Reuse corneal tissue to manage multiple conditions

Small incision lenticule extraction (SMILE) surgery was first approved by the FDA in 2016.¹ Since then, the procedure has expanded from managing myopia to managing myopia with astigmatism, and studies are ongoing for other possible applications.

SMILE is a flapless laser-refractive surgery where a femtosecond laser creates a stromal cornea lenticule that is extracted with a small incision.¹ More than 3.5 million SMILE procedures have been performed globally in the past 10 years.² As this procedure has become more popular, accuracy of lenticule creation also has improved. This has helped yield better visual and refractive outcomes for patients, rivaling those attained with LASIK surgery.¹

With SMILE, study results have demonstrated a reduction in corneal sensation loss and a quicker recovery of corneal sensation when compared with results of patients who have had LASIK surgery.¹ This is, in theory, due to the creation of the small incision within the anterior stroma through which the lenticule is removed, which disrupts fewer anterior corneal nerves.¹

The removal of intact corneal tissue provides us with new opportunities: preservation and reimplantation. This lenticule can be reused, resized, and reshaped in a multitude of ways. As a result, it may help manage hyperopia, presbyopia, and keratoconus.

Presbyopic allogenic refractive lenticule (PEARL) technique uses cryopreserved SMILE lenticules.^2,3 The donor lenticles are placed centrally, and the laser creates a 1-mm disc.^2,3 A femtosecond laser creates a pocket within the corneal stroma, and the lenticule is implanted within it.^2,3 This produces a prolate corneal shape, increasing the depth of focus in the nondominant eye., effectively inducing monovision.^2,3 Unlike synthetic corneal lenticules that have been used in the past, such as Raindrop and KAMRA, SMILE lenticules are biocompatible and have greater potential for integration with the host corneal tissue.³

Results from a study of 4 patients with emmetropic presbyopia who underwent PEARL inlay in their nondominant eye showed an improvement of near vision of 3 to 5 lines and J3 to J5 at intermediate distance at their 6-month follow-up.² Upon examination, the inlay was not visible to the naked eye, and there were no lenticule-related complications observed.²

Similarly, these donor lenticules can be used to manage hyperopia under the same principle of changing the corneal shape to be more prolate. Lenticule intrastromal keratoplasty (LIKE) uses a laser-created flap under which a lenticule is placed.⁴ A second method, small-incision lenticule intrastromal keratoplasty (sLIKE), creates a small incision through which the lenticule is inserted into a stromal pocket.⁴ Both methods have been shown to correct high hyperopia between +3D and +10D.⁴

Results of a recent case report found use for the SMILE lenticule in a patient with post-LASIK corneal ectasia. A 29-year-old man developed bilateral ectasia 10 years after LASIK.⁵ Prior to implantation, the refraction in the left eye was -13.50-6.00 x 010. The lenticule was implanted within the patient’s corneal stroma of the left eye, with a significant postoperative flattening of the patient’s cornea.⁵ Ten months after surgery, the patient’s refraction in the left eye was -3.25 - 1.50 × 010 and best corrected visual acuity was 20/40.⁵

Another application of stromal lenticule implantation is obtaining stability in patients with keratoconus. Study outcomes thus far have been positive. One such study looked at 10 patients with stage III and IV stable keratoconus.⁶ A corneal femtosecond laser flap was made to produce an intrastromal pocket where the lenticule was subsequently implanted.⁶ The patients were followed for 6 months, and results of the study showed statistically significant improvement in both uncorrected distance visual acuity and corrected distance visual acuity, with a gain between 1 to 3 lines.⁶ More importantly, data at 6 months showed positive flattening of the cone when comparing postsurgical anterior mean corneal curvature to presurgical value.⁶ Data also showed an increase in thickness of the central and midperipheral cornea.⁶ Both these markers are important for keratoconus stability.

Another study looked at 22 eyes with advanced keratoconus. Participants had implanted customized lenticules within a corneal lamellar pocket created by a femtosecond laser.⁷ At 1 year, all patients had no complications and achieved similar results to those of the previous study, noting an improvement in best corrected distance visual acuity and central corneal thickness.⁷ Keratometry readings also decreased from an average of 54.68 to 51.95, indicating flattening of the cornea.⁷ This study also looked at confocal bimicroscopy before and after implantation to monitor densitometry, endothelial cell density, and inflammation.⁷ Postsurgical 1-year findings of confocal bimicroscopy found an improvement in corneal densitometry.⁷ More interestingly, the bimicroscopy showed a positive collagen reactivation with lack of inflammation in the collagen surrounding the lenticule.⁷

Rejection rate of these corneal lenticules, in theory, is lower than that of a full-thickness transplant or lamellar keratoplasty. This may be because the lenticule has a less antigenic load to cause an immunological response, fewer stromal keratocytes, and no epithelial or endothelial cells that can lead to an antigenic reaction.^8-10 Another theory is that the lenticule is not in direct contact with tears or the aqueous humor, both of which can trigger immune response.^8-10

More studies need to be performed to better understand how to obtain consistent outcomes and more applications for lenticules. There are a few hurdles; at this time, there is no standard method to customize the lenticules reliably and consistently prior to their implantation. The use of excimer laser ablation for thinning and reshaping is being investigated, as is the necessity of lenticular dehydration prior to thinning.³ Ability to customize would significantly improve visual outcomes in patients and reduce need for flap lifts or postimplantation LASIK-reshaping treatments.

Another hurdle is that lenticule storage and biobanking are still developing. Some countries have standardized these postsurgical procedures, but the vast majority have not. Results of one study found lenticules maintained similar structural integrity stored at room temperature or within reagents at 4°C for up to 48 hours, allowing for transport time to more permanent storage. Long-term cryopreservation of lenticules for 178 days found no evidence of tissue rejection or loss of best corrected visual acuity when implanted in 9 patients who were followed for 310 days.³ Automation and standardization of this process will need to develop, because there is no current consensus.

As one can see, there are many possibilities for reusing SMILE-created lenticules. One person’s waste may be another’s much-needed treasure. Continued patient studies and the standardization of procedures and storage protocols will help further lenticules as an option for patients.

References

1. Reinstein DZ, Archer TJ, Gobbe M. Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes. Eye Vis (Lond). 2014;1:3. doi:10.1186/s40662-014-0003-1

2. 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. doi:10.3928/1081597X-20170111-03

3. Santra M, Liu YC, Jhanji V, Yam GHF. Human SMILE-derived stromal lenticule scaffold for regenerative therapy: review and perspectives. Int J Mol Sci. 2022;23(14):7967. doi:10.3390/ijms23147967

4. Moshirfar M, Shah TJ, Masud M, et al. A modified small-incision lenticule intrastromal keratoplasty (sLIKE) for the correction of high hyperopia: a description of a new surgical technique and comparison to lenticule intrastromal keratoplasty (LIKE). Med Hypothesis Discov Innov Ophthalmol. 2018;7(2):48-56

5. Li M, Zhao F, Li M, Knorz MC, Zhou X. Treatment of corneal ectasia by implantation of an allogenic corneal lenticule. J Refract Surg. 2018;34(5):347-350. doi:10.3928/1081597X-20180323-01

6. Mastropasqua L, Nubile M, Salgari N, Mastropasqua R. Femtosecond laser-assisted stromal lenticule addition keratoplasty for the treatment of advanced keratoconus: a preliminary study. J Refract Surg. 2018;34(1):36-44. doi:10.3928/1081597X-20171004-04

7. Doroodgar F, Jabbarvand M, Niazi S, et al. Customized stromal lenticule implantation for keratoconus. J Refract Surg. 2020;36(12):786-794. doi:10.3928/1081597X-20201005-01

8. Riau AK, Liu YC, Yam GHF, Mehta JS. Stromal keratophakia: corneal inlay implantation. Prog Retin Eye Res. 2020;75:100780. doi:10.1016/j.preteyeres.2019.100780

9. Liu YC, Teo EPW, Ang HP, et al. Biological corneal inlay for presbyopia derived from small incision lenticule extraction (SMILE). Sci Rep. 2018;8(1):1831. doi:10.1038/s41598-018-20267-7

10. Dana MR, Qian Y, Hamrah P. Twenty-five-year panorama of corneal immunology: emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection. Cornea. 2000;19(5):625-643. doi:10.1097/00003226-200009000-00008