Outcomes of Of Cataract Surgery may Differ from Clinical and Patient’s Point of View

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Posted on 1st August 2013 by Pacific ClearVision Institute in Cataracts |General

The study “Analyzing Patient-Reported Outcomes to Improve Cataract Care”, appeared in the August issue ofOptometry and Vision Science, official journal of the American Academy of Optometry.

Using well-designed and validated tools to assess patient-reported outcomes can lead to new insights for improving the results of cataract care, suggests the study by Mats Lundström, MD, PhD, of Lund University and Ulf Stenevi, MD, PhD, of Sahlgren’s University Hospital, Sweden. Their paper is part of a special theme issue on “Measuring the Patient’s Perspective” in optometry research and clinical practice.

Study Compares Clinical and Patient-Reported Outcomes of Cataract SurgeryUsing a nationwide registry, Drs Lundström and Stenevi evaluated clinical and patient-reported outcome measures in nearly 10,000 cataract surgeries performed in Sweden between 2001 and 2011. For example, a major clinical outcome measure after cataract surgery is visual acuity. But improved visual acuity may not always reflect patient ratings of change in vision from before to after the procedure—especially in performing everyday functional tasks.

Not surprisingly, a comparison of the two sets of outcomes found that patient-reported measures were affected by clinical measures. Factors affecting patient-reported outcomes included visual acuity in both the operated and nonoperated eyes, change in visual acuity in the operated eye, and any other eye-related conditions (“ocular comorbidity”).

However, more useful information was gained by looking at factors related to better or worse patient-reported outcomes. For example, patients who reported better visual function before surgery or who had poor visual acuity in the nonoperated eye were more likely to have poorer patient-reported outcomes after cataract surgery.

Implications for Decisions about Cataract CareOcular comorbidity was also related to worse patient-reported outcomes. These findings may indicate that, as in other chronic diseases, “some patients are too healthy and some too sick to benefit” from cataract surgery, Drs Lundström and Stenevi write. “It is possible that patients who are very satisfied with their vision and have no problems in performing daily life activities should not have cataract surgery at present.”

The study also looked at situations where the clinical outcomes were good but patient-reported outcomes were poor—which happened in about seven percent of cataract surgeries. In many of these cases, poor near vision after the procedure was a major contributor to patient dissatisfaction.

There’s a growing emphasis on patient-reported outcomes and quality of life in assessing various medical or surgical treatments. But there’s been little attention to linking patient-reported outcomes to clinical outcomes in an attempt to improve health care. Age-related cataract is a good model for quality outcome studies: it is a very common, progressive condition that affects daily life and activities, and one for which surgical treatment is effective.

The new study helps vision care professionals in understanding how patient-reported outcome measures might be used to improve on the results of cataract surgery from the patient’s perspective. For example, Drs Lundström and Stenevi suggest that surgery could be delayed or not performed in patients who feel they aren’t having a lot of problems with daily activities—perhaps especially if they have good near vision.

The special theme issue presents 20 papers on topics related to the use of patient-reported outcomes in vision care. “These papers focus on new tools that are being increasingly used to assess the patient’s perspective on a wide range of important conditions, problems, and outcomes,” comments Anthony Adams, OD, PhD, Editor-in-Chief of Optometry and Vision Science. “These measures allow us to rigorously measure the outcomes important to patients, and to do so in a very meaningful way.”

Cheaper Anti-Cancer Drug as Effective as Expensive Drug in Treating Most Common Cause of Blindness in Older Adults

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Posted on 1st August 2013 by Pacific ClearVision Institute in General |Retina

An anti-cancer drug has been proven to be equally as effective in treating the most common cause of blindness in older adults as a more expensive drug specifically formulated for this purpose.

The results of a two-year trial, led by Queen’s scientist Professor Usha Chakravarthy, and published in The Lancet today (Friday 19 July), show that two drug treatments Lucentis and Avastin are equally effective in treating neovascular or wet age-related macular degeneration (wet AMD).

Wet AMD is a common cause of sight loss in older people with at least 23,000 older people diagnosed with the condition in the UK each year. Without treatment two thirds of people with this condition will experience severe loss of sight within two years of being diagnosed.

Lucentis, the drug most commonly used in the UK at present to treat wet AMD, costs about £700 per injection and Avastin costs about £60 per injection. The NHS could save £84.5 million annually based on injecting 17,295 eyes each year by switching from Lucentis to Avastin. Avastin is already used to treat wet AMD in some parts of the UK and extensively elsewhere in the world and also for other eye conditions.

Over the past five years, a team of scientists and eye specialists from 23 hospitals and UK universities, including Queen’s University Belfast, University of Bristol, University of Liverpool, University of Southampton and University of Oxford, have investigated whether Lucentis and Avastin and the way they are given are equally effective and safe.

610 people with wet AMD entered a two-year trial known as IVAN which is one of the largest ever carried out in the field of eye disease in the UK. Patients received injections of the drug into the affected eye every month for the first three months. Patients were then subdivided to receive the injections at every visit (monthly group) or only if the specialist decided there was persistent disease activity (as needed group).

The IVAN study’s two year results show that sight was equally well preserved with either of the two drugs. Giving the treatment regularly every month, resulted in slightly better levels of sight which was detected through testing of near visual acuity and contrast sensitivity. The ‘as needed’ group received on average 13 injections over the two year period compared to 23 for the monthly treatment group. However, continuous treatment caused a higher proportion of eyes to develop a condition known as geographic atrophy which is a thinning of the retina and its blood supply.

Professor Usha Chakravarthy of Queen’s University Belfast’s Centre for Vision and Vascular Science, who led the research study team said: “The IVAN results at the end of year two show that Lucentis and Avastin have similar functional effectiveness regardless of the drug received. With respect to monthly versus as needed treatment, while there was marginally better eyesight in the former, the development of atrophy is a matter of concern in the longer term.”

The IVAN study was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme. The Belfast Health and Social Care Trust sponsored the clinical trial. Professor Ian Young, Director of Research and Development at the Trust said: “The findings of the IVAN study will be of great importance for the management of patients with wet AMD throughout the world. Research to improve patient care is a key aspect of the work of Belfast Trust, and we are committed to sponsoring and leading important clinical trials of this kind which allow our patients early access to new treatments.”

Dr Janice Bailie, Assistant Director, Health and Social Care Research and Development Division of the Public Health Agency, which supported the trial said: “With increasing life expectancy and a growing proportion of older people in the population, slowing the progress of conditions like AMD is key to maintaining their independence. The IVAN trial is an example of research led from Northern Ireland with international significance — the findings have the potential to influence how AMD is managed in the future.”

The IVAN study also monitored the drugs for serious adverse events which included death, heart attacks, strokes, and any other event that was life threatening, disabling or resulted in hospitalisation. These were similar for the two drugs. However, deaths occurred less frequently in the group that received monthly treatment, although there were fewer deaths overall among people taking part in the trial than were expected based on their age and gender and national death rates. When these safety results were combined with those of a similar study called the CATT trial which was performed in the USA, the resultant findings continued to indicate fewer deaths when treatment was given monthly.

The researchers state that their findings will be of relevance to the next round of technology appraisals by the National Institute for Health and Care Excellence and could lead to important changes to the way wet AMD is treated. In the meantime, for an older person starting a course of Lucentis or Avastin, it will be important to explain the trade-off between the number of injections, and the chances of developing geographic atrophy and risk of mortality in two years.

Protein Responsible for ‘Bad’ Blood Vessel Growth Discovered

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Posted on 1st August 2013 by Pacific ClearVision Institute in General |Retina

The discovery of a protein that encourages blood vessel growth, and especially ‘bad’ blood vessels – the kind that characterise diseases as diverse as cancer, age-related macular degeneration and rheumatoid arthritis – has been reported in the journal Nature.

The team at the UCL Institute of Ophthalmology discovered the new protein, called LRG1, by screening for mouse genes that are over-expressed in abnormal retinal blood vessels in diseased eyes.

In these diseased retinas the LRG1 protein is expressed by blood vessel endothelial cells, which line blood vessel walls. LRG1 is also present in the eyes of patients with proliferative diabetic retinopathy – a vascular complication of diabetes that can lead to blindness.

The study shows that, in mouse models, LRG1 promotes the growth of blood vessels in a process known as ‘angiogenesis’. Conversely, inhibition of LRG1 in mouse models reduces the harmful blood vessel growth associated with retinal disease.

The authors of the study suggest that blocking LRG1′s activity is a promising target for future therapy.

Professor John Greenwood, senior author of the research from the UCL Institute of Ophthalmology said: “We have discovered that a secreted protein, LRG1, promotes new blood vessel growth and its inhibition prevents pathological blood vessel growth in ocular disease.

“Our findings suggest that LRG1 has less of a role in normal blood vessel growth and so may be particularly applicable to ‘bad’ blood vessel growth. This makes LRG1 an especially attractive target for therapeutic intervention in conditions where vessel growth contributes to disease.”

Angiogenesis is an essential biological process that is required for development, reproduction and the repair of damaged tissues. However angiogenesis also plays a major role in many diseases where new vessel growth can be harmful.

For example, in the retina uncontrolled and irregular blood vessel growth in diseases such as age-related macular degeneration and diabetic retinopathy can result in a catastrophic loss of vision. Another example is the growth of cancerous solid tumours, which are dependent on the proliferation of new blood vessels. Angiogenesis is also an important feature of rheumatoid arthritis, where it contributes to the inflammation of the joint.

In previous studies, many signaling molecules have been identified that control angiogenesis, with the secreted protein vascular endothelial growth factor (VEGF) being considered as the master regulator. Therapeutic targeting of VEGF has resulted in improved outcomes in eye diseases with vascular complications and in some cancers but it is clear that additional therapeutic targets need to be identified.

The mechanism through which LRG1 promotes angiogenesis is by modifying the signalling of a multifunctional secreted growth factor called transforming growth factor beta (TGF-beta). TGF-beta regulates both the maintenance of normal healthy blood vessels, and the unwanted growth of harmful blood vessels, but precisely how it promotes two opposing outcomes is a biological paradox.

This study indicates that in the retinal diseases investigated LRG1 production is ‘turned on’ in blood vessels. This causes a switch in TGF-beta signalling away from a normal vessel maintenance pathway towards a pathway that promotes the growth of new harmful blood vessels.

Professor Stephen Moss, senior author from the UCL Institute of Ophthalmology said: “Genetic studies have revealed that the gene that codes for LRG1 is conserved in vertebrates, and this study confirms that mouse and human blood vessels express LRG1.

“We predict, therefore, that abnormal blood vessel growth is also a conserved process and that the role of LRG1 is equally applicable to human pathological angiogenesis.”

He added: “Work is already underway to develop a therapeutic antibody that targets LRG1.”

Researchers Regenerate Retina in Mice Using Neuronal Reprogramming

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Posted on 1st August 2013 by Pacific ClearVision Institute in Retina

Researchers from the Centre for Genomic Regulation (CRG) in Barcelona have managed to regenerate the retina in mice using neuronal reprogramming. There are currently several lines of research that explore the possibility of tissue regeneration through cell reprogramming. One of the mechanisms being studied is reprogramming through cell fusion.

The researcher Pia Cosma and her team have used the cell fusion mechanism to reprogram the neurons in the retina. This mechanism consists of introducing bone marrow stem cells into the damaged retina. The new undifferentiated cells fuse with the retinal neurons and these acquire the ability to regenerate the tissue.

“For the first time we have managed to regenerate the retina and reprogram its neurons through in vivo cell fusion. We have identified a signalling pathway that, once activated, allows the neurons to be reprogrammed through their fusion with bone marrow cells,” explains Pia Cosma, head of the Reprogramming and Regeneration group at the Centre for Genomic Regulation and ICREA research professor. “This discovery is important not only because of the possible medical applications for retinal regeneration but also for the possible regeneration of other nervous tissues,” says Daniela Sanges, first author of the work and postdoctoral researcher in Pia Cosma’s laboratory.

The study, published by the journal Cell Reports, demonstrates that the regeneration of nervous tissue by means of cell fusion is possible in mammals and describes this new technique as a potential mechanism for the regeneration of more complex nervous tissue.

This research is in the very early stages but already there are laboratories interested in being able to continue the work and take it to a more applied level.

Complete Description of Gene Expression in the Human Retina

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Posted on 1st August 2013 by Pacific ClearVision Institute in Retina

Investigators at Massachusetts Eye and Ear and Harvard Medical School have published the most thorough description of gene expression in the human retina reported to date. In a study published today in the journal BMC Genomics, Drs. Michael Farkas, Eric Pierce and colleagues in the Ocular Genomics Institute (OGI) at Mass. Eye and Ear reported a complete catalog of the genes expressed in the retina.

The retina is the neural tissue in the back of the eye that initiates vision. It is responsible to receiving light signals, converting them into neurologic signals and sending those signals to the brain so that we can see. If one thinks of the eye as a camera, the retina in the “film” in the camera. For these studies, the investigators used a technique called RNA sequencing (RNA-seq) to identify all of the messenger RNAs (mRNAs) produced in the human retina. The resulting catalog of expressed genes, or transcriptome, demonstrates that the majority of the 20,000+ genes in the human body are expressed in the retina. This in itself is not surprising, because the retina is a complex tissue composed of 60 cell types.

In a more surprising result, Dr. Farkas and colleagues identified almost 30,000 novel exons and over 100 potential novel genes that had not been identified previously. Exons are the portions of the genome that are used to encode proteins or other genetic elements. The investigators validated almost 15,000 of these novel transcript features and found that more than 99 percent of them could be reproducibly detected. Several thousand of the novel exons appear to be used specifically in the retina. In total, the newly detected mRNA sequence increased the number of exons identified in the human genome by 3 percent.

“While this may not sound like a lot, it shows that there is more to discover about the human genome, and that each tissue may use distinct parts of the genome,” said Dr. Pierce, Director of the OGI and the Solman and Libe Friedman Associate Professor of Ophthalmology, Harvard Medical School.

This work is valuable to help scientists understand how the retina works, and how it is affected by disease. For example, Dr. Pierce and colleagues in the OGI study inherited retinal degenerations, which are common causes of vision loss. These diseases are caused by misspellings or mutations in genes that are needed for vision. To date, investigators have identified more than 200 retinal degeneration disease genes, but still can’t find the cause of disease for up to ½ of the patients affected by these disorders. Identification of new exons used in the retina may help find the cause of disease in these patients.

Identifying the genetic cause of patients’ retinal degeneration has become especially important with the recent success of clinical trials of gene therapy for RPE65 Leber congenital amaurosis (LCA). As a follow-up to these initial proof-of-concept trials, clinical trials of gene therapy for 4 other genetic forms of inherited retinal degeneration are currently in progress. Further, studies in animal models have reported successful gene therapy for multiple additional genetic types of IRD. There is thus an unprecedented opportunity to translate research progress into provide sight preserving and/or restoring treatment to patients with retinal degenerative disorders.