Ronald R. Krueger

Lamellar refractive surgery with scanned intrastromal picosecond and femtosecond laser pulses in animal eyes.

PURPOSE To evaluate the use of scanned intrastromal picosecond and femtosecond laser pulses in lamellar refractive surgical procedures. METHODS Intrastromal corneal photodisruption was performed in fresh porcine and primate cadaver eyes with a solid-state femtosecond laser. Laser pulses were focused 150 to 200 microns below the epithelial surface and scanned in a spiral pattern to create a plane. A flap was made by scanning an arc pattern from the plane of the spiral to the surface of the cornea. Tissue plane separation was graded using a standard scale, while internal surfaces were analyzed by scanning electron microscopy. Comparison was made to a picosecond laser system using the same delivery system device. Creation of a stromal lenticule for in situ keratomileusis was also demonstrated and compared with both laser systems. RESULTS For femtosecond pulses, tissue separation was achieved best with pulse energies from 4 to 8 microJ and spot separations from 10-15 microns. Picosecond pulses accomplished less complete separations with pulse energies of 25 microJ and spot separations from 10 to 20 microns. Surface quality corresponded to dissection results, with high-grade dissections resulting in a smooth surface appearance, versus a more irregular surface for low-grade dissections. Although high-grade dissections could be created with picosecond pulses (with optimal parameters) in ex vivo porcine eyes, only femtosecond parameters produced similar results in ex vivo primate eyes. CONCLUSION In contrast to previous attempts using picosecond lasers which require additional mechanical dissection, high precision lamellar refractive surgery may be practical with femtosecond laser pulses.

First clinical results with the femtosecond neodynium-glass laser in refractive surgery.

PURPOSE We evaluated four femtosecond laser intrastromal cutting procedures: creation of a corneal flap for laser in situ keratomileusis (LASIK), tunnel and entry cut for intracorneal ring, corneal flap and removable lens for keratomileusis, and intrastromal ablation for myopia and hyperopia. METHODS A clinical trial using a femtosecond surgical laser (IntraLase Corporation) was performed in partially sighted eyes. Femto-LASIK treatment was performed on 46 eyes up to -14.00 D; 16 patients received intracorneal ring segments (Femto-ICRS); 5 patients each with one highly myopic eye had femtosecond laser keratomileusis (FLK), and 13 patients each with one myopic or hyperopic eye had intrastromal ablation (ISPRK). In Femto-LASIK, excimer laser ablation was done under the flap. In Femto-ICRS, ring segments were introduced into the laser-created channels. In femtosecond laser keratomileusis, a lens-shaped block of stroma was removed manually from under the flap. RESULTS No difference was found between the results obtained with Femto-LASIK and a standard microkeratome. No refractive effects occurred when the created flap was not elevated. In cases of Femto-ICRS and conventional ICRS produced the same refractive results. With Femto-ICRS, no intraoperative complications occurred and visual acuity improved immediately after surgery. In femtosecond laser keratomileusis, high myopia was corrected without using excimer laser ablation; centralization of the treatment area was excellent. In intrastromal ablation, 1 to 2 hours after surgery the corneas were highly transparent; refractive results were stable. CONCLUSIONS Femtosecond lasers can produce precise intrastromal cutting, offering significant safety and other advantages (no razor blades, corneal trauma, partial resections, or sterilization issues) over current techniques.

Central and peripheral corneal thickness measured with optical coherence tomography, Scheimpflug imaging, and ultrasound pachymetry in normal, keratoconus-suspect, and post-laser in situ keratomileusis eyes

PURPOSE: To compare central (CCT) and peripheral corneal thickness (PCT) using Scheimpflug imaging (Pentacam), high‐speed optical coherence tomography (Visante OCT), and ultrasound (US) pachymetry (Sonogage Corneo‐Gage Plus) in normal, keratoconus‐suspect, and post–laser in situ keratomileusis (LASIK) eyes. SETTING: Department of Refractive Surgery, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. METHODS: The CCT and PCT were retrospectively measured using US pachymetry, Scheimpflug imaging, and high‐speed OCT from January 2006 to March 2008. The influence of age and absolute magnitude of corneal thickness were also analyzed. Analysis was by multivariate generalized estimating equations, multivariate linear regression, and linear regression plots. RESULTS: One hundred sixty‐three eyes were analyzed. Ultrasound pachymetry CCT measurements were consistently higher than Scheimpflug and OCT measurements (mean difference 6.5 μm ± 1.8 [SD] and 7.5 ± 1.4 μm, respectively) (both P<.0005) in normal eyes; the difference was statistically similar and not greater with keratoconus suspicion, age, or absolute magnitude of corneal thickness (P>.05). Scheimpflug measurements were significantly lower than US pachymetry in post‐LASIK eyes (P<.0005). There was no statistically significant difference (mean 0.9 ± 1.4 μm) in Scheimpflug and OCT CCT measurements (P>.5), although Scheimpflug measurements were significantly lower in post‐LASIK eyes (P<.0005). Scheimpflug PCT measurements were higher than OCT measurements, showing more agreement with increasing age (P = .017). CONCLUSIONS: Scheimpflug and OCT CCT measurements were reproducible but always thinner than US pachymetry in normal and keratoconus‐suspect eyes. In post‐LASIK eyes, OCT pachymetry maps were more accurate than Scheimpflug maps. The influence of age on PCT requires further study.

Femtosecond Laser and Microkeratome Corneal Flaps: Comparison of Stromal Wound Healing and Inflammation

PURPOSE To examine early postoperative wound healing in rabbit corneas that had LASIK flaps formed with three different models (15 KHz, 30 KhZ, and 60 KHz) of a femtosecond laser compared with flaps formed with a microkeratome. METHODS Thirty-nine rabbit eyes were randomized to receive either no surgery or corneal flaps formed with one of the lasers or the microkeratome. Sixteen eyes also had lamellar cuts with no side cuts with the 30 KHz laser. Animals were sacrificed and corneas processed as frozen sections or fixed for transmission electron microscopy. Frozen sections were evaluated with the TUNEL assay to detect apoptosis, immunocytochemistry for Ki67 to detect cell mitosis, and immunocytochemistry for CD11b to detect mononuclear cells. RESULTS Rabbit corneas that had flaps formed with the 15 KHz laser had significantly more stromal cell death, greater stromal cell proliferation, and greater monocyte influx in the central and peripheral comea at 24 hours after surgery than corneas that had flaps formed with the 30 KHz or 60 KHz laser or the microkeratome. Results of the 60 KHz laser and microkeratome were not significantly different for any of the parameters at 24 hours, except for mitotic stromal cells at the flap margin. Transmission electron microscopy revealed that the primary mode of stromal cell death at 24 hours after laser ablation was necrosis. CONCLUSIONS Stromal cell necrosis associated with femtosecond laser flap formation likely contributes to greater inflammation after LASIK performed with the femtosecond laser, especially with higher energy levels that result in greater keratocyte cell death.

Experimental increase in accommodative potential after neodymium:yttrium–aluminum–garnet laser photodisruption of paired cadaver lenses ☆

PURPOSE Loss of lens elasticity is one of several proposed mechanisms responsible for the decline in accommodation with age and is the most accepted explanation for presbyopia. We wish to confirm the lens elasticity premise and attempt to experimentally reverse the age-dependent loss of accommodative potential as measured by polar strain. DESIGN Experimental human autopsy eye study. PARTICIPANTS AND CONTROLS Thirty-six cadaver lenses were tested to determine the age-dependent polar strain. Eleven lens pairs were then tested with one lens treated with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser and the other left untreated before rotation as an age control. TESTING Using a custom-made rotational apparatus (described by Fisher, 1971), freshly excised cadaver lenses (<48 hours postmortem) were rotated at 1000 rpm on a 9-mm diameter pedestal to simulate the physiologic pull of the zonules. Lenses were initially tested to determine the age-dependent polar strain. One lens in a pair was then treated with an Nd:YAG laser and the other left untreated before testing. Treatment consisted of 100 suprathreshold pulse placed in a central annular pattern of 2- to 4-mm diameter. Treatment energies varied from 2.5 to 7.0 mJ/pulse, depending on the relative clarity of the lenses. Polar strain was both microscopically measured and calculated from projected photographs before and after rotation of both lased and unlased lenses. Statistically significant differences were determined by paired t test. MAIN OUTCOME MEASURES Polar strain (decrease in axial thickness with rotation) of the lens. RESULTS An age-dependent decrease in polar strain was observed that paralleled the findings of Fisher. Both measured and projected polar strain were greater in the lased than unlased lens, and this difference was highly significant by paired t test (P = 0.001 and P = 0.004, respectively). CONCLUSIONS Age-dependent loss of lens elasticity (polar strain) can be experimentally reversed (increased) by selective intralenticular photodisruption.

First safety study of femtosecond laser photodisruption in animal lenses: Tissue morphology and cataractogenesis

PURPOSE: To determine through safety studies the tissue effects and potential cataractogenesis of laser modification of the crystalline lens (photophaco modulation). SETTING: Laser Zentrum Hannover, Hannover, Germany. METHODS: Six fresh porcine lenses and 6 living rabbit eyes (with the contralateral eye as a control) were radiated with a low‐energy femtosecond laser to induce lens fiber disruption. After 3 months, the rabbit eyes were extracted and tested for light scatter and lens function and fixed for histology and ultrastructure. RESULTS: After laser treatment, all lenses displayed a tightly packed array of intralenticular bubbles, which resolved with time. In the porcine eyes, the bubbles coalesced unless spacing of 9 μm or greater was applied at an energy of 2 μJ. In the rabbit eyes, an energy of 1 μJ and spacing of 10 μm was chosen for transcorneal delivery, showing minimum bubble coalescence. After 3 months, the rabbit lenses showed good transparency, with only 1 rabbit having cataract formation unrelated to the laser. Laser scanning studies show essentially identical values for the back focal length and sharpness of focus (variability of back focal length). Ultrastructurally, the rabbit eyes showed a 0.5 μm electron dense border layer with adjacent normal lens architecture. CONCLUSIONS: Femtosecond laser photodisruption of the ocular lens yields a self‐limited lesion with bubbles that resolve with time. In living animal eyes, no cataract formation was found with no loss of lens function or induced light scatter after 3 months. These results suggest that use of a low‐energy femtosecond laser might be safe when modifying the lens for presbyopia correction.

Stability of simultaneous topography-guided photorefractive keratectomy and riboflavin/UVA cross-linking for progressive keratoconus: case reports.

PURPOSE To follow the stability of a simultaneously delivered therapy that corrects aberrations and stiffens the corneal collagen of eyes with progressive keratoconus. METHODS Two patients with progressive keratoconus underwent partial treatment (70% cylinder and sphere up to 50-μm central depth) with topographic customized photorefractive keratectomy (PRK) using the T-CAT module of the ALLEGRETTO WAVE Eye-Q excimer laser (Alcon Laboratories Inc), and then immediate corneal collagen cross-linking (CXL) with riboflavin 0.1% drops every 2 minutes while exposed to mean 365-nm ultraviolet A (UVA) light at 3.0 mW/cm² for 30 minutes (the Athens Protocol). Pre- and postoperative evaluations included manifest and cycloplegic refraction, Scheimpflug corneal tomography and pachymetry, and slit-lamp examination of corneal clarity with a minimum follow-up of 30 months. RESULTS Both treated eyes experienced rapid healing of the epithelial surface within 5 days and progressive improvement of vision. In the first case, partial treatment reduced the astigmatism and aberrations, allowing for successful soft contact lens wear at 3 months. Follow-up at 13, 19, 30, and 36 months showed progressive reduction of refractive myopia and keratometric power. In the second case, laser treatment led to a near emmetropic refraction with an uncorrected visual acuity of 20/20 at 3 months, which remained unchanged at 21 and 30 months postoperative. CONCLUSIONS Partial topography-guided PRK followed by riboflavin/UVA CXL is a safe and effective therapy that halts the progression of keratoectasia and reduces the spherocylindrical refraction and aberrations to improve the visual function of patients with progressive keratoconus. Stability and progressive improvement over time is observed, although limitations may exist for steeper and thinner corneas.

Corneal biomechanics as a function of intraocular pressure and pachymetry by dynamic infrared signal and Scheimpflug imaging analysis in normal eyes.

PURPOSE To evaluate corneal biomechanical deformation response using Ocular Response Analyzer (ORA) and Corvis ST data. DESIGN Prospective observational case-control study. METHODS A total of 1262 eyes of 795 patients were enrolled. Three groups were established, according to the corneal compensated intraocular pressure (IOPcc): Group I (10-13 mm Hg), Group II (14-17 mm Hg), and Group III (18-21 mm Hg). Each group included 3 subgroups, based on central corneal thickness (CCT): Subgroups 1 (465-510 μm), 2 (510-555 μm), and 3 (555-600 μm). In addition, similar groups of CCT were divided into subgroups of IOPcc. Corneal hysteresis (CH) and corneal resistance factor (CRF) were derived from ORA. The parameters of highest concavity with the parameters of first and second applanation were recorded from Corvis ST. RESULTS CH and CRF, applanation 1 time, and radius of curvature at highest concavity showed significant differences between CCT subgroups for each IOPcc group (P < .0001). CH, applanation 1 and 2 time, and applanation 2 velocity, as well as deformation amplitude (DA), showed significant differences by IOP subgroups for all CCT groups. IOPcc is correlated negatively with CH (r = -0.38, P < .0001). There are positive correlations of IOPcc with applanation 1 time, applanation 2 velocity, and radius and negative correlations with applanation 2 time (r = -0.54, P < .0001), applanation 1 velocity (r = -0.118, P < .0001), and DA (r = -0.362, P < .0001). CONCLUSION ORA and Corvis ST parameters are informative in the evaluation of corneal biomechanics. IOP is important in deformation response evaluation and must be taken into consideration.

Expanding depth of focus by modifying higher-order aberrations induced by an adaptive optics visual simulator

PURPOSE: To evaluate the impact of higher‐order aberrations on depth of focus using an adaptive optics visual simulator. SETTING: Refractive Surgery Department, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. METHODS: An adaptive optics simulator was used to optically introduce individual aberrations in eyes of subjects with a 6.0 mm pupil under cycloplegia (coma and trefoil, magnitudes ±0.3 μm; spherical aberration, magnitudes ±0.3, ±0.6, ±0.9 μm). A through‐focus response curve was assessed by recording the percentage of Sloan letters at a fixed size identified at various target distances. The subjects ocular depth of focus and center of focus were computed as the half‐maximum width and the midpoint of the through‐focus response curve. RESULTS: The dominant eyes of 10 subjects were evaluated. The simulation of positive or negative spherical aberration had the effect of enhancing depth of focus and resulted in linearly shifting of the center of focus by 2.6 diopters (D)/μm of error. This increase in depth of focus reached a maximum of approximately 2.0 D with 0.6 μm of spherical aberration and became smaller when the aberration was increased to 0.9 μm. Trefoil and coma appeared to neither shift the center of focus nor significantly modify the depth of focus. CONCLUSION: The introduction of both positive and negative spherical aberration using adaptive optics technology significantly shifted and expanded the subjects overall depth of focus; simulating coma or trefoil did not produce such effects.

Monovision Laser in situ Keratomileusis for Pre-presbyopic and Presbyopic Patients

PURPOSE To evaluate the outcome and success of refractive surgery in pre-presbyopic and presbyopic patients with monovision after laser in situ keratomileusis (LASIK). METHODS We performed a retrospective analysis of 748 eyes of 374 patients over 35 years of age treated in one or both eyes for a monovision outcome using the Alcon LADARVision 4000 laser. Analysis of age at the time of surgery, gender, bilateral versus unilateral treatment, targeted outcome, and patient acceptance are reported. RESULTS The success rate of monovision patients in this study was 92.5%. Acceptance rate was higher in older patients, although there was no significantly greater acceptance of monovision for any of the variables studied (P values >.26). CONCLUSIONS Monovision is a valuable option for pre-presbyopic and presbyopic patients considering refractive surgery.