The induced thermal damage in retinal photocoagulation depends on the temperature increase and the time of irradiation. The temperature rise is unknown due to intraocular variations in light transmission, scattering and grade of absorption in the retinal pigment epithelium (RPE) and the choroid. Thus, in clinical practice, often stronger and deeper coagulations are applied than therapeutically needed, which can lead to extended neuroretinal damage and strong pain perception. This work focuses on an optoacoustic (OA) method to determine the temperature rise in real-time during photocoagulation by repetitively exciting thermoelastic pressure transients with nanosecond probe laser pulses, which are simultaneously applied to the treatment radiation. The temperature-dependent pressure amplitudes are non-invasively detected at the cornea with an ultrasonic transducer embedded in the contact lens. During clinical treatment, temperature courses as predicted by heat diffusion theory are observed in most cases. For laser spot diameters of 100 and 300 μm, and irradiation times of 100 and 200 ms, respectively, peak temperatures range between 70°C and 85°C for mild coagulations. The obtained data look very promising for the realization of a feedback-controlled treatment, which automatically generates preselected and reproducible coagulation strengths, unburdens the ophthalmologist from manual laser dosage, and minimizes adverse effects and pain for the patient.
Laser coagulation is a treatment method for many retinal diseases. Due to variations in fundus pigmentation and light scattering inside the eye globe, different lesion strengths are often achieved. The aim of this work is to realize an automatic feedback algorithm to generate desired lesion strengths by controlling the retinal temperature increase with the irradiation time. Optoacoustics afford non-invasive retinal temperature monitoring during laser treatment. A 75 ns / 523 nm Q-switched Nd:YLF laser was used to excite the temperature-dependent pressure amplitudes, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. A 532 nm continuous wave Nd:YAG laser served for photocoagulation. The ED50 temperatures, for which the probability of ophthalmoscopically visible lesions after one hour in vivo in rabbits was 50%, varied from 63°C for 20 ms to 49°C for 400 ms. Arrhenius parameters were extracted as ΔE = 273 J mol − 1 and A = 3 · 1044 s − 1. Control algorithms for mild and strong lesions were developed, which led to average lesion diameters of 162 ± 34 μm and 189 ± 34 μm, respectively. It could be demonstrated that the sizes of the automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.
Retinal photocoagulation is an established treatment for various retinal diseases. The temperature development during a
treatment can be monitored by applying short laser pulses in addition to the treatment laser light. The laser pulses induce
optoacoustic pressure waves that can be detected at the cornea. Aim of this work is the investigation of the accuracy of
the determined temperatures during a treatment.
To calibrate the temperature dependency of the measured pressure, whole enucleated porcine eyes were heated using an
infrared laser beam, while probing the retina optoacoustically. The temperatures and the optoacoustic pressure waves
were measured simultaneously using thermocouples and a piezoelectric element, respectively. From the deviation of the
individual measurements an error of less than 15% in the calibration regime between 37 °C to 55 °C was found.
Furthermore, the spatial and temporal temperature course was investigated. Calculations were performed to simulate the
temporal and spatial temperature development during photocoagulation. A theoretical model to determine the peak
temperature of the irradiated tissue from the mean temperature measured by optoacoustics was developed.
The validity of the model was experimentally examined by heating the retina of porcine eyes with a laser beam diameter
of 500 μm while successively measuring the temperature optoacoustically with a probe beam diameter of 500 μm and
100 μm at the center of the heated area, respectively. The deviation of the theoretical model and the experimental results
were found to be less than 7%.
Retinal laser photocoagulation is an established treatment method for many retinal diseases like macula edema or
diabetic retinopathy. The selection of the laser parameters is so far based on post treatment evaluation of the lesion
size and strength. Due to local pigment variations in the fundus and individual transmission the same laser
parameters often lead to an overtreatment. Optoacoustic allows a non invasive monitoring of the retinal temperature
increase during retinal laser irradiation by measuring the temperature dependent pressure amplitudes, which are
induced by short probe laser pulses. A 75 ns/ 523 nm Nd:YLF was used as a probe laser at a repetition rate of 1 kHz,
and a cw / 532 nm treatment laser for heating. A contact lens was modified with a ring-shaped ultrasonic transducer
to detect the pressure waves at the cornea. Temperatures were collected for irradiations leading to soft or invisible
lesions. Based on this data the threshold for denaturation was found. By analyzing the initial temperature increase,
the further temperature development during irradiation could be predicted. An algorithm was found to calculate the
irradiation time, which is needed for a soft lesion formation, from the temperature curve. By this it was possible to
provide a real-time dosimetry by automatically switching off the treatment laser after the calculated irradiation time.
Automatically controlled coagulations appear softer and more uniformly.
Considerable improvement in the reproducibility of retinal photocoagulation is expected if degree and extend of the heat-induced tissue damage can be visualized on-line during the treatment. Experimental laser treatments of the retina with enucleated pig eyes were investigated by high speed phase-sensitive OCT. OCT could visualize the increase of tissue scattering during the photocoagulation in a time-resolved way. Immediate and late tissue changes were visualized with more than 15 µm resolution. Changes of the reflectance in the OCT images had a similar sensitivity in detecting tissue changes than macroscopic imaging. By using Doppler OCT slight movements of the tissue in the irradiated spot were detected. At low irradiance the thermal expansion of the tissue is observed. At higher irradiance irreversible tissue changes dominate the tissue expansion. OCT may play an important role in understanding the mechanisms of photocoagulation. This may lead to new treatment strategies. First experiments with rabbits demonstrate the feasibility of in-vivo measurements.
Selective retina treatment (SRT) is a laser based method to treat retinal diseases associated with disorders of the retinal
pigment epithelium (RPE) while preserving photoreceptors and choroid. Applying microsecond laser pulses to the 100-
200 strongly absorbing melanin granules inside the RPE cells induces transient micro bubbles which disrupt the cells.
Aim of this work is to understand bubble dynamics in clusters with respect to the influence of the adjacent retina. Bubble
dynamics were investigated in vitro on porcine RPE. An about 200 μm thick layer of agarose gel was applied to the RPE
layer in order to simulate the mechanical properties of retina. Different laser pulse durations from 1 ns (532 nm,
Nd:YAG) to 1.7 μs (527 nm, Nd:YLF) were used. The bubbles were investigated interferometrically (fiber
interferometer @ 830 nm) and with fast flash photography (25 ns flash duration). Bubble lifetimes were measured. The
results show that with retina phantoms the bubble formation threshold was reached at 2.5 times higher irradiation than
without retina phantom for 1.7 μs laser pulses. The microbubbles generated with 1 ns laser pulses were almost not influenced by the agarose layer. Irradiation twofold over bubble formation threshold resulted in 3.5 times longer bubble lifetimes for μs and 2 times longer for ns pulse durations, respectively.
Retinal photocoagulation is a long time established treatment for a variety of retinal diseases, most commonly applied for
diabetic macular edema and diabetic retinopathy. The damage extent of the induced thermal coagulations depend on the
temperature increase and the time of irradiation. So far, the induced temperature rise is unknown due to intraocular
variations in light transmission and scattering and RPE/choroidal pigmentation, which can vary inter- and intraindividually
by more than a factor of four. Thus in clinical practice, often stronger and deeper coagulations are applied than
therapeutically needed, which lead to extended retinal damage and strong pain perception. The final goal of this project
focuses on a dosimetry control, which automatically generates a desired temperature profile and thus coagulation
strength for every individual coagulation spot, ideally unburden the ophthalmologist from any laser settings. In this paper
we present the first realtime temperature measurements achieved on patients during retinal photocoagulation by means of
an optoacoustic method, making use of the temperature dependence of the thermal expansion coefficient of retinal tissue.
Therefore, nanosecond probe laser pulses are repetitively and simultaneously applied with the treatment radiation in
order to excite acoustic waves, which are detected at the cornea with an ultrasonic transducer embedded in the contact
lens and then are processed by PC.
Selective retina treatment (SRT) is a laser based therapy of retinal diseases associated with disorders of the retinal pigment epithelium (RPE) while preserving photoreceptors and choroid. Microsecond laser pulses applied to the 100-200 strongly absorbing melanin granules inside the RPE cells induce transient micro bubbles which disrupt the cells. Aim of this work is to understand bubble dynamics in clusters.
Investigations were carried out on porcine RPE explants and on a floppy disc based model system. Laser pulse durations
of 3 ns (532 nm, Nd:YAG) and 1.7 μs (527 nm, Nd:YLF) were used. Bubble dynamics was explored with a fiber interferometer (830 nm) and fast flash photography (25 ns). Bubble sizes, velocities and lifetimes were measured. Single nucleation sites, which coalesce after some μs, are observed with ns pulses. Using μs pulses, fewer but larger cluster sites are observed which become two times bigger at the same factor above threshold. A linear increase of the
bubble hight with radiant exposure is found for both pulse durations. RPE Bubble formation thresholds of 85 mJ/cm2
and 255 mJ/cm2 for ns and μs pulses are found, respectively. Typical expansion velocities are 5 m/s while collapsing
bubbles can reach 30 m/s. Bubble heights are up to 5 μm.
Earlier investigations on single melanosomes showed a bubble size limitation to 4 μm with μs pulses. The melanosome clusters do not show this size limit. It has to be investigated whether the results are transferable to whole eye globes.
Selective retina treatment (SRT) is a new laser based method to treat retinal diseases associated with disorders of the
retinal pigment epithelium (RPE). Applying microsecond laser pulses tissue damage spatially confined to the retinal
pigment epithelium (RPE) is achieved. The RPE cell damage is caused by transient microbubbles emerging at the
strongly absorbing melanin granules inside the RPE cells. Due to the spatial confinement to the RPE the photoreceptors
can be spared and vision can be maintained in the treated retinal areas. A drawback for effective clinical SRT is that the
laser induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is
necessary in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry
system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an
optical fiber interferometer operated with a laser diode at 830nm. We present current results obtained with a laser slit
lamp using porcine RPE explants in vitro and complete porcine eye globes ex vivo. The RPE cell damage is determined
by Calcein fluorescence viability assays. With a threshold criterium for RPE cell death derived from the measured
interferometric signal transients good agreement with the results of the viability assays is achieved.
Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.
In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is
obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming
around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share
the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for
effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback
system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue.
We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The
system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current
results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.
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