Quick Hits

One surgeon’s DMEK learning curve

Making the transition from DSAEK.

By Jerry Helzner, Senior Editor

As more corneal transplant surgeons make the transition to Descemet’s membrane endothelial keratoplasty (DMEK) from Descemet’s stripping automated endothelial keratoplasty (DSAEK) as their preferred technique for treating Fuchs’ dystrophy and bullous keratopathy, much is being made of the difficult learning curve involved in mastering this procedure. The primary challenges are in successfully first stripping, and then manipulating, the thin and fragile donor tissue used in DMEK.

In an effort to document one surgeon’s initial experience with DMEK, Lloyd M. Cuzzo, MD, and Jennifer C. Lee, MD, of the USC Eye Institute of the University of Southern California, recorded the details of the first 35 DMEK cases performed by Neda Shamie, MD, associate professor at the institution. They presented their findings at ARVO 2014 in Orlando, Fla.

The first group of 35 consecutive eyes encompassed 20 with Fuchs’ endothelial dystrophy, 14 with pseudophakic bullous keratopathy and one with a Descemet’s membrane tear. Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density, and the range of intra- and postoperative complications.

The researchers were prepared to report on such potential early complications as iatrogenic primary graft failure (IPGF), graft separation or detachment requiring rebubbling, pupillary block, reversed graft positioning and other complications. But of the first 35 DMEK patients, five eyes required one rebubbling to obtain graft adhesion.

No IPGF, upside down graft, nor pupillary block occurred. Average pre-stripping endothelial cell count before DMEK was 2,581 cells mm² compared to 2,540 cells mm² six months postoperatively. Average BCVA was 20/25 at six months after DMEK compared to 20/60 before surgery. The researchers concluded that during a surgeon’s learning curve in DMEK, acceptable results can be achieved with low complication rates and excellent visual outcomes.

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Regeneron partners with Avalanche on gene therapy

Moving the target from chronic disease to a cure?

By Jerry Helzner, Senior Editor

Regeneron Pharmaceuticals and privately owned Avalanche Biotechnologies have formed a broadly based collaboration to discover, develop and commercialize novel gene therapy products for the treatment of eye diseases. The partnership may signal that Regeneron, the developer of Eylea (aflibercept), now views a range of retinal diseases as potentially curable rather than chronic.

“We feel that the eye is one of the most attractive places to do gene therapy,” said George Yancopoulos, MD, PhD, Regeneron’s chief scientific officer. “The advantages include the ability to apply the therapy locally, deliver the gene therapy to the specific cells of interest, and directly observe its effect. Ultimately, the goal would be to have long-lasting effects or even cures.”

The new collaboration covers novel gene therapy vectors and proprietary molecules, discovered jointly by Avalanche (Menlo Park, CA) and Regeneron (Tarrytown, NY), and developed using the Avalanche Ocular BioFactor, an adeno-associated virus (AAV)-based, proprietary, next-generation platform for the discovery and development of gene therapy vectors for ophthalmology.

This rendering shows how Avalanche’s therapeutic protein binds to VEGF to eliminate proliferating blood vessels.

Avalanche will receive an up-front cash payment, contingent payments of up to $640 million based on certain development and regulatory milestones, plus a royalty on worldwide sales. The collaboration covers up to eight therapeutic targets. Regeneron will have exclusive worldwide rights for each product it moves forward in clinical development. Regeneron also has a time-limited right of first negotiation for certain rights to AVA-101, the therapeutic protein targeting vascular endothelial growth factor, upon completion of the phase 2a trial.

Shire to file NDA for dry eye drug

Following a meeting with the FDA, Shire plc, of Lexington, Mass., says it intends to submit a New Drug Application (NDA) next year for lifitegrast (5% ophthalmic solution) as a treatment for dry eye.

Parallel to preparing the NDA, Shire says it will also evaluate the need for gathering additional clinical data to support of the US and potential international regulatory submissions.

Lifitegrast, a small-molecule integrin antagonist in a preservative-free topical solution, has been studied in 1,800 patients. Shire says Lifitegrast is believed to work by reducing inflammation by inhibiting lymphocyte function-associated antigen 1 (LFA-1) and preventing its binding to intercellular adhesion molecule-1 (ICAM-1) that influences T-cell activation and cytokine release.

Dealing with retained lens fragments after phaco

Study compares immediate vs. delayed vitrectomy.

The presence of intravitreal retained lens (RLF) fragments following phacoemulsification is a rare but potentially serious complication. Researchers led by Steven J. Ryder, MD, of Weill Cornell Medical College, New York, conducted a retrospective, nonrandomized study to determine whether any differences in outcomes could be found in a comparison of immediate (same setting) pars plana vitrectomy and delayed vitrectomy.

Researchers began by conducting a retrospective, nonrandomized study of all patients undergoing pars plana vitrectomy (PPV) for RLF following cataract surgery from 2007 to 2012. Outcomes included visual acuity and the development of various complications such as retinal detachment, elevated IOP greater than 30 mm Hg and cystoid macular edema. A multivariate analysis adjusted for potentially confounding variables such as age and preoperative visual acuity.

Twenty-eight consecutive eyes (13 same setting, 15 delayed setting) were included in the analysis. Patients in the same setting group on average were older than in the delayed one (81 vs. 73 years). No other preoperative differences existed between groups (axial length, preoperative vision, IOP).

Mean time to PPV in the delayed group was 26.6 days. Mean follow up time was 363 days (same setting) and 643 days (delayed). At the most recent follow up, no significant differences existed in mean vision between the same setting (logMAR 0.42) and delayed group (logMAR 0.57).

Although the researchers found a trend for eyes in the same setting group to obtain good vision (20/40 or better) faster, a higher percentage of eyes in the delayed group obtained good vision at the most recent follow up (66.7% vs 23.1%). More eyes in the delayed group had IOP measured at greater than 30 mm Hg at any point. No significant differences were found between groups in any other complications, such as retinal detachment, during follow-up.

The researchers concluded same-setting PPV offered no significant visual acuity advantage over delayed PPV among patients with retained lens fragments in their cohort. Fewer eyes in the same-setting group ever had IOP of 30 mm Hg or greater during follow up, while no other complication differences were seen between groups.

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Question unnecessary tests and procedures

tips of the month

Choosing Wisely, an initiative of the American Board of Internal Medicine Foundation, aims to encouraging physicians and patients to think and talk about medical tests and procedures that may be unnecessary, and in some instances can cause harm. Specialty societies, including the American Academy of Ophthalmology, have created lists of “Things Physicians and Patients Should Question.” The AAO’s list comprises these five items:

1. Don’t perform preoperative medical tests for eye surgery unless there are specific medical indications.

2. Don’t routinely order imaging tests for patients without symptoms or signs of significant eye disease.

3. Don’t order antibiotics for adenoviral conjunctivitis.

4. Don’t routinely provide antibiotics before or after intravitreal injections.

5. Don’t place punctal plugs for mild dry eye before trying other medical treatments.

More information is available at www.choosingwisely.org.

New physician compensation rises

The environment for recruiting and retaining physicians continues to be competitive and has led to higher first-year median guaranteed compensation for newly hired doctors. Primary-care physicians reported $186,475 in median first-year guaranteed compensation, and specialists reported $260,000 in a new practice, according to the 2014 Physician Placement Starting Salary Survey by the Medical Group Management Association (MGMA).

Some practices also have enhanced their benefits to recruit physicians. Sixty percent of physicians hired in new practices reported receiving signing bonuses, and 72% received relocation packages.

In 2013, respondents to MGMA research predicted a slight increase in their practice’s patient population due to more people getting insurance through the exchanges and impending physician shortages.

“With the initial uncertainty surrounding how ACA insurance exchanges would impact health-care organizations, medical practices were very savvy in planning ahead and anticipating how potential changes to their population may affect their ability to accommodate patients,” MGMA analyst Laura Palmer said.

Quality of life with keratoconus is ‘fair’

Young adults encounter daily challenges.

Researchers at the Hospital de la Luz in Mexico set out to determine how keratoconus patients viewed their quality of life. They gave a VFQ-25 self-assessment questionnaire to 38 patients (19 women) diagnosed with keratoconus at the hospital between May and October 2013. After reviewing the questionnaires, they concluded that the young adults who make up the majority of those afflicted with the disease tend to have a fair quality of life burdened by problems they encounter in daily living.

The results, presented at ARVO 2014 in Orlando, Fla., were obtained through multiple-choice answers regarding the vision-related problems in their daily tasks. The researchers divided the groups according to questionnaire score as having good, fair or poor quality of life.

The researchers used the Amsler-Krumeich scale to classify keratoconus severity. Most patients (90%) were classified with moderate severity, while the remainder (10%) had severe keratoconus. Median age of the patients was 26 years (range 13-58 years), with an increased incidence in patients 21- and 30-years-old, with no predominance of sex.

Results from the VFQ-25 questionnaire showed overall mild problems with near and distance activity, role difficulties, mental health and ocular pain. The effect on driving was the most significant problem, with 53% of respondents specifically citing it.

“We found a fair life quality in most patients with moderate keratoconus, which allows them to perform their activities of daily living, but without obtaining total satisfaction,” the researchers concluded. Young adults “require the highest possible visual acuity, so that the control of quality of life they expect is of equal importance as the clinical monitoring and management of these patients.”

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