GLG News by Sanjay Rao, MD

Implications: This article describes the perspective of a retinal specialist on the Avastin/Lucentis controversy.  In mid-February the National Institutes of Health announced that it would conduct a head to head trial comparing the effectiveness of Lucentis and Avastin for the treatment of wet  age related macular degeneration.  Both drugs are made by Genentech, but only Lucentis is FDA-approved.  In their current dosing regimens, the cost of treatment with Avastin is only between 1-3% of the cost of Lucentis.  Current projections suggest that the cost to treat the half million patients in the U.S. with wet macular degeneration is greater than $10 billion per year.  $10 billion is more than the entire Medicare budge for all of ophthalmology.t

Analysis: Because most macular degeneration patients are over 65, any pricing changes in medications in likely to have a major impact on Medicare.  Moreover, anything that impacts the Medicare ophthalmology budget is likely to affect reimbursment for the other major procedures in ophthalmology such as cataract surgery.  Already, Medicare reimbursement for cataract surgery is below $700.  Any further reduction may begin to affect procedure volumes which have been growing at 7-8% per year.      

The results of the Avastin/Lucentis trial will probably be available in early to mid 2008.  While many expect Avastin to be equally effective, how these drugs are priced will ultimately have a major impact on the Medicare budget.  Genentech may be forced to lower their prices for Lucentis or change how Avastin is currently provided to pharmacies.  Either way, the Medicare ophthalmology budget is in for a rough ride.  And that rough ride will certainly impact reimbursement for other eye-related procedures and potentially eye procedure volumes.

Implications: This New York Times article describes many of the vision correction options available to individuals with presbyopia.  Because of the growing population of baby boomers, there is significant public interest in options that allow individuals freedom from reading glasses.  Multifocal contact lenses which provide distance, intermediate, and near vision correction are discussed.  Also discussed is surgical correction of presbyopia.  Current options for surgical correction of presbyopia include multifocal intraocular lenses, conductive keratoplasty, and accommodative intraocular lenses.  In clinical trials for presbyopia are corneal inlays, scleral expansion bands, and LASIK for presbyopia.

Analysis: The quality of vision achieved with multifocal contact lenses continues to improve.  And for many baby boomers it has become an excellent option for vision correction.  With that said, multifocal contacts are unlikely to have a significant effect on the market for presbyopic IOLs.  Patients who are having presbyopic IOLs often have cataracts or are looking for visual freedom from glasses or contact lenses.  Alternatively, an individual who sees an optometrist looking to get rid of their reading glasses or bifocals in unlikely to be encouraged to look into surgical options.  These two markets will continue to grow as boomers look for more visual freedom, but they are unlikely to threaten each other significantly.

Implications: This article presents the results of a study comparing standard phacoemulsification to Aqualase.  Complication rates were similar between the two procedures.  The 63 patient study looked in particular at foveal thickening after surgery.  While no statistical significance was demonstrated, the study showed a trend towards less foveal thickening in the Aqualase group for diabetics.  Foveal thickening can be a marker for a common complication after cataract surgery, cystoid macular edema.  Unfortunately, the clinical significance of foveal thickening is often unpredictable.

Analysis: This study certainly does not provide a convincing argument for Aqualase for several reasons.  First, no statistical significance was achieved so it is very difficult to assume that Aqualase causes less foveal thickening.  Second, there is no consensus on what level of foveal thickening is clinically significant.  From a clinical perspective, Aqualase does have its drawbacks particularly in that it is certainly less efficient or not usable for more dense cataracts.  While the technology is worth utilizing for refractive cataract surgery, it is unlikely that it will become the technology of choice for most cataract surgery.

Implications: The early results of a new corneal inlay (PresbyLens, ReVision Optics) are presented.  A corneal inlay is placed underneath a LASIK corneal flap in the non-dominant eye to correct presbyopia.  This version of a corneal inlay is 1.5mm in diameter.  The outcomes of 15 patients showed good uncorrected distance and near vision with 86% with 20/40 or better uncorrected near vision and 64% with 20/40 or better uncorrected distance vision.

Analysis: This version of a corneal inlay joins several other corneal inlays currently in clinical trials.  Inlays from AcuFocus and Biovision incorporate a pinhole to improve near vision by increasing depth of field.  On first glance the early clinical results of the Presbylens corneal inlay do not seem impressive compared to those of AcuFocus.  The AcuFocus corneal inlay began clinical trials in February, 2006.  The Acufocus results on a cohort of 34 patients from Istanbul presented before the clinical trials began showed most patients achieving 20/20 vision and J1 reading vision.  Of note, Bausch and Lomb has made a major investment in Acufocus and is betting that this inlay will become the treatment of choice.

With a potential market of 141 million, the entry of another corneal inlay into the presbyopia treatment area speaks to the fact that this area is very hot.  When compared to other presbyobia treatments, corneal inlays have several advantages including reversibility, limited decrease in distance vision, and ease of implantation.  While the Presbylens may not be a winner in this area, corneal inlays are a treatment option certainly worth watching. 

Implications: The recent approval of the aspheric version of the Restor multifocal intraocular lens is positive as most surgeons already understand the value of aspheric optics.  As shown with monofocal aspheric lenses, such as the Alcon IQ, Advanced Medical Optics' Tecnis, and Bausch and Lomb's Sofport, aspheric lenses improve visual functioning and contrast sensitivity.  With the incorporation of aspheric optics in Alcon's Restor platform, Restor becomes the first and only aspheric presbyopia-correcting IOL.  The data that led to the FDA approval has not been released.

Analysis: The FDA approval of the Restor aspheric will further solidify Alcon as the market leader in this area and serves as a significant blow to Advanced Medical Optics.  AMO by all accounts had the headstart in this area as they had already released their aspheric multifocal (Tecnis multifocal) in Europe.  Unfortunately, the approval of the Tecnis multifocal in the U.S. has been delayed as the FDA has asked for more data to be submitted by AMO.  It is possible the Tecnis multifocal will not be approved in the U.S. until late 2008.

Prior to the approval of it aspheric Restor, Alcon was already the market leader in multifocals.  AMO was hoping that the Tecnis multifocal would strengthen its position.  But with the approval of the Restor and its own difficulties with Tecnis, AMO finds itself in a chasing Alcon.  It appears that Alcon's position of strength in this area will only grow.

Implications: The article describes some of the legal concerns in billing for presbyopia-correcting IOLs.  The ruling by the CMS (Centers for Medicaid and Medicare Services) in 2005 that essentially allowed surgeons to charge patients an additional out-of-pocket cost related to the implantation of these lenses has fueled the steady growth of these lenses.  However, the ruling is now being scrutinized carefully.  One significant issue is whether the implantation of these lenses actually involves additional work to justify the out-of-pocket cost.  If there is no additional work beyond what is involved with standard cataract surgery, surgeons may not bill the patient for services that are covered by Medicare as part of the cataract surgery procedure.  Despite the CMS ruling, it appears that there are still significant issues surrounding the billing for these lenses.

Analysis: The steady increase in utilization of presbyopia-correcting IOLs may be challenged if CMS scrutinizes its ruling.  Currently, the implantation of these deluxe lenses is about only 4-5% of the overall lenses implanted but is a a significant source of revenue for many practices.  Indeed, some refractive/cataract practices are implanting as many as 20%.  If CMS forces surgeons to document and justify the "additional work", the utilization of these lenses may be affected.  The problem is however that the patients now have knowledge of these lenses as an option and limiting their access to them would prove problematic.  Another issue is how the CMS scrutiny may affect future development.  Many companies are currently working on different versions of presbyopia-correcting lenses. Any change in how CMS views these lenses would have a chilling effect on development.  Overall, increased scrutiny will probably force surgeons to be more careful about documentation but should not affect utilization.

Implications: The Phase III Trials of Xibrom showed excellent efficacy in the treatment of post cataract surgery pain and inflammation.  The trial involved 500 cataract patients and is important in that it demonstrates that a once-a-day formulation is effacacious in treating patients post-operatively.  Xibrom was previously formulated and approved to be dosed twice-a-day in the post-operative setting.  The once-a-day formulation compares very favorably to other anti-inflammatories used in the post-operative setting which are usually dosed four times day

Analysis: While the phase III results are certainly positive with Xibrom, there are significant barriers that may limit its market share moving forward.  First, the post-operative eye pharmaceutical area is dominated by Alcon and Allergan because they have the full line of post-operative eyedrops.  These include an antibiotic, a steroid, and a nonsteroidal anti-inflammatory.  Because both companies have this full line up they are able to bundle their products together in a post-operative kits for physicians.  This presents a significant barrier to entry for Ista because they do not have an antibiotic.  Second, their may be some skepticism among eye surgeons that a once-a-day regimen will work effectively for their patients.  Post-operative inflammation varies among patients due to age, race, post-operative technique, etc.  Most surgeons are used to tailoring their post-operative regimen based on the patient/surgical characteristics.  With that said, I would expect Xibrom to hit the market in 2008 and gain market share due to its convenience.  But Alcon and Allergan will fight hard to make sure the existing barriers to entry remain high.

Implications: This article describes the Phase II trial results of the PreView Scleral Implants (ReFocus Group Inc.) for the treatment of presbyopia.  Presbyopia is the natural age related loss of accommodation, or near focusing ability that leads to people wearing reading glasses. Scleral implants alter the configuration of the eye around the lens equator allowing some restoration of accommodation.  The Phase I trials with scleral implants were of limited success.  The Phase II Trials utilized an automated tunneling device designed to ease the surgical procedure.  As well, changes were made to the scleral implants enhancing stability.  The six month postoperative data shows that 80% of patients had 20/40 vision at near without significant loss of distance vision.  Phase III trials began enrolling in summer of 2006 and have currently enrolled more than 150 eyes. 

Analysis: While the visual results of scleral implants appear to be promising, there are still significant questions about the safety and the difficulty of this procedure.  When evaluating treatments for presbyopia, several important issues exist including quality of near vision, preservation of distance vision, reversibility of the procedure, technical difficulty of the procedure, and overall safety of the procedure.  When compared to the other available options for presbyopia, scleral implants are significantly more invasive and have a higher potential for complications.  This is due to the fact that the implants have to be placed in the sclera which can lead to inflammation and erosion. Given the other less invasive presbyopia options available such as multifocal lenses, intracorneal lenses, conductive keratoplasty, and multifocal LASIK, it is unlikely that a more invasive procedure is likely to catch on.

Implications: AMO's acquisition of Intralase for $808 million has been seen by most financial industry analysts as positive.  Most financial analysts point to the improved diversification and strengthening of AMO's refractive portfolio which includes intraocular lenses, phacoemulsification equipment, VISX excimer lasers, and now Intralase femtosecond lasers.

Analysis: AMO's acquisition should be positive for clinicians for several reasons.  First, the acquisition should allow faster integration of excimer and femtosecond technology.  Currently, femtosecond lasers which perform the first step in LASIK and excimer lasers which perform the second step are housed in separate units.  Moreover, these units have to be housed in separate surgical rooms because of their size.  Because VISX and Intralase will be partnered under AMO, we should expect that these technologies will finally be housed in a single unit.  The improved efficiency of a single unit laser system should encourage the purchase of new Intralase lasers particularly by efficiency conscious corporate laser centers. 

Secondly, AMO's acquisition should further cement AMO's position as a one stop stop for refractive technology because their portfolio will include excimer lasers, femtosecond lasers, microkeratomes, as well as multifocal intraocular lenses.  This should allow AMO to bundle refractive technology packages together for surgeons. 

Third, AMO's acquisition will allow the company to entire the corneal surgery market.  Intralase has developed corneal transplant technology which has significant advantages over existing technology. 

Implications: This article describes the results of a "newer" refractive surgery technique known as sub-Bowman's keratomileusis or SBK.  SBK involves creating a corneal flap just below the epithelial layer of the cornea.  This flap is approximately 60-70 microns in thickness compared to a traditional LASIK flap which is approximately 120-160 microns.  

This prospective, randomized, contralateral eye study compared SBK and surface ablation (PRK) in 100 eyes of 50 patients.  The eyes that underwent SBK showed decreased postoperative dry eye, lower corneal sensitivity, similar higher-order aberrations and a higher rate of overall patient satisfaction.  In this study, flap creation was performed utilizing the Intralase femtosecond laser and the laser ablation was performed using an Alcon LadarVision excimer laser.

Analysis: Creating a thinner flap for corneal refractive surgery is not a new concept.  Indeed, several variations on this theme already exist - including epi-LASIK and other surface ablation techniques.  The rationale behind creating a thinner flap is primarily tissue preservation as LASIK utilizes an additional 120-160 microns of tissue. 

Alternatives to LASIK, such as PRK and epi-LASIK, have their own disadvantages including slowed post-operative recovery, risk of corneal scarring, and increased post-operative pain.

What is exciting about SBK or sub-Bowman's keratomileusis is that utilizing the Intralase femtosecond laser can create consistent thin flaps without the disadvantages of other surface ablation techniques.  As more surgeons look for tissue preserving techniques, consistency is critical. 

Look for more surgeons to begin using the Intralase for SBK.  And more SBK will probably mean more interest in Intralalse.

Implications:

This article describes early experience with Intralase enabled keratoplasty.  Conventional keratoplasty, or corneal transplantation, is performed using specialized blades called trephines.  These blades are limited in that they can produce only a single type of cut.  Intralase enabled keratoplasty utilizes a femtosecond laser to vary the size and shape of the cuts for keratoplasty.  Initial surgeon experience suggests that the Intralase-aided cuts improves wound healing, leads to faster recovery, and potentially decreases the rate of transplant rejection.

To utilize Intralase enabled keratoplasty requires surgeons who have an Intralase to purchase a $50,000 upgrade.  The upgrade has been available to all Intralase owners since September, 2006. 

Analysis: While Intralase technology holds tremendous promise for corneal transplantation, it is doubtful that the technology will help Intralase sell significant more lasers.  There are several reasons for this.  First, the number of traditional keratoplasties that could potentially utilize the Intralase is shrinking.  Approximately 32,000 corneal transplants were performed in the U.S. last year.  A new transplantation technique called DSAEK is increasingly being used by corneal specialists for approximately 50% of all transplants; this technique does not utilize the Intralase.  Second, the current insurance reimbursement structure does not pay any additional money for an Intralase enabled keratoplasty.  Third, at this point the technology does not speed up the operating time.

Most corneal surgeons are not performing enough keratoplasties to warrant purchasing a $250,000 Intralase for that indication alone.  LASIK is essentially what pays for the Intralase, not keratoplasty.  With that said, Intralase does have the potential to change how conventional keratoplasty and other corneal surgeries are done.  Justifying a $50,000 upgrade for current Intralase owners may not be as difficult.

Implications: This article describes the experience of 3 European surgeons with the Tecnis multifocal intraocular lens.  Currently, the only two FDA approved multifocal lenses in the U.S. are Alcon's Restor and AMO's Rezoom.  The Tecnis multifocal is unique among current multifocal options in that it incorporates aspheric technology with multifocal technology.  The advantages of aspheric lenses have been documented with the introduction of monofocal aspheric lenses such as AMO's Tecnis, Alcon's IQ, and Bausch and Lomb's aspheric lens.  Aspheric lenses decrease spherical aberration and improve visual acuity and contrast sensitivity.

The experience of these surgeons in Europe has generally been positive with the Tecnis multifocal.  All 3 surgeons noted excellent distance and near performance with this lens.  Intermediate vision performance was not as strong as near.  The surgeons also cautioned that these lenses cannot be recommended for all patients with presbyobia, and seem to perform best with hyperopic patients.

Analysis: The Tecnis multifocal, when it enters the U.S. market, will certainly compete with Restor and Rezoom.  In particular, the Tecnis multifocal may be a better competitor for Alcon's Restor because of its excellent near performance.  Restor has led the multifocal market because its near performance tends to be better than Rezoom.  But as importantly, Alcon has strong marketing and brand loyalty.  Rezoom has been slowly increasing its market share against Restor primarily because it provided better intermediate vision when compared to Restor and is being used increasingly in "mixed lens" situations. 

Based on the European data, the Tecnis multifocal provides better near performance than Rezoom, and potentially better distance vision than Restor because of its aspheric design. The real question is whether this "better" visual performance is enough to overcome the superior marketing and brand loyalty of Alcon.  In any case,  the Tecnis multifocal should help AMO's overall multifocal market share.   

Implications: This article describes how the Intralase laser can be used to perform corneal transplantation.  The Intralase femtosecond laser has traditionally been utilized to create a corneal flap in the LASIK procedure.  This article describes the experience of a team of Italian corneal surgeons utilizing the Intralase for the purpose of replacing diseased corneas.  Traditional corneal transplant surgery is performed by removing a circular portion of the cornea, the host corneal button, and replacing that portion with a healthy corneal button from a donor.  Prior to the Intralase, the cutting of the corneal buttons was performed by a trephine, a metallic surgical blade. 

The surgeons suggest that the Intralase adds accuracy, predictability, and faster visual recovery to the procedure.  Because the Intralase allows surgeons to vary shape and size of the corneal buttons, surgeons can better tailor the procedure to the disease process.  The authors cite that the two most common indications for corneal transplants, keratoconus and Fuch's dystrophy, warrant very different graft sizes and shapes.  The Intralase allows surgeons to effectively customize the procedure in ways not easily done with a blade. 

Analysis: The utilization of Intralase technology for uses other than LASIK is growing and will continue to grow.  Corneal surgeons are becoming increasingly interested in using this technology because of its safety profile and more importantly because of its customization ability.  At this point, using an Intralase for corneal transplants probably will not speed up the procedure.  But because the technology allows variable sizes and shapes, it does have significant potential to improve the visual outcomes of corneal transplants.

Another important question is whether broadening the potential uses of Intralase will help to sell more lasers and disposables.  This is a more difficult question as Intralase lasers have probably reached a saturation point for LASIK in many geographic markets.  Surgeons who are not performing significant volumes of LASIK would probably not purchase a new Intralase laser for the purposes of corneal transplants because Intralase technology is expensive. However, centers that already have an Intralase will most certainly begin to utilize this technology more and more for non-LASIK indications.  This increasing utilization will help sell more of the disposables used with the Intralase.  And because the margins on the sales of disposables are high, this should help to keep Intralase moving forward.