laser in ophthalmology
TRANSCRIPT
Photoablation
In Fig. 3.30, the cross-section of a cornea is shown which was exposed to an ArF excimer laser. The removal of tissue was performed in a very clean andexact fashion without any appearance of thermal damage such as coagulation or vaporization. Instead, evidence is given that the tissue was very precisely “etched”. This kind of UV light-induced ablation is called photoablation and will be discussed in this section.
Photoablation was first discovered by Srinivasan and Mayne-Banton(1982). They identified it as ablative photodecomposition, meaning that material is decomposed when exposed to high intense laser irradiation. Typicalthreshold values of this type of interaction are 107–108 W/cm2 at laser pulsedurations in the nanosecond range. The ablation depth, i.e. the depth of tissue removal per pulse, is determined by the pulse energy up to a certainsaturation limit. The geometry of the ablation pattern itself is defined bythe spatial parameters of the laser beam. The main advantages of this ablation technique lie in the precision of the etching process as demonstratedin Fig. 3.30, its excellent predictability, and the lack of thermal damage toadjacent tissue. First studies regarding ablative photodecomposition were performed with polymethyl-metacrylate (PMMA), polyimide, Teflon, and other syntheticorganic polymers7. Soon after, biological tissues were also ablated. Today,photoablation is one of the most successful techniques for refractive cornealsurgery, where the refractive power of the cornea is altered in myopia, hyperopia, or astigmatism (see lec 4). In this section, for the sake of simplicity,
we will follow the explanations given by Garrison and Srinivasan (1985) in thecase of synthetic polymer targets. Due to the homogeneity of these materials,their behavior under certain experimental conditions is easier to understand.Thus, experimental data on the ablative process are very reliable and theoretical modeling is strongly facilitated. However, most of the theory appliesfor the more inhomogeneous biological tissues, as well.Organic polymers are made up of large molecules consisting of more than103 atoms, mainly carbon, hydrogen, oxygen, and nitrogen. A smaller molecular unit of up to 50 atoms is called a monomer. It is repeated several times along a well-defined axis to form the polymer chain. In Figs. 3.31a–b, thebasic chemical structures of the most popular polymers – PMMA and polyimide – are illustrated.
For PMMA, the temporal progress of photoablation was modeled byGarrison and Srinivasan (1985) using Newton’s equation of motion. The polymer is described by structureless monomer units held together by strongattractive forces. The interaction with laser radiation is simulated by allowing each monomer unit to undergo excitation directly from an attractive toa repulsive state. This promotion is associated with a change in volume occupied by each monomer, leading to a transfer of momentum and, thus, tothe process of ablation. For the sake of simplicity, a face-centered cubic (fcc)crystalline array is assumed. With a density of 1.22g/cm3 and a monomermass of 100amu, a lattice constant of 0.81nm is calculated. The main attractive forces holding the monomer units together are the two carbon–carbonbonds along the chain. The strength of such a C–C bond is approximately3.6eV (see Table 3.8). The basic repulsive term is proportional to 1/r12,where r denotes a mean distance of two monomers. With these assumptions,the process of photoablation was simulated as shown in Fig. 3.32.
we find that only photons from UV lasers – typically excimer lasers – providean energy sufficient for dissociating such bonds. Therefore, the interactionmechanism of photoablation is limited to the application of UV light.The ejected photoproducts of excimer laser ablation have been analyzed in several studies, e.g. by Srinivasan and Mayne-Banton (1982) andBrannon et al. (1985). Usually, a mixture of single atoms (C, N, H, O),molecules (C2, CN, CH, CO), and stable fragments (MMA-monomer, HCN,benzene) were detected. It is interesting to add that the product compositionwas found to be wavelength-dependent. Srinivasan et al. (1986b) found thatradiation at 248nm generates fragments of a higher molecular weight thandoes 193nm radiation. Thus, the corresponding etched surface at 248nm isrougher and less predictable than at 193nm.
Moreover, it was observed that a certain threshold intensity must be applied to achieve photoablation. Above this intensity, a well-defined depth isablated, depending on the absorption coefficient and the incident intensity. Atthe same time, an audible report is heard and visible fluorescence is observedat the impact site. If the incident intensity is moderate and such that theablation depth is smaller than the corresponding optical absorption length,subsequent pulses will enter partially irradiated tissue as well as unexposedtissue underlying it. Therefore, only the first few pulses are unique. Afterthese, a linear relation between the number of applied pulses and the totaletch depth is obtained. In practice, the etch depths are averaged over several pulses and noted as ablation depth per pulse. This value is reproduciblewithin an uncertainty of about 10% for most materials which is an excellentvalue when taking all the inhomogeneities of tissue into account. The physicalprinciples of photoablation are summarized in Table 3.10.
We stated above that photoablation is a process which is restricted to theapplication of UV light. However, it is not limited to excimer lasers, sincegenerating higher harmonics of other laser types can result in UV radiation,as well. The 4th harmonic of a solid-state laser, for instance, also induces photoablation as reported by Niemz et al. (1994b). In Figs. 3.34a–b and 3.35a–b,a sample of corneal tissue is shown which was partially exposed to either thesecond or the fourth harmonic of a Nd:YLF laser. In both cases, the pulseduration at the fundamental wavelength was set to 30ps. The higher harmonics were induced by means of two BBO crystals. The pulse energies wereapproximately 150 μJ in the green and 20 μJ in the UV, respectively. Thelaser beam was scanned over the surface within a 1×1mm2 pattern. Whereasdistinct impact sites of the focused laser beam are clearly visible in the sectionexposed to the second harmonic, a clean and homogeneous layer is ablatedwith the fourth harmonic. Only the latter belongs to the group of photoablation, whereas the other effect is attributed to plasma-induced ablation whichwill be discussed in Sect. 3.4.
In order to distinguish photoablation or ablative photodecomposition fromthermal interaction, we take a closer look once more at the energy level diagram shown in Fig. 3.33. In the case of photoablation, we concluded thatthe energy of a single UV photon is sufficient to dissociate the former boundmolecule AB. In thermal interactions, the situation is completely different.The photon energy is not high enough for the molecule to reach a repulsive state. The molecule is promoted only to a vibrational state within theground level or to a rather low electronic state including any of its vibrational states. By means of nonradiative relaxation, the absorbed energy thendissipates to heat, and the molecule returns to its ground state. Hence, thecrucial parameter for differentiating these two mechanisms – photoablationand thermal interaction – is the photon energy or laser wavelength. Only ifhν > 3.6 eV, or in other measures λ < 350nm, is the single photon dissociation of C–C bonds enabled. Of course, several photons with hν < 3.5eVcan be absorbed. Then, these photons add up in energy and may thus lead toa dissociated state, as well. However, during the time needed for such a multiphoton absorption process, other tissue areas become vibrationally excited,hence leading to a global increase in temperature and an observable thermaleffect (usually either vaporization or melting).
If this effect is associated withablation, the whole process is called thermal decomposition and has to bedistinguished from pure ablative photodecomposition. These statements holdtrue, unless ultrashort pulses with a pulse duration shorter than 100ps areused at pulse energies high enough to induce a localized microplasma. Then,even VIS- and IR-lasers can interact nonthermally. But the discussion of thismechanism shall be deferred to Sect. 3.4.In reality, pure photoablation is only observed for the 193nm wavelengthof the ArF excimer laser. Higher wavelengths are usually associated witha more or less apparent thermal component. Sutcliffe and Srinivasan (1986)
even postulated that the thermal component of the radiation from a XeCl excimer laser at 308nm is 100% thermal if its radiation is incident on PMMA.In Fig. 3.37, the thermal components of three excimer lasers are comparedwith each other. Obviously, each laser induces thermal effects at low energydensities. In the cases of the ArF laser and the KrF laser, the slope of thecurve strongly decreases above a certain threshold, i.e. the threshold of photoablation. Radiation from the XeCl laser, on the other hand, continues toact thermally even at higher energy densities.
Lasers in Ophthalmology
In ophthalmology, various types of lasers are being applied today for eitherdiagnostic or therapeutic purposes. In diagnostics, lasers are advantageousif conventional incoherent light sources fail. One major diagnostic tool isconfocal laser microscopy which allows the detection of early stages of retinalalterations. By this means, retinal detachment and also glaucoma1 can berecognized in time to increase the probability of successful treatment. Inthis book, however, our interest focuses on therapeutic laser applications.The first indications for laser treatment were given by detachments of theretina. Meanwhile, this kind of surgery has turned into a well-establishedtool and only represents a minor part of today’s ophthalmic laser procedures.Others are, for instance, treatment of glaucoma and cataract. And, recently,refractive corneal surgery has become a major field of research, too.The targets of all therapeutic laser treatments of the eye can be classifiedinto front and rear segments. The front segments consist of the cornea, sclera,trabeculum, iris, and lens. The rear segments are given by the vitreous bodyand retina. A schematic illustration of a human eye is shown in Fig. 4.1. Inthe following paragraphs, we will discuss various treatments of these segmentsaccording to the historic sequence, i.e. from the rear to the front.
Cornea
Cornea and lens together account for the total refraction of the eye. However, since the anterior surface of the cornea is exposed to air with an index of refraction close to unity, refraction at the anterior surface of thecornea represents the major part. A list of refractive properties of the human eye was first provided by Gullstrand at the beginning of this century.A theoretical analysis of the refractive properties is found in the book byLe Grand and El Hage (1980). Both sets of data are given in Table 4.1 together with a third column called the simplified eye. In the simplified eye, thesame principal planes and focal distances are assumed as for the theoreticaleye. However, a round value of 8mm is chosen for the radius of curvatureof the anterior corneal surface. And, because also assuming the same indicesof refraction for the cornea and aequous humor, refraction at the posteriorcorneal surface is neglected. From these data, it can be concluded that thepower of the cornea is approximately 42 diopters, whereas the total power ofthe eye is roughly 59 diopters. Therefore, about 70 % of the overall refractionarises from the cornea.
The transparency of corneal tissue in the spectral region from 400nm to1200nm can be attributed to its extremely regular microscopic structure aswill be discussed below. The optical zone of the human cornea has typicaldiameters ranging from 2mm to 4mm and is controlled by the iris. Theoverall thickness of the cornea varies between 500 μm at the center of theoptical axis and 700 μm at the periphery. Corneal tissue is avascular andbasically consists of five distinct layers: epithelium, Bowman’s membrane,stroma, Descemet’s membrane, and endothelium. A schematic cross-sectionof the human cornea is shown in Fig. 4.11.
According to Le Grand and El Hage (1980), the epithelium is made upof two to three layers of flat cells which – in combination with tear fluid –provide the smooth surface of the cornea. These cells are the only cornealcells capable of regenerating. Bowman’s membrane consists of densely packedcollagen fibers. All these fibers are oriented in planes parallel to the cornealsurface, resulting in extremely high transparency. Due to its high density,Bowman’s membrane is primarily responsible for the mechanical stability ofthe cornea. Almost 90% of the corneal thickness belongs to the stroma. It hasa structure similar to Bowman’s membrane but at a lower density. Since thestroma contributes the major part of the cornea, refractive corneal surgeryrelies on removing stromal tissue. Descemet’s membrane protects the corneafrom its posterior side. And, finally, the endothelium consists of two layersof hexagonally oriented cells. Their main function is to prevent fluid of thefront chamber from diffusing into the cornea.
In general, two types of corneal surgeries are distinguished: removal of anypathologic conditions and refractive corneal surgery. The first group includestreatments of irregularly shaped corneas, e.g. keratoconus, externally inducedcorneal injuries, and corneal transplantations. Prior to laser surgery, all thesetreatments had to be performed with mechanical scalpels. Today, ophthalmiclasers – among these especially the ArF excimer laser – offer a noninvasiveand painless surgery. Successful circular trephinations and smoothing of irregular surfaces were, for instance, reported by Loertscher et al. (1987) andLang et al. (1989). Very clean corneal excisions can also be obtained whenusing short pulsed neodymium lasers as shown in Figs. 4.12 and 4.13. Thedependence of the ablation depth on pulse energy is illustrated in Figs. 4.14and 4.15.
The other group of corneal surgeries aims at an alteration of its refractive power. Although most cases of wrongsightedness cannot be attributedto a pathologic condition of the cornea5, it is the corneal power which isthe easiest to change. First successful studies on refractive corneal surgerywere reported by Fjodorov and Durnev (1979) using a diamond knife. Thewhole procedure is called radial keratotomy (from Greek: κρας = cornea,τoμαιν = to be cut). By placing radial incisions into the peripheral cornea,tensile forces are rearranged which leads to a flattening of the central anterior surface, i.e. a decrease in refractive power. Radial keratotomy has meanwhile been investigated by a variety of surgeons. Several profound reviewsare available today, e.g. by Bores (1983), Sawelson and Marks (1985), andArrowsmith and Marks (1988).In the following paragraphs, a geometrically derived instruction is givenof how the reshaping of a myopic eye has to be done. In Fig. 4.17, the pre- andpostoperative anterior surfaces of the cornea are shown together with othergeometrical parameters. The optical axis and an arbitrary axis perpendicularto it are labeled x and y, respectively. The curvature of the cornea is givenby R, and the indices “i” and “f” refer to the initial and final states of thecornea, respectively
