At Press Time

Corneal Inlays to Treat Presbyopia

AcuFocus sees large potential for investigational device.

By Jerry Helzner, Senior Editor

■ As middle-aged people begin to experience the visual deficits associated with presbyopia, they normally turn to such corrective measures as bifocals, progressive lenses or a laser procedure that results in monovision. However, if a US clinical trial of the AcuFocus Kamra corneal inlay results in FDA approval, another elective presbyopia-correcting option will be available.

“We will submit our PMA early next year,” says Yari Mitchell, director of medical education and professional relationships for California-based AcuFocus. “We will be submitting two-year data. Most of the patients in the US trial have had their 18-month visit and many have completed 24 months with the device implanted.”

Ms. Mitchell notes that the Kamra inlay is already in commercial use in parts of Europe, Asia and the Middle East, with more than 5,000 of the devices implanted worldwide.

AcuFocus says the Kamra inlay, which is implanted monocularly in the non-dominant eye in a few minutes in a laser suite, is smaller than a contact lens and looks like a black ring. A tiny aperture or hole is in the center of the inlay. The inlay works by blocking unfocused light and allowing only focused light to reach the retina. AcuFocus explains that when light rays are focused, a person may have a wider range of vision at near, intermediate and distance.

Robert P. Rivera, MD, of Sandy, Utah is an ophthalmologist whose practice is participating in the Kamra clinical trial. At age 55, he decided to have the inlay implant to improve his own vision.

A rendering of the Kamra corneal inlay as it looks in the eye. The Kamra inlay is implanted monocularly in the non-dominant eye.

“What I sought was some return of my near vision, for which I had essentially become completely dependent on reading glasses to see anything at all up close,” says Dr. Rivera. “Over the last couple of years, I became more and more presbyopic and couldn't function at all without them. Understand that this is very frustrating for somebody who has essentially lived their entire life as an emmetrope. I would find myself leaving home without thinking to bring along my readers, only to get a cell phone call or text along the way, which I could not see to respond to. After having that experience a hundred times, I decided it was time to act.”

Perhaps even more importantly, Dr. Rivera was seeking a return of his near vision without a compromise in his distance acuity, in which case the AcuFocus made perfect sense to him.

“I'm an avid outdoorsman and do myriad activities which require good depth perception, and monovision or even a modified version of it were not at all solutions for me,” he asserts.

Dr. Rivera notes that the effects of the Kamra inlay are permanent.

“It is a one-size-fits-all inlay that does not have to be enhanced or tweaked as one continues to age,” he explains. “Also, the inlay is removable, so in the unlikely instance of not being satisfied with the implant, the patient could have it removed.”

Ms. Mitchell says that patients who are candidates for the Kamra inlay and who have dry eye should be treated for the dry eye before the inlay is implanted. But she notes that the inlay has been used successfully with patients who had prior LASIK and has also been left in place for some patients during cataract removal.

AcuFocus is currently a one-product company and is financed by venture capital. The company said the cost of the elective Kamra procedure to US patients has not yet been determined but could vary a bit on a case-by-case basis as determined by the patient's individual needs.

Pediatric Eye Study is Largest of its Kind

NIH-funded study fills in gaps on children, especially minorities.

By Rene Luthé, Senior Associate Editor

■ A study of nearly 10,000 US children examines risk factors for vision impairment including age, ethnicity, access to health insurance and exposure to smoking. Funded by the National Institutes of Health, the study found that 4% of preschoolers have myopia, 21% have hyperopia and 10% have astigmatism. Broken down by ethnicity, myopia was more common among African-American children—at 6%—than among Hispanic children (3%) and non-Hispanic white children (1%).

For hyperopia, non-Hispanic white children ranked first, at 25%, with Hispanics at 23% and African-Americans at 17%. Hispanic children ranked first with astigmatism: their rate was 13%, versus 9% for African-Americans and 6% for non-Hispanic white children.

A lack of access to health insurance meant that children were almost three times more likely to have amblyopia as those who did have such access. And smoking received yet another mark against it when the researchers found that children whose mothers smoked during pregnancy had a 1.5 times increased risk of hyperopia and astigmatism, and twice the risk of strabismus, as children whose mothers did not smoke during pregnancy. The study population was approximately 44% African-American, 32% Hispanic and 25% non-Hispanic white. It was evenly split by gender and the children ranged from six months to six years old.

The study also indicates that myopia and astigmatism may resolve with age. While 23% of children ages six months to one year had astigmatism, that rate decreased to 9% for children ages five to six years. Similarly, 6% of children in the six-months to one-year group had myopia, versus 3% for the five to six years group. Hyperopia, on the other hand, became more common as the children aged: 18% of those ages two to three years were hyperopic, with the rate increasing to 23% for children ages five to six years.

Data for pediatric vision, especially that of minority children, had previously been lacking. The study's findings were published online in the journal Ophthalmology and will appear in the print version of the journal in the October and November issues. The study was a collaboration between the Multi-Ethnic Pediatric Eye Disease Study and the Baltimore Pediatric eye Disease Study.

Glaucoma Implant Has Promising Results

In combination with cataract surgery and alone.

■ Ivantis, a California-based developer of intraocular devices designed to treat glaucoma, has announced encouraging six-month results from its multicenter, international Hydrus I study. The results were presented recently by Manfred Tetz, MD, the first European surgeon to implant the Hydrus device.

Ivantis' Hydrus Intracanalicular Implant, roughly the size of an eyelash, is placed through a minimally invasive, microsurgical procedure and is designed to reduce IOP by re-establishing the patient's conventional outflow pathway. The Hydrus device relies on a twofold mechanism of action that creates a relatively large opening through the traditional source of flow blockage, the trabecular meshwork, and then dilates and scaffolds the most critical quadrant of the outflow pathway through which fluid exits the eye—Schlemm's canal.

The Hydrus I study was a prospective clinical trial at six centers that included 69 patients with mild-to-moderate glaucoma and was intended to assess the safety and efficacy of the Hydrus implant in two distinctly different surgical settings.

Twenty-nine patients received the Hydrus device in conjunction with cataract surgery, while 40 patients received the device alone. Six month follow-up included measurements of change in IOP and change of medication burden to patient.

According to Dr. Tetz, in the “combination surgery” group, the patients' average IOP decreased from 21.1 mm Hg before surgery to 15.6 mm Hg at six-month-follow up, and medication burden was reduced from an average of 2.1 to 0.4 eye drops per patient. In the “device-only surgery” group, the average IOP decreased from 21.6 mm Hg before surgery to 16.9 mm Hg at six-month follow-up, and average medication burden was reduced from 1.7 to 0.6 eye drops per patient. Eighty-five percent of patients in the “combination surgery” group and 70% of “device-only surgery” patients were free of medication at follow-up.

“The results were consistent and stable on a per patient basis from three to six months, and variability of effect across patients was low, meaning it's consistent in its effectiveness per patient, and this was true in both groups,” said Dr. Tetz.

Dr. Tetz noted that site-by-site data were “remarkably” consistent, showing reproducibility of outcomes across operators.

Thomas W. Samuelson, MD, glaucoma specialist at Minnesota Eye Consultants in Minneapolis and Medical Monitor of the study, found the Hydrus results “compelling.”

He said the Hydrus implant significantly lowered IOP while also reducing the patient's medication burden. This was true even when the device was implanted as an isolated procedure without coincident cataract surgery.

“Such data is quite important clinically, as we are well aware that cataract surgery alone can lower IOP,” he noted.

In combined procedure protocols, discerning the effect of cataract surgery on IOP from that of a glaucoma implant effect is critical in evaluating these new minimally invasive surgical approaches.

“This study demonstrates that the Hydrus device alone can significantly lower IOP and reduce medications independent of cataract surgery,” Dr. Samuelson concluded.

Research Digest

New & Noteworthy Journal Articles

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Avastin for corneal neovascularization. The use of anti-VEGF drugs in ophthalmology has had its greatest impact in retina, but they've also gained support in neovascular glaucoma and corneal neovascularization. However, the question of how the ophthalmic use of anti-VEGF agents address these conditions remains largely unanswered. To determine better these effects, ophthalmologists in South Korea undertook a study of bevacizumab in corneal neovascularization. They report their findings in the October 2011 issue of Cornea.

Fifteen patients with corneal neovascularization were subconjunctivally injected with 5 mg/0.2 mL bevacizumab, and tear samples were collected at one day, one week and one month. A number of growth factors and cytokines were monitored over these periods, and anterior-segment photographs were taken.

Ten of the 15 patients had improvement in their neovascular lesions, while five eyes showed no response. All the eyes with immunological disease showed improvement, while only half of the eyes that had suffered trauma or infection fared as well. While there were expected decreases in VEGF, there were also significant increases in epidermal growth factor, basic fibroblast growth factor interleukin 1β and tumor necrosis factor α. There were complications in six eyes, but none were severe.

The study authors view the reductions in inflammatory cytokines as particularly interesting, and theorize that increases in the above-mentioned cytokines may signal corneal remodeling but may also leave the patient susceptible to the observed adverse effects. Modulation of these factors, along with VEGF, may form the basis of future treatments for corneal neovascularization.

► Learning effect in dark adaptation testing. Poor dark adaptation is a hallmark of several ophthalmic disorders, and learning effect, i.e., the tendency for increased sensitivity of certain psychophysical vision tests as they are repeated, is a common finding among ophthalmologists. Uncertainty persists regarding learning effect in dark adaptation testing. In the September 2011 Graefe's Archive of Clinical and Experimental Ophthalmology, there is a report on this topic from two doctors at Ohio State University College of Medicine.

To test the learning effect, 16 normal subjects had their dark adaptation measured with a Goldmann-Weekers dark adaptometer and then were retested at an average interval of 1.38 ±0.40 months. The two tests were compared with nonlinear regression using seven dark adaptation parameters.

Fourteen of the patients subjectively reported that their adaptation had worsened on retesting, and both rod and cone adjustment were found, on average, to be less sensitive. However, most of the measurements did not reach statistical significance, even upon further testing to assess the precision of the initial measurements.

Thus, the authors were compelled to conclude that there was no learning effect in the dark adaptation testing that they examined. They chalk up their finding to the reproducibility of the testing, but the paradoxical finding that subjective reporting on adaptation had “worsened” remains to be studied further.

► Noncompliance in glaucoma. To better understand noncompliance in glaucoma patients, scientists in Belgium administered questionnaires on compliance to 663 patients and their ophthalmologists, reporting their results in the September 2011 issue of the Journal of Glaucoma.

The study began with the prospective enrollment of 120 Belgian ophthalmologists and 10 of their patients with glaucoma or ocular hypertension. Questionnaires were then administered to the doctors and their patients, and the responses to both were merged into a single adherence assessment. Several other baseline and treatment-related variables were also recorded to determine any correlations between noncompliance and these data.

A total of 39.2% of the responding patients indicated that they were noncompliant with their treatment plans, while the surveyed ophthalmologists only believed that 2.1% of the patients were noncompliant. Male sex, younger age and higher dose frequency were significantly correlated with worse compliance. Further, patients visiting their ophthalmologists at least every three months were more likely to adhere to their treatment plans.

The study authors conclude that ophthalmologist reporting of noncompliance is not a valid method for measuring this phenomenon, and they urge that ophthalmologists undergo training in adherence measurement and intervention. More frequent visits could also help.

► SD-OCT for glaucoma. Continuing the study of OCT in the evaluation of retinal nerve fiber layer (RNFL) thickness, doctors in Switzerland undertook a comparative study of time-domain and spectral-domain OCT in glaucoma patients and normal controls. Their study appears online in Graefe's Archive of Clinical and Experimental Ophthalmology.

In 50 eyes of 25 normal volunteers and 22 eyes of 11 patients with primary open-angle glaucoma, OCT scans were performed three times by two independent observers, and overall mean RNFL was assessed. Intraobserver repeatability for TD-OCT was good, but it was better with SD-OCT. The coefficient of variance, a measure of variability in different readings, was greater in patients with glaucoma.

The authors conclude that SD-OCT may offer better monitoring of RNFL damage in glaucomatous eyes, owing both to its greater repeatability and also its smaller variance between readings in patients with glaucoma.

Retina Roundup

Timely and Important Retina News of Interest to All Ophthalmologists

Compiled by Andrew E. Mathis, PhD, Medical Editor

► Anti-VEGF injection side effects. As more AMD patients and other patients receive greater numbers of intravitreal injections of anti-VEGF agents, the issue of long-term adverse events related to these injections and the agents themselves remains. The September 2011 issue of Retina includes a review of the literature on these injections by a team of doctors in the Netherlands.

The team included 278 articles on intravitreal injections of ranibizumab, bevacizumab and pegaptanib sodium, culled from searches of four medical research databases. Compiling all the adverse effects listed in the articles, the team found that serious ocular events and adverse systemic side effects occurred less commonly than once per 100 injections, while mild ocular adverse effects occurred at a rate of less than five per 100 injections.

Among these adverse events, endophthalmitis occurred at rates of 0.04 and 0.05 per 100 injections with ranibizumab and bevacizumab, respectively, with more than double that rate (0.11 per 100) occurring with pegaptanib. Retinal and retinal pigment epithelium detachments and tears had varying rates among the three drugs, with the best record for detachments (0.01 per 100) being seen for ranibizumab and the best rate for RPE tears (<0.02 per 100) for pegaptanib. Pegaptanib was associated with a comparatively higher rate (0.34 per 100) of cardiovascular events.

The authors note that pegaptanib was associated with more side effects than reported by the FDA for that drug, while bevacizumab's side effect rate matched those of ranibizumab, which were in line with the FDA. The authors are confident in suggesting that continued off-label use of bevacizumab is not dangerous, and they also state that while the rates of side effects for pegaptanib were higher, the overall rates were still very low.

► Speaking of AMD. Thanks to the AREDS study of vitamins and supplements to prevent AMD, data from a very large (2,846-patient) cohort of AMD patients is available for analysis. Retinal physicians collaborating among several centers attempted to design a risk-assessment model for advanced AMD using these data, reporting their findings online at Archives of Ophthalmology.

The authors identified several independent variables using their model, including age, smoking history, family history of AMD and two previously identified genetic variations. Several other hypothesized factors were not borne out with the model, including other genetic markers, AMD in a fellow eye and very large drusen. The model was externally validated.

Near the conclusion of the article, a figure provides a blank version of the risk calculation form, with spaces provided for demographic/environment factors, retinal examination findings, and genotype (if known). The article can be used to calculate the estimated number of years until advanced AMD develops, as well as percentage risks of advanced AMD, neovascularization, and geographic atrophy. For a population similar to that included in the AREDS study, the authors of the Archives article suspect their risk-assessment model will be of tremendous use.

► Why does retinal detachment surgery fail? To determine the preoperative factors predisposing patients to surgical failure, surgeons in the United Kingdom collaborated on a large, prospective trial of more than 600 patients. They report their findings in the September 2011 issue of the British Journal of Ophthalmology.

Of 615 patients, 96 individuals had redetachments and 37 had surgical failures due to proliferative vitreoretinopathy. Failures occurred despite the entire cohort being administered low-weight heparin and 5-fluorouracil to protect against PVR.

Surgical failure was directly related to the number of retinal quadrants that had detached. Further, repeated surgery for retinal detachment demonstrated a trend toward reduced visual acuity at six months, and PVR was associated with significant deterioration in VA. Notably, neither inferior retinal breaks nor previous phacoemulsification were identified as risk factors. OM