Study Identifies Medium Drusen That May Signal Worsening AMD

Marlene Busko

April 09, 2015

A 15-year study of more than 1300 Australian men and women who were initially free of early or late age-related macular degeneration (AMD) has shed light on the incidence and progression of medium drusen. Overall, 13.9% of the participants developed medium drusen, and older people and those with risk alleles in the CFH and ARM2 genes had a greater risk of developing medium drusen.

In addition, 5.0% of patients with medium drusen alone and 23.0% of patients with medium drusen plus retinal pigment epithelium abnormalities progressed to late-stage AMD.

"This paper sets the stage for further studies and investigations on treatments for dry AMD, and it helps us know what a given patient's risk is, if they have so-called medium-sized drusen," Carl D. Regillo, MD, director of Retina Service at Wills Eye Hospital and professor of ophthalmology at Thomas Jefferson University in Philadelphia, Pennsylvania, told Medscape Medical News. The key take-away message for clinicians, he said, is that patients with medium drusen plus retinal pigment epithelial abnormalities have a fourfold greater risk of progressing to a form of AMD with a risk for vision loss compared with patients with medium drusen alone.

The study, by lead author Nicole D. L. Joachim, BSc(Hons), from the Centre for Vision Research in the Department of Ophthalmology at the University of Sydney in Australia, and colleagues, was published online April 2 in JAMA Ophthalmology.

Little Known About Significance of Medium Drusen

Medium drusen (ie, intermediate soft drusen, with a maximum diameter of 63 to less than 125 μm) have not been as well studied as large drusen, soft drusen, and pigmentary lesions, Joachim and colleagues write. Despite recent interest in medium drusen and their inclusion in AMD incidence studies, little is known about their associated risk factors and how they might predict progression of AMD.

Joachim and colleagues assessed the incidence of medium drusen in 1317 individuals who were aged 49 years and older and were free of early or late AMD or large soft distinct drusen when they were enrolled in the Blue Mountains Eye Study in Australia between 1992 and 1994. The patients had follow-up eye examinations with retinal photographic grading at 5, 10, and 15 years after enrollment and had genetic tests to detect single-nucleotide polymorphisms in the CFH and ARMS2 genes.

The authors found that 13.9% of the study participants developed medium drusen by 15 years. The incidence did not differ across three age groups from 49 to 74 years, but it was slightly higher in women than in men.

After adjusting for age, sex, smoking, zinc supplements, and the presence of risk alleles on the CFH and ARM2 genes, each decade of older age was associated with a 40% increased risk for medium drusen at the 15-year eye examination (odds ratio, 1.4; 95% confidence interval, 1.2 - 1.8).

Finding at least three risk alleles of the CFH rs1061170 or ARMS2 rs10490924 genes, as opposed to not finding any risk alleles of these two genes, more than doubled the risk of finding medium drusen at the 15-year eye exam (odds ratio, 2.1; 95% confidence interval, 1.1 - 4.1).

Past or current smoking were not associated with increased risk of developing medium drusen.

Eyes with medium drusen located closer to the fovea or eyes with large total macular areas involved by medium drusen were more likely to progress to early AMD.

Notably, among people with medium drusen, those who also had retinal pigmentary abnormalities were more likely to progress to late AMD. "This observation supports the use of severity scales that incorporate multiple lesion types to better classify risk of the progression to late AMD," Joachim and colleagues write.

According to Dr Regillo, on the basis of this research, clinicians can reassure patients with medium drusen alone and no retinal pigment changes that their risk of progression is not very high.

In contrast, patients who have both medium drusen and retinal pigment epithelial abnormalities can be instructed to monitor their vision more closely at home and report any new symptoms right away, as "that's how we get good outcomes now. If we catch patients that have just [progressed to wet AMD], when [their vision is] 20:40 or better, we can keep them at 20:40 in the vast majority of cases," he said.

The study was supported by grants from the National Health and Medical Research Council of Australia. One coauthor reported being paid by Bayer Inc and Novartis Inc for consultancy, lectures (including service on speakers bureaus and travel), accommodation, and meeting expenses. The other authors have disclosed no relevant financial relationships.

JAMA Ophthalmol. Published online April 2, 2015. Abstract

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