2003. Available online 31 May 2004.

Abstract

Objective

To investigate whether there is an association between the use of medication and the incidence of early age-related maculopathy (ARM).

Design

Pooled data from 3 prospective, population-based cohort studies.

Participants

Subjects without early and late ARM at baseline who participated in the follow-up of the Beaver Dam Eye Study (n = 3012), the Rotterdam Study (n = 3434), and the Blue Mountains Eye Study (n = 2203).

Methods

Stereoscopic color fundus photographs of all participants were graded according to a standardized protocol. At baseline, current use of prescription and over-the-counter medication was assessed by interview, and the drug name was confirmed at the research centers. Procedures and definitions were similar at both baseline and follow-up across the 3 study sites.

Main outcome measures

Incidence of early ARM, defined as the presence at follow-up of either soft distinct drusen with pigmentary changes or soft indistinct or reticular drusen.

Results

In the pooled cohort, 53.3% of participants used at least one of the medications selected for this study. Within a mean period of 5.6 years, a total of 683 subjects developed early ARM. Users of antihypertensive medication in general, and -blockers in particular, had a borderline statistically significant increased risk of early ARM (odds ratio [OR] for -blockers, 1.3; 95% confidence interval [CI], 1.01.6) when adjusted for systolic (or diastolic) blood pressure and other confounders. A protective effect of borderline significance was found among women using hormone replacement therapy (OR, 0.6; 95% CI, 0.41.0) and in persons using tricyclic antidepressants (OR, 0.4; 95% CI, 0.21.0). In contrast with -blockers, the direction and magnitude of the association with hormone replacement therapy and tricyclic antidepressants were inconsistent among the 3 study populations.

Conclusions

Pooled data from 3 population-based studies showed no strong associations between medication use and the incidence of early ARM. Of borderline significance were a slightly increased risk among users of -blockers and a reduced risk among users of hormone replacement therapy and users of tricyclic antidepressants. Although -blocker use could be a proxy for systemic hypertension, these findings warrant further investigations, preferably including information on the dosage and duration of drug exposure.

Age-related maculopathy (ARM) is a progressive, degenerative disorder of the retina, and its pathogenesis is poorly understood. Many potential risk factors have been examined, but for most the results were negative or inconsistent.[1] Only smoking, hypertension, and the intake of antioxidants have been identified as risk factors that can be modified. [2, 3, 4 and 5]

It is thought that the retinal pigment epithelium (RPE), a monolayer of pigmented cells lining the photoreceptor cells, plays an important role in ARM pathophysiology.[6 and 7] Endogenous or exogenous influences on the RPE may interfere with the homeostatic function of this metabolically highly active tissue, and initiate or exacerbate pathologic processes. An example of the exogenous influences is medication use, given the well-known fact that certain drugs, like chloroquine and chlorpromazine, are toxic to the RPE. [6 and 8] Furthermore, the study of medication use as a potential risk factor for ARM may give relevant clues to a correlation between ARM and the disease for which the medication was prescribed. Only a few studies have included medication use in their risk analyses, and they have produced mixed results. [9, 10, 11 and 12] Klein et al published a separate article on this issue, but did not observe striking associations with the 5-year incidence of early ARM. [13]

Investigations into the association between medication use and late ARM are hampered by the relative infrequency of this end-stage disease in the population. Moreover, because specific types of many drugs are not commonly used, the statistical power to demonstrate the presence or absence of a relationship is small, especially when adjusting for relevant confounders. Therefore, we decided to pool data on the incidence of early ARM, a recognized precursor of late ARM,[14, 15 and 16] from 3 cohort studies that have previously cooperated in a risk factor analysis of prevalence data. [2] These population-based studies used similar methods regarding ARM grading and definition and the assessment of medication use. Within this large data set, we studied the association between use of different categories of medications and the incidence of early ARM.