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Saturday, 22 June 2013

Eyelid Disorder Controlled with Botulinum Toxin (CME/CE)

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By Ed Susman, Contributing Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerNote that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.Patients with blepharospasm, an involuntary closure of the eyelid caused by spasms of the ocular muscles, can get relief with injections of botulinum toxin.Note that blepharospasm secondary to Parkinson's disease appeared to achieve greater relief with botulinum toxin than patients diagnosed with primary blepharospasm.

SYDNEY -- Patients with blepharospasm, an involuntary closure of the eyelid caused by spasms of the ocular muscles, can get relief with injections of botulinum toxin, researchers found.

Scores on the Jankovic Rating Scale dropped from a baseline of 1.96 to 1.34 (P=0.0018) for all 27 consecutive patients during the 4 week trial, Achinoam Socher, PhD, of Chaim Sheba Medical Center in Tel-Hashomer, Israel, reported here at the International Conference of Parkinson's Disease and Movement Orders.

The patients all scored significantly better on various standard assessment instruments, the research team noted in a poster presentation: Scores on the Blepharospasm Disability Scale decreased from 10.54 to 9.29 (P=0.045)Scores on the Blepharospasm Movement Scale decreased from 5.04 to 4.00 (P=0.039)Scores on the Severity Rating Scale dropped from 1.61 to 1.19 (P=0.013)Scores on the Blepharospasm Disability Index decreased from 5.22 to 4.11 (P=0.147, ns)The blink rate decreased from 30 to 21.86 (P=0.023), largely driven by a reduction in blink rate among those with Parkinson's disease who did not undergo deep brain stimulation (P=0.22)

In addition, 21 of the 27 patients appeared to have achieved improvement in their condition on the Clinician Global Impression of Change outcome measure.

"In this study, we found that botulinum toxin A was an effective treatment for blepharospasm," the researchers reported. They did acknowledge the small numbers of patients in their study. "Larger studies are needed to assess the effect of botulinum toxin A on Parkinson's disease patients in comparison to other patients suffering from blepharospasm."

The researchers stratified patients by types of blepharospasm, identifying 10 with primary disease; 6 with blepharospasm secondary to Parkinson's disease; 6 with Parkinson's disease treated with deep brain stimulation, and 6 with various other types of blepharospasm.

There were 15 men in the study and 12 women. The average age was 65.1 years, and the patients had been diagnosed with blepharospasm for an average of 7.7 years prior to undergoing the treatment at the clinic.

The patients were enrolled consecutively and their outcomes were videotaped and then read by outside neurologists who were unaware of etiology. They were evaluated prior to start of therapy and after 4 weeks of treatment. They received one treatment course during that time frame.

Socher and colleagues from Tel Aviv University determined that patients who had blepharospasm secondary to Parkinson's disease appeared to achieve greater relief of the condition than patients diagnosed with primary blepharospasm.

"Blepharospasm occurs frequently in older individuals and in patients with Parkinson's disease and in dystonia patients. It can arise due to both the disease and from treatments for the disease," said Francesca Morgante, MD, assistant professor of neurology at the University of Messina in Sicily, Italy.

"Botulinum toxin works very well in these patients to control blepharospasm. I use it in my patients," she told MedPage Today.

Socher and Morgante had no disclosures.

Primary source: Movement Disorders Society
Source reference:
Faust-Socher A, et al "Botulium toxin treatment for blepharospasm" MDS 2013.

Friday, 21 June 2013

Procedure Seals Up Corneal Perforation (CME/CE)

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By Todd Neale, Senior Staff Writer, MedPage Today Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerNote that this case series demonstrated acceptable results for temporary repair of perforated corneal ulcers using an autologous fibrin membrane and solid platelet-rich plasma.Be aware that preparation of the membrane and platelet clot is time-consuming and costly.

The combination of an autologous fibrin membrane and platelet-rich plasma clot appears to be safe and effective for treating perforated corneal ulcers, a pilot study showed.

The approach sealed the perforations in all 11 patients included in the study, without any signs of inflammation or infection, according to Jorge Alió, MD, PhD, of Vissum Corporación Oftalmológica in Alicante, Spain, and colleagues.

And at the end of follow-up 90 days after the procedure, there were no relapses or additional perforations, the researchers reported online in JAMA Ophthalmology.

The procedure "is a safe and effective surgical alternative for the closure of corneal perforations," they wrote. "This technique can be considered as a temporary measure until the condition of the cornea permits definite intervention."

They added that its use deserves further study to confirm its place in clinical practice.

Corneal perforations can be caused by trauma or ulcerative disease and "constitute a major ophthalmic emergency necessitating the intervention of corneal surgeons because of the severity and major consequences, such as infection, severe anatomic distortion of the anterior segment of the eye, retinal detachment, phthisis bulbi, and total blindness," according to the researchers.

Various methods are used to treat them, including ocular adhesives, conjunctival flaps, heterologous amniotic membrane transplants, and corneal grafting.

Alió and colleagues explored another alternative -- the combination of a fibrin membrane and a platelet-rich plasma clot, which were both derived using 40 to 60 mL of each of the 11 patients' own blood before the operation. The patients, ranging in age from 23 to 82, had perforations stemming from severe corneal ulcerative diseases.

During the procedure, part of the fibrin membrane was attached to the conjunctiva using nylon stitches. The clot was then placed over the corneal perforation underneath the fibrin membrane, after which the membrane was attached to the rest of conjunctiva. At the end of the procedure, the researchers performed a temporal partial tarsorrhaphy.

The patients received systemic ciprofloxacin 750 mg every 12 hours for 5 days after the operation, as well as ibuprofen 800 mg every 8 hours for 3 days.

Follow-up lasted at least 3 months after the procedure.

The perforations were sealed in all patients, with the fibrin membrane disappearing after the first 3 to 5 days. Finger pressure revealed "acceptable levels of ocular tonus" for all of the patients from postoperative Day two.

None of the patients reported any pain, discomfort, or complications after the operation.

Seven of the patients ultimately underwent definite corneal grafting.

The researchers explained the role the platelet-rich plasma played in the recovery of the patients.

"Platelets play a central role in hemostasis, promoting coagulation in vascular injuries. At the same time, platelets constitute natural reservoirs of growth factors, cell adhesion molecules, and cytokines stored in their alpha granules," they wrote. "Between these growth and mitogenic factors are epidermal growth factors, platelet-derived growth factors, fibroblast growth factors, insulin-like growth factors, and transforming growth factors.

"They also contain important cell adhesion molecules, such as fibrin, fibronectin, and vitronectin, which enhance growth factor activities. The release of these molecules at the site of injury helps initiate and modulate wound healing, thus promoting tissue reparation in both soft and hard tissues.

"We assume that this formulation [used in the study] contains the proper growth factors of blood and platelets, although their concentration was not measured in this study," the investigators wrote.

The primary advantage for the studied approach was the use of autologous material, Alió and colleagues noted, although there is some downside.

"The main disadvantage of this technique would be the cost, especially when compared with the cost of cyanoacrylate glue," they added. "Specialized technicians are needed to prepare the autologous fibrin membrane and [platelet-rich plasma] clot, and the process requires at least 2 hours of laboratory work."

The study was supported in part by a grant from the Spanish Ministry of Science and Innovation.

The authors reported that they had no conflicts of interest.

Todd Neale

Senior Staff Writer

Todd Neale, MedPage Today Staff Writer, got his start in journalism at Audubon Magazine and made a stop in directory publishing before landing at MedPage Today. He received a B.S. in biology from the University of Massachusetts Amherst and an M.A. in journalism from the Science, Health, and Environmental Reporting program at New York University.

Thursday, 20 June 2013

Screening Finds Retinopathy Early in Diabetes (CME/CE)

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By Kristina Fiore, Staff Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerA screening program for diabetic retinopathy eventually diminishes the likelihood of eye disease in patients with diabetes.Point out that the results provide further support to the argument for less frequent monitoring of patients who do not have retinopathy detected on their initial screening.

A screening program for diabetic retinopathy eventually diminished the likelihood of eye disease in patients with diabetes, English researchers found.

There was no significant decline in sight-threatening diabetic retinopathy (STDR) 4 years after the program was implemented among those getting screened for the first time, Alice Forster, PhD, of King's College London, and colleagues reported online in Diabetes Care.

But among patients with no retinopathy on the first screen, the proportion with STDR at the second or later screen fell from 9.2% in 2008 to 3.2% in 2011 (P<0.001), they reported.

"Four years after the introduction of population-based, annual diabetic eye screening, patients who are at lower risk of STDR comprise a greater proportion of the screening population and may be suitable for less frequent screening," they wrote.

Annual retinopathy screening for diabetic patients has been implemented in England since 2008. Its aim is that all patients with diabetes are invited for eye screening within 3 months of their diagnosis.

To estimate the changes in the detection of retinopathy in the first 4 years of the program, Forster and colleagues looked at data on 32,340 patients with type 2 diabetes living in three London boroughs who had at least one screen between 2008 and 2011.

Patients had a total of 87,570 screens during that time. Participants identi?ed as having STDR were referred for ophthalmologic care and treatment, and left the screening program.

The proportion of screens that were first-ever screens fell from 31.3% in 2008 to 15.4% in 2011.

Among the 16,621 patients having their first-ever screens, the frequency of STDR was 7.1% in 2008, falling to 6.4% in 2011, but this was not a significant change.

More patients started getting second or later screens over the study period, with the proportion rising from 68.7% in 2008 to 74.6% in 2011.

For those who didn't have retinopathy at first screen, the rate of STDR on the second or later screen fell from 9.2% in 2008 to 3.2% in 2011 (annual change -1.8%, P<0.001).

And for those who had mild noproliferative retinopathy at first screen, the rate STDR at second screen or later declined from 21.6% in 2008 to 8.4% in 2011 (annual change -2.2%, P<0.001).

The decline in frequency of STDR among patients who had a second or later screen is most likely attributed to the fact that patients with existing STDR had been identified at the first screening, and so were removed from the eligible population.

Thus, lower-risk patients made up a larger fraction of the population for subsequent screening rounds, they wrote.

"Our findings provide further support to the argument for less frequent monitoring of patients who do not have retinopathy detected at [initial] screening," they wrote.

"Screening patients less frequently may increase the cost-effectiveness of diabetes eye screening programs," they concluded, noting that several American groups, particularly insurers, recommend screening every other year for patients with no retinopathy on the original screen.

The study was supported by the South London Health Innovation and Education Cluster and the National Institute for Health Research.

The researchers reported no conflicts of interest.

Kristina Fiore

Staff Writer

Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She's had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine.

Diabetic Teens Show Early Eye Changes (CME/CE)

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By Nancy Walsh, Staff Writer, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerNote that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.In this study of young people with type 2 diabetes, retinopathy was present in a significant number after approximately 5 years of followup.

WASHINGTON -- Retinopathy had already developed within 5 years of the onset of type 2 diabetes in a substantial number of teens with the disease, a researcher reported here.

Among a cohort of patients ages 10 to 17 at baseline, 13.7% had evidence of retinopathy during follow-up of 2 to 6.5 years, according to Lynne L. Levitsky, MD, of Massachusetts General Hospital in Boston, and colleagues.

That's similar to an estimated 15.5% prevalence over 3 years previously identified among adults, Levitsky said at the annual meeting of the Pediatric Endocrine Society.

The finding emerged from the TODAY study, an NIH-funded multicenter intervention trial that included 699 young patients with type 2 diabetes.

"The detailed characterization of the early course of retinopathy in adults with type 2 diabetes has been hindered by the long lag time after diagnosis. We sought to more closely examine the natural history of this in younger patients," Levitsky said.

To do that, the researchers obtained digital fundus photographs for 517 of the TODAY participants. They were classified as having retinopathy if one or more retinal lesions were present in at least one eye.

The types of lesions included microaneurysms, intraretinal hemorrhages, and cotton wool infarcts.

At the time of retinal examination, patients' average age was 18.1. Two-thirds were female, all were overweight or obese, and 80% were minorities.

Mean body mass index (BMI) was 36, and average hemoglobin (Hb) A1c was 7.1%.

All patients with retinopathy had mild nonproliferative changes, and none had macular edema.

Factors that were associated with an increased risk of retinopathy included disease control, age, and duration of disease.

"There was a gradual, significant increase in the prevalence of retinopathy depending on HbA1c such that those in the lowest tertile had a prevalence of retinopathy of 4.7%, rising to 12.4% in the middle tertile and to 25% in those with the most poorly controlled disease," she said.

Compared with the lowest tertile of HbA1c, odds of retinopathy in patients with higher concentrations were: Tertile 2, OR 2.497 (95% CI 1.058 to 5.894)Tertile 3, OR 6.311 (95% CI 2.840 to 14.023)

For patients ages 12 to 16, the prevalence of retinopathy was 5.7%, increasing to 12.4% in those ages 17 to 18, and to 19% for those 19 to 24.

The odds ratio in the oldest group was 3.005 (95% CI 1.270 to 7.112), which was statistically significant, according to Levitsky.

Prevalence was 5.3% among those who had had diabetes for 24 to 49 months, reaching 22.3% for those with disease duration ranging from 67 to 101 months (OR 3.649, 95% CI 1.5 to 8.8).

"But the most interesting finding was that there was no difference in prevalence of retinopathy between patients in the lower ranges of BMI, which was 16.3% in the lowest tertile and 15.6% in the second tertile, and the prevalence was actually lower in the very obese," she said.

For those with a BMI ranging from 37.87 kg/m2 to 68 kg/m2, only 9.3% had retinopathy (OR 3.649, 95% CI 0.377 to 0.810).

"This is known as the obesity paradox, and has been observed in adult retinopathy as well as for adult mortality from heart failure, hypertension, and a number of other conditions," Levitsky said.

But it has not previously been reported in young people, she added.

"We can speculate that extreme insulin resistance in the very obese is in some way protective, but the mechanism is still unknown," she said.

"If we could understand this association, we might separate out the effects of hyperglycemia from the direct effects of insulin or the inflammatory effects of obesity in retinopathy development," she said.

Continuing follow-up of this large cohort of young patients with type 2 diabetes will help define the natural history of the disease and the course of retinopathy, she concluded.

Levitsky has consulted and received support from Novo Nordisk and Eli Lilly.

Primary source: Pediatric Endocrine Society
Source reference:
Levitsky L, et al "Prevalence of retinopathy in young people with type 2 diabetes in the TODAY study" PES 2013; Abstract 3490.2.

Nancy Walsh

Staff Writer

Nancy Walsh has written for various medical publications in the United States and England, including Patient Care, The Practitioner, and the Journal of Respiratory Diseases. She also has contributed numerous essays to several books on history and culture, most recently to The Book of Firsts (Anchor Books, 2010).

Poor Vision Tied to Poor Balance (CME/CE)

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By Michael Smith, North American Correspondent, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerVisual impairment, correctable or not, is associated with poor balance.Note that the findings might partly explain why people with visual impairments have been observed to have a greater risk of falling.

Visual impairment -- correctable or not -- is associated with poor balance, researchers reported.

In a large cross-sectional study, people with visual impairment or uncorrected refractive errors (such as near- or farsightedness) were more likely to lose their balance in a standard test, according to Pradeep Ramulu, MD, PhD, of the Johns Hopkins University School of Medicine, and colleagues.

Self-reported problems with falling were also associated with worse visual impairment, although not with worse uncorrected refractive errors, Ramulu and colleagues reported online in JAMA Ophthalmology.

The findings might partly explain why people with visual impairments have been observed to have a greater risk of falling, Ramulu and colleagues concluded.

"One putative link between vision and falls is poor balance," they noted, but studies evaluating the issue have largely been done in clinic-based samples, where a bias exists because participants have already sought care.

To overcome that issue, they turned to the National Health and Nutrition Examination Surveys for 2001-2002 and 2003-2004, which reflect a representative sample of the U.S. civilian, non-institutionalized population.

In those years, participants underwent visual acuity testing, objective balance testing, and assessment of peripheral neuropathy, the researchers noted, while interviews yielded self-reported medical history and demographic data.

To test balance, participants stood with feet together on a firm or soft foam surface with eyes open or closed. The eyes-closed test on the foam surface, Ramulu and colleagues reported, minimized visual and proprioceptive inputs in order to assess vestibular balance.

The main outcome measure was how long it took for balance to fail in each of the four tests, which were taken in order -- eyes open and then closed, first on a firm surface and then on the soft foam.

Participants also reported any difficulties with falling during the previous year.

Of the 6,785 participants who were 40 or older, 4,590 had complete data on vision, balance, and peripheral neuropathy, including 4,201 with normal vision, 248 with an uncorrected refractive error, and 141 with visual impairment.

On the firm surface, Ramulu and colleagues reported, there was little difference among the groups with eyes closed or open.

However, multivariable analysis found higher rates of balance loss on the foam surface with eyes closed: Among people with vision loss linked to visual impairment. The hazard ratio was 1.7 per unit change in the logarithm of the minimum angle of resolution (logMAR), and was significant at P=0.02.Among those with vision loss associated with an uncorrected refractive error. The hazard ratio was also 1.7 per unit change in the logMAR, but was significant at P=0.04.

Self-reported difficulties with falling were associated with worse visual impairment; the odds ratio was 3.7 per logMAR unit change, which was significant at P=0.03. The odds ratio for falling problems, given an uncorrected refractive error, was similar, but did not reach statistical significance.

The finding that worse balance was associated with poor vision during the eyes-closed foam test was "surprising given that eye closure would be expected to neutralize the effect of decreased vision on balance," Ramulu and colleagues commented.

One possible explanation, they noted, is that reduced input from the eyes weakens the vestibulo-ocular reflex, which maintains the effectiveness of vestibular balance. On the other hand, they added, common degenerative pathways or lower physical activity levels might affect balance and be especially severe among those with visual impairment.

They cautioned that about a third of the NHANES participants did not complete the tests in the study and in general those who did not complete balance testing were older and sicker than those who did, which might underestimate the effects.

The researchers did not report external support for the study. The journal said they made no financial disclosures.

Michael Smith

North American Correspondent

North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.

AMD Remains Leading Cause of Vision Loss (CME/CE)

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By Cole Petrochko, Staff Writer, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerAge-related macular degeneration remained the most common cause of severe visual impairment over a 20-year period.Note that the incidence of visual impairment increased with age.

Age-related macular degeneration (AMD) remained the most common cause of severe visual impairment over a 20-year period, researchers found.

In a study of nearly 5,000 people, of the 184 eyes with severe visual impairment at the patient's first visit and the 256 eyes in which severe visual impairment developed between visits, late age-related macular degeneration was the primary cause in 44% of eyes, followed by branch or central retinal vein occlusion in 8% and cataract in 10%, according to Ronald Klein, MD, of the University of Wisconsin School of Medicine and Public Health in Madison, and colleagues.

Rates of the condition "changed little over the 20 years of the study," they wrote online in the journal Ophthalmology.

However, the overall odds of incidence of visual impairment decreased from the first 5-year period studied to the last by 47% (OR 0.53, 95% CI 0.32 to 0.87, P=0.01), the authors noted.

Little research has been done to track trends in incidence of visual impairment over long periods of time and these details may be important because of an aging U.S. population, "who are most vulnerable to loss of vision resulting from age-related diseases," the investigators wrote in their introduction.

They analyzed 20-year trends in visual impairment and associations with age-related eye diseases and socioeconomic factors as found in the Beaver Dam Eye Study, a population-based cohort study.

The study included a baseline population of 4,926 participants ages 43 to 86 who were followed from 1988 to 1990, 3,721 participants who were followed up from 1993 to 1995, 2,962 participants followed up from 1998 to 2000, 2,375 participants followed up from 2003 to 2005, and 1,913 participants followed up from 2008 to 2010. The main reason for nonparticipation in the follow-up visits was death.

Outcomes included incidence of visual impairment and severe visual impairment. Visual impairment was defined as best-corrected visual acuity of poorer than 20/40 in the better eye among participants whose eyes both measured 20/40 or better at the beginning of a 5-year interval. Severe visual impairment was similarly defined using a measure of 20/200.

Mean participant age from the beginning to the end of the study increased from 62 years at baseline to 75.4. The study population included a great increase in the proportion of participants ages 85 and older, from 1% at baseline to 15% at the end of the fifth 5-year interval.

Of 9,548 person-visits, visual impairment developed in 1.4% (95% CI 1.1% to 1.6%) and severe visual impairment developed in 0.4% (95% CI 0.2% to 0.5%) of person-visits. Incidence was associated with age and ranged from 01.% among patients ages 50 to 54 to 14.6% among patients age 85 and older.

There were no statistically significant interactions between time period and age, nor was there a statistically significant difference in visual impairment between time periods, except with a comparison of periods 1 and 2 with periods 4 and 5, when incidence dropped by nearly half.

Additionally, a significant interaction between age, income, and age-related macular degeneration with incident visual impairment, cataract status, and cataract-age interaction was observed, though data on this interaction were not reported.

Overall incidence of severe visual impairment was associated with age, with no patients ages 50 to 54 and 60 to 64 reporting severe visual impairment, compared with 0.2% of patients ages 70 to 74, 1.6% of patients ages 80 to 84, and 6.9% of patients ages 85 and older. Age and age-related macular degeneration were associated with severe visual impairment incidence.

"Although the decline in incidence of impairment is not statistically significant after adjustment for age-related macular degeneration, the suggestions of a period effect may have public health implications," they concluded. "Age-related macular degeneration remained the leading cause of severe visual impairment in the [study], affecting a similar proportion of eyes throughout the 20 years."

The authors suggested that continued surveillance of visual impairment is needed to monitor changes in incidence and prevalence of impairment and the diseases associated with it in order to derive a cost-benefit analysis of new interventions.

They added that the study was limited by selective survival and visual acuity measures tainted by cognitive decline and comorbidities.

The study was funded by the National Institutes of Health, Research to Prevent Blindness, and the National Eye Institute.

The authors declared no conflicts of interest.

Primary source: Ophthalmology
Source reference:
Klein R, et al "Incidence of visual impairment over a 20-year period" Ophthalmology 2013; DOI: 10.1016/j.ophtha.2013.11.041.

Cole Petrochko

Staff Writer

Cole Petrochko started his journalism career at MedPage Today in 2009, after graduating from New York University with B.A.s in Journalism and Psychology. When not writing for MedPage Today, he blogs about nerd culture, designs websites, and buys and sells collectible card game cards. He is based out of MedPage Today's Little Falls, N.J. Headquarters.

Tuesday, 18 June 2013

IL-1 Blocker Safe, Effective for Dry Eye (CME/CE)

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By Michael Smith, North American Correspondent, MedPage Today Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse PlannerEye drops containing an interleukin-1 antagonist were safe and efficacious for patients with dry eye disease.Note that anakinra, a recombinant interleukin-1 receptor antagonist, is approved to treat rheumatoid arthritis and is used off-label for other conditions in which interleukin-1 plays a role.

Eye drops containing an interleukin-1 antagonist were safe and efficacious for patients with dry eye disease, researchers reported.

Patients suffered no serious adverse events from drops containing anakinra (Kineret) in a 12-week randomized phase I/II trial, according to Reza Dana, MD, of the Massachusetts Eye and Ear Infirmary in Boston, and colleagues.

Compared with a commercial eye drop preparation, the anakinra drops significantly reduced the signs and symptoms of dry eye disease, Dana and colleagues reported online in JAMA Ophthalmology.

Using a topical protein-based biologic agent is "unprecedented" in dry eye disease, the researchers concluded, and the findings offer "proof-of-concept support" that it's efficacious.

Dry eye disease is one of the most common ophthalmic conditions, Dana and colleagues noted, but experts do not completely understand its pathogenesis. However, they added, the cytokine interleukin-1 plays a central role in ocular surface inflammation, and animal studies have shown the benefits of blocking the substance.

Anakinra, a recombinant interleukin-1 receptor antagonist, is approved to treat rheumatoid arthritis and is used off-label for other conditions in which interleukin-1 plays a role.

To see if it would be useful in dry eye disease, Dana and colleagues enrolled 75 patients with the condition and randomly assigned them to one of two doses of anakinra (2.5% and 5%) or to a vehicle eye drop containing 1% carboxymethylcellulose (marketed as Refresh Liquigel). They were instructed to put in one drop three times a day for 12 weeks.

The primary efficacy endpoints of the study included reduction in corneal epitheliopathy as measured by corneal fluorescein staining (CFS), the proportion of patients in whom the CFS cleared from both eyes within 3 minutes, and reduction in symptoms as measured by the Ocular Surface Disease Index.

At 12 weeks, the researchers found: The average reduction in the CFS scores was 46% in the 30 low-dose anakinra patients, 17% in the high-dose group, and 19% in the vehicle group.The difference from baseline was significant only for the low-dose anakinra patients, at P<0.001.The low-dose patients also did better in achieving complete bilateral CFS clearance – 29% versus 7% in the high-dose and vehicle groups. The difference from vehicle was significant at P=0.03.Dry eye symptoms – such as dryness and a burning sensation -- were reduced by 30% in the low-dose anakinra group, by 35% in the high-dose group, and by 5% in the vehicle group. The differences from vehicle were significant at P=0.02 and P=0.01, respectively.

Dana and colleagues weren't able to attribute any serious adverse reactions to the drug. Participants also said all types of discomfort associated with using the drops were more common in the vehicle group.

Finally, the researchers couldn't explain why the higher dose was less effective. One possible explanation is that the lower dose is enough to occupy almost all interleuklin-1 receptors, but Dana and colleagues said it might also be that the 5% dose is less stable.

The study was supported by the NIH. Dana is a co-inventor in a patent application pertaining to use of IL-1 blockers for ophthalmic use. The patent is licensed to Eleven Biotherapeutics; Dana reported holding equity in the company.

Primary source: JAMA Ophthalmology
Source reference:
Amparo F, et al "Topical interleukin 1 receptor antagonist for treatment of dry eye disease: A randomized clinical trial" JAMA Ophthalmol 2013; DOI: 10.1001/jamaophthalmol.2013.195.

Michael Smith

North American Correspondent

Retinal Vessels Leak at High Elevations (CME/CE)

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By Todd Neale, Senior Staff Writer, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerAt high altitude, marked bilateral leakage of peripheral retinal vessels was observed in half of the participants in this small study which completely reversed after descent.The peripheral leakage was not correlated with acute mountain sickness.

Leakage of the retinal vessels is common at high altitudes, although it doesn't appear to be a major contributing cause of acute mountain sickness, researchers found.

Half of healthy volunteers who ascended to nearly 15,000 feet had "marked bilateral leakage of peripheral retinal vessels" confined to the temporal-inferior periphery, according to Florian Gekeler, MD, of the University of Tübingen in Germany, and colleagues.

All evidence of leakage disappeared when the participants returned to a baseline elevation of 1,119 feet, the investigators reported in a research letter in the Journal of the American Medical Association.

"To our knowledge, this finding in the most distal vascular bed of the retina (where tissue hypoxia is most severe) has not been detected in previous studies," they wrote. "Retinal capillary leakage should be considered a part of the spectrum of high-altitude retinopathy."

However, the leakage is unlikely to be a primary cause of acute mountain sickness -- as has been hypothesized -- because the retinal findings were not associated with either scale used to define the condition in the study.

The researchers examined retinal vessel integrity at high altitudes among 14 healthy volunteers (mean age 35; 50% female) using fluorescein angiography with a confocal scanning laser ophthalmoscope.

Retinal examinations were performed at the baseline elevation, again after the participants ascended to an elevation of 14,957 feet within 24 hours, and finally more than 14 days after returning to baseline.

The severity of acute mountain sickness was assessed using the Lake Louise and AMS cerebral (AMS-C) scores, which included both self-reported and objective measurements.

None of the participants had retinal abnormalities at baseline, but 50% developed leakage of the peripheral vessels at high altitude.

Half of the participants also met criteria for acute mountain sickness, although the condition was not associated with retinal vessel leakage. Leakage was seen in 43% of those with and 57% of those without acute mountain sickness.

Leakage also was not associated with peak peripheral oxygen saturation measured by pulse oximeter; the peak saturation was 70.1% in those with and 74.1% in those without leakage (P=0.21).

Only one participant had a retinal hemorrhage, which was not associated with vessel leakage.

The researchers noted that "a comparable hemispherical presentation [of retinal vessel leakage] occurs in zone III of retinopathy of prematurity. Leakage of retinal vessels with vasogenic edema of surrounding tissue suggests impairment in the tight junctions of the retinal capillary endothelial cells, the blood-retinal barrier."

"Whether similar disruptions in the blood-brain barrier cause acute mountain sickness is unknown, but (taking into account the moderate sample size of this study) the lack of correlation between the retinal findings and [the condition] does not support this hypothesis," they wrote.

The study was supported by the Charles S. Houston Award from the Wilderness Medical Society. Heidelberg Engineering provided the confocal scanning laser ophthalmoscope.

Gekeler reported serving as a consultant to Retina Implant AG.

Primary source: Journal of the American Medical Association
Source reference:
Willmann G, et al "Retinal vessel leakage at high altitude" JAMA 2013; 309: 2210-2212.

Todd Neale

Senior Staff Writer