Wednesday, June 17, 2009

Femtosecond Lasers Proposed for Use in Cataract Surgery

As readers of this Journal know, I’ve been actively following developments in the use of femtosecond (FS) lasers. An old friend of mine, Larry Haimovitch, who contributes to Biomedical Business & Technology, just sent me a copy of his ASCRS 2009 report that was included in the June issue of BB&T. It features what he learned about the three companies proposing the use of FS lasers to perform cataract surgeries.

I requested and received permission from both Larry and the powers-to-be at AHC Media, the publishers of BT&T, to reproduce Larry’s report in its entirety.

Please note that the table numbers shown in the report are those used in the original writeup.

Femtosecond Laser Technology May Mark a Quantum Leap


BB&T Contributing Editor

SAN FRANCISCO– The annual gathering of the American Society of Cataract and Refractive Surgery (ASCRS; Reston, Virginia) was held here this spring as specialists from three key ophthalmic specialties – cataract, refractive and glaucoma surgery – gathered to hear the latest clinical information.

With the economy reeling and laser vision corrections (LASIK) procedures down about 35% from last year, the expectation was that physician attendance would decline. However, the allure of a meeting in the spring in San Francisco, one of the great cities in the world, overcame the economic concerns and physician attendance was at record levels.

It is rare that any medical specialty experiences a revolution in new technology. More typically it is a gradual, evolutionary process. However, in a presentation titled “Initial Clinical Experience with a Femtosecond Laser System in Cataract Surgery” at a session on cataract removal techniques and technology, a potentially disruptive new technology was presented.

The talk, which was delivered to a captivated and standing room audience, was given by Zoltan Nagy, MD, an associate professor at Semmelweiss Medical University in Budapest, Hungary. He presented initial human results with a cataract removal system that has been developed by privately owned, venture capital-backed LenSx (Aliso Viejo, California). The company is describing this new technology as the “next-generation femtosecond laser phaco for refractive cataract surgery.”

Femtosecond (FS) lasers have been widely used in refractive surgery over the past several years. The technology was pioneered by IntraLase (Irvine, California) as a laser-based alternative to manual microkeratomes for the precise creation of a corneal flap prior to LASIK. After a slow start, the technology gained tremendous momentum and in the past couple of years had become the “standard of care” for LASIK procedures. This led to its acquisition in April 2007 by Advanced Medical Optics (AMO; Santa Ana, California) for $850 million.

AMO, which was purchased earlier this year for about $2.8 billion (including assumption of its debt) by Abbott laboratories (Abbott Park, Illinois), is now known as Abbott Medical Optics.

The removal of the cloudy natural lens, commonly referred to as a cataract, with today’s technology is manual and requires several steps. The surgical skill to do a “perfect” removal of the cataract is considerable and the procedure is fraught with risks. These adverse events, which are well-documented in the ophthalmic surgical literature, include posterior capsule rupture, the loss of endothelial cells, macular edema, retinal detachment, compromised zonules (ligaments that hold the lens in place) and perhaps most serious of all, the dreaded infection in the eye (endophthalmitis).

The basic concept behind this new approach is to convert the several manual and multi-steps in today’s cataract removal procedure into one that utilizes laser created, surgeon-controlled precision. The belief is that laser-accuracy will significantly enhance the results that are achieved by the surgeon’s hands.

Nagy outlined the several clinical applications of FS laser technology for the cataract removal procedure and these are shown in Table 4.

As an example, Nagy showed a comparison between the gold standard of today’s approach to cataract removal — ultrasonic phaco-emulsification — with the LenSx device. Phaco, which became popular about 20 years ago, is used in virtually every one of the estimated 3 million cataract procedures performed annually in the U.S. Nagy’s analysis showed that the LenSx system was extremely accurate for capsulotomy diameter, with 100% achieving the desired diameter. Conversely, manually performed procedures attained an accuracy of +/- 0.25 millimeters in only 20% of the time. Nagy also pointed out that the LenSx system required less power and effective phaco time to complete the procedure.

A less obvious but potentially huge benefit of this new technology is that it will provide a better capsulotomy prior to implantation of a “premium” intraocular lens (IOL). Premium IOLs encompass both multifocals and accommodating IOLs and enable most patients to either reduce or eliminate their need for reading glasses after cataract surgery. They are significantly premium-priced compared to standard monofocal IOLs and therefore patient expectations of an excellent outcome are far higher.

In part because most cataract surgeons are unable to perform a “perfect” cataract removal, the results from these premium IOLs has been mediocre. According to Andy Corley, global president of the Bausch & Lomb (B&L; Rochester, New York) Surgical Products division, the modest 5% domestic market penetration of premium IOLs is partially due to the limitations of today’s cataract removal process, which has caused some patients to experience disappointing results.

A list of the myriad potential benefits of a femtosecond laser cataract procedure is displayed in Table 5.

The cataract surgery market is a very large and significant ophthalmic market. According to MarketScope (St. Louis), the global market for cataract equipment and related disposable packs approximated $840 million in 2008, with the U.S. accounting for about one-third of this total.

Replacing manual cataract surgery with a highly precise FS laser could have dramatic impact on the competitive landscape in cataract surgery. Alcon Laboratories (Fort Worth, Texas) dominates this market with an estimated 60% global share. Other key players in the sector are AMO and B&L.

In addition to LenSx, which has assembled an outstanding and experienced management team and highly respected board of directors, two other private companies with VC backing are developing similar femtosecond laser technology.

LensAR (Winter Park, Florida) was founded by Randy Frey, who successfully started and sold his former excimer laser vision correction company, Autonomous Technologies. LensAR has also began its human clinical trials several months ago.

OptiMedica (Santa Clara, California) is expected to be another contender in this fledgling sector. This company has been in business for several years, successfully addressing the retinal market with its Pattern Scan Laser (PASCAL). Its proprietary approach to diabetic retinopathy photocoagulation features laser delivery technology that utilizes a short pulse duration, uniform predictable pulses and a precise pattern spacing. The benefits of the PASCAL technology and are shown in Table 6.

OptiMedica has demonstrated very robust growth in recent years, despite a price point for its laser that is approximately twice as much as conventional single-spot lasers. Clearly, its superior technology has enabled it to gain market share and become a force in this segment.

In addition to leveraging PASCAL into the glaucoma market, OptiMedica is ramping up a major effort to become a key player in the FS cataract market. The company has completed its pre-clinical studies and has recently initiated its human trials. Like LensAR and LenSx, OptiMedica hopes that its FS laser technology will enable it to perform an “all laser” procedure that will ultimately supplant manual cataract extractions.

All three companies will need to complete extensive clinical trials prior to entering the U.S. market but it appears that they will be able to file a 510(k) rather than a full PMA to achieve approvals. Based on their progress to date, it is unlikely that entry in the U.S. market will be attained until late 2010 or early 2011.

Glaucoma, Cornea programs

Before the exhibits opened, ASCRS sponsored two meetings, “Glaucoma Day” and Cornea Day” which provided attendees with the latest clinical, legislative and reimbursement from these two important areas.

Glaucoma is a group of disorders that is characterized by elevated intraocular pressure (IOP) that progressively damages the optic nerve in the eye. Without treatment, this can cause visual disability and eventually result in blindness. It affects an estimated 65 million people worldwide and is the second-leading cause of blindness globally. In the U.S., glaucoma currently afflicts at least 2 million Americans.

The risk of glaucoma increases dramatically with age. People who are 80 years old are nearly seven times more likely to have glaucoma than those who are 50. The U.S. Census Bureau has projected that Americans who are 60 and older will increase in number from 40 million to 76 million by 2025. Given this growth, the incidence of glaucoma is expected to increase to at least 3 million by the year 2020. This disease is typically managed medically, and it is estimated that a panoply of pharmaceuticals account for more than 90% of the treatment costs in the U.S. Glaucoma medications account for roughly 40% of the global market for ophthalmic pharmaceuticals, which exceeds $10 billion annually.

The shortcomings of the medical management of glaucoma are numerous and include:
1) Annual costs that for some patients can exceed $3,000.
2) Inconvenient dosage regimens.
3) Lack of efficacy, that is, the drugs often fail to control the elevated IOP.
4) Myriad side effects, including blurred vision, ocular irritation, pain, headaches, elevated blood pressure and gastrointestinal problems.

The disease is completely pain-free and asymptomatic, causing many patients to stop their regimens while their condition deteriorates. It is estimated that less than half of glaucoma patients are even aware they are afflicted. The result of all these barriers is that the compliance rate for patients on glaucoma medications is abysmally low, well below 50%. And, as one physician wryly observed years ago at an ophthalmic conference “drugs do not work when patients do not take them.”

The drawbacks of glaucoma drugs would appear to provide fertile ground for surgery and/or device based solutions. But, this has not occurred, as the mainstays of devices and surgery — drainage devices such as shunts, and filtration surgery (also known as trabeculectomy or trab) — have had modest efficacy and a relatively high level of adverse effects.

The number of trabs has declined from about 50,000 procedures in the mid-1990s to about 20,000 today. It is a complex surgery, and suffers from numerous adverse effects. The number of shunts has not grown either, as they are relegated as a “last resort” for patients in whom all other modalities have failed.

At this year’s “Glaucoma Day,” an interesting debate on the merits of selective laser trabeculoplasty (SLT) compared to medical management took place. SLT, which generally is regarded as the best form of laser therapy, creates tiny holes in the trabecular meshwork, allowing outflow from within the eye and thus reducing IOP.

Taking the side of promoting SLT was Douglas Rhee, MD, a glaucoma specialist from the Massachusetts Eye & Ear Infirmary (Boston), who provided a host of data to support the use of SLT as a primary option for treating glaucoma. He concluded by saying, “Based on effectiveness, compliance, impact on quality of life, risk comparison and cost, I think we’ve settled the argument of medical therapy over SLT.”

Defending medical management was Anissa Jamil, MD, from Glaucom Consultants North West (Seattle), who said that drugs are very effective for the vast majority of patients and are more reliable than a laser intervention.

During a Q & A period following the formal debate, the moderator asked Dr. Rhee what percentage of his patients actually received SLT as primary therapy. Much to the surprise of the audience, his answer was “less than 1% of the time.” When questioned as to why his treatment regimen so heavily favored drugs, he responded that “my patients expect me to prescribe drugs. This is a cultural expectation.” This rather surprising revelation perhaps best explains why prescription drugs utterly dominate the glaucoma therapy landscape today.

One of the more interesting concepts discussed during the program was the possible use of phacoemulsification (ultrasonic emulsification of the natural lens) as a means to lower IOP. It is estimated that in the U.S. about 10% of patients have co-existing cataracts and glaucoma.

There have been numerous studies over the past decade suggesting that phaco can lower elevated IOP. For example at last year’s ASCRS annual meeting in Chicago, Brooks Poley, MD, presented a retrospective study on nearly 600 eyes of the long-term effect of phaco in normotensive and ocular hypertensive eyes. Poley and colleagues found that the eyes with the highest pre-surgical intraocular pressure showed the biggest improvement. He compared this study with the landmark Ocular Hypertensive Treatment Study (OHTS), which was a prospective trial that examined the use of prescription eye drops in more than 1,600 patients, who were followed for over five years.

In the OHTS trial, 817 patients were treated with glaucoma drops and 819 were not. Of those treated with medication, 4.4% converted to glaucoma, compared to 9.5% converted to glaucoma not treated with drops. This compares unfavorably to the 1.1% the rate of glaucoma conversion after phaco alone.

After his presentation at ASCRS a year ago, Poley was adamant about phaco vs. drugs, saying that “drops don’t solve the problem, they just slow the progression. On the other hand . . . the patients that had ocular hypertension, their pressures went down after surgery for the 10 years of our study. We returned them to a normal status. How many patients treated with drops did that? None. That’s mind-boggling.”

These data were corroborated by Reay Brown, MD, who was inspired to conduct his own study to see how phaco reduces IOP. His data was presented at the March meeting of the American Glaucoma Society (AGS; San Francisco).

Brown and his colleagues examined 83 patients with angle-closure glaucoma or narrow angles who had phaco and IOL implantation. They found that 90% of the patients showed an improvement in pressure. At this year’s ASCRS, Brown said that “if you did a multicenter study and found what we had found in our highest pressure group, the FDA would approve cataract surgery as a treatment for angle-closure glaucoma. In other words, if cataract surgery came in a bottle, the label could say that cataract surgery has been found to be effective in the treatment of angle closure glaucoma.”

Several device companies, many venture-capital backed, are hoping to impact the glaucoma market with innovative devices. Some of these companies exhibited at this year’s ASCRS meeting, while some are too early stage to be making a public presence.

Prominent companies include iScience Interventional (Menlo Park, California), which features an innovative and new category of therapy, which it calls interventional ophthalmology. This encompasses microcatheter-based therapies designed to access a wide range of anatomical structures within the eye to aspirate ocular fluids or deliver sterile ophthalmic solutions to the eye. Specific to glaucoma, iScience features iCat canaloplasty, which is the first and only microcatheter-based procedure that safely reduces intraocular pressure (IOP) and dependence on medications in open-angle glaucoma patients. While specific information is not available, it is believed that this procedure is catching on slowly, due to its steep learning curve.

The company recently announced the closing of a Series “F” venture capital financing raising more than $20 million.

Another VC-backed company is Glaukos (Laguna Hills, California), which has developed an
implantable titanium stent called the iStent. This tiny implant, with a 120 mm lumen, is implanted through a tiny corneal incision and positioned so that aqueous fluid can bypass the clogged area of the eye and flow out through another route called Schlemm’s canal. Glaukos has completed its U.S. pivotal trial and filed its PMA in late 2008. Based upon this filing date, final FDA approval could be received in late 2009 or early 2010. The company’s initial marketing strategy will be to address patients who are undergoing a cataract procedure and who have an elevated IOP. These patients would receive an iStent concomitant to their cataract removal and IOL implant.

Another VC-backed company is Transcend Medical (Menlo Park, California), which has also developed a stent-like device. The company’s describes glaucoma as “ophthalmology’s greatest unmet need” and is hoping to begin its U.S. clinical trial in the near future. Like iStent, Transcend intends to initially address the cataract patient with elevated intraocular. The “perfect” glaucoma device, as described by the company, is shown in Table 7.

About the Author

Larry Haimovitch is president of Haimovitch Medical Technology Consultants, a Mill Valley, CA-based health care consulting firm. His firm specializes in the analysis of the medical device industry, with particular emphasis on the current trends and the future outlook for emerging medical technology. The current areas of emphasis are ophthalmology, interventional medicine (cardiology, electrophysiology, radiology and neuroradiology), urology, ophthalmology, minimally-invasive surgical technologies and medical lasers.

He can be reached at: Larry Haimovitch


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