Intracorneal inlays for the correction of presbyopia and low hyperopia

In short: New alloplastic materials are being used as intracorneal inlays to offer predictable and safe refractive surgical correction of presbyopia and low hyperopia. The major problem with such inlays is the wound-healing response following their insertion; however, they can easily be removed.

By Dr Perry S. Binder, MD

Many materials have been used as intracorneal inlays to correct various ametropias. ¹ Recently, new alloplastic materials have been implanted in the cornea to correct presbyopia and/or low hyperopic refractive errors. Each inlay has its own merits. The mechanisms of achieving a refractive change are increasing anterior corneal curvature, increasing anterior corneal curvature in combination with a single diffractive optic or the use of the pinhole effect to achieve increased depth of focus. The inlays are implanted under a corneal flap or within a femtosecond-laser-dissected stromal pocket, at various depths. These inlays create excellent near visual acuity. Table 1 on Page 12 summarises the published literature for currently available inlays.

Inlays that increase anterior corneal curvature to achieve a refractive change create a fixed focal length; as the eye becomes more presbyopic/hyperopic with age, the initial benefits are lost, necessitating an exchange of inlay – a process that can be performed with minimal risk.² The negative aspect of increasing anterior corneal curvature is a decrease in the uncorrected distance visual acuity.³ The worse the distance visual acuity, the more the impact of loss of distance vision in the operated eye creates a simulation of standard monovision. Increasing a focal portion of the central cornea or providing a diffractive optic has the benefit of minimally impacting distance vision but carries the risk of creating a multifocal cornea with associated optical side effects such as induced high-order aberrations.⁴ The small-aperture pinhole approach allows for a wider range of continuous vision from near to far that is independent of age, but potentially results in a reduction in quality of vision under scotopic conditions in the inlay eye, bearing in mind that all reading is more difficult under scotopic conditions.

A hydrogel inlay is optically clear, whereas the annular, small aperture inlay is by optical necessity darker to block peripheral light rays; it is therefore more easily discernible in eyes with light coloured irises. All inlays allow normal examination of the anterior chamber angle and the peripheral and central retina without impacting the field of vision. One of the major advantages of these inlays over other methods of surgical correction of presbyopia is the fact that they can be removed, permitting the eye to return to its pre-implantation refractive state.^2,5

In my opinion, the major issue with all current presbyopia-correcting inlays is the cornea’s wound-healing response. All currently available inlays are a corneal foreign body. Numerous laboratory and clinical studies, including many of my own, have demonstrated that inlay thickness, edge design, water permeability, diameter, material content, surface quality and depth of implantation⁶ all affect biocompatibility with the cornea. Of the many materials previously tested, many but not all hydrogel copolymers were found to be biocompatible, producing the least wound-healing responses in animal and human eyes⁷ but, because of the convex shape and thickness required to modify anterior corneal curvature and their smooth, hydrophilic surfaces,⁸ they are prone to decentration in the postoperative period.³ The small-aperture inlay is hydrophobic, unlike the hydrophilic hydrogels, and is therefore very adherent to the stromal surface once placed during surgery. If an inlay 30–50 mm or thicker in the centre is implanted in a pocket, there is potential to push the posterior stroma towards the anterior chamber instead of changing the anterior curvature.⁸

The wound-healing response can be seen clinically with the slit lamp to range from no visible reaction to an optical haze anterior to or surrounding the inlay. There is a paucity of published clinical data on the nature of this wound-healing response.^9,10 The reported incidence for two of the inlays is between 2% and 9%. My personal laboratory studies of hydrogel implants,^{2,7,8,11–18} have documented that keratocytes tend to enter the optical interface on one or both sides of the inlay (anterior or posterior) and may undergo lipoidal degeneration in the periphery of the inlay interface, which appears as crystal formations; very rarely did we find interface deposition of new collagen or proteoglycans. I recently examined some removed presbyopic inlays of a type currently available. They did not demonstrate any form of acute inflammation or the implantation of epithelium; a few cases had CD38-positive immunostaining, suggesting the presence of giant cells.

In some cases the wound-healing response has no clinical impact, whereas in others it can degrade the optical quality of the inlay, negating its visual benefits. The advantage of the small aperture over other inlay models is the absence of material in the visual axis, so that a wound-healing response with this model does not invade the visual axis. Some inlays can be associated with a postoperative change in the refractive error in the hyperopic or myopic direction, which most likely relates to the cornea’s wound-healing response but may also be related to the hydration of the overlying cornea stroma and epithelium. Proper hydration of the corneal surface combined with the topical, short-term use of glucocorticoids can return most of these eyes to satisfactory visual performance. When removed, there can be an optical “imprint” of the inlay seen in retro illumination that carries no optical side effects and disappears over time (unpublished observations).

A unique issue for corneal inlays is the centration of the inlay optics for the individual optics of a given eye.^19–23 Different instruments and techniques are used by inlay companies to achieve proper centration at surgery. An inlay that increases anterior corneal curvature, if decentred, can induce high-order aberrations and probably monocular diplopia. The diameter of the inlay in such cases will determine the degree of these side effects: the larger the inlay diameter, theoretically the less impact a given amount of decentration will produce. A decentred multifocal inlay will most likely create similar issues. The small-aperture inlay is somewhat less insensitive to decentration creating a loss of optical results; good acuity outcomes have been documented (data on file, AcuFocus, Inc. Irvine, California, USA) when the optics are within 300 mm X and Y of the desired centration, which is considered to be the line of sight, which is closely represented by the first Purkinje image.

Laser refractive corneal surgery and intraocular lens procedures create permanent refractive changes. Although these procedures can be enhanced, for example PRK over a LASIK case, a LASIK flap lift enhancement, IOL removal or exchange, there is a given, fixed risk in obtaining these improvements. The corneal inlay, no matter which company model, can easily be removed and can be exchanged if necessary. The inlay implantation procedure is technically easy and carries less risk than an intraocular procedure. LASIK and inlay implantation may be combined in order to address refractive error and presbyopia.^24–27 It is also possible to perform PRK over a small-aperture inlay to reduce post-implant ametropias (personal communication: Kevin Waltz, OD, MD; Vance Thompson, MD; Roger Zaldivar, MS, MD; and Daniel Durrie, MD) without having to remove the inlay. I suspect the same will be true for all inlays. Creating a femtosecond laser flap or performing femtosecond laser cataract surgery in an inlay-implanted eye should be avoided because of potential risk to the inlay, as it is theoretically possible that the inlay could absorb or distort the infrared femtosecond laser energy in the same way that it may absorb unfocused retinal laser energy. It is also possible to use a YAG laser, or any laser source for capsulotomies or retinal procedures in inlay eyes; however, direct laser contact with the inlay should be avoided.²⁸

These inlay procedures are surgical and, like any lamellar refractive procedure, carry a risk of complications. Corneal sensation is temporarily reduced, as it is with any penetrating or lamellar corneal procedure, increasing the risk of a dry ocular surface and secondary infections.²⁹ It should be noted that pocket procedures have fewer of these risks than flap procedures because the dimensions of incised corneal surface and nerves are much smaller.

Inlays can be damaged or folded at the time of insertion. If the corneal surface is disrupted at the primary procedure or at the time of removal or exchange, there is an increased risk of infection. Epithelium can be implanted into the optical interface. Although it is rare, thicker inlays and those implanted more superficially have the potential to decrease nutrition to the anterior cornea, which increases the risk of corneal thinning.⁶ The indiscriminant use of topical steroids to control wound healing carries risks of secondary glaucoma, PISK syndrome³⁰ and/or cataract formation.

Why use an inlay in an elderly patient elderly patients, when cataract surgery is expected in the near future? One cannot perform cataract surgery with an inlay in place. Inlays do not interfere with visualization during cataract surgery (personal communication: Kevin Waltz OD, MD, March 2014).^31,32 In addition, if one leaves an inlay in place with the implantation of a monofocal IOL, one also gains near visual acuity and better quality optics compared with some multifocal IOLs.³³ The surgical risk of intraocular surgery is much higher than a corneal-based procedure. The inlay offers a better range of vision compared with the standard monovision that is regularly offered to presbyopic patients in this age range. In addition, the topographic impact of laser corneal surgery makes subsequent IOL calculations less accurate. Of course, many patients over 60 years of age do not require cataract surgery.

I have heard that there is a new miotic eye drop that simulates the small-aperture inlay, although miotics have a risk of retinal detachment. The effect of such drops lasts 4 to 6 hours maximum and takes time to develop. Patients desire instant near acuity and do not wish to wait 15–30 minutes before they can read. Having to take frequent drops is not much better than wearing reading glasses. The ideal aperture size for the small-aperture inlay diameter at the corneal plane is 1.6 mm. In order for a small aperture to work at the lens plane, the aperture needs to be reduced to 1.34 mm (data on file, AcuFocus, Inc.). Consequently, in order to achieve a similar result, a miotic drop would need to provide reliable pupil constriction to less than 1.6 mm. The penetration of eye drops and the drop’s effect on pupil diameter is individual and unpredictable. If the pupil is smaller than optically necessary to achieve the optimum acuity, the eye will lose significant scotopic acuity. If the constricted pupil is too large, there is no optical gain. Movement from mesopic to scotopic conditions and back again with a 4–6 hour constricted pupil will be challenging for the patient. However, the impact of such a topical eye drop on non-small aperture inlays has the potential to enhance their outcomes.

The cornea is not the best place to correct presbyopia, but it is the best option we have today and is optically better than some laser refractive procedures when calculating an IOL power at a later date.

Potential features of future inlays

Custom modification of any inlay’s dimensions based on the eye’s mesopic pupil size has the potential to improve/reduce some optical side effects. Modification and/or change of the inlay materials has the potential to further reduce some, if not all, of the cornea’s biologic wound-healing response(s). Improvement in the quality of the incised stromal surface(s) with smoother femtosecond laser ablations has the potential to improve all outcomes (data on file, AcuFocus, Inc.). It may be possible to change the colour of the small-aperture inlay for those with light-coloured irises whose inlay is visible. Customised centration procedures, improved inlay implantation techniques and determination of the best implant depth for a given corneal thickness may also improve outcomes and safety. Ultimately, we will need to develop algorithms to improve the predictability of inlay implantation on corneal parameters.

Conclusion

Today, only the small-aperture KAMRA inlay has US approval for the correction of presbyopia. All of the inlays have CE Mark approval and are expected to gain FDA approval in the future. Based on my current knowledge of available inlays, I think there may be overlapping clinical indications for each. This can only benefit patients’ needs. Until we develop a safe and predictable means of replacing the ageing dysfunctional lens with a biocompatible intracapsular polymer, the intracorneal inlay in its current iteration and possibly newer alloplastic materials will offer the most predictable, easily removable and safe refractive surgical correction of presbyopia.

References

• P.S. Binder, L. Lin and C. van de Pol . Cont. Lens Anterior Eye 2015;41:197-203.

• P.S. Binder, E.Y. Zavala and J.K. Deg . Cornea 1983;2:119-125.

• R.F. Steinert et al ., J. Cataract Refract. Surg. 2015;41:1568-1579.

• A. Yoo et al. , J. Refract. Surg. 2015;31:454-460.

• U. Vossmerbaeumer, K. Ditzen and J. Jonas . J. Refract. Surg. 2007;23:102-104.

• D.M. Maurice, in Corneo-Plastic surgery: Proceedings of the Second international Corneo-Plastic Conference , P.V. Rycroft, editor, 1969, Pergamon Press: Oxford. pp. 197-207.

• E.Y. Zavala et al ., Curr. Eye Res. 1984;3:1253-1262.

• J.R. Samples et al., Invest. Ophthalmol. Vis. Sci. 1984;25: 843-850.

• M.R. Santhiago et al., J. Refract. Surg. 2012;28:144-149.

• A. Abbouda, J. Javaloy and J.L. Alió . J. Refract. Surg. 2014;30:172-178.

• T.P. Werblin et al., Refract. Corneal Surg. 1992;8:12-22.

• P.S. Binder . Refract. Corneal Surg. 1989;5:98-120.

• J.K. Deg and P.S. Binder . Ophthalmology 1988;95:506-515.

• E.Y. Zavala et al. , CLAO J . 1986;12:54-58.

• P.S. Binder et al., CLAO J. 1984;10:105-111.

• P.S. Binder et al., Ophthalmology 1984 ; 91:806-814.

• P.S. Binder . Curr. Eye Res. 1983;2:435-441.

• P.S. Binder et al., Curr. Eye Res. 1981/1982;1:535-542.

• M. Karhanová et al., Acta Ophthalmologica 2015;93:e123-e128.

• C.C.C. Corpuz et al., J. Cataract Refract. Surg. 2015 ; 41:162-170.

• D.H. Dang and G.I. Waring . Am. J. Ophthalmol. 2014;158:863-874.

• J. Tabernero and P. Artal . J. Cataract Refract. Surg. 2012;38:270-277.

• D. Gatinel et al. , J. Refract. Surg. 2012; 38:2186-2191.

• M. Tomita and G.O. Waring IV . J. Cataract Refract. Surg. 2015;41:152-161.

• E.B. Garza and A. Chayet . J. Cataract Refract. Surg. 2015;41:306-312.

• T. Huseynova et al., Clin. Ophthalmol. 2013; 7:1937-1940.

• M. Tomita et al., J. Cataract Refract. Surg. 2012; 38:495-506.

• M. Mita, T. Kanamori and M. Tomita . J. Cataract Refract. Surg. 2013;39:1768-1773.

• E.S. Duignan et al., Br. J. Ophthalmol. 2015 June 29/ [Epub ahead of print].

• B.R. Randleman and G.R. Lesser . J. Refract. Surg. 2012;28:2011-2012.

• G.D. Parkhurst, E.B. Garza and A.A. Medina . J. Refract. Surg. 2015;31:206-208.

• T.E. Tan and J.S. Mehta . Clin. Ophthalmol. 2013;7:1899-1903.

• M. Ziaei and A.A. Mearza . J. Cataract Refract. Surg. 2013;39:1116-1117.

References cited in table

• R.L. Lindstrom et al., Curr. Opin. Ophthalmol. 2013;24:281-287.

• D.I. Bouzoukis et al., J. Refract. Surg. 2012;28:168-173.

• A.N. Limnopoulou et al., J. Refract. Surg. 2013;29:12-18.

• C. Baily, T. Kohnen and M. O’Keefe. J. Cataract Refract. Surg. 2014;40:1341-1348.

• T. Porter et al., Invest. Ophthalmol. VIs. Sci. 2012;53: E-Abstracts 4056.

• A. Lang et al., Invest. Ophthalmol. VIs. Sci. 2013;53: Abstract 3130 Poster D0065.

• E.B. Garza, et al., J. Refract. Surg. 2013; 29:166-172.

• A.S. Roy et al., Invest. Ophthalmol VIs Sci. 2013;53: Abstract 3129 Poster 0064.

• A. Chayet and E.B. Garza. J. Cataract Refract. Surg. 2013;39:1713-1721.

• A. Yoo et al., J. Refract. Surg. 2015;31:454-460.

• E.B. Garza and A. Chayet. J. Cataract Refract. Surg. 2015;41:306-312.

• R.F. Steinert et al., J. Cataract Refract. Surg. 2015;41:1568-1579.

• O.F. Yılmaz et al., J. Cataract Refract. Surg. 2011;37:1275-1281.

• O. Seyeddain et al., J. Cataract Refract. Surg. 2012;38:35-45.

• M. Tomita et al., J. Cataract Refract. Surg. 2012;38:495-506.

• M. Tomita et al. J. Cataract Refract. Surg. 2013; 39:898-905.

• T. Huseynova et al., J. Refract. Surg. 2014;30:110-115.

• M. Tomita et al., J. Refract. Surg. 2014;30:448-453.

• A.K. Dexl et al., J. Cataract Refract. Surg. 2015;41: 566-575.

• M. Tomita and G.O. Waring IV. J. Cataract Refract. Surg. 2015;41:152–161.

Dr Perry S. Binder, MD

e: garrett23@aol.com

Dr Binder, from the Gavin Herbert Eye Institute, University of California, is the Medical Monitor for AcuFocus, Inc., and is a stockholder in the company, but did not receive support or editorial assistance for this article. The opinions expressed herein are solely those of the author and not AcuFocus, Inc.