Laser modification of corneal tissue has been an intense topic of research efforts. Early work12 showed that well-defined patterns of corneal tissue could be excised (photoetched) from the surface with single pulses from an ArF excimer laser. This work was followed by subsequent studies in polymers and then applied to corneal sculpturing.'38 These latter surface ablation techniques have been effective in achieving corneal reshaping and, therefore, refractive modification. The invasive characteristics and possible tissue healing questions have encouraged a search for less invasive methods.
In a study of alternative approaches, we have developed a new surgical probe and observed a laser-corneal tissue interaction process which has well-localized refractive effects. The physical optics aspects of the technique have been reported in some detail elsewhere.9"11 In this brief note, we report further preliminary experimental results.
The laser used in these preliminary studies was an acousto-optic Q-switched, CW lamp-pumped Nd: YAG laser. It was operated in the TEM(OO) mode with 1064 nm, 100-nanosecond pulses at a pulse rate ranging from 500 to 2000 Hz. The tip of the probe was gently placed on the surface of the cornea of experimental eyes and moved along the surface, so as to deposit a concatenated string of laser-induced vacuoles within the corneal stroma, labelled as "plasma ablation" in Figure 1. The vacuolization process in all medias tested was accompanied by a tiny luminescent plasma flash. Although a wide range of patterns of delivery are feasible, a pattern that emulated a typical radial keratotomy was t/ned for this preliminary study.
Figure 1 : New contact probe method for refractive intrastromal laser treatment. TEM(OO) laser radiation enters hand probe, passes through lens system Ll and L2 and focuses sharply in the mid stroma.9
Figure 2: Rhesus primate eye, slit-lamp microscopic view approximately 5 minutes after laser treatment with radial pattern. Note the mid stroma highly localized vacuoles in the slit illumination to left of pupil.
Figure 3: Corneascope ring mires reflected from a Dutchbelted rabbit immediately after laser treatment. The mires show modifications and flattening effect comparable to radial keratotomy.
Our laser corneal intrastromal treatment was applied in this preliminary study to a number of experimental eyes: human eye-bank eyes, excised bovine eyes, and eyes of living properly anesthetized rabbits and primates. Methods for observation of the effects included direct visual inspection, slit-lamp biomicroscopy, corneascopy, and for excised tissues, visible and electron microscopy Generally, observations were made immediately after treatment, 24 hours after treatment, 48 hours after treatment, and 5 months after treatment. For histological observations, a laser treated eye-bank eye was perforated and immersed in 4% formaldehyde with Vk glutaraldehyde mixture to facilitate fixation. After overnight fixation, the cornea was removed and routinely processed for paraffin infiltration and embedding. The intact cornea was then sectioned at planes 3 µ apart and re-embedded together on their side to obtain their sagittal sections. The 3-micron sections were stained with hematoxylin and eosin.
In all cases, the application of the laser probe resulted in the immediately observable appearance of a track of connected vacuoles contained within the cornea. The vacuole tract formation required the movement of the probe. Holding the probe stationary tended to inhibit further plasma formation at the same site. The vacuoles appeared well localized in the midstroma as seen in the slit-lamp photomicrograph of the treated eye of a properly anesthetized rhesus primate (Fig 2), taken approximately 5 minutes after treatment. The corneal epithelium and endothelium under slit-lamp microscope observation appeared not to be affected at 5 minutes to as long as 5 months after treatment. An additional immediate effect is a refractive modification of the corneal curvature as noted in the corneoscope photograph of the eye of a properly anesthetized Dutch-belted rabbit (Fig 3). This effect was similar to that noted for a typical radial keratotomy treatment. The vacuolar track also exhibited the notable effect of virtually disappearing optically to unaided visual inspection at 24 to 48 hours. The refractive effects, however, persisted for the duration studied, 5 months.
Figure 4: Light micrograph of the transverse section of the cornea of an eyebank eye immediately after treatment in which several laser treatment tracks are localized perpendicular to the section. Vl through V5 are the laser vacuoles at a consistent level of approximately 320 µm and the areas designated by P are protrusions caused by the tissue preparation. Protrusions (P) on the inner edge were not associated with the treatment effects; for example, protrusions occurred where there were no treatment sites nearby. These were due to the buckling of the tissue in preparing the section for microscopy. Displacement of vacuole V4 toward the surface was caused by the slight pull back of the probe during the exposure from contact with the cornea. Vacuole V2 was interpreted as a composite of several laser pulse events, side by side. The stromal fibers in the vacuolar region were apparently disintegrated as they ended abruptly at the vacuole boundary. There was only slight displacement of the fibers. Vacuole V4 did not have any protrusion directed outward toward the surface.
Figure 5: Transmission electron micrograph taken of the same tissue in Figure 4 immediately after treatment with 90 000 × magnification in the region near a laser vacuole. NOR is the normal collagen microfibrile region and VAC is the laser-induced vacuolar region. There is a relatively thin transition zone of modified fibriles. The zone is no greater than about 0.2 µ. The magnification in this micrograph is such that the vacuole would cover a region of about 10 m in diameter.
Histological examination of the treated cornea corroborated the slit-lamp microscopic observations on the localizability of the treated site (Fig 4). The epithelium and endothelium were not preserved in the histological preparation process for this eyebank eye because of postmortem degradation.
A transmission electron micrograph in the region of the boundary between the vacuole and adjacent tissue is shown in Figure 5.
SUMMARY OF RESULTS
The results of this study indicate the following characteristics for the new form of corneal microsurgery:
1. The laser foci at a predetermined distance (320 ± 20 µ) from the contact plane induces a microscopic plasma point.
2. The plasma event creates a vacuole of the order of 100 µ in diameter in the tissue.
3. Vacuoles can be connected to form a linear or area treatment region.
4. Material that occupied the vacuole space appears to be clearly disintegrated into a fluid state.
5. Tissue fibriles beyond a range of 0.50 µ of the vacuole appear normal and not pyrolized.
6. Displacement of tissue (plasty) in the vacuolar region, although not completely absent, is notably minimal, contributing no more than 20 µ to the diameter.
7. Vacuolar tracks disappear to the unaided eye within 24 to 48 hours.
Since the laser surgical process reported here significantly eliminates target site tissue by disintegration, it is not merely cutting as in keratotomy but, it is more like a keratectomy. Tissue in a sense is "removed" but as a metabolically diffusive liquid. We would suggest defining the process as intrastromalphotokeratectomy.
That the cornea curvature flattens with radial intrastromal-photokeratectomy tracks may be attributed to the cutting of circumferential lamellar fibers as suggested by Fyodorov in explaining conventional radial keratotomy.14 These fibers are located at a 90-percent depth within the peripheral cornea. The present intrastromal-photokeratectomy probe reaches these fibers without affecting the adjacent tissues. Thus, radial keratotomy apparently can be achieved with a sealed internal keratectomy process which promotes rapid healing and optical uniformity.
There are a number of additional characteristics of the probe that are presently being studied such as the automatic control of delivery including depth control. It should be particularly noted that the process is fairly safe in that the plasma formation ceases at a given site with the occurrence of vacuoles. The probe is fairly easy to use and its laser system is relatively simple in design.
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