Features

Douglas Clarkson describes laser interactions which occur in tissue and fluids in the anterior chamber and which the product literature often fails to explain accurately

The specific laser interactions which occur in tissue and fluids in the anterior chamber caused by short pulse durations, such as the Q switched Nd:YAG are typically not accurately described in product literature.

Experimental observations which tend not to be widely referenced in the clinical and scientific literature have described basic characteristics of tissue interactions of such modes of pulse energy. Deeper understanding, for example, of energy partition between modes of plasma formation, expanding shock waves and cavitation bubble can, however, provide useful insight into the suitability of specific techniques and configurations of pulse duration, pulse energy and focal spot size. Such an insight can also reveal where future product development might lead.

With the development of laser technology, even shorter pulse durations in the range of femto seconds (10^-15s) have become available in applications within ophthalmology. These newer techniques have begun to impact on processes of corneal flap production as a precursor to the Lasik procedure.

Current techniques using such laser technology are entirely dependent on precision-guided energy deposition using beam scanning technology and this is perhaps an indication that the full potential of ultra-short laser pulses in the anterior chamber could also be dependent on the incorporation of smart beam scanning, for example, at the rear capsular interface.

The applications of lasers within the anterior chamber tend to involve utilisation of specific characteristics of tissue interactions which include:
 
High photon energy (excimer laser) 
Microdisruptive energy (shock waves/ cavitation)
Specific wavelength absorption for thermal effect 
Selective photothermolysis (rapid heating of selected tissue)
Electron disassociation (plasma formation).

Transmission of 'light' within

Figure 1. Schematic representation of laser pulse interaction in water of 30ps (pioseconds) pulse at 1mJ (upper section) and at 44ns after initial laser pulse.  The zone of plasma formation is indicated in red and the expanding cavitation bubble as blue .  The black boundary represents the zone of expanding shock wave

transparent non-scattering ocular media provides the opportunity to focus a laser pulse of energy within a relatively small volume - typically of diameter 10 microns or less. This window of transmission includes the wavelength range from approximately 400nm to 1,400nm (where nm = nanometres).

Where, however, light is transmitted through tissue in which significant scattering takes place, the potential to bring energy to a well-defined focus is lost. From the point at which light makes contact with such scattering tissue, mechanisms of scattering and absorption take place. This form of limitation, for example, is all too evident in relation to laser interactions within vascular tissue.

It will be seen, however, that while the sclera may be considered unsuitable for sub surface focusing laser techniques, there are ways and means of rendering the sclera functionally able to transmit laser radiation.

 
Observing Interactions of ns and ps Laser Pulses
The phenomenon of laser microdisruption where intense laser energy is brought to a well-defined focus has been extensively studied by Vogel.1

The specific measurement techniques captured separate time resolved images showing the generation of the plasma, the expanding cavitation bubble and the radiating shock wave. In the experimental method, laser radiation at 1,064nm was delivered to the target site. A component of this light using frequency doubling techniques (visible light at 532nm) was used to illuminate the target area after a variable delay using an optical delay line within the range 2ns (nanoseconds) and 132ns. The radiating shock wave is identified in such images as a differentiated contour of fluid radiating out from the point of focal energy.

Also, the basic work by Vogel indicates the elongation of the zone of plasma production and radiating shock wave rather than the 'spherical' symmetry which is often assumed. This also stresses the importance of the cone angle of the laser beam and the use of additional focusing lenses.

Subsequent analysis of such images was used to derive the shock-wave velocity and validate the models of bubble expansion and shock-wave generation. The authors were able to utilise an Nd:YAG laser with pulse durations of 30ps (1ps = 10^-12s) and 6ns (1ns = 10^-9s) over a range of energy settings. Independent measurements were also made of pressure using a hydrophone some 5mm from the target site.

For specific pulse durations of 30ps (1mJ) and 6ns (10mJ), the appearance of the zones of activation are subtly different, as shown diagramatically in Figure 1. The upper section of Figure 1 at 44ns after laser irradiation with 30ps pulse shows the contour of the expanding shock wave extending beyond the contour of the cavitation bubble.

Note the scale of 100 microns in the figure. Also, at the core of the cavitation bubble, the zone of active plasma can be identified. It is apparent that the plasma - once initiated - continues to be present for some time and exists for longer than the specific initial laser pulse.

The pattern for the 6ns Nd:YAG pulse shown in lower section of Figure 1 - again at 44ns after irradiation - is generally similar, with the characteristic central plasma, expanding cavitation bubble and shock wave. Eventually, the cavitation bubble will contract and collapse back on itself - producing a localised shock wave at the point of collapse. This can also be associated with streaming of fluid around the collapsing bubble site.

The initial pulse energy contributes to the initial zone of plasma production, the radiated initial shock wave and the expanding cavitation bubble. Energy released into the expanding bubble can also be partially released by the processes associated with bubble collapse.

According to Vogel, it is the initial plasma formation which provides the tissue cutting effect. The other energy interactions are indicated to contribute to tissue disruption and collateral damage. The shock wave, for example, will tend to

Figure 2. Appearance after Nd:YAG iridotomy (Courtesy of J Kanski, Clinical Ophthalmology 4th Edition, Butterworth Heinemann)

 cause a transitory temperature increase - probably of around 30^oC and will result also in compression of tissue as the wave radiates.

Also, significant amplitudes probably only exist for up to 200 microns from the centre of plasma formation.

The formation of the cavitation bubble - which can expand typically to at least 800 microns - has the potential to lead to very fast displacement of surrounding tissue material and which can in turn cause tissue damage. The energy of the collapsed expanded bubble also has the potential to radiate an additional end of collapse shock wave.

With identification of the desired clinical effect being that of the formation of the plasma which vapourises any tissue at the point of focus, it is observed that the threshold for plasma generation is typically around a factor of 13 less at 30ps compared with 6ns pulse durations.

This indicates, in theory, that successful plasma generation can occur at 30ps and with a marked reduction in the energy translated to radiated shock wave and cavitation bubble growth. Thus develops the idea of a 'laser scalpel' with a precise point of action but where there is reduced collateral damage at the laser beam focus. This potentially expands the role of lasers in techniques principally within the anterior chamber.

In vitro observations of ns and ps laser intercations of bovine eye specimens and also human lenses with varying degrees of cataract have been investigated by Vogel² using essentially the same experimental techniques as previously described¹ for free fluid work.

One key observation identified the threshold for plasma formation in cornea (stroma and Descemet's membrane), lens and vitreous - as outlined in Table 1. The typical threshold ratio, however, of the ns value to the corresponding ps value is around 12.

In general, the typical threshold for photodisruption for cornea varies with the square root of pulse duration as indicated in Figure 3.

In observations on human lenses in vitro, the threshold for plasma breakdown varies considerably even within a single lens - due presumably to the variations in optical properties of the lens. Typically, the plasma formation was achieved at ps pulse durations at pulses energies reduced by a factor of seven compared with ns pulse excitation.

Vogel was able to use the 30ps laser to dissect along the boundary of Descemet's membrane at pulse energy of 50micro J (mJ). With the ns laser, however, excessive collateral damage is observed along the zone treated when 1mJ pulses are used.

 
Clinical Observations of ps Lasers
Oram³ carried out a study involving iridotomy on 11 patients using a 10ps laser at 1,053nm and indicated that successful procedures could be undertaken at lower energies compared with conventional Q switched Nd:YAG systems.

Geerling⁴ described a limited study involving iridectomies and capsulotomies. It was the impression of the observers that, while the ps laser pulses were of reduced energy value and produced less collateral damage by shock wave effects, it was more difficult to spatially control the rapid train of ps pulses in the region of the curved posterior surface of the implanted intraocular lens and minimise pitting damage.

It was considered, however, that iridotomies were generally easier to perform with the ps laser. A limited study by Frangie⁵ identified the intrinsic advantages of reduced energy per ablative pulse and decreased collateral damage. This issue of lens pitting with ps lasers is further described by Loya⁶ based on in vitro observations.

It is probable, however, that the perceived difficulties of minimising pitting damage to intraocular lenses using ps lasers has preserved the dominance of existing ns Q switched Nd:YAG systems. The literature, however, appears not to identify large-scale studies comparing the effectiveness of ns and ns lasers for iridotomy and capsulotomy.

Evolution of femto Second Laser Pulses
The subsequent availability of even shorter pulses - femto second duration - as a result of advances in laser technology has allowed the extensive study of the potential of this technique for subsurface tissue ablation.

Specific experimental observations of the photodisruptive effects of femto second lasers undertaken by Juhasz^7,8 has confirmed the reduced levels of collateral damage associated with such shorter pulse durations. Cavitation bubbles are observed to typically extend only to around a diameter of 14 microns instead of the significantly higher values with pico second and nano second lasers. Also, from interpretation of dynamics of the initial shock wave, values decrease to near zero within a distance of 20 microns. The smaller cavitation bubble produced is also more rapidly absorbed.

With mechanisms of corneal tissue interaction always being of interest, the ps laser was observed when activated with corneal stroma. It was observed with 300mJ pulses that cavitation bubble formation is constrained - with typical sizes being about 30 per cent of free fluid values.

Such intrastromal cavities collapse slowly and typically dissapear within one hour of their initial generation. Observations of 80mJ pulses within the corneal stroma indicated cavities of around 60 microns - some 10 times the actual volume of the laser plasma. Thus while the plasma effect is likely to remove localised stromal tissue, collateral damage would also occur due to deformation of collagen structures.

Evolution of subsurface ablation technology using femto second lasers
The early demonstration of dissection of corneal tissues using pico second (ps) lasers pre-empts the subsequent development of femto second lasers for photorefractive surgery.

With the technique of femto-Lasik as a mechanism of creating corneal flaps, the scope of the precise plasma cutting is also being assessed for more conventional surgical techniques. Jonas,⁹ for example, has described the technique in animal studies of using a femto second laser (20/10 Perfect Vision) to cut sections of excised cornea as would be undertaken for conventional lamellar keratoplasty. It was identified that corneal sections could be excised, leaving intact Bowman's layer. Excised sections could be exchanged with sections which had been similarly excised due to the reproducibility of the cutting process.

So far only one system, the Interlase FS laser, is actively used in Lasik flap cutting. The laser uses a wavelength of 1,053nm with a focal spot of 3 microns and with an accuracy of 1 micron. The core of the technology was originally patented by a team of scientists and ophthalmologists at the Center for Ultrafast Optical Science at the University of Michigan.

The key to subsurface photodisruption is that the targeted tissue is sufficiently non scattering for sufficiently high focal intensities to be created to generate plasma photodisruption. Normal sclera would be tend to prevent creation of such photodisruption effects. With the use of dehydrating agents, however, it is possible to significantly increase the optical transmission of sclera - making it possible to undertake precision photodisruption within such tissue.

Saks has been able to confirm¹⁰ the potential of using dehydrating agents in in vitro scleral tissue samples with femto second lasers at 775nm and 1,060nm. While untreated sclera will typically have less than 10 per cent transmission at 1,000nm, this can be increased to around 70 per cent by using agents such as Hypaque.

Electron microscopy of treated sub surface zones confirmed the ability to cut channels of around 10 microns bore. This therefore identifies the potential of developing this technique, for example, to cut channels for assisting draining of the anterior chamber.

Subsequently, Sacks¹¹ has investigated the use of a longer wavelength of 1,700nm with femto second laser pulses to perform subsurface photodisruption in human sclera without the use of dehydrating agents.

Using excised human sclera samples, it was shown that it was possible to create effective subsurface photodisruption. At shorter wavelengths such as 775nm, the laser energy is absorbed in the initial contact zone of the laser with the tissue surface - preventing, therefore, subsurface focusing of the laser energy.

The authors indicate the potential of the technique in glaucoma surgery to increase aqueous outflow.

Laser Cataract Fragmentation
Lasers have been extensively investigated for cataract fragmentation. Such techniques, however, depend on fibre contact technology rather than plasma-induced photodisruption at a site of focused energy.

Wetzel¹² investigated the ability of Er:Yag energy (wavelength 2,940nm) to fragment in vitro cataract tissue. The specific wavelength has a very high absorption for water. While the absorption peak for Er:Yag is often quoted as the key factor for its interaction, the absorption process is somewhat non linear with output power.

Also, this technique is also used to cut tooth enamel in dentistry by directing the laser energy within a spray of water particles which are impelled towards the target site. One component of the cutting effect in situ for cataracts could be the rapid water streaming forces established at the cutting tip.

Lens fragmentation using lasers with contact fibre probes has been described by Kanellopoulos¹³ using the Dodick PhotoLysis System which utilises a Q switched Nd:Yag system at 1064nm. Maximum pulse energy parameters of this system are typically 10mJ with a pulse duration of 10ns with a repeat frequency between 1 Hz and 20 Hz.

Conclusion
It is apparent that significantly more options are technically available for laser interactions in the anterior chamber than are available as clinical systems.

Also, the basic concept that the tissue cutting effect of current Q switch Nd:YAG is produced by the shock waves and associated cavitation effects would appear to ignore the key role of plasma formation. There is also the probability that ps lasers did not become accepted into clinical practice on account of difficulty of adequate targeting accuracy in proximity to intraocular lenses. With more advanced targeting systems, this problem could be overcome.

It would also be useful if existing Q switched Nd:YAG lasers could indicate parameters such as peak shock wave pressure and diameter to 50 per cent of peak shock pressure as part of device specifications. The use of shorter laser pulse durations, however, makes verification of output characteristics of such systems difficult to undertake - with pulse energy being the most basic type to be undertaken. This provides a focus on developing suitable target systems which could provide details of effectiveness of energy disruption modes.

References
1 Vogel A, Busch S. Shock wave emission and cavitation bubble generation by picosecond and nanosecond optical breakdown in water. J Acoust Soc Am, 1996; 100, 148-165.

2 Vogel A, Capon MRC, Asiyo-Vogel, MN, Birngruber R. Intraocular photodisruption with pico second and nanosecond laser pulses:, tissue effects in cornea, lens and retina. Investigative ophthalmology and visual science, 1994; 35, 3032-3044.

3 Oram A, Gross RL, Severin TD, Orengo-Nania S, Feldman RM. Picosecond Neodymium:Yttrium Lithium Fluoride (Nd:YLF) Laser peripheral iridotomy. Americal Journal of Ophthalmology, 1995; 119, 408-414.

4 Geerling G, Roider J, Schmidt-Erfurt U, Nahen K, El-Hifnawi E, Laqua H, Vogel A, Initial clinical experience with the picosecond Nd:YLF laser for intraocular therapeutic applications. Br J Ophthalmol, 1998; 82, 504-509.

5 Frangie JP, Park SB, Aquavella JV. Peripheral Iridotomy Using Nd:YLF. Laser Ophthalmic Surgery, 1992; 23, 220-221.

6 Loya N, Basage S, Vyas S, Park SB, Del Serro M, Aquavella JV. Effects of the pico second Neodymium:YLF laser on poly(methyl methacrylate) in intraocular lenses during experimental posterior capsulotomy. J Cataract Refract Surg, 1995; 21, 586-590.

7 Juhasz T, Kastis GA, Suarez C, Bor Z, Bron WE. Time-resolved observations of shock waves and cavitation bubbles generated by femto second laser pulses in corneal tissue and water. Lasers in surgery and medicine, 1966; 19, 23-31.

8 Juhasz T, Hu XH, Turi L, Bor A. Dynamics of shock waves and cavitation bubbles generated by picosecond laser pulses in corneal tissue and water. Lasers in surgery and medicine, 1994; 15, 91-98.

9 Jonas JB, Intrastromal lamellar femto second laser karatoplasty with superficial flap. British Journal of Ophthalmology, 2003; 87, 1195.
10 Sacks ZS, Kurtz RM, Juhasz T, Mourau GA. High precision subsurface photodisruption in human sclera. Journal of Biomedical Optics, 2002; 7, 442-450.

11 Sacks ZA, Hurz RM, Juhasz T, Spooner G, Mouroua GA. Subsurface photodisruption in human sclera: wavelength dependence, Ophthalmic surgery, lasers and imaging, 2003; 34, 104-113.

12 Wetzel W, Brinkmann R, Koop N, Schroer F, Birngruber R. Photofragmentation of lens nuclei using the Er:Yag laser: preliminary report of an in vitro study. German J Ophthalmology, 1996; 5, 281-284.

13 Kanellopoulos AJ, Dodick JM, Brauweiler P, Alzner E. Dodick photolysis for cataract surgery: early experience with the Q-switched neodymium: YAG laser in 100 consecutive patients. Ophthalmology, 1999; 106, 2197-202.

Douglas Clarkson is development and quality manager at the department of clinical physics and bio-engineering, Coventry and Warwickshire University Hospital Trust

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