Two-year observation of morphologic and histopathologic changes in the monkey cornea following small incision allogenic lenticule implantation

https://doi.org/10.1016/j.exer.2020.107935Get rights and content

Highlights

  • Small incision allogenic intrastromal lenticule implantation is feasible and safe for reshaping the cornea.

  • Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years.

  • The mechanism of histopathologic change require further investigation.

Abstract

Purpose

To observe the morphologic and histopathologic changes of femtosecond laser assisted small incision allogenic intrastromal lenticule implantation (AILI) in monkey corneas.

Methods

6 healthy adult monkeys were included. One eye of two monkeys and both eyes of one monkey received femtosecond lenticule extraction with a −4.0 diopter (D) correction. Each extracted refractive donor lenticule was immediately allogeneically transplanted into a corneal stromal pocket created by a femtosecond laser in another monkey's eye. A postoperative two-year follow-up was performed with slit lamp microscopy, corneal topography, anterior segment optical coherence tomography and in vivo confocal microscopy. All eyes were enucleated for Hematoxylin-Eosin staining and transmission electron microscopy (TEM) observation.

Results

No complications were observed in the follow-up period. At postoperative 2 years, the corneas remained clear and the lenticules were integrated with the surrounding tissue under slit lamp microscopy. Nerve fiber regeneration was detected in the lenticule layer as observed through confocal microscopy. Corneal power was increased by 1.83 ± 1.36 D after 2 years, which was less than at 6 months (3.27 ± 1.2 D). Disordered fibers and decreased keratocytes in the implanted lenticules could be detected under light microscopy and TEM, with a clear boundary between the lenticules and the surrounding tissue.

Conclusions

Small incision AILI is feasible and safe for reshaping the cornea. Corneal healing remained stable while refraction showed a moderate regression within postoperative 2 years.

Section snippets

Text

Small incision lenticule extraction (SMILE) has gained popularity around the world as a new refractive procedure to correct refractive error (Sekundo et al., 2011, 2014; Shah et al., 2011; Reinstein et al., 2014). Previous studies in both experimental research and clinical interventions showed that an intrastromal refractive lenticule, created precisely by femtosecond laser during a SMILE procedure, could be used for autologous or allograft tissue transplantation to treat presbyopia, hyperopia

Animals

Six healthy adult rhesus monkeys, weighing between 4.5 and 5.5 kg and provided by XiShan Zhongke Laboratory Animals Co. Ltd. (Jiangsu, China) were used in this study. All experimental and animal handling procedures adhered to the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research.

Methods

Monkeys were anesthetized with an intramuscular injection of ketamine hydrochloride (15–20 mg/kg) and acepromazine maleate (0.15–0.2 mg/kg) before surgery and each measurement. One eye of two monkeys and both eyes of one monkey, acting as the donors, received femtosecond lenticule extraction (FLEx) using the VisuMax femtosecond laser system (Carl Zeiss Meditec, Jena, Germany). The intended diameter of the corneal flap was 6.0 mm, with a 100 μm thickness and a side-cut angle of 90°. The optical

Slit lamp microscopy

After lenticule transplantation, corneal edema gradually absorbed from days 5 to post 1 month, with all corneas achieving transparency by postoperative 6 months. At postoperative 2 years, the corneas remained transparent and the implanted lenticules were completely integrated with the adjacent stroma without visible boundaries. The edge of the corneal cap was poorly defined but still visible. No infection, diffuse lamellar keratitis (DLK), haze, epithelial ingrowth or transplantation rejection

Discussion

In our previous study, we demonstrated that AILI can safely, viably and effectively increase corneal thickness and refractive power, which may provide a useful method for treating corneal ectasia, presbyopia and hyperopia (Liu et al., 2015; Zhao et al., 2017). Although this new technique has been applied in some experiments and clinical trials (Sun et al., 2015; Wu et al., 2015; Zhang et al., 2015), the long term refractive outcomes and alterations in histological ultrastructure have not been

Financial disclosure

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

Acknowledgments

The authors would like to thank Elizabeth Wadium who provided valuable review and editing of this manuscript.

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Supported in part by the National Natural Science Foundation of China for Young Scholars (Grant No. 81600762 & 11702063), the National Natural Science Foundation of China (Grant No. 81570879) & (Grant No. 81770955), Project of Shanghai Science and Technology (Grant No .17140902900)(Grant No .17411950200).

1

These authors contributed equally to the work present here and should therefore be regarded as equal first authors.

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