Sunday, June 21, 2009

CATT Study Update 9: The CATT Study is On Track

I first learned of the possibility of there being a comparative study of Avastin vs. Lucentis in June 2007. I then followed its progress until it finally became a reality in February 2008. The eighth installment traces how it became a reality in the author's own words.

According to an official with the CATT Study, it is on track and proceeding well. The 44 participating centers have recruited over 850 of the called-for 1200 enrollments and anticipate completing patient enrollment by the end of the year.

One-year results from the study are expected to be released in early 2011.

The study began enrolling patients in February 2008.

For more on this historic study, please see my prior Updates listed below:

CATT Study Update
(June 2007)
The first hint that there might be a study.

CATT Study Update 2: Avastin vs. Lucentis – It’s Official!
(September 2007)
Confirmation that the study will get underway.

CATT Study Update 3: Avastin vs. Lucentis – To Get Underway by Year’s End! (September 2007)
Additional information from the September meeting of potential clinical participants. Patient enrollment was supposed to begin by end of 2007 – it was delayed by announcements from Genentech

CATT Study Update 4: Avastin vs. Lucentis Study Ready to Roll
(November 2007)
.UPenn gets its official website up and running.

CATT Study Update 5: First Official Listing of Clinical Trial Sites
(January 2008)
NIH gets its website up and running.

CATT Study Update 6: Official Announcement of Trial Start from NEI
(February 2008)
NEI releases press release announcing official start of the program.

CATT Study Update 7: An Interesting Commentary by Dr. James Folk
(September 2008)
Interesting commentary by Dr. James Folk on the CATT Study.

CATT Study Update 8: The Story Behind The CATT Study
(October 2008)
The story behind the story of how the CATT Study really happened – by the people who made it happen.

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

Friday, June 12, 2009

Menu – Part 13: A Few Updates and Some New Posts

Since the last menu posting, I have added two updates for AMD; a new approach for treating myopia with femtosecond lasers; a list of my private client studies while at Arthur D. Little and with Spectrum Consulting; revisited thermal keratoplasty as a technique for treating myopia; and posted two columns, one on my early contact lens days written for Vision Monday and the second on cast-molded eyeglass lenses, done for Ocular Surgery News.

First, the AMD Updates:

AMD Update 4: Does Visualizing RPE Cells Hold the Key to Understanding AMD?

David Williams and his team at the Center for Visual Sciences at the University of Rochester came up with a method of visualizing RPE cells in the retina in vivo, using adaptive optics. This could be a breakthrough in understanding how drugs and other treatments for AMD effect these important cells in the retina.

AMD Update 5: Emerging Technologies for Treating AMD

In this posting, I summarized some of the important techniques and technologies under development in the treatment of AMD – including the Ellex 2RT retinal regeneration technique; the potential use of stem cells to regenerate healthy retinal tissue by two research efforts; and a recap of the visualization techniques described in AMD Update 4 that could play an important role in showing the changes in RPE cells affected by some of these techniques.

Another Approach to Intrastromal Ablation

Dr. Rupal Shah, responding to my history of ISA*, told me of her research in using a femtosecond laser to form and remove a lenticle in the corneal stroma to correct myopia. She kindly allowed me to reproduce a report she had written on her research, describing her use of the Zeiss-Meditec VisuMax femtosecond laser in the FLEx technique (Femtosecond Lenticle Extraction).

* Intrastromal Ablation: A Technology Whose Time Has Come?

Private Client Studies – Arthur D. Little (1972 - 1994) and Spectrum Consulting (1994 - 2001)

In addition to the hundreds of articles and columns written over my 30-plus years of consulting, I led over 100 client-sponsored studies, covering a variety of topics. In this posting I have listed the titles of most of the reports I either wrote or was in charge of producing.

Thermal Keratoplasty Revisited

In reading about the work being done by John Marshall and his colleagues at King’s College in London, as well as by old friend David Muller with his new company Avedro, in trying to use microwave energy to flatten the cornea to correct myopia, I was reminded that I had written about earlier attempts do the same thing with a variety of thermal techniques. I looked up the column I had written for Ophthalmology Management in October 1990 and decided it was time to reproduce it on the web.

Vision Monday Columns: A Bit of Nostalgia

In searching for the columns I had written for Vision Monday back in the early 1990s, I came across this piece that described my early history with soft contact lenses. Again, I decided that it should be available online for contact lens historians and researchers, so I posted it to my online Journal.

Cast-Molded Eye Glass Lenses

I recently heard from a couple of old friends back from my contact lens days. They are starting a new company, QSpex Technologies, to produce ophthalmic lenses in an eye care professional’s office. I had done some consulting work on in-office plastic lens molding in the early 1990s and had also studied the high-index plastic lens business. I wrote about one of the innovative in-office lens molding companies in an Ocular Surgery News Technical Update column in 1993, and my friends were wondering if I still had a copy of the column. I managed to find it and have reproduced it on my Journal.

Saturday, June 06, 2009

Another Approach to Intrastromal Ablation

I have heard from several people since I wrote about intrastromal ablation. Some believe that incisions in the stroma to affect corneal shape can be done, as described by Dr. Ruiz, and others believe, in the long term, that it will not succeed.

I have just heard from Dr. Rupal Shah from the New Vision Laser Centers in India. She is amongst the latter. However, she has been involved over the past ten months in a lenticle removal technique using the VisuMax Femtosecond laser and has agreed to allow me to reproduce the paper she has written about this procedure in my Journal.

Note: The technique of forming and removing a lenticle from within the cornea is not a new approach. I wrote about developmental work on shaped lenticles by IntraLase in my 2000 AAO Meeting Roundup, that appeared in the January 15, 2001 issue of Ocular Surgery News. However, as has been pointed out by Dr. Shah, the method of planar applanation and the strong scleral suction used by the Intralase could compress the cornea in an unpredictable way, and therefore reduce the chances of success with such a procedure. The curved interface of the VisuMax Femtosecond Laser, as shown below in her article, along with the light corneal suction and low pulse energy of the VisuMax system seems to be necessary to get good results with such a technique.

Here is what Dr. Shah has written:

FLEx®- A New Paradigm for Laser Refractive Surgery

Dr. Rupal Shah, Clinical Director, New Vision Laser Centers-LaseRx

Trokel and Srinivasan first proposed the use of the excimer laser for corneal photoablation in 1983. Corneal Photoablation involves breaking the intermolecular bonds between tissue molecules, thus enabling precise removal of corneal tissue from the surface of the cornea. In 1988, the first sighted eyes were treated for refractive errors with the excimer laser using a procedure known as photorefractive keratectomy (PRK). PRK was performed by first removing the epithelial cells from the cornea, and then ablating a precise lens from the cornea, using repeated pulses of the excimer laser. PRK allows the safe and predictable correction of refractive errors. However, the procedure has certain limitations, particularly because the corneal epithelium is removed during the procedure. There is extreme pain for the first 24 hours after the procedure, visual acuity is impaired for several weeks after the procedure, there is typically a hyperopic shift during the first few weeks after PRK, and finally there is the risk of corneal haze and regression, particularly in the case of large refractive error correction.

To overcome these limitations, a new procedure called Laser In-Situ Keratomeleusis (LASIK) was developed in the early 1990’s. LASIK married the excimer laser with the microkeratome, an instrument designed for lamellar keratectomy. In LASIK, the microkeratome is used to create a hinged flap at about 130 microns depth on the cornea. The flap is then lifted to one side, and subsequently, excimer laser keratectomy is performed on the stromal bed. After the keratectomy is finished, the flap is then replaced, where it sticks back in its original location, initially by surface tension forces, and later by epithelial “glue” around the flap edges. LASIK overcame most of the limitations of PRK, and thus led to a sharp rise in the popularity and appeal of laser vision correction, both for physicians and patients.

It quickly became clear that the Achilles heel of the LASIK procedure is the microkeratome itself. It is prone to error, particularly due to the demands placed on what is a really precise but ultimately mechanical instrument. Free Caps, incomplete flaps, irregular flaps, button-hole flaps, displaced flaps, epithelial abrasions and other complications occur in approximately 1% of all LASIK cases. In most of these cases, it is not surgeon error but a result of malfunction, or mechanical error or other infirmities (related to blade quality, for example). In addition, the microkeratome flap is prone to thickness variation. This increases the risk of corneal ectasia, particularly for large corrections and thin corneas.

The Femtosecond Laser was introduced to overcome these limitations of mechanical microkeratomes. The Femtosecond Laser is capable of delivering laser energy in an extremely short time (femtosecond pulse width) and very tightly focused in space (in the μm regime). It causes photodisruption within corneal tissue, converting a tiny volume of corneal tissue into a gas bubble, with every laser pulse. When millions of such pulses are laid down in a precise plane at a fixed depth around the center of the cornea, it is possible to create a lamellar slice of the cornea. Thus, the Femtosecond Laser can be used to substitute the mechanical microkeratome in the LASIK procedure. Over the last few years, the Femtosecond laser has developed an excellent safety profile, and is increasingly replacing the mechanical instrument as the instrument of choice for making LASIK flaps. It has several advantages over mechanical microkeratomes in this respect-the flap thickness is more precise, there is little or no chance of flap complications such as button-holes, free caps and irregular flaps, and there is less chance of a displacement, since the Femtosecond laser creates a deep gutter in which the flap “fits” back, thus making it less likely that eyelid movements and such will displace the flap from its place. There is also some evidence that flaps made with the Femtosecond Laser induces lesser higher order aberrations in the eye.

While the Femtosecond Laser is very useful for the LASIK procedure, it is not without issues of its own. It means that the surgeon or eye hospital must invest in two rather expensive lasers, i.e. the Femtosecond Laser and the Excimer Laser. The Femtosecond Laser is used to make the flap, while the Excimer Laser is used to ablate the corneal surface to provide the refractive correction. They must pay for the consumables, license fees and maintenance of two lasers. There are also workflow issues related to a two step procedure as well. The patient must at best be moved only from one laser to another while lying on a pivoting patient bed. Due to the two laser configuration extra space is required in the surgery theatre, and the overall procedure time for a complete LASIK procedure is increased. Moreover, now that the Femtosecond Laser has removed the likelihood of flap problems during LASIK, attention is drawn to the limitations of the excimer laser itself. The excimer laser performance is affected by environmental factors such as humidity, there is peripheral energy loss during laser ablation, and the laser ablation is affected by the environment and other factors like corneal hydration, humidity, and the presence of organic vapors.

Recently, Carl Zeiss Meditec has introduced a new Femtosecond Laser into the ophthalmic market, the VisuMax® (Fig 1). Unlike other popular Femtosecond Lasers, like the Intralase (e.g. FS60, iFS) or the Zeimer Femto LDV, the VisuMax® has a curved (as opposed to a planar) contact glass (Fig 2). It has special optics to create a very precise spot focused in the cornea with extremely high accuracy (Fig 3). The scanning and focusing optics of the VisuMax® make it capable of placing the laser spot at a specified 3 dimensional position almost anywhere in the cornea. It is already a popular instrument to make LASIK flaps.

Figure 1. Zeiss-Meditec VisuMax FS Laser

Figure 2. Curved Contact Glass of the VisuMax Laser

Figure 3. Difference Between Conventional Optics and Zeiss Optics

However, the Visumax is also capable of a procedure, which is called Femtosecond Lenticule Extraction (FLEx®). FLEx® first involves the calculation of the kind of lenticule which needs to be removed for correcting the refractive error of the patient. The VisuMax® is then used to lay down pulses within the corneal stroma to form the lenticle, illustrated in the four steps shown in Fig 4. In the first step, the lenticule backside cut is created. The second step creates the lenticle frontside cut. In another step, the VisuMax® is used to lay down pulses which separate the anterior surface (upper cut) of the lenticule from the stroma. The upper cut of the lenticule is extended a fraction of a millimetre beyond the edge required for the lenticule. It thus serves as the flap. In the third step, the flap side cut is then created to make a hinged flap.

Figure 4. Steps in Formation of the Lenticle

The flap is lifted (Fig 5), and the lenticule extracted from the stroma (Fig 6 & 7). The flap is then replaced (Fig 8). The corneal tissue which otherwise would have been ablated off by the excimer laser is removed physically as a whole in the FLEx® procedure (lenticule extraction instead of tissue ablation). Thus, there is no need for an excimer laser for the refractive correction. FLEx® represents the first “All in One” procedure which uses only the Femtosecond laser to complete all steps of the LASIK procedure.

Figure 5. Flap Pushed Aside

Figure 6. Lenticle Lifted

Figure 7. Lenticle Removed

Figure 8. Flap Replaced

FLEx® promises to change the way eye surgeons perform LASIK. It requires investment in only one laser, and paying for only one laser’s consumables and maintenance. It simplifies workflow within the laser suite. There is less total energy incident on the cornea, and there are none of the limitations of excimer lasers, such as the dependence on corneal hydration levels and environmental humidity. It thus represents a possible paradigm shift in the way laser vision correction is carried out.

Since 2006, Dr. Walter Sekundo and Dr. Marcus Blum have performed FLEx® in Germany on more than 250 eyes, with a follow-up period of more than 2 years for some cases. They established the initial feasibility and safety of the procedure. The Femtosecond laser, of course, does not need new safety tests related to laser-tissue interaction, since it is routinely used for making flaps on the cornea. New Vision Laser Centers’ Vadodara Center was the third center in the world to start FLEx® and, moreover, also represented the first high volume site to test reliability and performance for high patient throughput clinical environments. We have recently completed a prospective study on 250 eyes, and have at least one month follow-up for all patients. This is an ongoing pre-commercial study supported by from Carl Zeiss Meditec. All patients were informed that the procedure was relatively new, with very little worldwide experience, and with results that were not very certain. A single surgeon (Dr. Rupal Shah) did all the procedures. All the procedures were done within a 5 month period, starting from August 2008. Complete pre-operative and post-operative testing was done.

We treated myopia and myopic astigmatism, with a high limit of -10 Diopter Spherical Equivalent. Theoretically, there is no limit on the kind of error that could be treated. Practically, the currently available software limits the treatments to -10 Diopters for safety reasons during the approval phase.

The results of the study are quite satisfying. The refractive stability is excellent. There was hardly any change in the refractive status of the patients from the first day onwards. The refractive predictability is also excellent. 96% of all eyes at one month were within a half diopter of the intended correction, which is at least comparable to or superior to all U.S. FDA trials of excimer lasers. There was a very slight tendency towards overcorrection in the low myopes and a very slight under correction for the high myopes. Interestingly, this was all we found in terms of nomogram optimization so far, although we started with a zero nomogram! It demonstrates the capabilities of the FLEx® and shows that FLEx® is more neutral and less sensitive to factors that normally affect excimer laser ablation (e.g. hydration state of the cornea). At three months, more than 85% of all eyes had an uncorrected visual acuity which was the same or better than their preoperative best corrected visual acuity. At three months, more than 90% of eyes had a best corrected visual acuity which was better than or the same as their pre-operative best corrected visual acuity. However, at one month, this figure was only 67%, which indicates that the visual acuity recovers more slowly than with standard LASIK. There were very few adverse events. One eye suffered from DLK, which resolved over time, while we aborted treatment in another patient, because of a suction loss appearing during the procedure. There were hardly any induced wavefront aberrations, and also an excellent topography outcome (Fig 9).

Figure 9. Topography Maps for an Eye with High Myopic Astigmatism

Thus, FLEX® compares very well with standard LASIK on stability, predictability, efficacy and safety. However, the visual acuity at the time being recovers more slowly than with standard LASIK. With an improvement in the laser energy parameters, as well as an improvement in surgical technique, visual recovery improved even during the study itself. However, we continue to do more work to find out the origin of the slower visual recovery, and a correction thereof. We are also doing more studies to study the biomechanical stability of the cornea post FLEx®, since there are good reasons to believe that the biomechanical stability after FLEx® would be better than with standard LASIK.

In conclusion, FLEx® represents a completely new way of doing laser refractive correction. It takes a familiar technology (Femtosecond Laser) with an excellent safety profile, and uses it exclusively for refractive correction, thus eliminating today’s two laser solution. Although studies in terms of hyperopia correction or the implementation of methods to perform retreatments are currently still ongoing, we clearly see FLEx® becoming part of the refractive surgery main stream. Based on our current results, FLEx® seems to represent a paradigm shift on the way in the field of refractive surgery.

Dr. Rupal Shah.

Dr. Shah is the Clinical Director of New Vision Laser Centers, and LaseRx, Institute of Laser Medicine. She practices in both Mumbai and Vadodara, India and is a consultant for Carl Zeiss Meditec.

Dr. Shah can be reached at: Email: Dr. Rupal Shah

Addendum: Since the above article was prepared, Dr. Shah informed me that she has now treated over 350 eyes in this study. Today, with optimization of laser parameters, she gets excellent refractive results, but visual recovery is also nearly similar to standard Femto-LASIK.