The annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) – held in the United States city of Fort Lauderdale, in Florida, in May this year – explored the impact of modern genetics on eye health. In this article, six Australian ophthalmologists from various specialties report on the conference highlights, covering a range of topics from genetic applications in ophthalmology to retinal and corneal diseases as well as glaucoma.
Advances in genome sciences and related technologies are revolutionising biology and medicine, with scientists now able to identify genetic variations associated with vision diseases.
More than 10,000 eye and vision experts gathered for the 2011 meeting of the prestigious Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO 2011), which carried the theme of ‘Visionary Genomics’, to explore how genome technology is leading to new understandings of vision health,
disease and treatment.
AMD: Understanding New Risk Factors: Is Weight Related to AMD?
In a poster session by Usha Chakravarthy and colleagues, the age of onset of neovascular age-related macular degeneration (AMD) was significantly related to body mass index (BMI). For the study, 194 patients with angiographically-confirmed diagnosis of neovascular AMD were recruited from a macular clinic in the United Kingdom.
These data will help shed more light on the mechanism of disease for FED and may lead to genetic identification of those at high risk of FED
The age of onset – defined as the first record of central visual loss in either eye of a participant – was approximately three years earlier in those classified as obese compared to those with a normal BMI. The age of onset was four years earlier in current smokers when compared to those who had never smoked, and five years earlier in those with two copies of the age-related maculopathy susceptibility protein 2 (ARMS2) risk allele compared to those with none. This study suggests that weight reduction and smoking cessation may delay the onset of neovascular AMD, even in the presence of high-risk genotypes.
Coffee Consumption and AMD
Using data from a multi-ethnic cohort in Singapore, Kumari Neelam and colleagues examined the association between coffee intake and AMD. Information relating to coffee consumption habits was gathered using a validated semi-quantitative food-frequency questionnaire as part of dietary history. A positive history of coffee consumption was recorded in 2,908 study participants (70.58 per cent). Older age and male gender were associated with a higher prevalence of coffee consumption.
No significant association was observed between coffee consumption and the risk of early or late AMD [(early AMD: odds ratio (OR), 1.27; confidence interval (CI), 0.91-1.78; late AMD: OR, 1.68; CI, 0.19-14.57)]. There was also no relationship between the number of cups of coffee consumed per day and the risk of AMD. Thus, it appears that coffee has no effect on an individual’s risk of AMD. We can all continue to enjoy our lattes!
Fuchs’ Endothelial Dystrophy
Two important posters relating to the cornea were presented at this year’s ARVO meeting. These replicated the association and linkage to the FCD2/TCF4 locus on chromosome 18 in Fuchs’ endothelial dystrophy (FED). At ARVO last year, this association was first presented by Keith Baratz and colleagues, and subsequently published in the New England Journal of Medicine.1
His team identified a major genetic association with FED, with the majority of FED cases having two abnormal single nucleotide polymorphisms (SNPs) in the TCF4 gene. Interestingly, the TCF8 gene had earlier been linked to severe familial FED. John Gottsch and colleagues studied 170 late-onset Fuchs’ corneal dystrophy cases and 180 matched controls with nine SNPs spanning the entire TCF4 region. They found that the risk allele, G of rs613872 – adjacent to TCF4, was significantly associated with FED with an odds ratio of 4.2.
This work supports the original study and confirms the major contribution of this gene to FED. A further study by Mollie Minier and colleagues, also confirmed the association of TCF4 with FED. They looked at the frequency of the TCF4 SNP in populations around the world and found that the risk allele was most common in Europeans but rare in Asians or Africans, based on data from the Human Genome Diversity Project. This supports the greater association of FED in European populations and is probably related to genetic differences in the TCF4 gene between ethnic groups. These data will help shed more light on the mechanism of disease for FED and may lead to genetic identification of those at high risk of FED.
Global Diabetic Retinopathy
Tien Wong’s group at the Centre for Eye Research Australia, University of Melbourne, Australia, presented a paper on the global epidemiology of diabetic retinopathy (DR) in a session titled ‘Diabetes and Retinal Vessels’. This was selected as an emerging or ‘hot topic’ by ARVO. Previous studies have reported the prevalence of DR in different countries, but there has been marked variation between studies, with some suggesting that only 15 per cent of diabetic patients have retinopathy while others report prevalence of more than 50 per cent.
To estimate the global prevalence of DR more precisely as well as the vision-threatening stages of DR, including proliferative retinopathy (PDR) and diabetic macular oedema (DME), they performed a systematic review and pooled data from population-based studies in the USA, Australia, Europe and Asia. They selected only population-based studies with participants from the general or diabetic populations where DR status was ascertained from fundus photography. From 58 studies initially approached to participate, a total of 35 studies provided individual-level data totalling 22,896 diabetic persons aged from three to 97 years. The median duration of diabetes was 7.8 years and mean HbA1c was 8.0 per cent.
Complement Cascade Inhibitors, High IOP and Glaucoma
The proteins of the complement cascade system have been implicated in the development of AMD. However, complement proteins have also been shown to accumulate around ganglion cell dendrites in eyes with high intra-ocular pressure (IOP), targeting ganglion cell synapses for destruction. Complement protein levels increase in human glaucoma, peaking in moderate disease but dropping as severe disease leaves fewer ganglion cells to be damaged. If, however, this complement cascade is switched on in all eyes with high IOP, why do not all these eyes develop ganglion cell damage? Cells also produce powerful inhibitors of the complement system. The hypothesis by Luis Vazquez and the team from the Doheny Eye Institute, Los Angeles, USA, suggested that genes for complement inhibitors may be missing or altered in glaucoma patients with high IOP. So they examined SNPs for key complement inhibitors in the population-based Los Angeles Latino Eye Study (LALES).
Remarkably, SNPs from the key C2 and BF complement inhibitors were completely absent from the glaucoma patients studied. The Y402H polymorphism of complement factor H, which is found in AMD, was also present in glaucoma patients. In fact, rates of glaucoma were higher in AMD patients in the LALES.
Apples and Blackberries Good for the Eye (Doctor)
Through the explosion of applications (apps) that are currently available (the iPhone has more 330,000 and the Android platform is expanding rapidly with more than 200,000), smartphones have quickly expanded their utility in ophthalmology.
‘Dragon Dictation’ has good voice recognition and provides an excellent means for dictating clinic notes or letters, although the medical vocabulary is currently somewhat limited. ‘Citrix’ is an application that can be used to access programs or files remotely and is now available as an app to access electronic health records when out of the office.
A number of apps have also been designed to facilitate patient education. ‘Portis Eye’ contains 3D images of eyes that can be shown on a tablet to patients, and provides an alternative to plastic models. ‘Sight Selector’ contains 3D videos of surgical procedures that might help with the gathering of informed consent. ‘Medical Translator’ can be useful with non-English speaking patients. The novel aspect of this app is that you do not type in what you want translated; rather, you speak into the phone and the phone then provides an audible verbal translation.
The ‘Eye Handbook’ also has patient information that can be emailed directly to a patient. Ophthalmology registrars about to sit for exams may derive help from ‘gFlashPro’, which syncs with Google and allows you to easily create flash cards for revision. Glaucoma risk calculators, colour vision and Amsler charts alongside charts to test visual acuity are all readily available.
Sleeping on Glaucoma
Two interesting posters at ARVO discussed research relating to sleep and the risk of glaucoma.
Sonya Thomas and colleagues from the Yale School of Medicine, Connecticut, USA, presented data on visual field asymmetry and sleep position in low-pressure glaucoma. Low or normal tension glaucoma (NTG) is often associated with asymmetric field loss. It has also been noted that people are more likely to sleep on their right side (60 per cent) compared to their left (19 per cent). This tendency increases as people age.2
Their team studied 57 NTG and 90 primary open-angle glaucoma patients with bilateral field tests. They conducted a sleep history of right, supine, left and prone positions, and validated this in a subset using a sleep-monitoring device. In their participants, 37 per cent slept on the right, 32 per cent supine, 23 per cent left and eight per cent prone. Right-sided sleepers had a greater frequency of asymmetric fields with the left eye having a worse visual field.
Christoph von Sonnleithner from Berlin, Germany, presented data on sleep-disordered breathing, or sleep apnoea syndrome (SAS), in patients with glaucoma.
Symptoms of SAS include snoring, apnoea and fragmentation of sleep, and are related to changes in blood pressure and oxygenation. SAS has been associated with an increased risk of glaucoma in several studies.3 His team questioned 66 glaucoma patients about SAS; 23 out of 66 had symptoms of SAS, with a higher proportion (12 out of 26) in those with NTG.
An important public health message about SAS is emerging – glaucoma patients should be questioned and possibly studied for SAS, and those with SAS should be referred for glaucoma examinations.
The ‘Eye on ARVO’ 2011 editorial team: Professor Jonathan Crowston, Professor of Ophthalmology, Centre for Eye Research Australia, Head of Ophthalmology, University of Melbourne, Vic; Associate Professor Samantha Fraser-Bell, Associate Professor, Sydney Eye Hospital and Save Sight Institute, Visiting Medical Officer, Royal North Shore Hospital, Sydney, NSW; Professor Mark Gillies, Professor and Director, Macular Research Group, Save Sight Institute, University of Sydney, NSW; Clinical Associate Professor Paul Healey, Director of Glaucoma Services, Western Sydney Eye Hospital, NSW; Professor David Mackey, Managing Director, Lions Eye Institute, WA; Professor Tien Wong, Professor, Centre for Eye Research Australia, University of Melbourne, Vic.
Footnote: The ophthalmologists who prepared this article from selected reports presented at ARVO 2011 were invited to attend the conference by Pfizer Australia. To obtain full reports or for information on how to receive reports from ‘Eye on ARVO’, please send your request to justin.shipway@pfizer.com.
Disclaimer: This material is provided for educational purposes. It contains excerpts from data presented at an international meeting. Accordingly, some reported uses of named products may not be registered or representative of the approved Australian Product Information (API). Please refer to the published, Australian-approved Product Information before prescribing any product mentioned in this report. The opinions expressed herein are those of the Eye on ARVO editorial team. Although they do not necessarily reflect those of the sponsor or publisher, both parties have made every effort to ensure that the authors’ opinions are accurate, fair, balanced and consistent with the general body of information.
References
1. Baratz K et al. N Engl J Med 2010; 363: 1016-1024.
2. De Koninck J et al. Sleep 1992; 15: 143-149.
3. Mojon DS et al. Ophthalmologica 2000; 214(2): 115-118.
