WITH THE INTRODUCTION OF PRESBYOPIA-CORRECTING drops, you may soon see an influx of patients seeking a remedy for correcting their near vision. While these drops hold great promise, providing a temporary improvement in near visual acuity, physicians should be aware of surgical options that may offer more permanent solutions. In particular, advances in corneal allogenic lenticules mean that this tissue can provide a solution for certain patients.

In this article, we’ll provide an update on the use of corneal allogenic lenticules to treat presbyopia, review some of the past obstacles with corneal presbyopic inlays, and discuss a new method that offers significant possibility for success. But first, let’s look at some of the advantages corneal allogenic lenticules provide.

Permanent Solution

For patients with presbyopia, corneal lenticules offer a number of advantages. Perhaps chief among them is that compared with presbyopia-correcting drops and multifocal contact lenses, lenticules offer a permanent solution.

Multifocal contact lenses offer a viable option, but contact lens dropout in this category is primarily due to poor vision and discomfort. Optically, if the contact lens is not centered on the line of sight, then instead of inducing desired spherical aberration to extend depth of focus, the lenses induce aberrations that degrade the quality of vision and can be more disruptive than helpful. In addition, patients in the presbyopia age range drop out of contact lens wear due to discomfort because of a higher prevalence of ocular surface issues, such as dry eye disease.¹

With a corneal lenticule, the surgeon physically produces a multifocal effect by creating a hyperprolate optical surface. As long as the lenticule is centered on the line of sight, it provides an increase in depth of focus by a combination of higher-order spherical aberrations (4th-, 6th-, and 8th-order Zernike spherical aberrations).

Long History

Corneal lenticules date from some 70 years ago, when in the late 1940s/early 1950s, Jose Barraquer, a Spanish ophthalmologist regarded as the father of refractive surgery, crafted the first artificial inlays using Plexiglas. Unfortunately, those inlays caused serious problems, including melting, ulceration, persistent epithelial defects, and deposits around the inlay.

Barraquer also used autologous grafts, removing corneal tissue, reshaping it, and then reapplying it to the cornea. Because he used the patient’s own corneal tissue, which obviously has high biocompatibility, such lenticules had very good survivability and great biocompatibility. However, without lasers available at that time to precisely optically shape the tissue, the results were less than optimal.

In 2016, the FDA approved two artificial inlays for treating presbyopia: Kamra and Raindrop. The Kamra corneal inlay (AcuFocus) produced a small aperture effect to create extended depth of focus. Made of polyvinylidene difluoride and pigmented with carbon nanoparticles, the inlay had microperforations that transported micronutrients. The Raindrop inlay (ReVision Optics), made of hydrogel, created multifocality using a hyperprolate profile to extend depth of focus.

Unfortunately, patients with the Raindrop inlay started to experience biocompatibility problems, including corneal haze, regression, corneal melting, interface deposits, material build-up, and the need for long-term corticosteroid use. These issues developed because the inlay blocked glucose transport from the posterior cornea and oxygen transport from the anterior cornea. As a result, this inlay sometimes would need to be explanted. Ultimately, complications with the Raindrop inlay were so frequent that the FDA recalled it.

The complications that can develop with these inlays carry an additional burden, because the inlays must be placed directly in the center of the line of sight. Those complications will affect the central cornea, which will have a significant impact on the patient’s vision.

Further Advances

Today, with excimer and femtosecond lasers, corneal allogenic inlays hold significant promise for presbyopia patients. Surgeons can easily create complex shapes that were impossible during Barraquer’s era.

In 2017, Jacob and coauthors published an article describing near-vision enhancement using a PrEsbyopic Allogenic Refractive Lenticule (PEARL) corneal lenticule, which used a small incision lenticule extraction (SMILE) lenticule. The PEARL created a hyperprolate shape, resulting in an increased depth of focus translating into a several-line improvement in near and intermediate visual acuity.^2,3

However, today, no tissue banks offer SMILE tissue. Fortunately, the continual increase in the use of endothelial keratoplasties— Descemet’s membrane endothelial keratoplasty (DMEK) and Descemet’s stripping automated endothelial keratoplasty (DSAEK)—in which surgeons peel the back layer off of the cornea and use it for a procedure, leaving the rest of the stroma, holds a solution.

Using e-beam sterilization or gamma radiation, that excess stroma can be sterilized. With the donor cells eliminated, the stroma no longer requires the level of nutrition that fresh corneal tissue needed for cell survival. Today, tissue banks store this sterilized tissue, which is shelf-stable for up to 2 years.

With this tissue preparation method, patients are unlikely to suffer from biocompatibility issues. The tissue is essentially stroma within stroma and should not block nutrient or oxygen transport.

Latest Tech

One of the latest developments in corneal allogenic lenticules, from Allotex Inc., involves using a laser to cut this sterilized corneal stroma into tiny lenticules, under the brand name TransForm Corneal Allograft (TCA; Figure 1). One cornea can render roughly 100 lenticules, allowing a large number of procedures to come from a small number of corneal donors. While the TCA is not yet approved for use in the United States, U.S. clinical trials are on the horizon.

In Turkey, Kiliç et al performed initial pilot studies on the safety and efficacy of TransForm lenticules in presbyopia on patients with emmetropic eyes.⁴ With a femtosecond laser, the researchers created a LASIK flap and then laid the TransForm lenticule onto the anterior stromal bed of the cornea. Then they touched the meniscus with a Weck-Cel to stabilize the lenticule, and replaced the flap.

Uncorrected distance visual acuity did not change, but best-corrected distance visual acuity did decrease by approximately half a line. However, patients gained 4 lines of uncorrected near visual acuity. Moreover, the researchers found almost no change in the corneal thickness in these procedures.

In a subsequent phase 2 multicenter trial in Europe, researchers treated 101 emmetropic eyes. The TransForm lenticule was placed monocularly, but visual acuity was tested binocularly. The researchers found that, binocularly, there was no loss of uncorrected visual acuity in distance vision. The researchers also found 2 lines of improvement at intermediate vision and 5 lines of visual acuity improvement at near vision, a significant jump.

In general, the TransForm lenticule has been laid under a lamellar flap into the cornea and placed in the line of sight. While more studies are needed, there is the possibility that the procedure could be as simple as an onlay or potentially implanting the lenticule through a pocket. Postop treatment will likely be the same as for LASIK.

Patient Selection

Patients who consider this procedure should be able to tolerate disparity between the eyes. They should be able to tolerate blended vision, with the nondominant eye taking a little bit less power than the dominant eye but providing more up-close reading ability.

The TCA is indicated for intrastromal implantation to provide near vision in the nondominant eye of presbyopic patients, 41 to 65 years of age, who have manifest refraction spherical equivalent of +1.00D to -0.75D with ≤0.75D of refractive cylinder; do not require correction for clear distance vision; but do require near correction of +1.75D to +3.50D of reading add.

More Permanent Solution

For patients who desire a more permanent presbyopia solution, lenticules such as those provided by Allotex can provide a significant treatment option. ■

REFERENCES

1. Pucker AD, Tichenor AA. A review of contact lens dropout. Clin Optom (Auckl). 2020;12:85-94.
2. Jacob S. Corneal allogenic inlays for presbyopia. Corneal Physician. 2020;1(1):12-15.
3. Jacob S, Kumar DA, Agarwal A, Agarwal A, Aravind R, Saijimol AI. Preliminary evidence of successful near vision enhancement with a new technique: PrEsbyopic Allogenic Refractive Lenticule (PEARL) corneal inlay using a SMILE lenticule. J Refract Surg. 2017;33(4):224-229.
4. Kiliç A, Tabakci BN, Özbek M, Muller D, Mrochen M. Excimer laser shaped allograft corneal inlays for presbyopia: Initial clinical results of a pilot study. J Clin Exp Ophthalmol. 2019;10(4):1-7.

Dr. Gelles is director of the specialty contact lens division of the Cornea and Laser Eye Institute in Teaneck, NJ, and a clinical assistant professor at Rutgers New Jersey Medical School.

Dr. Greenstein is director of the refractive surgery division at the Cornea and Laser Eye Institute. He is a clinical assistant professor at Rutgers New Jersey Medical School.

Dr. Hersh is founder and research director of the Cornea and Laser Eye Institute. He is a clinical professor and director of cornea and refractive surgery at Rutgers New Jersey Medical School and a visiting research collaborator at Princeton University.

Disclosures
Dr. Hersh serves on the medical advisory board at Allotex. Dr. Gelles and Dr. Greenstein declare no relevant disclosures.