Photochemical interaction

Photochemical interaction, sometimes referred to as photoactivation, takes place at long exposure times, ranging from seconds to continuously, and very low power densities or irradiances (typically 1 W/cm²). This type of interaction is based on the use of a photosensitizing dye (eg, rose bengal, riboflavin, or verteporfin), which serves as a chemical (electron reaction) catalyst. Laser irradiation, at a wavelength coupled to the specific dye used, causes a photochemical reaction only within tissues where the dye is present and when irradiated.

Table 2-5 Laser-Tissue Interaction Types and Associated Mechanisms

Figure 2-14 Laser-tissue interactions may be divided into 5 different types: photochemical interaction, thermal interaction, photoablation, plasma-induced ablation, and photodisruption. They are primarily determined by the power density (irradiance) and exposure time (pulse duration) of the laser light. All therapeutic laser–tissue interactions share a common characteristic, in that all meaningful energy densities (transferred energy to the tissue) vary typically between 1 and 1000 J/cm².

(Reproduced with permission from Niemz MK. Laser-Tissue Interactions: Fundamentals and Applications. 3rd enlarged ed. Berlin, Germany: Springer, Berlin, Heidelberg; 2007.)

This is for example used in photodynamic therapy (PDT), where a photosensitizing agent is injected into the circulation. The blood vessels are then treated with laser irradiation to activate the photosensitizer. A chemical reaction occurs, resulting in thrombosis and closure of the blood vessels. Other than retinal PDT in age-related macular degeneration (AMD), a specific example of this is the treatment of a vascularized cornea with rose bengal and green argon laser irradiation, to thrombose blood vessels and thereby reduce the chance of rejection of a subsequent graft. Another ophthalmic application is the use of ultraviolet-A (UV-A) light after application of riboflavin onto the corneal surface, to promote corneal crosslinking in the treatment of keratoconus.

Thermal interaction

At somewhat shorter exposure times—ranging from microseconds to a minute—and higher power densities—ranging from 10 W/cm² to 10⁶ W/cm²—diverse thermal effects at different temperatures may be distinguished (Table 2-6 and Fig 2-15). This type of interaction is based on the generation of heat (molecular motion) by the absorption of light.

Photocoagulation, which is associated with protein and collagen denaturation, is the most commonly used thermal laser–tissue interaction in ophthalmic surgery. Natural chromophores or dyes within the tissue absorb light and convert it to heat, which causes denaturation. Their absorption strongly depends on the wavelength of incident light. Thus, laser light of appropriate wavelength must be selected to target specific ocular structures. The main natural chromophores within ocular tissues that are targeted during photocoagulation are hemoglobin (eg, in blood vessels) and melanin (eg, in the iris or deep retinal layers), which strongly absorb wavelengths from about 400 nm to 580 nm. Laser wavelengths longer than 500 nm are generally the preferred choice, in particular when treating near or in the macula, as light between 450 nm and 500 nm is strongly absorbed by the yellow xanthophyll pigments in the macula. Formerly, large argon gas-filled tubes were used to create green laser beams (513 nm), but newer solid-state devices can emit the desired wavelengths, such as frequency-doubled Nd:YAG (ie, one-half of the fundamental 1064-nm wavelength of the Nd:YAG laser, thus 532 nm), or more compact diode lasers.

Table 2-6 Thermal Effects Occurring at Different Temperatures

Figure 2-15 Thermal interaction effects inside biological tissue.

(Reproduced with permission from Niemz MK. Laser-Tissue Interactions: Fundamentals and Applications. 3rd enlarged ed. Berlin, Germany: Springer, Berlin, Heidelberg; 2007. Redrawn by Kristina Irsch, PhD.)

The most common ophthalmic applications of photocoagulation include laser coagulation to prevent retinal detachments, photocoagulation of retinal vessel disease, panretinal photocoagulation in diabetic retinopathy, transpupillary thermotherapy for malignant choroidal melanoma and choroidal neovascularization in AMD, laser trabeculoplasty for open-angle glaucoma, and laser iridotomy for closed-angle glaucoma.

Photocoagulation is also used for photothermal shrinkage of stromal collagen, known as laser thermo-keratoplasty (LTK), in the treatment of hyperopia. The cornea does not absorb enough visible light, even highly concentrated light, to produce a significant temperature increase. However, the cornea is opaque to some infrared wavelengths, thus an infrared laser (eg, holmium: yttrium aluminum garnet [Ho:YAG]) is used in LTK.

Photoablation

If we deliver photons in a short enough time, so that no heat is transferred, and with sufficient energy—typically in the 5 to 7 electron voltage (1 eV ~ 1.602 × 10⁻¹⁹ J) range—then we can directly split molecules, that is, break their covalent chemical bonds. Excimer lasers generating photons with wavelengths in the UV range (eg, a 193-nm argon fluoride excimer laser) are ideally suited for photoablation. This results in ejection of fragments and very clean ablation without necrosis or thermal damage to adjacent tissue. We can think of this type of interaction as “vaporization” without the surrounding thermal effects from Figure 2-15. Typical threshold values for this type of interaction are irradiances of 10⁷ to 10⁸ W/cm² and pulses in the nanosecond range. Photoablation is used in the cornea, which absorbs UV light below around 315 nm, for refractive surgery of the cornea such as photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).

Plasma-induced ablation

Under even higher concentrated peak irradiances (but ideally low-pulse energies compared to photodisruption; see Fig 2-14), typically 10¹¹ to 10¹³ W/cm², and shorter exposure times, in the picosecond and femtosecond range, we can not only break molecules (as during photoablation), but even strip electrons from (ionize) their atoms and accelerate them (“optical breakdown”). The accelerated electrons, in turn, can collide with and ionize further atoms, as illustrated in Figure 2-16. This process is called cascade ionization and leads to a plasma formation, a highly ionized state. It enables a very clean and well-defined removal of tissue without any evidence of thermal or mechanical damage. This type of interaction also makes it possible to transfer energy to transparent media without the use of UV lasers, by creating a plasma that is capable of absorbing non-UV laser photons. Especially in ophthalmology, transparent tissues like the cornea, which is essentially transparent to wavelengths from about 315 nm to 1400 nm, can be treated with non-UV lasers using plasma-induced ablation.

Figure 2-16 Cascade ionization (electrons are stripped from their atoms) leading to plasma formation, a highly ionized state.

(Reproduced with permission from Niemz MK. Laser-Tissue Interactions: Fundamentals and Applications. 3rd enlarged ed. Berlin, Germany: Springer, Berlin, Heidelberg; 2007. Redrawn by Kristina Irsch, PhD.)

There are secondary mechanical side effects, however, such as the generation of a shock wave (ie, plasma electrons are not confined to the focal volume of the laser beam) and cavitation bubbles. But they do not define the global effect upon the tissue in the plasma-induced ablation process. Note that this kind of ablation is primarily caused by plasma ionization itself (the dissociation of molecules and atoms), which is distinct from the more mechanical interaction process called photodisruption and is what is generally attempted with emerging methods of corneal refractive surgery using femtosecond lasers (eg, intrastromal ablation or cutting, and formation of the corneal flap).

Photodisruption

At higher pulse energies (typically 1 to 1000 J/cm²), and thus higher plasma energies, mechanical side effects become more significant and might even determine the global effect upon the tissue, in which case we refer to the interaction process as photodisruption.

The most important ophthalmic application of this photodisruptive interaction is posterior capsulotomy using the Nd:YAG laser. During a photodisruption procedure, it is the mechanical (acoustic) wave and not the laser light itself (as with plasma-induced ablation) that breaks the capsule. Since both interaction mechanisms—plasma-induced ablation as well as photodisruption—rely on plasma generation and graphically overlap (see Fig 2-14), it is not always easy to distinguish between these 2 processes. In fact, most literature sources attribute all tissue effects evoked by ultrashort laser pulses to photodisruption. However, during photodisruption, the tissue primarily is split by mechanical forces, with shock-wave and cavitation effects propagating into adjacent tissue, thus limiting the localizability of the interaction zone. In contrast, plasma-induced ablation is spatially confined to the breakdown region and laser focal spot, with the tissue primarily being removed by plasma ionization itself. The primary distinguishing parameter between the 2 interaction processes is energy density (see Fig 2-14).

Why ultrashort laser pulses?

Per the definition of power (energy per second), the shorter the pulse duration, the higher the power that can be delivered at a given energy. In other words, picosecond or femtosecond (ultrashort) pulses permit the generation of high peak powers with considerably lower pulse energies than nanosecond pulses.

Another consequence of this is that, for ultrashort pulses, especially in the femtosecond range, considerably lower pulse energies are needed to achieve optical breakdown (plasma generation), and therefore purely plasma-induced ablation can be observed. For nanosecond pulses, on the other hand, as illustrated in Figure 2-17, the threshold energy density for optical breakdown is higher, so that purely plasma-induced ablation is not observed, but is always associated with photodisruption. Since disruptive effects can damage adjacent tissue, ultrashort laser pulses are generally preferred (depending on the application).

Note that for a laser with high-energy pulses (photodisruption regime), causing disruptive effects that propagate beyond its focal spot, lower repetition rates are needed; in contrast, for a laser with low-energy pulses (plasma-induced ablation regime), higher repetition rates are necessary and produce smoother surface cuts without increasing the time of the procedure (Fig 2-18).

Figure 2-17 Distinction of plasma-induced ablation and photodisruption according to applied energy density. Note that for nanosecond pluses, purely plasma-induced ablation is not observed but always associated with disruptive effects, even at the very threshold for optical breakdown.

(Reproduced with permission from Niemz MK. Laser-Tissue Interactions: Fundamentals and Applications. 3rd enlarged ed. Berlin, Germany: Springer, Berlin, Heidelberg; 2007. Redrawn by Kristina Irsch, PhD.)

Figure 2-18 Repetition rate versus energy density. For high-energy laser pulses (photodisruption regime), causing disruptive effects that propagate beyond its focal spot, lower repetition rates are needed, whereas for low-energy pulses (plasma-induced ablation regime), higher repetition rates are necessary. Note that the latter will produce smoother surface cuts without increasing the time of the procedure.

(Courtesy of Rowiak GmbH. Modified by Kristina Irsch, PhD.)

Excerpted from BCSC 2020-2021 series : Section 3 - Clinical Optics. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.