Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy

Burri, Christian; Al-Nawaiseh, Sami; Wakili, Philip; Salzmann, Simon; Krötz, Christina; Považay, Boris; Meier, Christoph; Frenz, Martin; Szurman, Peter; Schulz, André; Stanzel, Boris V.

doi:10.1167/tvst.10.10.17

Cited by 10 publications

(9 citation statements)

References 47 publications

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“…In particular, in the regular SRT application mode using pulse ramps, with a pulse duration of 8 µs, the performance (AUC: 98%) and the accuracy of 97% (sensitivity: 99%, specificity: 93%) are remarkable. This setting has already emerged in previous experiments [ 19 , 22 , 31 , 33 , 42 ] and is, therefore, currently also being evaluated clinically (ClinicalTrials.gov Identifier: NCT04968756). Therefore, in vivo RFD data on our SD-OCT M-scan based algorithm and the Spectralis Centaurus device should be available soon.…”

Section: Discussionmentioning

confidence: 99%

“…Sets of laser pulses with increasing energy grouped in durations of 8, 12, 16, and 20 µs were applied. The pulse energy was adapted according to a recent in vivo animal study [ 22 , 42 ] to meet the microsecond pulse duration range described in detail in the introduction. As depicted in Figure 1 c, the pulse duration was increased from top to bottom and the pulse energy was increased from left (20 µJ) to right (160 µJ).…”

Section: Methodsmentioning

confidence: 99%

“…Lee et al substantiated this theoretical assumption when they showed that, in the case of 1, 5 and 10 µs laser pulse duration, more than 95% of dead RPE cells were associated with MBF, whereas the ratio decreased to 65% and 45% for longer 20 µs and 40 µs pulses, respectively [ 21 ]. Complementarily, an in vivo experiment by Burri et al showed that for pulse durations of 20 µs, more pronounced morphologic retinal changes occur according to optical coherence tomography (OCT) B-scans compared to pulse durations of 4 µs [ 22 ]. It can be concluded that the pulse duration range of around 10 µs up to 20 µs, respectively, has to be carefully evaluated to achieve the desired effect according to SRT, but at the same time to avoid suprathreshold lesions with unwanted collateral effects to ensure clinical safety.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium

Burri,

Salzmann,

Amstutz

et al. 2023

Life

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Optical microsurgery confined to the retinal pigment epithelium (RPE) requires locally optimized laser parameters and reliable real-time feedback dosimetry (RFD) to prevent unwanted neuroretinal overexposure. This study aimed to compare pulses of different durations and application modes (single, ramp, burst). Moreover, optical coherence tomography (OCT)-based RFD was investigated in an ex vivo experiment, utilizing nine porcine eyes that were exposed to laser pulses of 8, 12, 16 and 20 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm2, radiant exposure: 247 to 1975 mJ/µm2). Simultaneously, time-resolved OCT M-scans were recorded (central wavelength: 870 nm, scan rate: 85 kHz) for RFD. Post irradiation, retinal changes were assessed with color fundus photography (CFP) and cross-sectional OCT B-scans. RPE cell damage was quantified via fluorescence-based cell viability assay and compared to the OCT dosimetry feedback. Our experiments indicate cumulative RPE damage for pulse bursts of 16 µs and 20 µs, whereas no cumulative effects were found for pulse durations of 8 µs and 12 µs applied in ramp mode. According to statistical analysis, OCT-RFD correctly detected RPE cell damage with 96% sensitivity and 97% specificity using pulses of 8 µs duration in ramp mode.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium

Burri,

Salzmann,

Amstutz

et al. 2023

Life

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“…Recently, the Spectralis Centaurus device was used at a pulse duration of 8 µs in an in vivo rabbit model to remove the RPE over a large area, allowing for a simplified subretinal injection [ 86 ]. This procedure should one day benefit RPE cell therapies and remove the host RPE cells prior to the injection of new stem cell–derived RPE cells.…”

Section: Discussionmentioning

confidence: 99%

Real-time OCT feedback-controlled RPE photodisruption in ex vivo porcine eyes using 8 microsecond laser pulses

Burri,

Salzmann,

Wandel

et al. 2023

Biomed. Opt. Express

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Selective retinal pigment epithelium (RPE) photodisruption requires reliable real-time feedback dosimetry (RFD) to prevent unwanted overexposure. In this study, optical coherence tomography (OCT) based RFD was investigated in ex vivo porcine eyes exposed to laser pulses of 8 µs duration (wavelength: 532 nm, exposure area: 90 × 90 µm2, radiant exposure: 247 to 1975 mJ/µm2). For RFD, fringe washouts in time-resolved OCT M-scans (central wavelength: 870 nm, scan rate: 85 kHz) were compared to an RPE cell viability assay. Statistical analysis revealed a moderate correlation between RPE lesion size and applied treatment energy, suggesting RFD adaptation to inter- and intraindividual RPE pigmentation and ocular transmission.

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“…In addition, TxCell technology allows for the making of confluent lesions in the treated area. Laser power was adjusted to reach the minimum visible threshold to compensate for the natural changes in the pigmentation of the pig eyes ( 59 ). Spot size of 200 μm and 330 ms of exposure time, DC of 1% (0.1 ms on to 9.9 ms off), 1.5% (0.1 ms on to 6.6 ms off), and 2% (0.1 ms on to 4.9 ms off) were used with laser power of 1800 mw (1% DC), 1600 mw (1.5% DC), and 1100 mw (2% DC).…”

Section: Methodsmentioning

confidence: 99%

A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing

Barone¹,

Amaral²,

Bunea³

et al. 2023

JCI Insight

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Over 30 million people worldwide suffer from untreatable vision loss and blindness associated with childhood-onset and age-related eye diseases caused by photoreceptor (PR), retinal pigment epithelium (RPE), and choriocapillaris (CC) degeneration. Recent work suggests that RPE-based cell therapy may slow down vision loss in late stages of age-related macular degeneration (AMD), a polygenic disease induced by RPE atrophy. However, accelerated development of effective cell therapies is hampered by the lack of large-animal models that allow testing safety and efficacy of clinical doses covering the human macula (20 mm 2 ). We developed a versatile pig model to mimic different types and stages of retinal degeneration. Using an adjustable power micropulse laser, we generated varying degrees of RPE, PR, and CC damage and confirmed the damage by longitudinal analysis of clinically relevant outcomes, including analyses by adaptive optics and optical coherence tomography/angiography, along with automated image analysis. By imparting a tunable yet targeted damage to the porcine CC and visual streak — with a structure similar to the human macula — this model is optimal for testing cell and gene therapies for outer retinal diseases including AMD, retinitis pigmentosa, Stargardt, and choroideremia. The amenability of this model to clinically relevant imaging outcomes will facilitate faster translation to patients.

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Selective Large-Area Retinal Pigment Epithelial Removal by Microsecond Laser in Preparation for Cell Therapy

Cited by 10 publications

References 47 publications

Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium

Investigation of the Influence of Pulse Duration and Application Mode on Microsecond Laser Microsurgery of the Retinal Pigment Epithelium

Real-time OCT feedback-controlled RPE photodisruption in ex vivo porcine eyes using 8 microsecond laser pulses

A versatile laser-induced porcine model of outer retinal and choroidal degeneration for preclinical testing

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