First Demonstration of Ocular Refractive Change Using Blue-IRIS in Live Cats

Savage, Daniel E.; Brooks, Daniel R.; DeMagistris, Margaret; Xu, Lisen; MacRae, Scott; Ellis, Jonathan D.; Knox, Wayne H.; Huxlin, Krystel R.

doi:10.1167/iovs.14-14373

Cited by 32 publications

(17 citation statements)

References 37 publications

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“…1) was identical to that described in our previous publications (Brooks et al ., 2014; Savage et al ., 2014). In brief, we used a mode-locked Ti:Sapphire oscillator (Vitesse; Coherent Corporation, Santa Clara, CA) emitting 800 nm, 100 fs pulses at 80 MHz.…”

Section: Methodsmentioning

confidence: 99%

“…The vibration exciter, in conjunction with the linear stage, provided for a raster scan motion while the vertical stage controlled the depth of the focal region in the stroma. The resulting pattern of RI change occupied an en-face area ~2.5 mm by 2.5 mm, consisting of 1 µm center-spaced lines written into the mid to anterior stroma (Brooks et al ., 2014; Savage et al ., 2014). …”

Section: Methodsmentioning

confidence: 99%

“…Once reproducible IRIS patterns were inscribed in hydrogels, we translated the procedure to cornea and using a high-repetition rate, 400 nm femtosecond laser, with intensities below the damage threshold of the cornea, we were able to locally modify the refractive index (RI) of the corneal matrix (Ding et al ., 2008; Nagy et al ., 2010; Xu et al ., 2010; Xu et al ., 2011a) – an approach termed Blue-Intra-tissue Refractive Index Shaping (Blue-IRIS). We subsequently showed that Blue-IRIS could be used to alter corneal refractive power in vivo (Savage et al ., 2014). The native two-photon absorption of the cornea at 400 nm, coupled with a high numerical aperture (NA) laser delivery system, created a highly localized region of refractive index (RI) change (Xu et al ., 2010; Xu et al ., 2011b).…”

Section: Introductionmentioning

confidence: 99%

“…The native two-photon absorption of the cornea at 400 nm, coupled with a high numerical aperture (NA) laser delivery system, created a highly localized region of refractive index (RI) change (Xu et al ., 2010; Xu et al ., 2011b). By translating this focal region through the cornea, it was possible to inscribe one to three closely-spaced, identically-written, custom gradient index (GRIN) layers and attain significant changes in refractive power (Brooks et al ., 2014; Savage et al ., 2014). We hypothesized that because Blue-IRIS did not require epithelial debridement, flap creation, or tissue removal, it should prove less invasive and damaging to the cornea than traditional laser refractive surgeries (Campos et al ., 1994; Møller-Pedersen et al ., 2000; Nakamura et al ., 2001; Netto et al ., 2007).…”

Section: Introductionmentioning

confidence: 99%

“…This correction was chosen to mirror previous IRIS refractive corrections performed in live cats (Savage et al ., 2014), thus providing an opportunity to study the biological consequences of those corrections. We chose to also study femto-LASIK because, like Blue-IRIS, this procedure uses a femtosecond laser.…”

Section: Introductionmentioning

confidence: 99%

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Contrasting cellular damage after Blue-IRIS and Femto-LASIK in cat cornea

Wozniak

Elkins

Brooks

et al. 2017

Experimental Eye Research

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Blue-intra-tissue refractive index shaping (Blue-IRIS) is a new approach to laser refractive correction of optical aberrations in the eye, which alters the refractive index of the cornea rather than changing its shape. Before it can be implemented in humans, it is critical to establish whether and to what extent, Blue-IRIS damages the cornea. Here, we contrasted the impact of −1.5 D cylinder refractive corrections inscribed using either Blue-IRIS or femtosecond laser in situ keratomileusis (femto-LASIK) on corneal cell viability. Blue-IRIS was used to write a −1.5 D cylinder gradient index (GRIN) lens over a 2.5 mm by 2.5 mm area into the mid-stromal region of the cornea in six freshly-enucleated feline eyes. The same correction (−1.5 D cylinder) was inscribed into another four cat eyes using femto-LASIK. Six hours later, all corneas were processed for histology and stained for terminal deoxynucleotidyl transferase-mediated dUTP35 digoxigenin nick end labeling (TUNEL) and p-γ-H2AX to label damaged cells. In Blue-IRIS-treated corneas, no tissue was removed and TUNEL-stained cells were confined to the laser focal zone in the stroma. In femto-LASIK, photoablation removed 14 µm of anterior stroma, but in addition, TUNEL-positive cells clustered across the femto-flap, the epithelium at the flap edges and the stroma below the ablation zone. Keratocytes positive for p-γ-H2AX were seen adjacent to all Blue-IRIS focal zones, but were completely absent from femto-LASIK-treated corneas. Unlike femto-LASIK, Blue-IRIS attains refractive correction in the cornea without tissue removal and only causes minimal, localized keratocyte death within the laser focal zones. In addition, Blue-IRIS induced DNA modifications associated with phosphorylation of γ-H2AX in keratocytes adjacent to the laser focal zones. We posit that this p-γ-H2AX response is related to alterations in chromatin structure caused by localized changes in osmolarity, a possible mechanism for the induced refractive index changes.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%