Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

            Femtosecond Laser-Induced Retina
              Damage Thresholds in Pig Eyes

                                       LAKE LARSON
                                    OPTICAL ENGINEER
                                EXTREME LIGHT LABORATORY
                              UNIVERSITY OF NEBRASKA-LINCOLN

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    Outline
    1.   Vitreoretinal Surgery and Limitations

    2.   Introduction to Laser-Surgical Applications

    3.   Femtosecond Laser Experimentation in Posterior Segment

    4.   Future Directions

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

    Invasive Vitreoretinal Surgery Practices
    Today, the only surgical practice for the retina is invasive.

    Number done a year: ~300,000

    Possible Morbidities

            •   Cataract Formation
            •   Glaucoma
            •   Infection
            •   Haemorrhage
            •   Vision Loss/Loss of Eye
    Developing non invasive approaches would
    improve outcomes.

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    Current Noninvasive Laser Surgical Practices
    Lasers are a promising approach to improve outcomes.
    Commonly used to treat anterior segment disease.
    but reaching the posterior segment requires passing through the vitreous
    without causing damage while maintaining the integrity of the laser pulse.

    Nanosecond lasers (SI unit: 10-9 seconds)
    Most commonly used for floater treatment.

    Limitations of Current Technology:
      •   Cannot be performed within 2mm of eye surfaces
      •   20% of the eye is inoperable
      •   The retina is unreachable

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

    Femtosecond Laser Introduction
    Femtosecond (SI unit: 10-15 seconds)

    Able to operate microns from the retina while minimizing collateral damage.

5

    Cavitation
    Tissue cutting done by ionization.
    Using femtosecond lasers, we must reach the
    retina while preserving:
     •   Focal spot quality
     •   Energy density
     •   High cutting precision
     •   Repeatability
    This will allow us to make micron sized cuts to the
    retina while minimizing collateral damage to the
    underlying and surrounding tissue.

    The goal is to make cuts to the retina as shown
    in the last slide.

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

                                           Experimentation

    How Can this be Done?                  1. Through Vitreous

    Using:

     • Femtosecond Lasers
     • Temporal Dispersion Control         2. At the Retina
     • Vitreous Cavitation

    precise micron, retinal cutting.

                                           3. Above the Retina

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    Parameters of Experiments

    Femtosecond Laser (Archimedes Laser)

     •   Ti:Saph, Broadband Laser System

     •   10 micron focal-spot diameter
     •   ~28 femtoseconds
     •   800nm central wavelength
     •   100nm total bandwidth
     •   Rep Rate: 10Hz

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

         Experiment 1                                       No Compensation
                                                     Compressed                       Uncompressed
        Vitreous Compensation

     Traveling through media such                                   Dispersive
                                                                     Media
       as vitreous adds dispersion;
         which decreases pulse
      duration and therefore pulse                                V(red) > V(blue)

                 intensity.
                                                           Pre Compensation
                                            Compensated                                 Compressed

       Pulse Morphology must be
     preserved through the vitreous.                                Dispersive
      Pre-Compensation (negative                                     Media
          dispersion) does this.

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         Experiment 1                                                                38 fs
                                       AIR

         Determining Dispersion
           Through Vitreous.

          Laser pulses were sent
      through various situations to
                                       VITREOUS

                                                                                     80 fs
         determine the negative
      dispersion required to deliver
      a compressed pulse through
        the vitreous to the retina.
                                       COMPENSATED

         FROG system used to                                                          38 fs
          measure temporal
        parameters of the pulse.

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

          Experiment 2
     Determining Damage Threshold

     Determining an energy-per-pulse
     that is able to cause retinal
     cavitation while not damaging
     underlying structures is essential for
     this practice.

                     Using multiple pulse
                     energies, we can
                     determine a threshold
                     for retinal surface
                     damage.

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          Experiment 2
       Determination of Cavitation
               Threshold.                               2
                                                    (um ±SD)            ENERGY

       Pulses were focused on the              2,346.7 ± 378.8 (n=4)     12 nJ
                  retina
                                               4,968.1 ± 347.1 (n=2)    115 nJ

      Four energy levels were used            15,220.4 ± 6974.3 (n=5)    12 uJ

                                              7,174.1 ± 2388.9 (n=5)     21 uJ
      Burn area on the retina was
      determined via SEM analysis                 F(3,12) = 7.52

                                                    p = 0.0043
         A damage threshold of
      6.4 mJ/cm2 was determined

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

         Experiment 3
                                          Gaussian Laser Focus

      Cavitation above the Retina

       We can make predictions
                                              Propagation
      about retinal cavitation as a
         function of distance.

     This will give us a safe range for
      vitreoretinal surgery and how
      far away cuts can be made
          from the retinal surface.

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         Experiment 3
       Distance to Damage Curve

      One energy level, 20nJ/pulse

     The focus (cavitation location)
      was scanned away from the
                 retina

       Expectation is a falloff of
     damage, and then a clear cut
                 off.

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

      Retinal Surface              Topography

                        Z-Axis Scan

     For three, shots; the depth was calculated to be
     ~200um deep from the surface of the retina.
     Used for depth and diameter of retinal damage.
     We look forward to having these results soon.

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                Summarization of Experiments

            EXPERIMENT 1                            EXPERIMENT 2                   EXPERIMENT 3

     Negative dispersion was                 A cavitation threshold was         Pulses were scanned
     used to compensate for                  determined using multiple          away from the retinal
     effects as the laser pulses              pulse energies to ablate       surface at the determined
     pass through the vitreous.              the retinal surface directly.   cavitation threshold to find
                                                                               a damage-to-distance
                                                                                        curve.

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
6/7/2021

                                         Future Directions

         OCT (Optical Coherence Tomography)                                                     Adaptive Optics System

      OCT will be used to determine both depth of                                   Aberration introduced from structures of the
      cuts performed by cavitation, and the retinal                                     eye and optical components will be
                     layers affected.                                                corrected using a closed-loop, wavefront
                                                                                       sensor and deformable mirror system.

17

     References
        Ben-Yakar, A., & Byer, R. L. (2004). Femtosecond laser ablation properties of borosilicate glass. Journal of Applied Physics, 96(9),
        5316–5323. doi:10.1063/1.1787145

        Retinal Detachment. Better Health Channel. (2017, July 27).
        https://www.betterhealth.vic.gov.au/health/ConditionsAndTreatments/retinal-detachment#bhc-content.

     Acknowledgements
        Dr. David E. Anderson       - Department of Ophthalmology and Visual Science, UNMC

        Junzhi Wang                 - Department of Physics and Astronomy, UNL

        Dr. Ronald Krueger          - Department of Ophthalmology and Visual Science, UNMC

        Dr. Renfeng Xu              - Department of Ophthalmology and Visual Science, UNMC

        Dr. You Zhou                - Department of Biology, UNL

        Dr. Geunyoung Yoon          - Department of Ophthalmology, University of Rochester Medical Center

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Femtosecond Laser-Induced Retina Damage Thresholds in Pig Eyes - UNMC
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     Supplementary

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     Adaptive Optics
          Incoming, distorted
       wavefronts are measured
       using a Wavefront Sensor
      such as a Hartmann Shack.

       The wavefronts are then
      corrected by a deformable
                mirror.

     This closed loop system allows
        for minimal aberration in
            pulse morphology.

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                                           10
6/7/2021

     Adaptive Optics in
         the Eye

                          175
                          um

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              Simplified Experimental Setup

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