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Timely translation of ophthalmic research into clinical practice
  1. C A McCarty
  1. Correspondence to: Catherine A McCarty PhD, MPH, Marshfield Clinic Research Foundation, Center for Human Genetics, 1000 North Oak Avenue (ML1), Marshfield, WI 54449, USA; mccarty.catherine{at}

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Collaboration is the key

The goal of all of the major federal funding agencies for medical research is to shorten the time between basic research discoveries and implementation at the “bedside” to improve human health. To that end, the National Institutes of Health in the United States (, the Medical Research Council in the United Kingdom (, and the Canadian Institutes of Health Research ( have all instituted strategies aimed at translating research for the public good. At the core of all these strategies is the need for inter-disciplinary, collaborative research involving both clinicians and scientists. What does this mean for ophthalmology and how can ophthalmologists and vision researchers contribute to this global effort to translate research results to improve patient care? The current status of research into the aetiology and treatment of age related macular degeneration (AMD), the leading cause of blindness in the elderly in developed countries, provides a topical example.

The paper by Xu et al1 in this month’s issue of the BJO (p 1087) represents a landmark: the first English language report of risk factors for AMD in a Chinese population. A PubMed literature search using the search strategy “AMD AND risk factor AND China” conducted in June 2006 revealed only four papers, three of them published in Chinese, with the most recent published in 1992.

Of the four previously published papers on AMD risk factors in China, the one English language paper was published in 2000, the authors concluding from their data that apolipoprotein E4 (apoE4) is unlikely to be an important risk factor for AMD in Chinese in part because of the lower allele frequency in comparison with white people.2 Interestingly, the association between apoE4 and AMD that was observed in the Chinese cohort, although not statistically significant owing to a relatively small sample size, is similar to what has been observed in white populations.3 A paper by Ioannidis et al supports the conclusion that the biological impact of genetic markers, such as apoE, is usually consistent across populations, although the frequency of the markers themselves varies by sex/ethnicity.4 It is important to have data from various populations to allow comparison of results and to provide clues about disease aetiology.

Complement factor H gene, involved in immunity, was recently estimated to explain up to 74% of AMD.5 Unfortunately, the published data related to complement factor H and AMD have only been quantified in white people and there are no data on population based allele frequencies in other ethnic groups. How does the epidemiologic data support the genetic results? A recent review of the epidemiology of AMD does not list biological markers of infection or inflammation,6 presumably because, unlike the genetic data, the epidemiological data have been inconsistent.

Future research into the aetiology of AMD (and other ocular conditions) needs to include both genetic and environmental risk factors

Although clearly important, genetics is not the sole determinant of AMD prevalence and incidence in the population. A twin study by Seddon et al7 found that genetic factors explain 46% to 71% of the variation in disease severity while environment explains 19% to 42%. Twenty seven per cent of AMD is estimated to be the result of smoking in New Zealand8 and 28 000 cases of AMD in people aged 75+ in the United Kingdom may be caused by smoking.9 A surprising finding in the Beijing Eye Study was the lack of an association between cigarette smoking and AMD prevalence where most previous studies have not only found a positive association, but also demonstrated dose-response, temporality, and reversibility of effect.10 A gene-environment interaction has been found for apoEand cigarette smoking,11 as well as the complement factor H gene and cigarette smoking.12 Perhaps the lack of an association between cigarette smoking and AMD prevalence in the Beijing Eye Study is caused by an unmeasured gene-environment interaction.

So what do these previous research results mean for future research and current clinical practice? To date, there has been little information to support primary prevention strategies. In Australia, data about the attributable risk of AMD and blindness due to cigarette smoking, estimated at between 14% and 20% in Australia, have been used in public health campaigns to decrease smoking rates ( In terms of secondary prevention, the recent genetic discoveries could lead to molecular targets for drug development and ultimately pharmacogenetics may assist physicians in personalised prescribing for patients but this may take many years. Until new therapies are available, one area of research that could immediately benefit patient care is the development of algorithms for risk prediction. For example, it would be useful for a physician to be able to tell a patient what their lifetime risk of developing AMD is if they have a family history of AMD and are a smoker compared to a non-smoker with no family history of AMD. These risk strata can be developed for all identified risk factors. Until reliable genetic tests are available and appropriate for clinical use, family history could serve as a proxy for genetic markers. To develop risk prediction models that have clinical utility, relevant data need to be collected in various racial/ethnic groups. Future research into the aetiology of AMD (and other ocular conditions) needs to include both genetic and environmental risk factors. This will allow the promise of personalised medicine to be reached in the field of ophthalmology.

In conclusion, continued collection of environmental and genetic data related to AMD and other ocular conditions of public health importance is needed for various racial/ethnic groups. Clinicians and scientists should work together to define clinically relevant research questions and then to answer them, such that the results can be used to enhance clinical practice and improve patient care. This is especially important in this era of decreasing funding for research. With the ageing of the population, AMD and other age related ocular conditions and associated blindness will increase unless true multidisciplinary, collaborative research is undertaken to shorten the time between scientific discovery and clinical application.

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Collaboration is the key


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