Probably the biggest news from this year’s ARVO Meeting was the presentation of results of the one-year results of the CATT Study, along with its publication in the NEJM.

Previously, I summarized the results from the NEJM that showed equivalency of Avastin and Lucentis, but with the latter having a 40x larger price tag.

During the presentation at ARVO, the study co-authors presented on some of the preliminary safety data that they had collected, but not yet published. This was, perhaps, to refute the charges made by Genentech later in the week that a retrospective study that they had had conducted by a researcher from Johns Hopkins showed that Lucentis was apparently safer than Avastin (surprise!). In the data presented by Drs. Martin and McGovern, there were no major differences in safety. See my writeup:

CATT Update 15: Preliminary Two-Year Safety Data Presented at ARVO

Alimera presented on a subset of their FAME Study using Iluvien to treat DME. In this study, the subset data showed that 34% of patients treated with the low dosage of Iluvien that had had DME for three or more years before treatment, gained three lines of vision after therapy.

This subset of data will be provided to the FDA in response to the CRL letter issued by the FDA in December 2010, in response to the New Drug Application filed last summer.

See: Iluvien Update 2: New Safety and Efficacy Data Presented at ARVO

I have been closely following the exciting news about the Ellex 2RT laser treatment for stopping the progression of dry AMD. Based on the 12-month data presented at ARVO, it appears that we may have a non-invasive treatment that might be able to stop dry AMD in its tracks and prevent the progression into the vision-losing forms of this disease.

See: Ellex 2RT Updated Clinical Results: ARVO 2011

• Prof. B. Randall Hammond from the University of Georgia presented work confirming that levels of lutein and zeaxanthin in the eye have an impact of visual function such as contrast sensitivity, glare disability and photo stress recovery.

• Prof. Bernstein from the Moran Eye Center, University of Utah studies why and how lutein is concentrated to the highest levels in the macula of the eye. His research has identified proteins in the macula that specifically bind lutein and zeaxanthin and their metabolites.  He is now trying to clarify what their role is.  He is also developing ways to image lutein and its carotenoid cousins in a live eye.

• Dr. Mina Chung from the Flaum Eye Institute, University of Rochester discussed the AREDS2 study, in which lutein and zeaxanthin alone or in combination with omega-3 fatty acids is being tested for its effects on AMD.  Preliminary results are due by 2013.

• Edward P. Norkus, Ph.D., from the Montefiore Medical Center in New York studies the efficacy of lutein supplements. His research shows that supplementing with a source of free lutein (as opposed to esterified luten) contained in micro-sized particles greatly improves the amount of lutein that gets into the blood.

All researchers used a branded lutein supplement called FloraGLO®, supplied by Kemin, and marketed exclsively by DSM, both sponsors of the conference.

To see a press release on the conference proceedings, click here.

Risa Schulman, PhD
Expert, Healthy Food and Dietary Supplement Science, Marketing and Regulatory
Tap~Root

Some quick tidbits:

• Lutein and zeaxanthin help to withstand a glare and to recover from a blinding flash of light
• Gene variants that lower xanthophyll (lutein and lycopene) binding proteins in the eyes correlate with AMD risk
• Measurements of carotenoids in skin and serum are not reliable biomarkers of macular pigment optical density

Carotenoid-rich plant food sources identified by several conference speakers were spinach, carrots, spirulina, hybridized yellow corn and bioengineered Golden Rice.

Click here for further details about the conference.

Risa Schulman, PhD
Expert, Healthy Food and Dietary Supplement Science, Marketing and Regulatory
Tap~Root

With the introduction of the Eye Cubed’s new 40MHz Ultrasound Biological Microscope (UBM) mode, practitioners will now be able view various types of pathology at a much higher level of resolution, expanding their anterior diagnostic capabilities when using the system pre-operatively for premium intraocular lens (IOL) sizing.

Click here to read the full release.

Presented in poster sessions at the 2011 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting in San Francisco, the results demonstrated that BEPREVE was statistically superior to placebo in reducing nonocular symptoms associated with allergic conjunctivitis.

Click here for the full press release.

I also attended the 2 day retinal subspecialty meeting which preceded the larger AAO meeting.  Thus, I had 5 days to expand my knowledge.

Most of the congress was focused on technology, especially electronic medical records.  Few discoveries were revealed.  This may be for two reasons:  there is nothing really new going on right now, and/or, the Internet allows such rapid sharing of information, that it is impossible to “wow” anyone at this meeting.  Probably both are true.

With regard to retinal disease, my particular specialty, there is little new, but lots to be excited about.

Avastin and Lucentis continue to be the mainstays of treatment for wet macular degeneration.  There is evidence that the two drugs are similar in clinical efficacy…a notion I support.  It is likely that these types of drugs will be delivered with a sustained release system, thus, obviating the need for repeated intraocular injections.

Ozurdex is now indicated for the treatment of uveitis.  It was originally FDA approved for the treatment of RVO only.  By itself, not earth-shattering, but does make sense clinically.  Sustained release steroids for chronic intraocular inflammation.  Sounds much better.

The highlight of the meeting is the potential for Iluvien to be FDA approved soon.  Iluvien is similar to Ozurdex in that both are injectable intraocular sustained release systems.  Iluvien will be a sustained release system that delivers intraocular steroids for the treatment of diabetic macular edema.   While this is a particularly promising development for patients with diabetic retinopathy, this has larger implications for eye treatment overall.

What Does This Mean?  Illuvien is likely to be the second FDA approved intraocular drug delivery system.  This will be a significant endorsement of drug delivery to the eye.  We are entering a new era of pharmaceutical therapeutics;  sustained release inside the eye.  For now, we are focused on retinal disease.  But soon, very soon, devices will emerge promising better therapeutics for almost any eye condition.

Just think, glaucoma may be treated by such a device.

Randall V. Wong, M.D.
Retina Specialist, Fairfax, Virginia

Over 400 attendees heard ten-minute presentations from twelve small  device companies and thirteen pharmaceutical companies, all developing innovative products aimed at ophthalmic diseases.

I have written up a full review of the meeting, listing the twenty five presenting companies, along with an interview of Dr. Cunningham speaking about the Summit and issues related to ophthalmic drug and device development.

Here is the link.

Here are the highlights:

October 25, 2009

Diabetic macular edema: Steroid implants start to deliver the goods

At yesterday’s (October 24th) Retina Subspecialty Day, Baruch D. Kuppermann, MD, PhD, provided a sneak peek at the reservoir and biodegradable steroid implants that may soon play a role in ocular drug delivery for diabetic macular edema (DME).

Already FDA-approved for uveitis, Bausch & Lomb’s fluocinolone acetonide (Retisert) implant—sutured to the sclera where it can last up to 1,000 days—has also been tested for DME. Clinical trial results showed visual acuity gain, macular edema resolution, and diabetic retinopathy stabilization, said Dr. Kuppermann. But concerns over side effects of cataract and glaucoma led the company not to file for FDA approval for DME.

Alimera Sciences’ Iluvien fluocinolone acetonide reservoir implant contains half as much drug to reduce the side effects seen with Retisert. The Iluvien implant is injected with a 25-gauge needle and floats in the vitreous cavity. Once empty, the nonbiodegradable polymer husk remains in place. Results of the phase 3 FAME trial for DME could be out by the end of this year.

Releasing triamcinolone, SurModics’ I-vation has a corkscrew design that increases the surface area for drug delivery. Screwed into the eye, the implant anchors to the sclera. At 36 months, the phase 1 study has shown macular edema reduction but also cataracts.

Called Ozurdex in the United States and Posurdex elsewhere, Allergan’s dexamethasone drug-delivery system is an injectable biodegradable copolymer implant approved by the FDA in June 2009 for persistent macular edema due to vein occlusion. In phase 2 trials involving DME patients, 35 percent of eyes receiving 700 micrograms improved 10 letters or more by Day 90, compared with 24 percent of those receiving 350 micrograms, and 13 percent in the observation group.

Dr. Kuppermann receives grant support from Alimera Sciences, is a consultant for SurModics and is a consultant and lecturer for Allergan and receives grant support from Allergan.

October 26, 2009

Gene therapy improves vision in patients with severe retinal dystrophy

Jean Bennett, MD, PhD, presented an update on her team’s ongoing development of gene therapy for Leber’s congenital amaurosis. Phase 1 study results for the treatment, the first gene therapy for a nonlethal pediatric disease and for inherited retinal degeneration in adults, were published in the Oct. 24 issue of The Lancet.

A rare autosomal recessive disease with early onset and that causes incurable retinal degeneration, Leber’s congenital amaurosis is often caused by mutations in the RPE65 gene, which is produced in the retinal pigment epithelium, where it helps to generate a vitamin A compound essential for vision. Dr. Bennett and her colleagues have developed a method to deliver a normal version of the RPE65 gene via a subretinal injection of a genetically engineered adeno-associated virus. Twelve patients ranging in age from 8 to 44 were treated in their worse eye in the phase 1 study.

Children responded best to treatment, Dr. Bennett reported, with all of them gaining ambulatory vision. Some patients improved to the extent of no longer being classified as legally blind. In addition, the pupillary light reflex was restored in eyes that were barely responsive before treatment. All patients demonstrated at least a 2-log unit response, and the subjects’ visual fields expanded. Dr. Bennett showed video of the youngest patient successfully completing an obstacle course in the laboratory using his treated eye three months after treatment, but he was unable to complete the course using only his untreated eye. The treatment appears safe and well-tolerated. A phase 3 study of the treatment is scheduled to begin in February.

Dr. Bennett reports no relevant financial disclosures.

Genetics may influence response to ranibizumab in wet AMD patients

A study conducted by Genentech researchers suggests that genetic polymorphisms may influence ranibizumab (Lucentis) treatment outcomes in wet AMD patients. These results, if validated by further research, could help determine future population selection for clinical trials, said Jason Ehrlich, MD, who presented the study results.

The research involved a genome-wide association study on 352 ranibizumab clinical trial subjects. The investigators identified multiple single nucleotide polymorphisms associated with significant differences in mean visual acuity change after 12 months of ranibizumab treatment. Visual acuity gains were smaller in patients with fewer of the beneficial SNPs, Dr. Ehrlich said.

For his presentation, Dr. Ehrlich accepted a Best Paper award at yesterday morning’s Retina Paper session.

Dr. Ehrlich is an employee of Genentech.

Tips for adding premium IOLs to your practice

Kerry D. Solomon, MD, offered advice on strategies for incorporating premium IOLs into a medical practice and introducing the high-technology IOLs to patients.

Here are some of his recommendations:

* Speak slowly and clearly.
* Sit lower than patients and look them in the eye.
* Have a family member present in the room.
* Provide balanced information.
* Remember that you are an educator, not a salesperson.
* Ask patients if they would prefer to perform more of their daily activities without glasses and provide examples of such activities.
* Don’t introduce too much new information during an office visit. If necessary, mail additional information to a patient’s home or make it available on a Web site.
* Make your own recommendations to patients regarding the best treatment for them.
* Make sure your office staff and technicians are knowledgeable about premium IOLs.
* Listen to your staff’s intuition.
* Make sure your patients are educated about their options. Provide enough information for patients to make decisions.
* Ask patients, “Have I answered all of your questions?” and “What can my staff do for you?”
* It’s not about improving your bottom line but about improving your treatment of patients.

Dr. Solomon is a consultant and speaker for AMO, Alcon and Bausch & Lomb, and he receives grant support from AMO and Alcon.

The following excerpts are taken from the Academy Live emails sent out to AAO members during the meetings.

Here are the highlights:

October 23, 2009

Laser technology for cataract surgery

Femtosecond laser technology first captured the attention of refractive surgeons in its role as an alternative to the microkeratome blades used in LASIK. Now, this same technology may change the way cataract surgeons perform anterior capsulotomies. Several companies, including LenSx Lasers, LensAR and OptiMedica, are working on laser technology as an alternative to manual capsulorhexis.

Louis D. Nichamin, MD, discussed initial results from a clinical trial at the APEC Hospital in Mexico City using the LensAR laser system to compare laser capsulotomy to manual capsulorhexis. Fifty-nine eyes of 59 patients underwent the laser capsulotomy, and a control group of 26 contralateral eyes underwent manual capsulorhexis. The mean difference between attempted and achieved capsulotomy diameter was 0.183 + 0.246 mm for the laser group and 0.456 + 0.735 mm for the manual group. Dr. Nichamin said these results indicate laser capsulotomy provides a more accurate and repeatable capsular opening with a more regular shape compared with manual capsulorhexis.

LenSx Lasers has received FDA clearance of its femtosecond laser for anterior capsulotomy during cataract surgery, and Dr. Nichamin said he predicts LensAR’s technology will start human trials in the United States in 2010.

“Without a doubt, laser technology for cataract surgery is a paradigm change for us,” he said. “It has potential not only in creating a perfectly centered and sized capsulotomy, but also making penetrating and nonpenetrating incisions, and in its ability to liquefy the lens.”

The only downside he sees is the cost of the technology. “In this tumultuous economic milieu, where everyone is so concerned on how to pay for medicine, we need to create a delivery model that makes sense,” Dr. Nichamin said. “But this technology is positioned to play an extraordinary role in lens-based surgical operations.”

Dr. Nichamin is a consultant for LensAR Lens Systems.

(Also see Dr. Weitzner’s posting on this subject: Will Femtosecond Laser Technology Revolutionize Cataract Sugery?)

When money and medicine work for a common good

Compelling progress in medical research is often possible only with muscular investment backing, and both of these found enthusiastic supporters at the Ophthalmology Innovation Summit, held yesterday (Thursday)  in San Francisco’s historic Palace Hotel. Cochaired by Emmett T. Cunningham Jr., MD, PhD, MPH, and William J. Link, PhD, the Summit brought together over 400 ophthalmologists, researchers, industry leaders and well-informed investors to discuss the latest ideas in ophthalmic drugs and devices—and the financial resources that could bring them to market.

The Summit—which is one of many satellite events this week—began with ophthalmic start-up developers presenting projects in various stages of development, including:

* a fluid-filled IOL that mimics natural accommodation,
* prokinase inhibitors to treat glaucoma,
* antisense agents and eotaxin inhibitors for diabetic macular edema,
* rapamycin-derived mTOR inhibitors for uveitis, AMD and diabetic eye disease,
* epimacular brachytherapy—as well as newly configured external beam radiotherapy—for AMD,
* ciliary neurotrophic factor for dry AMD,
* an antibacterial film to ensure watertight wounds at the close of surgeries,
* a retinal prosthetic platform using a scanning-dependent external camera attached to a retina-embedded electrode.

Executives from larger companies weighed in with criteria that, for them, makes a new idea worthy of investment. These included proof of concept in animal studies as well as some characteristics that will distinguish the drug or device from competitors’ products. None of the individual investors in the audience thought that a slow economy was a bad time, per se, to make investments, and, in fact, several commented that putting assets on the table now will enhance their potential returns when capital starts flowing again.

Wrapping up the Summit, Richard L. Lindstrom, MD, and Mark S. Blumenkranz, MD, each offered thoughts on what the next five years hold for ophthalmology. Dr. Lindstrom said that glaucoma surgeries may become a safe and more effective first-line alternative to medical management in patients who are regularly non-adherent with, or whose disease is refractory to, topical therapies. He also suggested that efforts to prevent cataractogenesis and presbyopia may someday preempt efforts to treat them.

Dr.  Blumenkranz said that ophthalmologists are learning what oncologists discovered years ago—combination therapy is often superior to monotherapy. He also noted that virtually all retinal diseases conform to one of four avenues of pathogenesis, and that all four of those are in some part VEGF-dependent.

Dr. Cunningham hopes to make the Summit an annual event.

[Editors note: This meeting was held on October 22nd, and featured 25 startup and early technology company presentations, half on devices, and the remainder on pharmaceutical treatments.]

October 24, 2009

Intraoperative wavefront aberrometer provides real-time data

One of the running themes during Refractive Surgery Subspecialty Day has been the low tolerance for small refractive errors in premium intraocular lens patients, with residual astigmatism a particular challenge. Eric D. Donnenfeld, MD, discussed the role of intraoperative limbal relaxing incisions (LRIs) in addressing this concern.

Karl G. Stonecipher, MD, covered the effectiveness of toric lenses for astigmatism, stressing the need for precise intraoperative identification of the correct lens orientation. Small errors in alignment and stability can reduce effectiveness.

Both speakers pointed to the ORange Intraoperative Wavefront Aberrometer, which can guide surgeon decision-making in real time. The device, which fits on the bottom of the surgical microscope, allows the surgeon to take on-demand wavefront images of the eye, and provides refraction data.

“This technology allows for confirmation of refractive outcomes before leaving the OR,” noted William B. Trattler, MD, who is one of 12 phase 3 investigators. “This device is particularly useful for determining the proper IOL power for a post-refractive patient, fine-tuning the toric IOL axis placement, as well as optimizing LRIs. Indeed, if the LRI is undercorrected, the surgeon is alerted and can perform intraoperative enhancements.”

Drs. Donnenfeld and Trattler are consultants for WaveTec Vision Systems. Dr Stonecipher does not have an interest in WaveTec.

ISRS/AAO survey: Laser vision correction volume down by 15 percent in 2009

The annual survey of ISRS/AAO members showed overall laser vision correction volume was down 15 percent among its members, said Richard J. Duffey, MD, who conducts the annual survey Trends in Refractive Surgery in the United States.

This year’s survey was conducted online for the first time and received a response rate of 19.4 percent.

Among the highlights:

* About 25 percent of refractive surgeons have had some form of modern refractive correction, three or four times greater than that of the general population. The rate is even higher among family members: 36 percent of spouses, 19 percent of children and 57 percent of siblings.
* Femtosecond laser use outstripped microkeratome use for the first time in 2009, with 52 percent of surgeons now using a femtosecond laser.
* VISX excimer laser still dominates the laser market with a 58 percent share, but the WaveLight laser system is on the rise with 28 percent of the market.
* Among premium IOLs, the ReStor is still the most popular, implanted in 9 percent of cataract surgery; the Crystalens, 6 percent, and the Tecnis, 4 percent.

Learn more about Dr. Duffey’s study online www.duffeylaser.com

The LX211-02 study was a double-masked, placebo-controlled, dose-ranging study that included 232 patients at 57 centers in North America, Europe and India. These patients had clinically inactive uveitis. Results of this trial showed that LX211 was able to reduce recurrence of inflammation by 50% over placebo at the 0.4 mg/kg twice daily dose (p<0.05)

Results of the LX211-01 study, which investigated LX211 in 218 patients with active, sight-threatening uveitis affecting the posterior segment of the eye. In this study, also a double-masked, placebo-controlled, dose-ranging trial, results showed the LX211 to be statistically significantly superior to placebo at weeks 16 and 24 in amount of vitreous haze.

Treatment with LX211 was well tolerated with moderate and manageable adverse effects.

Read the release here.