No abstract

Repetitive exposure to short laser pulses is shown to cause seective damage to absorbing structures (cells, organles, or enzymes) with pulse energies below the treshold energy for single-pulse damag. Detly adjacent strucures are spared in Wvo. Additvity of (presummbly nonphotochemical) (1,2). Depending on the exposure time, these effects may not be confined to the absorbing structures. During and after exposure, heat dissipates out of the absorbing volume, causing a substantial temperature increase in the surrounding tissue and undesirable side effects. In clinical retinal photocoagulation, for example, with exposure times of several hundred milliseconds, the nonabsorbing neural retina is thermally damaged because it is directly adjacent to the absorbing retinal pigment epithelium (RPE). However, in several diseases only the destruction of the RPE, a single cell layer, is required (3-5).Such confined effects require the use ofpulses shorter than the thermal relaxation time of the target structure (adiabatic heating) (6). Thermal effects are temperature-and timedependent and highly nonlinear (1, 6-8). As the exposure time and therefore the time of increased temperature becomes shorter, higher temperatures are necessary to achieve a given effect. If the energy is deposited in a very short time (typically microseconds or less), large spatial and temporal temperature gradients result, inducing mechanical effects such as microexplosions, displacement of absorbing structures (e.g., melanin granules), or hemorrhage (9-12). Such gross mechanical effects are often not tolerable in clinical applications. This paper discusses the concept of inducing tissue damage by repetitive short subthreshold pulses, each too small in energy to cause tissue damage by itself, in order to circumvent this limitation.Additivity has been demonstrated for multiple 40-p,s pulses at 488 nm and 647 nm on the retina (13) and for multiple 9-ms CO2 laser pulses on the cornea (14).As an experimental model for such a selective damage mechanism, the rabbit retina has been chosen. The goal of this study was to destroy selectively the RPE cell monolayer by using multiple subthreshold effects with minimal damage to the directly adjacent photoreceptors in the neural retina.The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact. ConceptThe transition from localized to more widespread thermal damage occurs as the exposure duration exceeds the thermal relaxation time (tr) of the target structure. For a thermal point source tr = r2/6k, where k is the thermal diffusivity (1.5 x 10-3 cm2-s-1 for water) (1, 15). tr is defined as the time at which the temperature at a point at distance r from the source has its maximum temperature. During exposure to long pulses (p >> tr), heat transfer occurs and the adjacent tissue is heated relatively uniformly, causing nonspecific necrosis.If the pulse duratio...

The origin of RPE cell damage for single pulse irradiation up to pulse durations of 3 microsec can be described by a damage mechanism in which microbubbles around the melanosomes cause a rupture of the cell structure. The threshold radiant exposure for RPE damage decreases with increasing number of pulses applied.

A thermal damage model including heat conduction for retinal lesions is described to explain thermal threshold damage and compare it to experimental values in the regime of 1 ms to 300 ms. With the aid of these model calculations unspecific thermal damage (denaturation of proteins) could be separated from thermally induced damage to the photoreceptors. Furthermore, the thermal model allows an extrapolation to hazards to the fundus from intense light irradiation that have not been investigated experimentally.