Ex vivo investigation of different μs laser pulse durations for selective retina therapy

Abstract

Selective retina therapy (SRT) is currently used in clinical studies to treat several chorioretinal diseases. For SRT a laser pulse duration of 1,7 µs is currently used. At this pulse duration the retinal pigment epithelium (RPE) cells are destroyed by transient microbubbles without damaging the neuronal retina. So far it is unclear whether slightly longer laser pulses are still acting thermomechanically or whether thermal effects show responsible for cell damage close above damage threshold. In order to investigate the damage threshold increase with pulse duration, a novel laser with adjustable pulse duration in the range of 2-20 µs was used to investigate RPE damage on ex-vivo porcine RPE explants. The specimen were fixed in an eye model and were exposed to laser pulse energies ranging from 15-150 µJ with a top hat square of 120x120µm², exhibiting a spatial intensity modulation factor of 1,3. Viability tests using binary evaluation result in threshold values with peak radiant exposures of 233 mJ/cm 2 and 389 mJ/cm 2 for 2 µs and 20 µs laser durations, respectively. An almost logarithmic increase of the threshold radiant exposure over pulse duration was found.

Dynamic OCT Signal Loss for Determining RPE Radiant Exposure Damage Thresholds in Microsecond Laser Microsurgery

“…To calculate the IMF, the treatment laser beam was imaged with a magnification of 9.81 onto a beam analyzer camera (BC 106 VIS, Thorlabs Inc., Newton, NJ, USA)) behind the laser aperture of the system. An IMF = 1.3 was determined, which indicates a high-quality top-hat beam profile [32].…”

Nanosecond multipulse retinal damage thresholds of elongated irradiance profiles in explant measurements and simulations

“…The images captured about 1 h after the irradiation are evaluated by human with the following criteria for the samples and every measurement point, binary information (damage: 1; no damage/not affected: 0) is assigned as done by Schulmeister et al., 14 Lipp et al., 32 , 33 and Schuele et al 41 – 44 …”

“…The images captured about 1 h after the irradiation are evaluated by human with the following criteria for the samples and every measurement point, binary information (damage: 1; no damage/not affected: 0) is assigned as done by Schulmeister et al, 14 Lipp et al, 32,33 and Schuele et al [41][42][43][44] • Samples where the RPE cells detached from the underlying tissue and where the visual check showed unhealthy or abnormal things, such as defects or dryout, are discarded. ) is considered as a lesion.…”

Determination of the biological variability of porcine explant tissue in retinal damage ex-vivo experiments with optical laser radiation

“…Schulmeister et al 16,17,33,46 expanded the data base for the laser safety standard with extensive ex-vivo experiments on bovine explant tissue, termed ex-plant studies, in the visible and near infrared wavelength to validate the computer models of their research. Hutfilz et al , 14 Seifert et al , 47 Lipp et al 15 and Herbst et al 27 had different approaches on special parameter sets such as the pulse duration or multi pulse aspects with porcine tissue.…”

“…The limits provided in the laser safety standard are based on damage thresholds empirically determined in experiments 2,3 and simulations. Therefore, researchers perform and have performed in-vivo experiments mostly on non-human primates (NHP) [4][5][6][7][8][9] or rabbits [10][11][12] and ex-vivo experiments with animal tissue such as porcine [13][14][15] or bovine 16,17 tissue in the past. 2,3,[18][19][20][21] However, novel optical scanning technologies, such as Lidar sensors or laser projection systems, feature complex architectures with e.g.…”