[In vitro and in vivo investigations on the treatment of presbyopia using femtosecond lasers]. / In-vitro- und In-vivo-Untersuchungen zur Presbyopiebehandlung mit Femtosekundenlasern.

BACKGROUND: Ultrashort (femtosecond) laser pulses can generate precise cuts in biological tissue without damaging the surface. The application of femtosecond laser technology at the lens was evaluated with respect to a possible treatment of presbyopia. MATERIALS AND METHODS: Femtosecond laser lentotomy was performed on 150 pig lenses in vitro. Cutting geometry and laser settings were optimized to generate smooth cuts with a minimum of produced gas bubbles. Four rabbit lenses were treated afterwards in vivo and were controlled for 3 months post-treatment. The lenses were then extracted and evaluated. RESULTS: With suitable laser settings, light scattering due to residual gas bubbles could be almost completely avoided in pig lenses. A pulse energy of less than 1.2 microJ and a cutting geometry with spot separations of more than 5 microm are important. The rabbit lenses stayed macroscopically clear for 3 months in vivo. Only the cell structures directly adjacent to the laser focus were cut; structures 5-10 microm away appeared to be intact. No cataract formation occurred during this time. CONCLUSION: Femtosecond laser application allows precise and smooth cuts inside pig and rabbit lenses without damage to adjacent tissue.

Interaction of ultraviolet laser light with the cornea.

The effect of pulsed ultraviolet (UV) laser light on the cornea depends on wavelength (photon energy), irradiance (photon flux), and pulse firing rate. At the available excimer laser wavelengths of 193, 249, 308, and 351 nanometers, the authors have varied the irradiance per pulse (10 to 2000 mj/cm2) as well a pulse frequency (1, 10, 25 Hz) and determined the thresholds for coagulation and ablation of the corneal stroma. The latter ablative action creates a groove resembling an incision and was present at all wavelengths studied. The threshold for ablation increased for longer wavelengths and lower pulse frequencies, except for 193-nm exposure, which was characterized by a constant threshold independent of laser pulse rate. The grooves at 193 nm were both biomicroscopically and histologically smooth and no coagulation effects were noted. Some degree of coagulation of adjacent tissues was noted at 249, 308, and 351 nm.

Quantitation of corneal ablation by ultraviolet laser light.

A surgical role has been suggested for the excimer laser. This followed the discovery of precision etching of biological materials by the laser's ultraviolet emissions. In studying the amount of tissue removed as the laser energy density (irradiance) was varied, we found significant differences for the 193-, 249-, and 308-nm laser emission lines. The most efficient cutting irradiance for each pulse appeared to be about 200 millijoules/sq cm for 193 nm, 1,000 millijoules/sq cm for 249 nm, and 1,500 millijoules/sq cm for 308 nm. The flat slope of the etch depth curve for 193 nm suggests it will be a stable frequency when used clinically.

Clinical analysis of steep central islands after excimer laser photorefractive keratectomy.

PURPOSE: To examine topographic irregularities known as steep central islands that may occur after excimer laser refractive surgery and affect visual acuity. METHODS: We reviewed the computed corneal topographic maps of 35 eyes that had undergone excimer laser photorefractive keratectomy with an excimer laser for compound myopic astigmatism or anisometropic myopia. Steep central islands were defined as areas of steepening of at least 3 diopters and 1.5 mm in diameter. A classification system was developed based on the presence of steep central islands during the postoperative period as follows: class 0, absent; class 1, present at 1 week; class 2, present at 1 month; class 3, present at 3 months. RESULTS: Steep central islands were seen in 25 eyes (71%) at 1 week, 18 eyes (51%) at 1 month, seven eyes (20%) at 3 months, and four eyes (11%) at 6 months. After surgery without nitrogen gas blowing, 16 of 25 patients had class 2 or 3 steep central islands compared with two of 10 eyes when gas blowing was used. Loss of best spectacle-corrected visual acuity of 2 Snellen lines or more was seen in eight of 18 eyes with class 2 or 3 steep central islands at 1 month and three of 18 eyes at 3 months. A similar loss occurred in one of 17 eyes with class 0 or 1 steep central islands at 1 month and none of 17 eyes at 3 months. In all eyes with only class 2 steep central islands, loss of at least 1 Snellen line of best spectacle-corrected visual acuity at 1 month was associated with visual restoration at 3 months when the island was no longer present. CONCLUSION: Loss of best spectacle-correlated visual acuity is associated with steep central island formation, and may prolong visual rehabilitation after excimer laser photorefractive keratectomy.

High-speed photography of excimer laser ablation of the cornea.

We have used laser-based high-speed photography to investigate excimer laser ablation of the cornea. Photographs of the ablation plume were obtained 500 ns to 150 microseconds after incidence of a 193- or 248-nm excimer laser pulse on the surface of the cornea. Ejection of material from the cornea begins on a time scale of nanoseconds and continues for 5 to 15 microseconds following the excimer pulse. At 193 nm the ablation plume resembles a burst of smoke, and individual particles are too small to be optically resolved with our apparatus. At 248 nm the plume resembles a spray of larger, discrete droplets. Material is ejected from the cornea at supersonic velocity but decelerates rapidly; the velocity for the first 500 ns following the excimer pulse averages 400 m/s at 193 nm. Plume size and velocity increase with increasing fluence.

New stroboscopic light source for intraoperative retinal fluorescein angiography.

We tested a new stroboscopic light source for intraoperative fluorescein angiography. A pulsed xenon light source and narrow-band interference filters are coupled to a 20-gauge endoilluminator and a 35-mm camera mounted on a surgical microscope. The system was tested with good success in a patient undergoing penetrating keratoplasty. An 18- to 22-microJ flash of 2 milliseconds' duration is achieved, which is well below the safety threshold level. This new stroboscopic light source provides a flash of sufficient light intensity to perform high-resolution, high-contrast fluorescein angiography during operations for the removal of opacified media.

Arachidonic acid metabolites after excimer laser corneal surgery.

OBJECTIVE: We investigated early mediators of inflammation following excimer laser ablation in a rabbit cornea model. The ability of topical anti-inflammatory agents to influence these responses was also examined. METHODS: Adult New Zealand white rabbits were subjected to photorefractive keratectomy with a 193-nm argon fluoride excimer laser. Prostaglandin E2 and leukotriene B4 levels were measured using an enzyme immunoassay, and leukocyte infiltration was determined histologically. RESULTS: Prostaglandin E2 production was rapid and sustained, but we were unable to detect the presence of leukotriene B4. Relative to control, postoperative topical diclofenac sodium treatment caused a significant decrease in prostaglandin E2 levels and a significant increase in corneal leukocytes at 10 hours. Fluorometholone treatment did not significantly alter prostaglandin E2 levels but markedly depressed leukocyte ingress. CONCLUSIONS: Diclofenac reduces prostaglandin E2 levels but not leukocyte infiltration in the cornea following photorefractive keratectomy and thus may be useful clinically to reduce postsurgical pain.

Corneal surface morphology following excimer laser ablation with humidified gases.

OBJECTIVE: To compare the effects of blowing dry (nitrogen or helium) and humidified gases over the corneal surface during photorefractive keratectomy. METHODS: Excimer laser myopic ablations were performed on porcine eyes (10 per group) using humidified and dry nitrogen and helium gas under ambient conditions. Surface smoothness was quantified with light and electron microscopy. RESULTS: Corneas that were ablated using humidified gas were smooth and equivalent to those ablated under ambient conditions. Dry nitrogen and helium blowing resulted in increased surface irregularity evident on light and electron microscopy (P < .001). The pseudomembranes in the humidified gas and ambient air groups had fewer surface discontinuities than did those in the nonhumdified gas groups and appeared to have a thinner electron-dense surface layer. CONCLUSIONS: The blowing of humidified gas during excimer laser corneal ablation produces a smoother surface than does the blowing of dry gas and is comparable to that produced under ambient (no blowing) conditions. Maintaining corneal moisture is important in photorefractive keratectomy. If blowing gas is necessary to remove debris from the surface, the gas should be humidified.

Double-armed McCannell suture for repair of traumatic iridodialysis.

PURPOSE: To repair iridodialysis in a traumatized eye with minimal surgical manipulation. METHODS: We examined a patient with traumatic iridodialysis. The separated iris obstructed the visual axis and was cosmetically disfiguring. RESULTS: At surgery we secured the iridodialysis to the anterior chamber angle by using a new technique with double-armed McCannell suture. CONCLUSION: Compared with other procedures, this technique is simple and provides the least amount of ocular manipulation for iridodialysis repair.

Central bump-like opacity as a complication of high hyperopic photorefractive keratectomy.

PURPOSE: A new complication is reported in association with high hyperopic excimer laser photorefractive keratectomy. METHODS: One thousand consecutive eyes were treated with a Meditec MEL-60 excimer laser (Meditec Inc, Heroldsberg, Germany) for hyperopic refractive error between +1 diopters and +7 diopters. RESULTS: Three eyes with high hyperopic corrections between +5 and +6 diopters had a central, round bump-like subepithelial scar develop 1 month after hyperopic photorefractive keratectomy, which reduced the uncorrected and spectacle-corrected visual acuity. CONCLUSION: Central bump-like opacity is a new, visually significant complication of unknown origin associated with high hyperopic photorefractive keratectomy. Possible causes of this complication include drying and edema of the cornea as a result of prolonged exposure, interruption of the peripheral superficial nerve plexus affecting the central anterior stroma, and abnormal epithelial or tear film function resulting from excessive central steeping.

Excimer laser therapy for experimental Candida keratitis.

In vivo treatment of experimental Candida albicans keratitis with the excimer laser achieved sterilization on culture and histopathologically in all corneas in which clinically visible infiltration was removed with the laser at the 193-nm wavelength. Treatment at the 248-nm wavelength was not successful in eradicating infection compared with untreated controls. The 193-nm wavelength is highly effective, probably because infected tissue is totally removed by ablative photodecomposition. At the 248-nm wavelength, thermal effects become more dominant and, therefore, fungal elements are incompletely ablated. Light microscopy two days after treatment at the 193-nm wavelength showed healing of ulcerated areas, fine basophilic stippling at the epithelial-stromal interface, and undamaged underlying stroma.

Improvement of visual function with glare testing after photorefractive keratectomy and radial keratotomy.

PURPOSE: To evaluate the effect of a glare source on visual function in patients after photorefractive keratectomy and radial keratotomy. METHODS: Thirteen patients (22 eyes) who underwent photorefractive keratectomy and 20 patients (40 eyes) who underwent radial keratotomy were evaluated in this cross-sectional study. LogMAR visual acuity and contrast sensitivity were measured. Pupils were measured with the Rosenbaum card. A halogen/tungsten glare source approximated the luminance of headlights of an oncoming car at 100 feet. RESULTS: In the photorefractive keratectomy and radial keratotomy groups, pupils were significantly smaller (P<.01) and the pupillary clearance of the ablation zone in photorefractive keratectomy and the clear zone in radial keratotomy were significantly larger under the glare condition (P<.01). In the photorefractive keratectomy group, visual acuity and contrast sensitivity under the glare condition were significantly higher than in the no-glare condition (P = .02). In the radial keratotomy group, contrast sensitivity under the glare condition was significantly higher than under the no-glare condition (P = .001 to .003). CONCLUSIONS: After photorefractive keratectomy or radial keratotomy, the traditional glare source constricted the pupil and partially masked the optical aberrations, which resulted in an improvement in visual function. A "pupil-sparing" aberration test is needed for evaluation of visual function after refractive surgery.

Clinical analysis of excimer laser photorefractive keratectomy using a multiple zone technique for severe myopia.

PURPOSE: In an investigational procedure, excimer laser photorefractive keratectomy for severe myopia was performed at three clinical trial centers to determine the effectiveness of the multiple zone technique. METHODS: A VisX Model Twenty/Twenty excimer laser (VisX, Santa Clara, California) was used to perform photorefractive keratectomy on 14 severely myopic eyes (-10.37 to -24.5 diopters) of 12 patients by using a multiple zone technique. Postoperative follow-up ranged from six months to two years; retreatments were performed on four patients, with a follow-up of at least nine months. RESULTS: At six months postoperatively, before retreatment, three of the 14 eyes were within 2 diopters and seven of the 14 eyes were within 4 diopters of attempted correction. Regression of effect to more severe myopia was worse in five eyes treated with nitrogen gas blowing. Retreatments also demonstrated considerable myopic regression. Three patients had loss of two or more lines of best-corrected visual acuity, and these patients also had moderate or severe levels of haze. CONCLUSION: Excimer laser photorefractive keratectomy for severe myopia using a multiple zone technique is associated with considerable regression, haze, and loss of best-corrected visual actuity, especially when performed in association with nitrogen gas blowing.

Highlights of the 1st International Congress of Wavefront Sensing and Aberration-free Refractive Correction.

As we review the many new and evolving techniques for treating patients with customized ablation, it is obvious that there is a rapid evolution of technology and thought. Newly refined diagnostic technology, such as wavefront sensing, and more sophisticated spot laser delivery systems with eye tracking gives the refractive surgical team greater flexibility in tackling challenging optical abnormalities. These highlights of the 2000 Congress now set the stage for further development, outlined in the following selected papers from the 2001 Congress.

Corneal iron line associated with steep central islands after photorefractive keratectomy.

PURPOSE: To report a new corneal iron deposit after excimer laser photorefractive keratectomy (PRK). METHODS: Two patients with symptomatic persistent steep central islands were noted to have a corneal iron ring at 6 months to 1 year after surgery. This is different from the central iron spot noted in most patients at 1 year. RESULTS: One patient had repeated PRK with improvement of his symptoms and resolution of the iron ring. CONCLUSIONS: A corneal iron ring after excimer laser PRK suggests the presence of a persistent steep central island of stromal origin. Since corneal iron deposition signifies chronicity, symptomatic patients should be retreated as resolution of the steep central island is not likely to occur.

Photorefractive keratectomy for astigmatism with the Meditec MEL 60 laser.

PURPOSE: To evaluate the results of photorefractive keratectomy (PRK) in eyes treated with astigmatic refractive errors. METHODS: Nine hundred forty eyes were treated with the Aesculap Meditec MEL 60 ArF excimer laser. Treatment groups were: Group 1 (n=746) eyes with compound myopic astigmatism, Group 2 (n=104) eyes with compound hyperopic astigmatism, Group 3 (n=75) eyes treated for mixed astigmatism, and Group 4 (n=15) eyes with simple myopic astigmatism (negative cylinder). RESULTS: In Group 1, the preoperative spherical equivalent refraction of -6.10 D with an average of -1.50 D cylinder decreased to -0.95 D with -0.13 D cylinder; uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 86% (642/746 eyes); 20/20 or better in 58% (433/746 eyes); 0.8% (6/746 eyes) lost two lines of spectacle-corrected visual acuity (SCVA); 74% (552/746 eyes) were within +/-0.50 D and 93% (694/746 eyes) were within +/-1.00 D of target refraction. In Group 2, preoperative mean +4.57 D spherical equivalent refraction with an average of +1.57 D cylinder decreased to +1.13 D with +0.38 D cylinder; UCVA of 20/40 or better was achieved in 84% (87/104 eyes); 20/20 or better in 46% (48/104 eyes); 14,4% (15/104 eyes) lost two or more lines of SCVA; 52% (54/104 eyes) were within +/-0.50 D and 82% (85/104 eyes) were within +/-1.00 D of target refraction. In Group 3, mean preoperative -4.20 D cylinder and +3.00 D spherical equivalent refraction decreased to -0.50 D cylinder and -0.50 D spherical equivalent refraction; UCVA of 20/40 or better was achieved in 83% (62/75 eyes); 20/20 or better in 32% (24/75 eyes); 13.3% (10/75 eyes) lost two or more lines of SCVA. In Group 4, mean preoperative -3.98 D cylinder decreased to -0.62 D cylinder; UCVA of 20/40 or better was achieved in 60% (9/15 eyes); none of the eyes achieved 20/20 or better; SCVA remained stable in 6.6% (1/15 eyes) and decreased two or more lines in 20.0% (3/15 eyes); 20% (3/15 eyes) were within +/-0.50 D and 53.3% (8/15 eyes) were within +/-1.00 D of target refraction. CONCLUSION: PRK with the Meditec MEL 60 laser produced the best results in eyes with compound myopic astigmatism (Group 1). In all other groups, results were less predictable.

The picosecond laser for nonmechanical laser in situ keratomileusis.

PURPOSE: To introduce the clinical use of the Nd:YLF picosecond laser as a nonmechanical microkeratome. METHODS: A commercially available Nd:YLF picosecond laser (25 microJ/pulse, 30 psec, 1053 nm) was used to deliver intrastromal pulses of focused high power laser light to generate a flap for laser in situ keratomileusis (LASIK) and perform picosecond laser keratomileusis (PLK) in two partially sighted patients with high myopia. RESULTS: Case #1: A 6 mm, 150 microns flap for LASIK was successfully created and the underlying stroma treated with an excimer laser for a target correction of -15.00 D of myopia. Good corneal clarity and a refractive change of -14.00 D was recorded 2 months postoperatively. Case #2: Both eyes of a high myope (-22.00 D right eye, -21.50 D left eye) underwent picosecond laser keratomileusis, removing a 3.2 mm diameter lenticule of 120 microns thickness under a 200 microns flap. Postoperative refraction was -2.00 D at 7 months in the right eye and -0.75 D at 2 months in the left eye with improvement of spectacle-corrected visual acuity from 20/200 to 20/70 in each eye. CONCLUSION: The Nd:YLF picosecond laser can be safely used in creating a corneal flap for LASIK and in performing picosecond laser keratomileusis for high myopia. Future refinements in the laser will include a larger flap diameter and femtosecond pulsing capability.

Surgically-induced astigmatism after laser in situ keratomileusis for spherical myopia.

PURPOSE: To characterize the surgically-induced-astigmatism (SIA) associated with spherical LASIK. METHODS: Refractive outcomes in 70 eyes that underwent primary myopic LASIK with purely spherical ablation were analyzed. The Summit Apex Plus excimer laser was used. The Bausch & Lomb Hansatome with the 180-microm plate was used to produce superiorly hinged flaps. The relationship between refractive astigmatism and corneal topographic astigmatism was analyzed using linear regression and vector analysis. RESULTS: There was a statistically significant negative correlation (slope = -0.21) between refractive surgically-induced astigmatism and preoperative topographic cylinder. A 0.24-D with-the-rule shift was also found. Surgically-induced astigmatism was not correlated with the magnitude of laser ablation. CONCLUSION: The lamellar keratotomy portion of LASIK reduces pre-existing corneal astigmatism and produces a relative steepening of the hinge meridian.

Picosecond laser in situ keratomileusis with a 1053-nm Nd:YLF laser.

BACKGROUND: Excimer laser in situ keratomileusis requires a microkeratome to generate an anterior corneal flap, plus an excimer laser to ablate the underlying stromal tissue. In this paper we introduce the concepts of laser flap formation and in situ keratomileusis using a picosecond laser. METHODS: A neodymium-doped yttrium-lithium-fluoride (Nd:YLF) laser with a plano-plano quartz applanation lens was used to generate various patterns of intrastromal photodisruption in human donor eyes to fashion anterior corneal flaps and generate intrastromal lenticules. RESULTS: Smooth intrastromal dissections, 6 mm in diameter, were generated 160 microns below the corneal surface when the laser delivered pulses at 1 kHz with energies of either 40 microJ/pulse or 60 microJ/pulse, placed 20 microns apart in an expanding spiral. This enabled us to fashion anterior corneal flaps. The ease of the surgery and quality of the dissection corresponded well, and it was evident that both deteriorated noticeably when the laser pulses were separated by 25 microns or 30 microns, regardless of pulse energy. Using 40 microJ laser pulses placed 20 microns apart we also created a 5-mm diameter, 320 microns thick (130 microns-450 microns deep) stromal lenticule below a corneal flap that was easily extracted when the flap was raised. CONCLUSIONS: Anterior corneal flaps were easily fashioned using a Nd:YLF laser. Picosecond laser in situ keratomileusis with a Nd:YLF laser could offer a favorable alternative to combined microkeratome/excimer laser in situ keratomileusis.

Ultrastructure of picosecond laser intrastromal photodisruption.

PURPOSE: To investigate the ultrastructure of the corneal stroma after picosecond intrastromal photodisruption with a neodymium-doped yttrium-lithium-fluoride (Nd:YLF) laser. METHODS: We performed picosecond intrastromal photodisruption on six human eye-bank eyes using a lamellar technique. Thirty picosecond pulses at 1000 Hz and 20 to 25 mJ per pulse were placed in an expanding spiral pattern, the pulses separated by 15 microns. Three layers were placed in the anterior stroma, separated from each other by 15 microns. In addition, intrastromal radial and arcuate incisions were generated in two living rabbit eyes in a plane perpendicular to the corneal surface. After the procedure, the corneas were processed for scanning and transmission electron microscopy. RESULTS: Scanning electron microscopy of the eye-bank eyes demonstrated multiple, coalescing intrastromal cavities forming a layer oriented parallel to the corneal surface. These cavities had smooth inner walls. Transmission electron microscopy demonstrated tissue loss surrounding some cavities, with the terminated ends of collagen fibrils clearly evident. Other cavities were formed by separation of lamellae, with little evidence of tissue loss. A pseudomembrane was present along the margin of some cavities. Although there was occasional underlying tissue disruption along the border of a cavity, there was no evidence of thermal damage or tissue necrosis. The perpendicular photodisruptions demonstrated intrastromal cleavage of corneal collagen similar to diamond-knife incisions, with the exception of intact overlying Bowman's and epithelial layers. CONCLUSION: Intrastromal photodisruption with a Nd:YLF picosecond laser induced no thermal necrosis or coagulative change in the region of tissue interaction. Lamellar intrastromal photodisruption demonstrated both tissue loss and lamellar separation when performed with the current treatment parameters, possibly limiting ablation efficiency and predictability.