Selective treatment of the retinal pigment epithelium (RPE) by using short-pulse lasers leads to a less destructive treatment for certain retinal diseases in contrast to conventional photocoagulation. The introduction of selective retina therapy (SRT) to clinical routine is still precluded by the challenges to reliably monitor treatment success and to automatically adjust dose within the locally varying therapeutic window. Combining micrometer-scale depth resolving capabilities of optical coherence tomography (OCT) with SRT can yield real-time information on the laser-induced changes within the RPE after a laser pulse or even during treatment with a laser pulse train. In the present study, SRT and OCT were combined to treat ex-vivo porcine eyes demonstrating closed-loop dose-control. We found a reliable correlation of specific signal changes in time resolved OCT images and physiological lesions in the RPE. First experiments, including 23 porcine eyes, prove the feasibility of the novel treatment concept.
Optical microsurgery of the retinal pigment epithelium (RPE) requires reliable real-time dosimetry to prevent unwanted overexposure of the neuroretina. The system used in this experiment implements optical coherence tomography (OCT) to detect the intentional elimination of RPE cells. We evaluated the performance of OCT dosimetry in terms of its ability to detect RPE cell damage caused by microsecond laser pulses of varying duration. Therefore, ex-vivo porcine RPE choroid sclera explants were embedded in an artificial eye and exposed to single laser pulses of 2–20 µs duration (wavelength: 532 nm, exposure area: 120 × 120 µm2, intensity modulation factor: 1.3). Simultaneously, time-resolved OCT M-scans were recorded (central wavelength: 870 nm, scan rate: 33 kHz). Post-irradiation, RPE cell damage was quantified using a calcein-AM viability assay and compared with an OCT-dosimetry algorithm. The results of our experiments show that the OCT-based analysis successfully predicts RPE cell damage. At its optimal operating point, the algorithm achieved a sensitivity of 89% and specificity of 94% for pulses of 6 µs duration and demonstrated the ability to precisely control radiant exposure of a wide range of pulse durations towards selective real-time laser microsurgery.
For ophthalmologic applications, specifically for refractive surgery, the wavelength range between 190 and 220 nm has been identified as particularly suitable, because of the high absorption coefficient in corneal tissue in this part of the spectrum.1 The most commonly used pulsed laser sources are the ArF excimer laser with a wavelength of 193 nm2 and upconverted solid-state lasers at 210 and 213 nm.3 Studies on corneal ablation with these lasers have shown a similar degree of precision and tissue damage.4–6 Moreover, no significant difference in corneal mutagenesis was reported.4,7,8 The main difference is the two- to threefold higher absorption coefficient at 193 nm and, as a consequence, the lower threshold fluence for ablation.9–11 Corneal ablation experiments were also performed with KrCl and KrF excimer lasers at 222 and 248 nm, respectively, but the severe thermal effects on the surrounding tissue12 made these lasers unsuitable for refractive surgery.
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.
The prevalent cause of retinal detachment is a full-thickness retinal break and the ingress of fluid into the subretinal space. To prevent progression of the detachment, laser photocoagulation (LPC) lesions are placed around the break in clinical practice to seal the tissue. Unlike the usual application under indirect ophthalmoscopy, we developed a semi-automatic treatment planning software based on a sequence of optical coherence tomography (OCT) scans to perform navigated LPC treatment. The depth information allows demarcation of the border where the neurosensory retina is still attached to the retinal pigment epithelium (RPE), which is critical for prevention of detachment progression. To evaluate the method, artificially provoked retinal breaks were treated in seven ex-vivo porcine eyes. Treatment outcome was assessed by fundus photography and OCT imaging. The automatically applied lesions surrounding each detachment (4.4–39.6 mm2) could be identified as highly scattering coagulation regions in color fundus photography and OCT. Between the planned and applied pattern, a mean offset of 68 µm (SD ± 16.5 µm) and a mean lesion spacing error of 5 µm (SD ± 10 µm) was achieved. The results demonstrate the potential of navigated OCT-guided laser retinopexy to improve overall treatment accuracy, efficiency, and safety.