Sutureless Synthetic Keratophakia
The armamentarium of refractive techniques and technologies is about to grow a little larger. An exciting new technology, the PermaVision® (Anamed Inc., Lake Forest, CA) intracorneal implant, is currently under investigation at multiple sites around the world, and is soon to begin Phase I FDA clinical studies in the United States.
Anamed Inc. has developed a material called Nutrapore®&Mac226 a microporous hydrogel, with properties that closely mimic natural corneal stroma. Anamed's PermaVision® implant has a water content of 78% and a refractive index substantially identical to that of the cornea (1.376). In vitro, it is highly permeable to glucose (400 mg/cm2 per hour), allows for satisfactory oxygen diffusion (diffusion coefficient =39), and sufficient transport of water molecules at implant thickness (100 µL/cm2 per hour). Finally, histological evaluations in animal studies have proven the material to have long-term biocompatibility1,2.
KERATOPHAKIA IN THE PAST
Historically, keratophakia pioneered by the grandfather of modern-day refractive surgery, Barraquer (1949), has had limited success secondary to difficulties of precisely creating lenticules on cryolathes, and limited access to adequate tissues. A search for materials that could more accurately and reproducibly yield excellent refractive results was also pioneered by Barraquer, who in 1964 attempted to implant lenticules manufactured from glass and plexiglass.3 Unfortunately, these studies ended in failure secondary to necrosis of the anterior corneal stroma and ultimate extrusion. Choyce and Lindstrom4,5 attempted to implant impermeable polysulfone lenses with satisfactory refractive results; however, failure this time was related to opacification of the lens implants deeming them unfit for long-term implantation in humans.4-6 Several decades in development, hydrogel materials have proven to be biocompatible when implanted in the cornea, and without histological evidence of a surrounding inflammatory reaction.7-12 However, the limiting factors of many of these techniques were implant thickness and shortcomings of the surgical instruments available to perform the procedures.
EXCITEMENT IN ADDITIVE TECHNOLOGY
Although difficulties in developing safe, stable, and predictable hydrogel materials delayed their potential widespread use in synthetic keratophakia, excitement in additive technologies continued in the 1990s with the introduction of INTACS (the first additive, removable FDA-approved refractive technology) manufactured by Keravision Inc. (Fremont, CA) The demise of INTACS has largely been related to a limited range of refractive capability, rigidity of the cornea secondary to an intact Bowman's layer, difficulties mastering the surgical technique, and lack of a “wow factor” in the early postoperative period, as refractive stability (not unlike PRK) can take up to 3 months to achieve.
As surgeons, we seek to provide safe, predictable surgery that has a limited learning curve, and utilize existing surgical techniques, if possible. Our patients want to have confidence that surgery on their eyes will be safe, predictable, painless, have fast visual recovery, and will not cause irreversible harm to their eyes. Therefore, reversibility, although not widely discussed and disregarded by many surgeons, is likely at the forefront of our patients' minds.
THICKER FLAPS ARE WELCOME
The PermaVision® implant appears to address both our surgical demands and our patients' expectations. As a surgical procedure, we are called upon to use our existing skills by performing an anterior lamellar keratectomy flap at a depth of 180 µm using any commercially approved microkeratome. Unlike LASIK, thicker flaps are welcome in the synthetic keratophakia procedure, while thinner flaps raise notes of caution. A keratectomy anterior to or at the level of the anterior corneal nerve plexus could lead to neurotrophic corneal ulcers and poor healing as nerve fibers cannot regenerate across the implant itself. Therefore, flaps of 200 to 240 µm would only help in the prevention of these problematic complications, while preserving a sufficient posterior corneal lamella of greater than 250 µm. After performing the anterior lamellar keratectomy, the interface is then irrigated to remove potential debris. The flap is reflected and the interface dried with merocel sponges. Next, the appropriate power lens implant is selected (central thickness varying from 30 to 60 µm), centered over the pupil, and allowed to dry in place. Finally, the flap is replaced with or without irrigation and dried as with LASIK.
STUDIES ABROAD
Current international investigations are being limited to the correction of hyperopia +1.00 to +6.00 D with less than 1.00 D of astigmatism. The PermaVision® hyperopic intracorneal implant is a bimeniscus lens. The effective optical zones achieved by the implant are between 5.50 and 6.00 mm based on lens implant varying in diameter from 5.0 to 5.5 mm. The optical zones achieved by the implants are larger than the actual lens implant size secondary to a draping effect of the flap over the implant achieving an additional 0.25 mm all around the lens.
NO HALOES HERE
As the material has the same refractive index as the cornea, there have been no reported incidences of visual aberrations, glare, or haloes in any patients with well-centered corneal implants. The optical zone dimensions currently under investigation have been determined by implantation of various diameter inlays in vivo. Effectiveness of the refractive result is a function of central thickness and total functional diameter. Preservation of a stable, well-centered lens over the visual axis is a function of the overall lens thickness and appropriate orientation of the lens implant.
Currently, the PermaVision® implants are available in 0.5 D increments. International results presented at the ASCRS Symposium in San Diego, CA13 suggest excellent accuracy even at this early phase of development. The mean preoperative spherical equivalent was +3.25 D (range, +1.75 to +6.50 D). One month postoperatively, the mean spherical equivalent was -0.06 D, and +0.35 D at 3 months.
NO SERIOUS COMPLAINTS
Complications have included decentrations of the PermaVision® implant measuring less than 1 mm. Some surgeons involved in an international study have successfully repositioned these decentered implants while others have elected to observe the implants, in patients who do not have any complications. According to Anamed Inc., one lens was explanted for persistent decentration. A discrete ring of border haze has been documented in several patients as well. This is likely related to the deposition of collagen material in the potential space at the edge that averages less than 10 µm. To date, no patients have experienced epithelial ingrowth or flap melting secondary to the implants.
LASIK'S LIMITS
Although synthetic keratophakia is unlikely to replace LASIK in the near future, it is likely to complement and/or present an alternative to LASIK that has surpassed more than one million procedures annually. There are several factors that limit the LASIK marketplace and currently hinder further growth.
The physiologic issues related to corneal thickness and keratometric values limit the safe range of treatment. Synthetic keratophakia could offer a similar or expanded range of treatment but also potentially act as an adjunct to LASIK expanding the safe range of treatment through a combined technique. Additionally, this could obviate the need to consider intraocular techniques such as phakic IOLs or clear lensectomy in prepresbyopic patients.
Equipment costs associated with ownership of excimer lasers and laser centers can run into millions of dollars. Not only has this created economic barriers for access by many competent ophthalmic surgeons worldwide, it is largely responsible for the development of the LASIK price wars and the demise of individual surgeons and corporations alike seeking to recoup their capital investments as quickly as possible.
Synthetic keratophakia will require much less of a capital investment on the part of surgeons choosing to provide this service to their patient. By lowering the financial barriers of entrance to the marketplace, there will be greater capacity for surgeons to provide these services without significant financial risk. Fundamentally, this should help eliminate the pressure surgeons feel to reduce fees as a means of maintaining cash flow.
The subtractive nature of LASIK causes irreversibility, decentered and irregular ablations, night vision aberrations, ectasia, and planning difficulties for future cataract surgery. All of these problems make the procedure a less-than-ideal choice for many surgeons seeking to provide patients with long-term safety, and perpetuate our patients' fear of the irreversible nature of LASIK.
LOOKING AHEAD
The PermaVision® intracorneal implant offers a reduced incidence of adverse events, and reversibility through the ability to re-center, exchange or remove the implants when necessary. Although current studies are limited to the treatment of hyperopia, feasibility studies to correct myopia have already successfully been performed. Furthermore, PermaVision® may be able to tackle all forms of astigmatism and possibly, presbyopia. One thing is certain—we can look forward with optimism that the PermaVision® lens will become a formidable weapon in our war on refractive errors worldwide.
1. Kaufman S, Kaufman H: Permavision intracorneal implant: 2-year biocompatibility in rabbits. Presentation ASCRS Symposium 2001
2. Shultz MC: Permavision intracorneal implant: 12-month biocompatibility study. Presentation ASCRS Symposium 2001
3. Barraquer JI: Conducta de la cornea frente a los cambios de espesor (Contribucion a la cirugia refractive). Arch Soc Am Oftalmol Optom 5:81, 1964
4. Choyce P: The correction of refractive error with polysulfone corneal inlays. Trans Ophthalmol So UK 104:332-342, 1985
5. Lindstrom RL, Lane SS: Polysulfone intracorneal lenses. Refractive Corneal Surgery. Thorofare, NJ, Slack, Inc., 1985, p 549
6. Horgan SE, Fraser SG, Choyce DP, et al: Twelve-year follow-up of unfenestrated polysulfone intracorneal lenses in human sighted eyes. J Cataract Refract Surg 22:1045-1051, 1996
7. Mester U, Heiming D, Dardenne MU: Measurement and calculation of refraction in experimental keratophakia with hydrophilic lenses. Ophthalmic Res 8:111-116, 1976
8. McCarey BE, Andrews DM: Refractive keratoplasty with intrastromal hydrogel lenticular implants. Invest Ophthalmol Vis Sci 21:107-115, 1981
9. McDonald MB, McCarey BE, Storie B, et al: Assessment of long-term corneal response to hydrogel intrastromal lenses implanted in monkey eyes for up to five years. J Cataract Refract Surg 19:213, 1993
10. Yamaguchi T, Koenig SB, Hamano T: Electron microscopic study of intrastromal hydrogel implants in primates. Am J Ophthalmol 91:1170-1175, 1984
11. Steinert RF, Storie B, Smith P, et al: Hydrogel intracorneal lenses in aphakic eyes. Arch Ophthalmol 114:135-141, 1996
12. Barraquer JI, Gomez ML: Permalens hydrogel intracorneal lenses for spherical ametropia. J Refract Surg 13(4):342-348, 1997
13. Shultz MC: Permavision early multi-center international experience. Presentation ASCRS Symposium 2001
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