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.
When irradiated with nanosecond laser pulses, gold nanoparticles allow for manipulation or destruction of cells and proteins with high spatial and temporal precision. Gold nanorods are especially attractive, because they have an up-to-20-fold stronger absorption than a sphere of equal volume, which is shifted to the optical window of tissue. Thus, an increased efficiency of cell killing is expected with laser pulses tuned to the near infrared absorption peak of the nanorods. In contrast to the higher-absorption, experiments showed a reduced efficacy of cell killing. In order to explain this discrepancy, transient absorption of irradiated nanorods was measured and the observed change of particle absorption was theoretically analyzed. During pulsed irradiation a strong transient and permanent bleaching of the near-infrared absorption band occurred. Both effects limit the ability of nanorods to destroy cells by nanocavitation. The existence of nanocavitation and transient bleaching was corroborated by optoacoustic measurements.
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.
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.
The retinal photocoagulation is an established treatment method for different retinal diseases. The extent of the thermal
coagulations depends strongly on the generated temperature increase. Until now the dosage is based on a pool of
experience of the treating physicians as well as the appearance of the whitish lesions on the retina. The temperature
course during photocoagulation can be measured in real-time by optoacoustics. A frequency-doubled Q-switched
Nd:YLF laser (523nm, 75 ns) is used for optoacoustic excitation and a continuous-wave Nd:YAG laser (532nm) with
adjustable irradiation time and power for heating of the fundus tissue. The onset of coagulation is determined by a
photodiode that is placed directly behind enucleated porcine eyes, which served as a model. The onset of coagulation is
observed clearly when scattering sets in. The required power for coagulation increases exponentially with decreasing
irradiation time. The first results on rabbit eyes in vivo indicate that the onset of coagulation defined by just barely
visibile lesions at a slit lamp sets in at an ED50 threshold temperature of 63°C for an irradiation time of 400 ms. In
conclusion, optoacoustics can be used to determine temperatures during retinal laser treatments in real-time. This allows
evaluating the time-temperature-dependence of retinal coagulation in vivo.
The extent of retinal laser coagulations depends on the temperature increase at the fundus and the time of irradiation. Due to light scattering within the eye and variable fundus pigmentation the induced temperature increase and therefore the extent of the coagulations cannot be predicted solely from the laser parameters. We use optoacoustics to monitor the temperature rise in real-time in vivo (rabbit) and ex vivo (porcine eye) and to automatically control the coagulation strength. Continuous wave treatment laser radiation and pulsed probe laser light (1-1100 ns) are coupled into the same
fibre and are imaged onto the retina by a laser slit lamp. The temperature dependent pressure waves are detected by an
ultrasonic transducer embedded in a customary contact lens. Below the coagulation threshold the increase in acoustic amplitude due to thermal tissue expansion is up to 40 %. Best signal to noise ratios > 10 are achieved with probe pulse durations of 1 to 75 ns. Further a time critical algorithm is developed which automatically ceases laser treatment when a certain preset coagulation strength is achieved. Coagulations with similar extent are obtained with this method in vitro and in vivo even when varying the power of the treatment laser by 50 %. These preliminary results are very promising, thus this method might be suitable for an automatic feedback controlled photocoagulation with adjustable coagulation