A team of ophthalmologists from various specialties in Australia travelled to the recent ARVO ophthalmology conference in Fort Lauderdale, Florida, USA. Below we’ve published excerpts from the team’s reports on topics ranging from retinal and corneal diseases to stem cell therapies and glaucoma.
Approximately 11,000 vision researchers and practitioners gathered at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in early May to discuss key developments at the forefront of ophthalmic research.
Professor Jonathan Crowston
Topic: Neural Rescue in Glaucoma
Jason Meyer described how retinal cells can be derived from embryonic stem cells
Although we now have good evidence from large, prospective, randomised controlled trials that Iowering intraocular pressure (IOP) delays glaucoma progression, it does not halt the disease and many patients continue to progress.
Despite disappointment that studies with oral glutamate antagonists did not reach primary endpoints, a large body of researchers continues to search for IOP-independent therapies for protecting the optic nerve.
Numerous studies have demonstrated neuroprotection in experimental models of glaucoma or optic nerve injury, but we currently lack compelling evidence to demonstrate neuroprotection in clinical studies. This may reflect fundamental differences between animal and human optic nerves or deficiencies in the experimental models used. However it is most likely that we lack sufficiently sensitive tests, that lend themselves to feasible clinical studies, for detecting changes on optic nerve health over time periods.
The lack of sufficiently robust tools for assessing the state of optic nerve health in clinical practice is a major challenge when it comes to translating experimental evidence of neuroprotection into clinical proof. A number of research groups are currently investigating biomarkers of retinal ganglion cell damage that are reversible and might inform a clinician whether glaucoma therapy is effective or not.
Professor Robyn Guymer
Topic: Growing an Eye from a Whisker! A Beginner’s Guide to Stem Cells
iPS stands for induced pluripotent stem cells. The ARVO session ‘Programming and signalling of iPS cells and retinal progenitors’ updated us on where we are in terms of our ability to grow cells that can potentially become retinae.
Jason Meyer (The Waisman Center, University of Wisconsin) described how retinal cells can be derived from embryonic stem cells. Starting with human pluripotent stem cells obtained from the early blast stage of an embryo, the first step is to drive these cells to become anterior neuroepithelial cells by applying specific transcription factors.
From the anterior neuroepithelium the rudimentary neural plate starts to develop. Once the neural plate starts to form the neural tube it will go on to develop the optic vesicle which grows out of the neural tube. It is possible to enrich this culture for neuro-progenitor cells based upon the morphological characteristics of the cell so that they can be handpicked and stained for Chx10, a specific marker for retinal progenitor cells, with the aim of obtaining a pure sample of neural retinal progenitor cells. Given the right transcription factors at the right time, the other cells will produce other neuronal cell types while the neural retina will differentiate into distinct retinal cell types; ganglion, amacrine and bipolar cells, photoreceptors, rods and cones. The differentiation occurs when the appropriate transcription factors are applied to the cells and the timing of the appearance of the various cells mimics the same timing in the embryo. Some cells from the optic vesicle start to become pigmented and these are the rudimentary retinal pigment epithelium.
Jason Meyer’s presentation was followed by a most intriguing discussion by Dr. C Jomary from The University of Southamptom, UK, who explained how to grow a retinal cell from hair follicle cells. He led us through the example of a whisker taken from a rat. The hair follicle stem cell was isolated and underwent expansion in a conditioned media, which transformed the cells into ones that expressed rhodopsin and blue opsin; i.e. they were behaving like photoreceptors.
Dr. Paul Healey
Topic: New Insights into Glaucoma Disease Progression – The Ocular Hypertension Treatment Study (phase II)
The Ocular Hypertension Treatment Study (OHTS) is the seminal randomised, controlled trial of treatment or no treatment for ocular hypertension (OH). The study found that about 10 per cent of people with untreated OH develop glaucoma over five years compared to about four per cent with medical therapy aimed at a 20 per cent IOP reduction. At the end of the first study period, all patients who were not already using drops (i.e. all the patients in the observation group who had not developed glaucoma) were placed on the same treatment regime as the initial treatment group. They were all then followed for another five years. This phase II study aimed to answer the question: “Do we lose anything by delaying treatment of OH until glaucoma develops?”
The early results from the OHTS phase II suggest that visual field and rim loss occur quite frequently in OH, and that event-based glaucoma diagnosis picks up only those whose rate of deterioration is greatest. The higher rates of second endpoints in those with field loss suggest that this is the group in whom progression tends to be fastest. This is consistent with our current understanding of glaucoma.
That optic disc size is a risk factor for rate of rim loss on HRT is intriguing. Previous data (including the Blue Mountains Eye Study) have shown larger disc size to be a risk factor for glaucoma, but only a very small one.
Lastly, the reduction in the rate of field loss after treatment shows that treatment of early glaucoma is effective. However, the much greater rate reduction in those without glaucoma raises the question as to whether treatment before, rather than after, event-based disease detection might be more effective. With more thorough data analysis, the journal articles that will arise from these presentations should give us very important information on the natural history of early glaucoma and the effects of delaying treatment.
Professor Tien Wong
Topic: New Risk Factors for Diabetic and Non-Diabetic Retinopathy
In this year’s ARVO session on ‘Diabetic retinopathy, retinal diseases and associated risk factors’, a range of new data were presented on risk factors for both diabetic and non-diabetic retinopathy.
Long-term Incidence and Risk Factors of Non-diabetic retinopathy
Dr. J J Wang from the Centre for Vision Research and Ophthalmology, University of Sydney, reported on the 10-year incidence of isolated retinopathy lesions and associated risk factors in people without diabetes. He used data from the Blue Mountains Eye Study, Sydney, which examined 1,678 participants, who were followed for up to 10 years, who did not have retinopathy signs at baseline. The authors showed that the cumulative 10 year incidence of new retinopathy lesions (microaneurysms, haemorrhages, hard or soft exudates) was 16 per cent (n=269). In people with moderate retinopathy, the risk factors were hypertension and obesity. Furthermore, of 291 people with retinopathy but no diabetes at baseline, most (>60 per cent) completely disappeared at follow-up, suggesting that the lesions were transient.
Inflammation, Body Mass Index and Diabetic Retinopathy
Dr. L Lim (Singapore Eye Research Institute) and colleagues, used data from the Singapore Malay Eye Study to examine the relationship between CRP, BMI and the presence and severity of diabetic retinopathy in adults with diabetes mellitus. The study examined 718 people with diabetes in this cohort. After adjusting for age, gender, HbA1c, hypertension and other risk factors, people with higher C-reactive protein (CRP) and body mass index (BMI) levels were less likely to have any diabetic retinopathy, vision-threatening diabetic retinopathy or clinically significant macular oedema. No significant interactions between BMI and CRP were found for diabetic retinopathy. These findings are counter-intuitive and suggest that people with diabetes who had both high CRP and BMI were less likely to have diabetic retinopathy.
Retinal Vessel Tortuosity and Diabetic Retinopathy
In another study, Dr. M B Sasongko from the Centre for Eye Research, University of Melbourne, showed that greater tortuosity of the retinal vasculature was associated with a higher risk of diabetic retinopathy. This study suggests that retinal vessel tortuosity may be a marker of early microvascular damage and that a quantitative measurement of tortuosity may be useful to predict eyes at risk of diabetic retinopathy.
Professor Minas Coroneo
Topic: Cataract Surgery: Great Expectations and Anticipation
The expectations of both cataract patients and surgeons have never been higher, and with good reason. While cataract surgery and intraocular lens (IOL) implantation is considered the best procedure ever developed for replacement of a body part, the procedure is highly dependent on surgical skills and patient idiosyncrasies. The continuous and ongoing ‘tweaking’ of the procedure was in evidence at ARVO 2010. The ante has been upped with the introduction of femtosecond laser surgery guided either by real-time optical coherence tomography (OCT) or Scheimpflug systems (dubbed the “seeing scalpel”).
One study used a long-range spectral domain OCT system to automatically delineate the anterior and posterior surfaces of the lens and cornea for treatment planning of capsulotomy, lens segmentation and corneal incisions. It was concluded that OCT-guided femtosecond laser cataract surgery greatly improves precision and reproducibility. This integrated system offers a previously unattainable level of precision that should result in improved IOL centration and correction of residual corneal astigmatism.
A second clinical study reported clinical outcomes for laser cataract surgery compared to conventional phacoemulsification. It was concluded that if the intended benefits of laser cataract surgery (which include more consistent capsulotomies and reduced phaco energy during lens extraction) can be realised, it appears there will be no adverse effect on clinical outcomes.
Drinking coffee at ARVO turns out to be a calculated risk. Previous suggestions of a link with elevated IOP and dry eye may be balanced by experimental findings of an anti-cataractogenic effect in a mouse model – likely mediated by antioxidant effects. The source of reactive oxygen species appears to be peripheral lens epithelial cells, in part by a mechanism involving the unfolded protein response. The importance of ongoing studies such as these is to find potential pathways where intervention may reduce the cataract burden.
Professor Minas Coroneo. Professor and Chair, Department of Ophthalmology, University of New South Wales, Prince of Wales Hospital, Sydney, New South Wales.
Professor Jonathan Crowston. Professor of Ophthalmology, Centre for Eye Research Australia, Head of Ophthalmology, University of Melbourne, Melbourne, Victoria.
Professor Robyn Guymer. Head, Macular Research Unit, Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria.
Dr. Paul Healey. Director of Glaucoma Services, Western Sydney Eye Hospital, Sydney, New South Wales.
Professor Tien Wong. Professor and Director, Retinal Vascular Imaging Centre, Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria.