Precise Nonlinear Optical Corneal Crosslinking (NLO CXL), Mechanical Stiffening, and Corneal Flattening Using Amplified Femtosecond Pulses

Abstract

Purpose : We have previously shown that corneal CXL, and mechanical stiffening can be achieved in ex vivo rabbit corneas using 80 MHz, 760 nm femtosecond (fs) laser. While this method allowed for highly controllable CXL the required laser power, 800 mW total energy with pulse energies on the order of nJ, is beyond the ANSI limit of 46 mW. The purpose of this study was to test the efficacy of amplified fs laser pulses for CXL.

Methods : A variable NA, custom laser scanning delivery system was coupled to a 760 nm, 50-150 kHz amplified fs laser producing 0.2-0.3 µJ/pulse, and total energy of 20-30 mW. Ex vivo rabbit corneas were then treated with a varying number of pulses/spot at 2 µm/spot separation. Induced collagen autofluorescence (CAF) and mechanical stiffening were then measured in treated eyes and compared to controls. NLO CXL was also performed on the right eye of 9 live rabbits over a 4 mm diameter area using amplified fs pulses. Changes in corneal topography were then measured over 2 months using an Orbscan.

Results : CAF intensity increased logarithmically with increasing number of pulses/spot according to the equation y=381.24ln(x)-193.02 (R2=0.97), and achieved equivalent CAF to UVA CXL with 13 pulses/spot. Indentation testing detected a 62% increase in stiffness using NLO CXL compared to control (P<0.05). CAF intensities of these samples were significantly higher than both UVA CXL and NLO CXL samples of previous studies using non-amplified pulses (P<0.05). In vivo corneal topography measurements revealed a significant decrease of 1.0 ± 0.8 diopter in the treated eyes by one month, which remained stable at two months.

Conclusions : These results show that NLO CXL using amplified pulses is capable of producing corneal collagen crosslinking to the same degree as UVA CXL or NLO CXL with non-amplified pulses. These results suggest that NLO CXL can be used to perform personalized corneal crosslinking for treatment of refractive errors and Keratoconus.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.