Journal of Refractive Surgery

Surgical Technique 

Preliminary Evidence of Successful Near Vision Enhancement With a New Technique: PrEsbyopic Allogenic Refractive Lenticule (PEARL) Corneal Inlay Using a SMILE Lenticule

Soosan Jacob, MS, FRCS, DNB; Dhivya Ashok Kumar, MD; Amar Agarwal, MS, FRCS, FRCO; Athiya Agarwal, MD, DO; Ramalingam Aravind, Boptom; A. I. Saijimol, BSc

Abstract

PURPOSE:

To describe a new technique (PrEsbyopic Allogenic Refractive Lenticule [PEARL] inlay) using an allogenic corneal inlay prepared from a small incision lenticule extraction (SMILE) lenticule.

METHODS:

A SMILE lenticule of specified thickness (mean: 61.5 ± 3.32 µm) was trephined at the center to 1-mm diameter and implanted in the cornea on the coaxially sighted light reflex under a femtosecond laser–created cap of 120 µm in the nondominant eye of presbyopic patients.

RESULTS:

Four emmetropic presbyopic patients underwent PEARL inlay implantation in the nondominant eye. In the operated eye, uncorrected near visual acuity at 33 cm improved from J8 to J2 in one and from J5, J6, and J7, respectively, to J2 in three operated eyes with improvement between three and five lines in all eyes. Uncorrected intermediate visual acuity ranged between J3 and J5 at 67 cm and uncorrected distance visual acuity remained 20/20 in the operated eye and binocularly. The patients were comfortable and reported independence from glasses for near, intermediate, and distance for all of their routine visual tasks for the 6-month follow-up period. There were no complaints of dysphotopsia or troublesome night glare/halos. All lenticules remained well centered during the follow-up and no lenticule-induced complications were seen. All patients reported satisfaction with the surgical procedure. Topography showed a central area of prolateness corresponding to the PEARL inlay. The inlay was not visible on naked eye examination.

CONCLUSIONS:

This preliminary study demonstrates the safety and efficacy of a PEARL corneal inlay for presbyopic correction. Further studies are recommended to determine long-term outcomes.

[J Refract Surg. 2017;33(4):224–229.]

Abstract

PURPOSE:

To describe a new technique (PrEsbyopic Allogenic Refractive Lenticule [PEARL] inlay) using an allogenic corneal inlay prepared from a small incision lenticule extraction (SMILE) lenticule.

METHODS:

A SMILE lenticule of specified thickness (mean: 61.5 ± 3.32 µm) was trephined at the center to 1-mm diameter and implanted in the cornea on the coaxially sighted light reflex under a femtosecond laser–created cap of 120 µm in the nondominant eye of presbyopic patients.

RESULTS:

Four emmetropic presbyopic patients underwent PEARL inlay implantation in the nondominant eye. In the operated eye, uncorrected near visual acuity at 33 cm improved from J8 to J2 in one and from J5, J6, and J7, respectively, to J2 in three operated eyes with improvement between three and five lines in all eyes. Uncorrected intermediate visual acuity ranged between J3 and J5 at 67 cm and uncorrected distance visual acuity remained 20/20 in the operated eye and binocularly. The patients were comfortable and reported independence from glasses for near, intermediate, and distance for all of their routine visual tasks for the 6-month follow-up period. There were no complaints of dysphotopsia or troublesome night glare/halos. All lenticules remained well centered during the follow-up and no lenticule-induced complications were seen. All patients reported satisfaction with the surgical procedure. Topography showed a central area of prolateness corresponding to the PEARL inlay. The inlay was not visible on naked eye examination.

CONCLUSIONS:

This preliminary study demonstrates the safety and efficacy of a PEARL corneal inlay for presbyopic correction. Further studies are recommended to determine long-term outcomes.

[J Refract Surg. 2017;33(4):224–229.]

Corneal inlays are becoming a favored modality for treatment of presbyopia.1,2 These have an advantage over monovision LASIK and PresbyLASIK3–7 in being additive technologies, thereby preserving future options for presbyopia correction. However, all current inlays use synthetic material that is implanted into the cornea and may therefore be associated with complications such as inflammatory response, potential interference with glucose and ion diffusion into the anterior stroma above the implant, and peri-inlay deposits.8–12 We describe a new technique (PrEsbyopic Allogenic Refractive Lenticule [PEARL]) that uses an inlay obtained from a small incision lenticule extraction (SMILE) lenticule. This has been described by one of the authors (SJ).

Technique

The study was approved by the institutional review board of Dr. Agarwal's Eye Hospital and the procedure conformed to the tenets of the Declaration of Helsinki. Informed consent was obtained from all patients. Emmetropic presbyopic patients between the ages of 40 and 45 years were included. Patients with any ocular or systemic disease were not included.

SMILE Lenticule Extraction

SMILE13,14 was performed with the VisuMax 500-kHz femtosecond laser platform (Carl Zeiss Meditec, Jena, Germany) in healthy donors (donor age: 21 to 30 years) for myopic correction of between −2.50 and −2.75 diopters sphere, and the anterior surface was marked for later identification. Serology testing was done for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus surface antigen in all donors. Anterior surface marking was done with an inked Sinskey hook by making three horizontal lines—a single line above separated from two closely placed parallel marks below (Figure 1A). A flipped lenticule would therefore be identified when the two closely placed lines are seen above the single line. The lenticule was kept aside safely in corneal preservation medium (Cornisol; Aurolab, Tamil Nadu, India) for implantation in an emmetropic presbyopic patient.


PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay preparation. (A) The small incision lenticule extraction (SMILE) lenticule is harvested and marked with three horizontal lines, a single one above separated from two closely placed parallel marks below. (B) The stored SMILE lenticule is spread out with anterior side facing up and dried with a surgical sponge. (C) The center is marked with the inked tip of a fine Sinskey hook. Orientation marks are clearly visible. (D) A 1-mm trephine is used to cut the lenticule. (E) Any uncut tags may be cut with a 15° blade. (F) The prepared PEARL inlay is ready for implantation.

Figure 1.

PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay preparation. (A) The small incision lenticule extraction (SMILE) lenticule is harvested and marked with three horizontal lines, a single one above separated from two closely placed parallel marks below. (B) The stored SMILE lenticule is spread out with anterior side facing up and dried with a surgical sponge. (C) The center is marked with the inked tip of a fine Sinskey hook. Orientation marks are clearly visible. (D) A 1-mm trephine is used to cut the lenticule. (E) Any uncut tags may be cut with a 15° blade. (F) The prepared PEARL inlay is ready for implantation.

PEARL Inlay Preparation

The anterior side of the stored SMILE lenticule was identified and it was spread out with the anterior side facing up, dried with a surgical sponge, and the center marked with the inked tip of a fine Sinskey hook (Figures 1B–1C). A 1-mm trephine was centered on the inked mark to fashion a small donor allogenic presbyopic corneal inlay (Figures 1D–1F).

PEARL Inlay Implantation

The light-constricted pupil of the nondominant eye of the emmetropic presbyopic patient was marked on the slit lamp over the first Purkinje reflex seen as the patient fixated coaxially. A pocket with a 295° hinge and 7.9-mm diameter was then created at 120-µm depth using the VisuMax 500-kHz femtosecond laser platform. A central 3.5- to 4-mm pocket was dissected and the PEARL inlay was inserted, aligned, and spread out in the pocket under the marked pupillary center. Intraoperative centration was achieved by gently pressing the center of the inlay while sliding it to the desired position (Figure 2). Retroillumination with the slit beam in the femtosecond laser platform was used to assess proper placement and absence of striae (Figure 2). Centration was further confirmed immediately on the slit lamp and by topography using the Orbscan II (Bausch & Lomb, Rochester, NY). A bandage contact lens was placed and the patient given instructions not to rub the eye. Postoperatively, topical ofloxacin with dexamethasone combination eye drops (OflacinDX; MicroVision, MicroLabs, Bangalore, India) was given six times a day for 1 month and then tapered to stop over the second month. Topical fluorometholone three times a day was then continued for an additional 2 months. All patients were also prescribed tear supplements for 2 months to prevent dryness associated with the femtosecond laser pocket creation (Video 1, available in the online version of this article).


PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay implantation. (A) A pocket with 295° hinge and 7.9-mm diameter is created at 120-µm depth using the femtosecond laser. (B) A central 3.5- to 4-mm pocket is dissected. (C) The PEARL inlay is inserted, aligned, and spread out in the pocket under the marked pupillary center. (D) Centration is achieved by gently pressing the center of the inlay while sliding it to the desired position.

Figure 2.

PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay implantation. (A) A pocket with 295° hinge and 7.9-mm diameter is created at 120-µm depth using the femtosecond laser. (B) A central 3.5- to 4-mm pocket is dissected. (C) The PEARL inlay is inserted, aligned, and spread out in the pocket under the marked pupillary center. (D) Centration is achieved by gently pressing the center of the inlay while sliding it to the desired position.

Results

Four emmetropic presbyopic patients underwent the procedure. The mean thickness of the SMILE lenticule used was 61.5 ± 3.32 µm. The average preoperative and postoperative refraction were +0.375 ± 0.25 and −0.125 ± 0.144 diopters sphere, respectively. Postoperative cycloplegic refraction was +0.78 ± 0.78. In the operated eye, uncorrected near visual acuity at 33 cm was J3 in one and J2 in three operated eyes. There was an improvement in all eyes of three to five lines. Uncorrected intermediate vision ranged between J3 and J5 at 67 cm and uncorrected distance visual acuity remained 20/20 in the operated eye and binocularly. There was no regression in near visual acuity over the 6-month follow-up period. Uncorrected distance visual acuity was also maintained during the entire period. Subjectively, the patients were comfortable and reported independence from glasses for near, intermediate, and distance for all of their routine visual tasks. There were no complaints of dysphotopsia or troublesome night glare/halos. Reading speed was better in the operated eye compared to the unoperated eye (Table 1). All patients reported satisfaction with the surgical procedure. The inlay was not visible on naked eye examination. Serial slit-lamp photography and anterior segment optical coherence tomography showed a well-centered inlay (Figure 3, Figure 4A) and inlay-induced complications such as opacification, extrusion, vascularization, or infection were not seen in any patient. Corneal topography showed an area of hyperprolateness in the central 3-mm zone (Figure 4B). The inlay did not interfere with fundus imaging or autoperimetry in any patient (Figure 4C).


Details of Patients Receiving the PEARL Inlay

Table 1:

Details of Patients Receiving the PEARL Inlay


Slit-lamp photograph of all four patients showing the PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay in situ. Note the clear transparent nature of the inlay and quiet cornea.

Figure 3.

Slit-lamp photograph of all four patients showing the PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay in situ. Note the clear transparent nature of the inlay and quiet cornea.


(A) Anterior segment optical coherence tomography showing a well-centered inlay. (B) Corneal topography showing a hyperprolate cornea in the central zone. (C) Fundus imaging through the PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay.

Figure 4.

(A) Anterior segment optical coherence tomography showing a well-centered inlay. (B) Corneal topography showing a hyperprolate cornea in the central zone. (C) Fundus imaging through the PrEsbyopic Allogenic Refractive Lenticule (PEARL) inlay.

Discussion

The PEARL inlay acts as a shape-changing inlay by increasing the central radius of curvature and resulting in a hyperprolate corneal shape. Unlike the synthetic implants, there is unhindered passage of oxygen and nutrients because the PEARL inlay is made of allogenic cornea, thus ensuring stable corneal conditions and decreasing the risk for corneal necrosis and melt. The use of allogenic tissue provides biocompatibility and good integration into the cornea, thus avoiding problems such as inflammation related to insertion of synthetic material into the cornea. As with synthetic corneal inlays, it has the advantages of reversibility and adjustability. Our results showed improved near vision with no loss of corrected distance visual acuity or other complications. All patients were satisfied with their surgical outcome and none reported troublesome night vision or other dysphotopsic symptoms. Preservation of good uncorrected distance visual acuity and no loss of lines in the operated eye was possible due to the use of a small (1-mm) inlay that covered only a small area of the pupillary zone (Figure 3). This is an advantage over currently available synthetic inlays, most of which are at least 2 mm in diameter.1

Refractive lenticule reimplantation has already been performed in animal models15,16 and also in human studies for hypermetropia,17–19 aphakia,17,19 and keratoconus,20 with favorable results and safety profile. LASIK for inducing monovision following reversal of myopic SMILE through refractive lenticule reimplantation has been reported in an experimental rabbit model.21 The use of these inlays for the correction of presbyopia is a natural logical extension. However, to the best of our knowledge, allogenic corneal inlay implantation has not been reported in human subjects for the treatment of presbyopia.

A disadvantage of this technique is the lack of easy availability of SMILE lenticules of the desired thickness. However, cryopreservation of SMILE lenticules is possible,16,17,19–22 which in the future would allow storage and transportation of these lenticules over long periods. Eye bank involvement in the manufacture and distribution of PEARL inlays can also make availability easier.

Although the risk of complications is low with allogenic tissue, a potential disadvantage is the risk of stromal rejection from donor tissue. However, this was not seen in any of our patients. It is possible that being only 58 to 66 µm (mean: 61.5 ± 3.32 µm) at its thickest point, the antigenic load was too small to provoke a reaction in the immunologically privileged cornea. Compared with deep anterior lamellar keratoplasty (DALK), where the volume of tissue transfer in a donor button of approximately 7.5-mm diameter and 500-µm thickness is 22.1 mm3, the volume of tissue transfer in the PEARL inlay implantation was 0.048 mm3 (less by a factor of 460 times compared to DALK). The immunogenicity is decreased even further because only stromal transfer (without the more antigenic donor epithelium and endothelium) is performed in the PEARL inlay implantation and because repopulation of the small lenticule by the patient's own keratocytes can occur from all sides and therefore is likely to occur faster. In addition, previous reports of use of the larger allogenic implants for aphakia, hyperopia, and keratoconus17–20 point to its safety. Treatment of the donor lenticule prior to use with gamma irradiation to deantigenize it further may be possible in the future.23–25

This preliminary report shows the feasibility of an allogenic presbyopic inlay and has shown safety and efficacy in our small case series. This is only an initial report with a limited number of patients and serves to lay a foundation for a larger study with a longer follow-up. Further studies are recommended to determine long-term safety and efficacy.

References

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Details of Patients Receiving the PEARL Inlay

VariablePatient 1Patient 2Patient 3Patient 4
Age (y)43454341
SexFFFM
Lenticule thickness (µm)61666158
Lenticule power (DS)−2.50−2.75−2.50−2.50
Preoperative UNVA (I) at 33 cmJ6J7J8J5
Postoperative UNVA (I) at 33 cmJ2J2J3J2
Postoperative DCNVA (I)J5J5J7J7
Preoperative UNVA (B) at 33 cmJ5J6J6J5
Postoperative UNVA (B) at 33 cmJ2J1J2J2
Preoperative UNVA (I) at 67 cmJ7J6J6J3
Postoperative UNVA (I) at 67 cmJ4J5J5J3
Preoperative UDVA (I)20/2020/2020/2020/20
Postoperative UDVA (I)20/2020/2020/2020/20
Preoperative UDVA (B)20/2020/2020/12.520/16
Postoperative UDVA (B)20/2020/2020/12.520/16
Reading speed (I) for 100 words1 min 37 sec38 sec1 min 4 sec1 min 2 sec
Reading speed fellow eye for 100 words2 min 53 sec1 min 5 sec2 min 5 sec2 min 10 sec
Authors

From Dr. Agarwal's Refractive and Cornea Foundation; Chennai, India (SJ, RA, AIS); and Dr. Agarwal's Eye Hospital, Chennai, India (SJ, DAK, Amar Agarwal, Athiya Agarwal, RA, AIS).

The authors have no financial or proprietary interest in the materials presented herein.

The authors thank Asha Jacob for technical and writing assistance.

AUTHOR CONTRIBUTIONS

Study concept and design (SJ); data collection (DAK, AR, AIS); analysis and interpretation of data (SJ, DAK, Amar Agarwal, Athiya Agarwal, AR); writing the manuscript (SJ, DAK); critical revision of the manuscript (SJ, Amar Agarwal, Athiya Agarwal, AR, AIS); statistical expertise (DAK); administrative, technical, or material support (Amar Agarwal); supervision (SJ)

Correspondence: Amar Agarwal, MS, FRCS, FRCO, Dr. Agarwal's Eye Hospital, 19 Cathedral Road, Chennai 600086, India. E-mail: dragarwal@vsnl.com

Received: June 24, 2016
Accepted: January 03, 2017

10.3928/1081597X-20170111-03

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