Converting rods into cones in a model of retinitis pigmentosa (RP) rescues retinal degeneration

Heritable retinal degeneration is a common cause of visual impairment and blindness, affecting millions of people worldwide. Many research groups have focused on targeted gene therapy as a treatment for these diseases. However, inherited retinal diseases can be caused by mutations in any one of more than 200 genes, and the pathogenic mechanisms of various mutations differ greatly. This was the motivating factor in the work by Dr James C Corbo and his team at the Washington University School of Medicine to develop gene-independent therapies that would be more widely applicable. This work has been published in the Proceedings of the National Academy of Sciences.

Results from AREDS-2 clinical trial & what it means for you

Age-Related Eye Disease Study (AREDS) and Age-related Eye Diseases Study-2 (AREDS-2) were landmark studies in providing a clue to show benefit from nutritional supplements. The article below, from Retina India's newsletter from 2013, is still relevant today to patients of Age-related macular degeneration.

Poor Avastin responders in AMD & DME may have increased risk to obstructive sleep apnea

from Wikipedia

Poor responders to Bevacizumab (Avastin) in patients with age-related macular degeneration (AMD) and diabetic macular edema (DME) may have increased risk to obstructive sleep apnea (OSA). To read more, click here.

Nanotechnology breakthrough will lead to a better bionic eye for the blind

(c) American Chemical Society

 
Scientists from Hebrew University of Jerusalem researchers, in collaboration with colleagues from Tel Aviv University and Newcastle University, have developed a new light-sensitive film that could one day form the basis of a bionic eye (or an artificial retina) that could help people suffering from retinal damage or degeneration.

Human stem cell-derived retinal cells show promise as treatment for macular diseases

Note: The post below is  from the study (pdf) published in The Lancet.

Since 1981, when pluripotential cell cultures were first derived by Evans and Kauffman, embryonic stem cells (ESC) have been regarded as a potential source of therapeutic cells for a wide range of diseases caused by tissue loss or dysfunction. Despite the great therapeutic potential, their plasticity and unlimited capacity for self-renewal raise concerns about serious safety issues, including the ability to form teratomas and other tumours, potential immune reactions, and the risk of differentiating into unwanted cell types. 

Stem cells close to cornea may help treat Macular Degeneration or Retinitis Pigmentosa

Scientists at the Southampton General Hospital and the University of Southampton have found a pool of stem cells around the corneal limbus that can be induced to become retinal cells. Such cells can then potentially be transplanted into the eye of the patient of macular degeneration or retinitis pigmentosa to stop the disease or even cure it.  

Japanese woman is first recipient of next-generation iPS stem cells for macular degeneration

A Japanese woman in her 70s has become the first person in the world to receive retinal cells derived from induced pluripotent stem cells (iPS). In a two-hour procedure on September 12, 2014, a team of three eye specialists lead by Dr Yasuo Kurimoto of the Kobe City Medical Center General Hospital, Japan, implanted a 1.3 by 3.0 millimetre sheet made of retinal pigment epithelium (RPE) cells into one eye of this patient, who was diagnosed with age-related macular degeneration (AMD).

A detailed molecular map for eye disease

Understanding eye diseases is tricky enough. Knowing what causes them at the molecular level is even more confounding.

To understand eye diseases better, University of Iowa (UI) researchers have created the most detailed map to date of a region of the human eye long associated with blinding diseases, such as age-related macular degeneration. The high-resolution molecular map catalogs thousands of proteins in the choroid, which supplies blood and oxygen to the outer retina, itself critical in vision. By seeing differences in the abundance of proteins in different areas of the choroid, the researchers can begin to figure out which proteins may be the critical actors in vision loss and eye disease.

Notal Vision's ForeseeHome AMD Monitor receives FDA clearance

Notal Vision's ForeseeHome™ AMD Monitor has received Section 510 (k) clearance from the U.S. Food and Drug Administration (FDA).

The ForeseeHome AMD Monitor is the first ophthalmic device linking patients and doctors between eye exams for ongoing monitoring of age-related macular degeneration (AMD). 

Patients complete a frequent but brief exam on their ForeseeHome AMD Monitor, in the comfort of their own home, and data is transmitted to the patients' eye care physician and the Notal Vision Data Monitoring Center.  The award winning ergonomic design of the ForeseeHome AMD Monitor is comfortable and easy to use for patients at risk of vision loss from wet AMD.

Wet AMD is the leading cause of blindness in people over the age of 60 in the western world. Recent breakthroughs in treatments place even greater importance on early detection, which can reduce the risks of vision loss associated with wet AMD.  Frequent monitoring is critical in detecting disease onset as early as possible and the ForeseeHome AMD Monitor is the first home monitoring device for following patients at risk of vision loss, offering hope for early intervention through early detection.

Numerous clinical studies have demonstrated the ForeseeHome AMD Monitor is an accurate and reliable tool for frequent monitoring of patients at risk for vision loss from wet AMD.

FDA Indication for Use: 

ForeseeHome is intended for use in the detection and characterization of central and paracentral metamorphopsia (visual distortion) in patients with age-related macular degeneration as an aid in monitoring progression of disease factors causing metamorphopsia including, but not limited to choroidal neovascularization (CNV). It is intended to be used at home for patients with stable fixation. ForeseeHome is not intended to diagnose; diagnosis is the responsibility of the prescribing eye-care professional.

Source

News Bulletin

• Monthly injections may not be necessary for patients with age-related macular degeneration. http://goo.gl/uldMFv

• Converting stem cells to eye tissue could restore sight. http://goo.gl/pJeuiv

• Post-operative healing aided by new gel-based eye fluid. http://goo.gl/YA1B04

• Reversible glue bandage could save injured soldiers' vision. http://goo.gl/fwD2e0

Phase 2b/3 clinical trial of Emixustat Hydrochloride in subjects with geographic atrophy associated with dry Age-related Macular Degeneration

Acucela Inc., a clinical-stage biotechnology company focused on developing new treatments for sight threatening eye diseases, announced phase 2b/3 clinical trial investigating emixustat hydrochloride in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD) has been initiated. 

AMD is the most common cause of irreversible vision loss in the developed world, the overwhelming majority of which is associated with dry AMD. There are currently no medications approved to treat GA associated with dry AMD. Emixustat hydrochloride is being studied to determine whether it slows the progression of GA in patients with GA associated with dry AMD. 

The SEATTLE study (for Safety and Efficacy Assessment Treatment Trials of Emixustat Hydrochloride) was initiated based on data from the recently completed phase 2a study, the results of which will be announced at the ARVO 2013 Annual Meeting, as well as feedback from the U.S. Food and Drug Administration (FDA).

Emixustat hydrochloride has a unique mechanism of action in visual cycle modulation, offers oral dosing and the ability to specifically target the visual cycle, representing a potentially novel therapeutic approach for the treatment of retinal diseases, such as GA associated with dry AMD.

The SEATTLE study of emixustat hydrochloride is designed as a phase 2b/3 multicenter, randomized, double-masked, dose-ranging study comparing the efficacy and safety of emixustat hydrochloride with placebo for the treatment of geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Approximately 440 patients with GA associated with dry AMD will be enrolled in the study across 56 sites, primarily in the United States.

There are more than 10 million people in the US and more than 120 million people worldwide who have age-related macular degeneration. AMD is associated with irreversible vision loss, the overwhelming majority of which is due to the dry form of AMD, representing approximately 90% of all cases. Dry AMD occurs when the light-sensitive cells in the back of the eye slowly deteriorate, gradually blurring the central field of vision. As the disease advances, and where patients typically present with GA, the blurred vision slowly progresses to blindness in affected areas of the eye.

To know more about AMD, please click here and here.

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A study for new treatments for wet age-related macular degeneration (AMD)

A University of Wisconsin School of Medicine and Public Health scientist, Dr Nader Sheibani, is spearheading a study of new treatments for wet age-related macular degeneration (AMD). Dr. Sheibani, a professor in the department of ophthalmology and visual sciences, was awarded $6.2 million over five years from the National Eye Institute. In the first year, the collaborators will receive $1.2 million.

The project is a collaboration among Dr. Sheibani’s lab and others in the department of ophthalmology and visual sciences; researchers in the UW department of pediatrics; scientists at Northwestern University Center for Developmental Therapeutics and Feinberg School of Medicine; and the University of Nebraska Center for Drug Delivery and Nanomedicine. Each specialist and team brings different skills and techniques to the question of treatment of exudative AMD.

Wet or exudative AMD is the leading cause of blindness among aging Americans. The global rate of AMD is expected to double in the next decade as the population ages.  A cause of vision loss in this type of AMD is associated with angiogenesis, the growth of new blood vessels which are leaky with severe consequences to vision.

Ophthalmologists have developed treatments known as anti-vascular endothelial growth factor (VEGF) to slow or stop new vessels from forming. The anti-VEGF treatments require frequent injections into the eye. They are an important tool for ophthalmologists to help save vision and their use has demonstrated that inhibiting VEGF slows damage from AMD. However, VEGF is essential for normal ocular integrity and function. Therefore, there is a great need for new treatments which preserve vision without interfering with normal functions.

Dr. Sheibani and his collaborators hope to develop treatments using small peptides that mimic those of the body’s own inhibitors of angiogenesis. These treatments will counter VEGF activity and inhibit vascular growth in eyes with exudative AMD while providing an environment resistant to new vessel growth. 

This study will develop peptide mimetics – shorter versions of the proteins the body makes – that will stop vessel growth. Researchers at Northwestern University are developing the peptides and those at the University of Nebraska are developing the drug delivery nanotechnology. Dr. Sheibani and his staff will test whether the treatments work in preclinical models of the disease for its translation to humans.

The hope is that this class of drugs, because they mimic the body’s own defenses, will be more effective and have fewer side effects than the treatments already available. Although human clinical trials are years away, this research is truly translational, with the potential to greatly impact quality of life by preventing a common cause of vision loss.

Source

A new potential treatment for Retinitis Pigmentosa & Macular Degeneration

A team of researchers from the University of California, Berkeley, in collaboration with researchers at University of Munich and University of Washington in Seattle have found a chemical that can temporarily restore some amount of vision in blind mice.

This compound could eventually help those with Retinitis Pigmentosa, a common genetic disease that leads to blindness, as well as Age-related Macular Degeneration.

The chemical, referred to as AAQ, acts on the remaining cells in the retina, which are normally "blind" cells, sensitive to light. AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells; when switched on by light, it alters the flow of ions through the channels and activates these neurons similar to the way rods and cones are activated by light.

This chemical has been shown to eventually wear off, and hence may offer a safer alternative to other approaches that restore sight, such as gene or stem cell therapies, which may permanently change the retina. It is also less invasive than implanting light-sensitive chips in the eye.

Considering that it is a simple chemical, it will be easy to change the dosage, use it in combination with other therapies, or discontinue the therapy if the need be. This would allow new and improved chemicals that may become available in time to be offered to the same patients.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, the researchers confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light. The mice also demonstrated light avoidance, a typical rodent behavior impossible without the animals being able to see some light. The researchers are hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

It will be a while before this compound will find its way in humans. The researchers have to show that these compounds are safe and will work in patients the way they work in mice. BUt these preliminary results demonstrate that this class of compound restores light sensitivity to retinas blind from genetic disease.

The current technologies being evaluated for restoring sight to people whose rods and cones have died include injection of stem cells to regenerate the rods and cones; "optogenetics," a type of gene therapy where a photoreceptor gene is inserted into blind neurons to make them sensitive to light; and installation of electronic prosthetic devices, such as a small light-sensitive retinal chip with electrodes that stimulate blind neurons.

Eight years ago, Kramer, Trauner, a former UC Berkeley chemist now at the University of Munich, and their colleagues developed an optogenetic technique to chemically alter potassium ion channels in blind neurons so that a photoswitch could latch on. Potassium channels normally open to turn a cell off, but with the attached photoswitch, they were opened when hit by ultraviolet light and closed when hit by green light, thereby activating and deactivating the neurons.

Subsequently, Trauner synthesized AAQ (acrylamide-azobenzene-quaternary ammonium), a photoswitch that attaches to potassium channels without the need to genetically modify the channel.

Newer versions of AAQ now being tested have demonstrated better results, as per the researchers. They activate neurons for days rather than hours using blue-green light of moderate intensity, and these photoswitches naturally deactivate in darkness, so that a second color of light is not needed to switch them off.

Source

FDA approves Eylea for patients with Age-related Macular Degeneration

Regeneron Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has approved Eylea (aflibercept) Injection, known in the scientific literature as VEGF Trap-Eye, for the treatment of patients with neovascular (wet) Age-related Macular Degeneration (AMD) at a recommended dose of 2 milligrams (mg) every four weeks (monthly) for the first 12 weeks, followed by 2 mg every eight weeks (2 months).

The approval of Eylea was granted under a Priority Review, a designation that is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.  This approval was based upon the results of two Phase 3 clinical studies.  In these studies, Eylea dosed every eight weeks, following three initial monthly injections, was clinically equivalent to the standard of care, Lucentis® (ranibizumab injection) dosed every four weeks, as measured by the primary endpoint of maintenance of visual acuity (less than 15 letters of vision loss on an eye chart) over 52 weeks.  The most common adverse reactions (frequency of 5% or more) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.  The adverse event profile was similar to that seen with ranibizumab.

As per the experts, Eylea offers the potential of achieving the efficacy that the ophthalmic world had come to expect from the current anti-VEGF agents, but with less frequent injections and no monitoring requirements. This, as per these experts, may reduce the need for costly and time-consuming monthly office visits for patients and their caregivers.

About Eylea™ (aflibercept) Injection:

Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body.  Its normal role in a healthy organism is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs.  However, in certain diseases, such as wet age-related macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability that leads to edema. Scarring and loss of fine-resolution central vision often results.  

Eylea, known in the scientific literature as VEGF Trap-Eye, is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration.  Eylea acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of these cognate VEGF receptors.

Eylea is indicated for the treatment of patients with neovascular age-related macular degeneration (wet AMD).  Eylea is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.

The recommended dose for Eylea is 2 mg administered by intravitreal injection every four weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg once every eight weeks (2 months).  Although Eylea may be dosed as frequently as 2 mg every four weeks (monthly), additional efficacy was not demonstrated when Eylea was dosed every four weeks compared to every eight weeks.

There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including Eylea, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs with Eylea in clinical trials was low (1.8%).

Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections with Eylea and include endophthalmitis, traumatic cataract, and increased intraocular pressure.

About the VIEW 1 and VIEW 2 Clinical Studies:

The safety and efficacy of Eylea were assessed in two randomized, multi-center, double-masked, active-controlled studies in patients with wet AMD.  A total of 2412 patients were treated and evaluable for efficacy (1817 with Eylea) in the two studies (VIEW 1 and VIEW 2). In each study, patients were randomly assigned in a 1:1:1:1 ratio to one of four dosing regimens: 1) Eylea administered 2 mg every eight weeks following three initial monthly doses Eylea 2Q8); 2) Eylea administered 2 mg every four weeks Eylea 2Q4); 3) Eylea 0.5 mg administered every four weeks Eylea 0.5Q4); and 4) ranibizumab administered 0.5 mg every four weeks (ranibizumab 0.5Q4).  Patient ages ranged from 49 to 99 years with a mean of 76 years.

In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at week 52 compared to baseline.  Data are available through week 52.  Both the Eylea™ (aflibercept) Injection 2Q8 and 2Q4 dosing groups were shown to have efficacy that was clinically equivalent to the ranibizumab 0.5Q4 group for the primary endpoint.

Select results of the VIEW 1 and VIEW 2 studies as described in the full Prescribing Information for the Eylea 2 mg every four weeks and Eylea 2 mg every eight weeks dosing groups as compared to ranibizumab dosed monthly group are shown below.

To check the efficacy outcomes at week 52 in VIEW 1 and VIEW 2 Studies, please click on the source below. 

Safety of Eylea:

Eylea™ (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in Eylea.

Intravitreal injections, including those with Eylea, have been associated with endophthalmitis and retinal detachments.  Proper aseptic injection technique must always be used when administering EYLEA.  Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with Eylea.  Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors.  Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately. There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including Eylea, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs with Eylea in clinical trials was low (1.8%). Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections with Eylea including endophthalmitis, traumatic cataract, and increased intraocular pressure. The most common adverse reactions (greater than or equal to 5%) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.

To see the full prescribing Information for Eylea, please click here.

Regeneron is collaborating with Bayer HealthCare on the global development of Eylea.  Bayer submitted an application for marketing authorization in Europe for wet AMD in June 2011.

Bayer HealthCare will market Eylea outside the United States, where the companies will share equally the profits from any future sales of Eylea.  Regeneron maintains exclusive rights to Eylea in the United States.

Source

Possible new treatment for Macular Degeneration

Researchers from University of Kentucky College of Medicine have identified an RNA-based mechanism in the retina that could be responsible for triggering the blindness associated with advanced dry age-related macular degeneration (AMD). The article has been published in Nature.

Unlike wet AMD, which results from scarring caused by leaky blood vessels and thus can be treated with a variety of angiogenesis inhibitors, dry AMD is initially characterized by the buildup of extracellular debris beneath the retina. Over time, those deposits cause significant atrophy of the retinal pigment epithelial (RPE) layer—a condition known as geographic atrophy—leading to loss of photoreceptors in the macula, the central and the most important part of the retina, which can ultimately advance to permanent blindness.

Although difficult to predict, dry AMD can turn into wet AMD at any time during disease progression. There are no medical or surgical treatments for dry AMD.

To find potential targets for geographic atrophy, Dr Jayakrishna Ambati and colleagues initially looked at levels of proteins and nucleic acids in eye samples from dry AMD patients. The researchers found that levels of the microRNA-processing enzyme dicer 1 ribonuclease type III (DICER1) were significantly lower in patient eyes than in non-AMD control eyes (p=0.0036). DICER1 levels were unchanged in the RPE layer of human eyes with other retinal diseases, suggesting that low DICER1 could be a specific marker of geographic atrophy.

The team next generated Dicer1 knockout mice to recapitulate the geographic atrophy phenotype in animals. All the Dicer1 knockouts showed degeneration of the RPE layer compared with wild-type littermate controls.

Subsequent studies in human RPE cells and mice revealed the specific mechanism by which low DICER1 levels led to degeneration of the RPE cells or layer, respectively. The decrease in DICER1 caused the accumulation of cytotoxic Alu RNA molecules in the RPE layer, where they caused degeneration of tissues making up the retina and macula.

Alu RNAs are retrotransposon sequences that exist throughout the human genome but do not code for proteins. Considered to be a toxic type of RNA that play a disease-causing role in a large section of the human genome, these Alu-related elements make up 11 percent of the human genome. They were considered "junk" DNA because researchers did not understand their role, but are now considered to play a crucial role in the death of retinal cells in those with geographic atrophy

In cultured human RPE cells with low DICER1 levels, antisense oligonucleotides targeting Alu RNA significantly blocked RPE cellular degeneration compared with control oligonucleotides (p<0.05).

Simply said, in patients with geographic atrophy, reduction of the Dicer enzyme in the retina leads to accumulation of Alu RNA, which leads to death of the retina.

The team has also developed two therapies that may prevent geographic atrophy. The first therapy increases Dicer levels in the retina by "over-expressing the enzyme", while the second therapy blocks Alu RNA with a drug that clings to the toxic structure and degrades it. Based on experiments performed in the laboratory, both therapies could efficiently prevent geographic atrophy.

The University of Kentucky has filed for patents on both therapies, and clinical trials are expected to begin by the end of this year.

Comparison of Avastin versus Lucentis for treatment of wet type of Age-Related Macular Degeneration Treatments (CATT trial)

People with vascular diseases of the retina, such as age-related macular degeneration (AMD), diabetic macular edema, vascular occlusions like the central retinal vein occlusion, even retinopathy of prematurity (ROP) have been offered treatment in the form of injections of Ranibizumab (trade name Lucentis)or Bevacizumab (trade name Avastin) into the eye every few weeks. These injections control the expression of vascular endothelial growth factor (VEGF), which is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. When VEGF is overexpressed, it can contribute to disease.

Genentech, a wholly owned susdiary of the Swiss pharmaceutical conglomerate Hoffmann-La Roche [], developed Lucentis, which is a monoclonal antibody fragment (Fab) derived from the same parent murine antibody as Avastin. It is much smaller than the parent molecule, and has a stronger binding to VEGF-A. This feature gives it anti-angiogenic properties, which has helped it get regulatory approval in many countries around the world to treat wet AMD, which is a common form of age-related vision loss. It is marketed in the United States by Genentech and elsewhere by Novartis. Avastin, developed specifically for use in colorectal cancers, was found to be useful in the eye for AMD as well. With a significant cost difference between Avastin at an average cost of $42 a dose (in the U.S.) versus Lucentis at an average cost of $1,593 a dose, there was a difference of opinion between retina specialists and those who marketed the drug, with the specialists claiming that the effect from both appeared to be equal, while the latter claimed they were not responsible for any untoward side-effects from the use of off-lable Avastin in the eye.

With an on-going debate that showed no signs of resolution, a clinical trial comparing the two treatments in patients with wet AMD (CATT) was planned to effectively answer the question whether Lucentis has any potential benefit over Avastin.

In a multicenter, single-blind, noninferiority trial, 1208 patients with neovascular (or wet) AMD were randomly assigned to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.

The study group recently reported its result in the New England Journal of Medicine, with the conclusion that Avastin administered monthly or as needed was equivalent to Lucentis administered monthly or as needed respectively. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, p = 0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (p>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with Avastin than with Lucentis (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66).

So the major conclusion from this CATT study is that at the end of 1 year, Avastin and Lucentis had equivalent effects on visual acuity when administered according to the same schedule. The authors mention that the differences in rates of serious adverse events require further study. (The study was funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.)

p.s. In this continuing saga of Lucentis versus Avastin, New York Times reports that Genentech has been  offering secret rebates to eye doctors as an apparent inducement to get them to use more of the company’s expensive drug Lucentis rather than a less costly alternative.

Abdominal obesity is a risk factor for AMD in middle aged men

Increasing weight in middle aged men could significantly increase the risk of blindness later in life, a study has found.

Melbourne University researchers, in a study that monitored changes in the waistlines of more than 21,000 men and women between 40 and 69 over several years, have noted that an expanding waistline puts men in danger of developing age-related macular degeneration (AMD), which is a leading cause of vision loss in the elderly. Even a small increase in waistline increases the risk of developing AMD. The researchers found that even for an increase of 0.1 in the waist/hip ratio, a man's chances of developing the disease soared by 75 per cent.

Women do not appear to be as affected as men, as found in this study, possibly due to pre-existing high levels of female hormone oestrogen acting as a preventive factor.

Digestion of abdominal fat releases oestrogen, which can cause inflammation in blood vessels at the back of the eyes. Such inflammation is considered to be one of the factors in developing AMD.

The disease is caused by the growth of new and abnormal blood vessels under the macula, a small oval-shaped area in the retina, which is an important part of the visual system in helping us see objects and print clearly. These abnormal blood vessels leak fluid, causing scar tissue to form and destroying vision in the centre of the eye. This makes it difficult to recognise faces, read or watch TV.

Around 90 per cent of cases develop dry AMD, a form of the disease which gradually progresses over many years, and for which there is no treatment currently. The rest of the cases develop wet AMD, which can progress fast and can quickly lead to blindness.

The current standard treatment involves monthly injections of agents, which can reduce the chances of developing the abnormal blood vessels, into the back of the eye. Given early enough, it can help to prevent complete loss of vision.

Research suggests eating healthy, with regular intake of fruit, vegetables and nuts in the diet, can reduce disease rates by up to 20 per cent. Also, eating chicken three times a week has been found to reduce the risk by half.

The article is sourced from here.

Age-related Macular Degeneration (AMD) may now be less common than in the past

Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in persons over 65 years of age, a group that is growing in numbers because of increased life expectancy.  AMD affects the center of the retina, the macula, where collection of fluid, fatty deposits, pigmentary changes, and blood, may cause significant visual impairment in about 10% of patients affected by ‘wet’ AMD. The rest 90% suffer from the non-progressive type of AMD, referred to as ‘dry’ AMD, where the features do not progress, and the vision largely remains stable, or deteriorates slowly.

AMD was considered to be more common in the Caucasian (or white) population, though recent studies from India indicate that the prevalence in India may be almost equal to the western population.

In the west, the prevalence was considered to be about 9.4 percent of US patients, based on a 1988-1994 Third National Health and Nutrition Examination Survey. But a recent study indicates the prevalence to be 6.5 percent in patients aged 40 and older, lower than the 9.4 percent reported earlier.

The new study involved 5,533 US adults, aged 40 years of older, who participated in the 2005-2008 National Health and Nutrition Examination Survey. Based on the digital photographs taken of both eyes, the researchers found that 6.5 percent of the participants had signs of some level of AMD, including tiny yellow or white deposits in the retina, pigment changes and deterioration of the retina and surrounding tissue. Less than one percent had the ‘wet’ disease, the advanced stage in which eyesight is more severely affected.

Extrapolating these new figures, an estimated 7.2 million people in the U.S. having any degree of AMD, with about 890,000 of these with advanced ‘wet’ disease. If that rate was correct and remained unchanged, it would mean about 18 million Americans should demonstrate signs of AMD. The new estimates represent a reduction of more than 30 percent in rates of AMD. The reasons for such a decrease in numbers is not very clear. The researchers feel it could reflect changes in time in smoking, diet and use of medications (anti-oxidant vitamins and zinc). A better understanding of the reduction of AMD in older population could help point to new prevention strategies that could lead to further reduction in numbers.

If we extrapolate the same percentage to Indian population, as some studies have indicated that the prevalence of AMD in Indian patients matches those of the western world, we have about 65 million patients in India. 

Source: Archives of Ophthalmology Jan 2011. Click here for the paper.