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Osteogenesis imperfecta (OI) is a disease causing bone fragility; however, it potentially affects all organs with a high content of collagen, including ears, teeth, and eyes. The study is cross-sectional and compares non-skeletal characteristics in adults with OI that clinicians should be aware of when caring for patients with OI. INTRODUCTION: Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder. The skeletal fragility is pronounced; however, OI leads to a number of extra-skeletal symptoms related to the ubiquity of collagen type 1 throughout the human body. The vast majority of knowledge is derived from studies performed in the pediatric population. Thus, we aimed to investigate the nature and prevalence of ophthalmologic, odontologic, and otologic phenotypes in an adult population with OI. METHODS: The study population comprises 85 Danish OI patients (age 44.9 ± 15.9 years). Fifty-eight patients had OI type I, 12 OI type III, and 15 OI type IV according to the classification by Sillence. Audiometric evaluations and dental examinations were performed in 62 and 73 patients, respectively. Ophthalmologic investigations were performed in 64 patients, including measurements of the central corneal thickness. RESULTS: All patients, except two, had corneal thickness below the normal reference value. Patients with OI type I and patients with a quantitative collagen defect had thinner corneas compared to patients with OI type III and other patients with a qualitative collagen defect. One patient in this cohort was diagnosed with and treated for acute glaucoma. Dentinogenesis imperfecta was diagnosed in one fourth of the patients, based on clinical and radiographic findings. This condition was predominately seen in patients with moderate to severe OI. Hearing loss requiring treatment was found in 15 of 62 patients, of whom three were untreated. The most prevalent type of hearing loss (HL) was sensorineural hearing loss, whereas conductive HL was solely seen in patients with OI type III. The patients with the most severe degrees of HL were patients with mild forms of OI. Age was associated with increased HL. CONCLUSION: Although significant health problems outside the skeleton are frequent in adult patients with OI, the patients are not consistently monitored and treated for their symptoms. Clinicians treating adult patients with OI should be aware of non-skeletal health issues and consider including regular interdisciplinary check-ups in the management plan for adult OI patients.

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PURPOSE: To evaluate the clinical and optical efficiency of topography modulated customized corneal ablations for irregular corneal astigmatism. MATERIAL & METHODS: Sixteen eyes of 16 patients with iatrogenic corneal astigmatism (post keratoplasty) were consecutively included. Based on preoperative corneal topographic measurements height deviations from a spherical corneal shape were calculated and transferred to a flying-spot excimer laser. Photo-refractive keratectomy of the topographic irregularities was then performed. Clinical and optical efficiency was evaluated by best corrected visual acuity and by computation of corneal wavefront aberrations before and up to one year after treatment. Wavefront aberrations were decomposed by Zernike polynomial analysis. RESULTS: Before treatment the average best-corrected visual acuity was 0.23. Three and 12 months after PRK the average best-corrected visual acuity had increased to 0.37 (p<0.05) and 0.45 (p<0.05), respectively. Corneal wavefront aberrations (root-mean-square) were 3.35 before surgery and 1.88 (p<0.05) and 1.51 (p<0.05) at three and 12 months after treatment. Zernike polynomial decomposition of the wavefront aberrations revealed that regular corneal astigmatism was the most important aberration component before and after surgery. Regular astigmatism was significantly decreased by the procedure, whereas coma, spherical aberrations, and higher-order aberrations were not reduced significantly. CONCLUSION: Topography modulated photorefractive keratectomy of highly astigmatic corneal grafts can improve best corrected visual acuity and reduce corneal wavefront aberrations. Even in apparently irregular topographic astigmatism, regular astigmatic wavefront aberration may be the most important contributor to wavefront errors.

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PURPOSE: To investigate the long-term effects and stability of refraction after radial keratotomy procedure. METHODS: Radial keratotomy was performed on 123 persons to reduce myopia (range: -1 to -13 diopters) in 1986 to 1989. A mean of 11.5 years later (range 10 to 13), 61 of these patients with 102 eyes underwent a standardised refractive examination where subjective spherical equivalent refraction was measured and compared to the preoperative and the one month postoperative refractive measurement collected from the patients records. RESULTS: There was a reduction in spherical equivalent from an average of -5.46 diopters (SD 2.38) preoperatively to -2.32 diopters (SD 1.96) 11.5 years postoperatively. The mean change in direction of myopia between 1 month and 11.5 years postoperatively was 0.17 diopters (SD 1.18). This change was not statistically significant. From 1 month to 11.5 years, 10 of the eyes had developed more than 1 diopter hyperopia, and 20% more than 1 diopter myopia. When asked directly, all patients were satisfied with the result of their operation in general; 2 patients still complained of glare. CONCLUSION: No significant changes in refraction were found between 1 month and 11.5 years after radial keratotomy. Previously reported long-term studies on this field have found a trend toward progressive hyperopia. No evidence of such change can be supported by this study.

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Myopia can today be reduced or eliminated by refractive surgery. Excimer laser surgery of the cornea by surface sculpturing (photorefractive keratectomy) or intrastromal tissue removal (LASIK) are the most widely used techniques, although implantation of intra corneal ring segments for low myopia also appears promising. Treatment of high myopia (> 10 diopters) is still difficult although epikeratoplasty or phakic IOL implantation are present possibilities. The perfect surgery for myopia remains to be developed, but the existing techniques will without doubt be further optimised. In 10 years time, supra normal visual acuity may even be obtained when surgical, optical, and biological variables can be described and controlled in each individual undergoing refractive surgery.

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PURPOSE: To compare a contact and a non-contact specular microscope in the determination of endothelial cell density. SUBJECTS AND METHODS: One hundred and twenty-one eyes from 70 patients who had undergone various degrees of photorefractive keratectomy for myopia were included. The endothelium was imaged by contact (Konan Clinical Specular Microscope) and non-contact (Topcon SP-1000) specular microscopy and the endothelial cell density estimated. RESULTS: The average endothelial cell density achieved by the contact specular microscope was 3011+/-298 cells/mm2 (mean+/-SD, n=121) and by the non-contact specular microscope 3015+/-265 cells/mm2 (n= 121). The difference in endothelial cell density between the contact and the non-contact specular microscope (contact minus non-contact) was -4+/-175 cells/mm2 (t=0.26, 2p>0.05 in a paired t-test). The sampling error on the estimated endothelial cell density was 76 cells/mm2 for the contact specular microscope and 74 cells/mm2 for the non-contact specular microscope. CONCLUSION: The average endothelial cell density and the precision of the measuring technique were similar for the contact and the non-contact specular microscope. Furthermore, the endothelial cell densities estimated by the two instruments at various values of anterior central corneal refractive power and central corneal thickness were similar. The two instruments can be used interchangeably.

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PURPOSE: Patients needing penetrating keratoplasty (PK) and cataract extraction with intraocular lens (IOL) implantation may be handled with a single triple procedure or a two-stage procedure with initial keratoplasty and cataract surgery in a later session. The latter approach is considered more safe by some surgeons and allows adjustment of the IOL power to the power of the actual corneal graft. The purpose of this study was to estimate the optimal timing of cataract surgery with IOL implantation by studying the refractive stability of 8 mm penetrating keratoplasty grafts. METHODS: Penetrating keratoplasty (8.0 mm graft and recipient bed) was performed in 28 eyes of 28 patients. Corneal topography (TMS-1) was studied at 1, 2, 3, 6, and 12 months after surgery and after suture removal (30 months). The central spherical equivalent graft power was computed from the topographical data (rings 2 through 4). RESULTS: On average, the spherical equivalent graft power was stable from one month after surgery up to suture removal (range: 41.9 to 42.7 diopters). After suture removal the graft steepened slightly (0.7 diopters). Corneal refractive power of single grafts fluctuated considerably over time. The standard deviation on time-dependent changes in graft power was from 3 months efter PK smaller than the standard deviation on the graft powers at 12 months. CONCLUSION: The average central spherical equivalent power of an 8.0 mm donor graft in an 8.0 mm recipient bed was stable from one month after penetrating keratoplasty until suture removal. A two-stage procedure with cataract surgery performed 3 months after PK can, compared to the triple procedure, reduce postoperative ametropia at 12 months if graft topography is taken into consideration at the time of cataract surgery. We recommend that cataract surgery with IOL implantation takes place from 3 months after penetrating keratoplasty.

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PURPOSE: To describe the effect of corneal refractive surgery on the magnification of a contact and a non-contact specular microscope. METHOD: The magnification of a contact specular microscope (Konan Clinical Specular Microscope) and a non-contact specular microscope (Topcon SP-1000) was experimentally and theoretically studied as a function of anterior corneal refractive power and central corneal thickness. RESULTS: The magnification of the contact and non-contact specular microscope was found to decrease slightly with decreasing central corneal thickness. In addition, the magnification of the non-contact specular microscope decreased slightly with decreasing anterior corneal refractive power. CONCLUSION: As the preoperative and postoperative measuring conditions are different in patients undergoing corneal refractive surgery a correction for magnification changes is necessary when small changes in endothelial cell density are looked for.

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PURPOSE: To study the fate of corneal grafts after extended organ culture (7 weeks). METHODS: Six patients with symmetrical eye diseases were grafted bilaterally, in one eye with a cornea prepared by routine organ culture (mean 16 days), in the other eye with a donor cornea kept for 7 weeks (mean 49 days) in organ culture. The outcome was evaluated by biomicroscopy, graft thickness, endothelial cell density and visual performance after an observation time of at least 1 year. RESULTS: Penetrating 7-8 mm grafting was uncomplicated in all cases. The endothelial densities were in both groups in the range 1000-2000 cells/mm2, and visual acuity 0.2-0.9 in cases with no other ocular pathology. Postoperative graft thickness and deswelling did not differ between 2- and 7-week cultured corneas. At final examination the thicknesses were 0.50 mm and 0.49 mm for 2- and 7-weeks cultured corneas. CONCLUSION: Seven-week cultured corneas give clinical results comparable to those obtained using shorter culture periods. An extended culture period may be used to improve other qualities of the graft (compatibility, cell number, cell metabolism) and microbiological control.

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OBJECTIVE: The purpose of the study was to develop methods for simultaneous description of astigmatic direction and magnitude on aggregate data, with special reference to refractive surgery. DESIGN: Mathematical analysis of astigmatisms employing bivariate statistical methods. RESULTS: The mean of several astigmatisms is a new astigmatism of specific direction and magnitude, while the confidence region is an area, which may be determined exactly. CONCLUSIONS: Astigmatisms may conveniently be symbolized as an astigmatic direction and magnitude, but are actually composed of refractive powers in the form of polar values. We are operating with two different entities, a net astigmatism and a power vector in the form of polar values. There is an unequivocal point-to-point correlation between these entities. Mathematical conversions can only be performed with polar values, but never by using net astigmatisms. All net astigmatisms must be converted to their appropriate refractive powers and the relevant calculations performed with these entities. The final result, such as an average of several astigmatisms, variances or confidence areas, may be point-to-point reconverted to and symbolized by a net astigmatism. These principles allow for exact description and comparison of surgical methods, but may be employed to describe and analyze any other population of astigmatisms, such as subjective cylinders and spectacle corrections.

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PURPOSE: To study the long-term effect of 193 nm excimer laser photorefractive keratectomy (PRK) on the human corneal endothelial cell density. SUBJECTS AND METHODS: One hundred and twenty-four eyes from 71 patients underwent photorefractive keratectomy for myopia or myopic-astigmatism. Endothelial cell density was examined a short time before the operation and on an average of 50 months after the operation using a contact specular microscope. A subgroup of 32 eyes from 20 patients treated only once was examined preoperatively and 7 and 52 months postoperatively. The endothelial cell densities were corrected for the changing magnification of the contact specular microscope with changing central corneal thickness and for the expected physiological cell loss with time. RESULTS: The average endothelial cell density was preoperatively 3098+/-283 cells/mm2 (mean+/-SD) and postoperatively 3048+/-294 cells/mm2 corresponding to a change of -50+/-157 cells/mm2. This was statistically significantly different from zero in a paired t-test (n=124, t=3.58, 2p<0.001). The average changes in endothelial cell density for the subgroup were -34+/-159 cells/mm2 for the postoperative time interval 0-7 months and -20+/-188 cells/mm2 for the postoperative time interval 7-52 months. These results were not statistically significantly different from zero in a paired t-test (n=32, t=1.21 and t=0.60, 2p>0.05). A statistically significant negative correlation between preoperative cell density and the change in cell density was found (n=124, r=-0.21, 2p<0.05). CONCLUSION: This study suggests a potentially harmful effect of PRK on the human corneal endothelium. It appears that most cells are lost during ablation or within the first period of time after PRK.

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PURPOSE: To study the effect of arcuate keratotomy on corneal astigmatism in previously grafted eyes compared to eyes with naturally occurring astigmatism. SUBJECTS AND METHODS: Twenty-three eyes with naturally occurring astigmatism and 21 eyes with post-keratoplasty astigmatism were treated by arcuate keratotomies in the steepest corneal meridian. Visual acuity, spherically equivalent refraction, and refractive cylinder were measured before surgery and 1 to 10 years after the operation. RESULTS: The preoperative refractive cylinder was reduced from 5.0 dioptres (median) to 1.25 dioptres in eyes with natural astigmatism and from 7.0 dioptres to 3.25 dioptres in post-keratoplasty eyes. Spherical equivalent refraction changed from -0.6 dioptres to -1.5 dioptres in eyes with natural astigmatism and from -3.5 dioptres to -4.5 dioptres in previously grafted eyes. The induced change in astigmatism, as calculated by Fourier analysis, correlated strongly with the existing preoperative astigmatism. The effect of the procedure did not correlate with the type of astigmatism (congenital vs. post-keratoplasty), time after surgery, or with patient age or sex. CONCLUSION: Arcuate keratotomy is a simple procedure to reduce naturally occurring astigmatism as well as induced astigmatism after keratoplasty. Parallel to the astigmatic change, negligible changes in the spherical equivalent are induced.

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PURPOSE: To investigate whether the immediate change in corneal power during radial keratotomy correlates with the long-term postoperative change in subjective refraction, and thereby being predictive for refractive outcome. METHODS: Manual keratometry was performed on 45 consecutively operated eyes of 45 young persons with myopia of 5 dioptres and less and immediately after radial keratotomy. Automated keratometry and subjective spherical equivalent refraction were investigated during a follow-up period of 6 months and correlated to the intraoperative keratometric measurements. RESULTS: On average, the majority of the change in corneal curvature after radial keratotomy took place within 1 min. There was no correlation between the intraoperative curvature change and the changes in curvature measured up to 6 months after surgery. There was a weak significant positive correlation between intraoperative curvature change and the change in subjective refraction at 6 months after surgery (R = 0.48, p < 0.01). The prediction error in estimating subjective refractive changes from intraoperative keratometry changes was, however, similar in patients who had bilateral radial keratotomy. Inclusion of such fellow-eye information together with the age of the patient in a multiple linear regression analysis increased the correlation coefficient from 0.48 to 0.75. CONCLUSIONS: The change in central corneal curvature takes place within minutes after corneal incision. As a single parameter, intraoperative keratometry cannot be used for titrating surgery. Information from the results of first eye radial keratotomy surgery with intraoperative keratometry is, however, predictive for radial keratotomy in the second eye. These findings suggest that a large source to refractive variability after radial keratotomy is related to individual patient factors, such as corneal biomechanics and wound healing.

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PURPOSE: To compare the induced regular and irregular astigmatism after scleral and corneal tunnel incision. SETTING: University hospital outpatient cataract clinic. METHODS: One hundred phacoemulsification patients with less than 1.0 diopter (D) of preoperative astigmatism were randomly assigned to have a clear corneal incision (50 patients) or a scleral tunnel incision (50 patients). All incisions were 3.5 to 4.0 mm wide and were made in the steepest axis of the corneal astigmatism. The surgically induced astigmatism was analyzed by vector analysis from keratometric data, as well as by Fourier harmonic series analysis of the topographic data. RESULTS: One day after surgery, the surgically induced astigmatism (vector analysis, keratometry) was 1.41 D +/- 0.66 (SD) and 0.55 +/- 0.31 D in the corneal incision group and the scleral incision group, respectively (P < .01). Six months after surgery, the induced astigmatism was 0.72 +/- 0.35 D and 0.36 +/- 0.21 D in the two groups, respectively (P < .01) The corneal topography data confirmed the regular astigmatism changes found by conventional keratometry. However, in addition, Fourier harmonic series analysis of the topography data showed significantly more irregular induced astigmatism with the corneal approach than with the scleral approach. CONCLUSION: The clear corneal incision induces significantly more regular as well as irregular astigmatism than the scleral tunnel incision.

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BACKGROUND: Photorefraktive keratectomy (PRK) is the most frequent refractive surgical procedure worldwide. The central corneal thickness is reduced due to removal of the anterior stroma, including Bowman's layer, with a laser beam. This procedure results in considerable alterations of the corneal structure. What does this mean for the mechanical properties of the cornea? METHODS: Intraocular pressure was increased via a 180 degrees tilt. Before and during this procedure, corneal topography was measured by photokeratoscopy. We examined 26 patients after PRK and 25 controls who had not undergone any surgical procedure. RESULTS: The corneal center flattened by 0.038 +/- 0.05 dpt (P > 0.05) in the PRK patients and by 0.187 +/- 0.045 dpt (P < 0.05) in the control group. PRK patients within 1 year after operation showed a minimal central corneal steepening, whereas PRK patients after more than 1 year showed a reaction similar to that in normal corneas (P < 0.05). CONCLUSION: Corneal stability is altered after PRK. After 1 year corneal stability seems to normalize due to stromal remodelling.

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PURPOSE: To investigate the accuracy and precision of automated keratometry, automated refractometry, and computerized corneal topography in estimating the subjective refractive outcome of photo-astigmatic refractive keratectomy six months postoperatively. METHODS: Photo-astigmatic refractive keratectomy (Aesculap-Meditec, MEL-60 Excimer Laser) was performed on 26 eyes with a preoperative myopia ranging from -4.0 to 7.6 dioptres, and a naturally occurring astigmatism from 0.75 to 5.0 dioptres. Six months postoperatively refractive outcome was evaluated by automated keratometry, automated refractometry (Nikon NRK-8000), computerized topography (TMS-1), and subjective refraction. Estimate errors were computed as the difference between the change in subjective refraction and the change in automated keratometry, automated refractometry, and surface topography, respectively. Astigmatic changes were evaluated by the second harmonic component in the Fourier series analysis. RESULTS: Subjective spherical as well as cylindrical values were reduced significantly six months postoperatively. The estimate error (mean +/- one standard deviation) for automated keratometry was -1.26 +/- 0.72 dioptres for the spherical equivalent and -1.36 +/- 1.02 dioptres for the cylinder; for automated refractometry it was -0.78 +/- 0.91 dioptres for the spherical equivalent and -0.66 +/- 0.92 dioptres for the cylinder. The best estimates of subjective changes were obtained when the average of ring 2 and 3 of the topographic data was used: -0.15 +/- 0.82 dioptres for the spherical equivalent and -0.78 +/- 0.80 dioptres for the cylinder. CONCLUSIONS: The computerized topographer with the Fourier analysis was superior to automated keratometry and automated refractometry in estimating the subjective spherical refractive outcome and comparable to automated refractometry in estimating the subjective cylinder refractive outcome after photo-astigmatic refractive keratectomy.

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PURPOSE: Refractive error after penetrating keratoplasty is a major clinical problem. The purpose of the present study was to investigate whether the topography of the donor cornea influence the topography of the graft after transplantation. METHODS: Twenty-five donor corneas were measured with a video-keratograph (TMS-1): in situ and before and after organ culture. Clinical video-keratographic images of the transplanted grafts were subsequently obtained one week, 1, 3, 6, 12, and 24 months after surgery. The central spherical equivalent power and corresponding regular and irregular astigmatic powers were computed. RESULTS: A statistically significant correlation between spherical equivalent central donor power and spherical equivalent central graft power after keratoplasty was found at all times up to two years after surgery. Only 13-50% of the variation in post-keratoplasty spherical graft power could, however, be explained by the donor graft power. Corresponding 95% confidence limits for prediction of post-keratoplasty power from donor graft power were approximately +/- 6.5 diopters. Post-keratoplasty regular or irregular corneal astigmatism did not correlate with astigmatism in the donor graft. CONCLUSION: Corneal donor graft spherical equivalent power does influence the spherical equivalent corneal power after keratoplasty, especially during the first months after surgery. The dependency is, however, not very strong and until other determinants of post-keratoplasty corneal shape are known and controllable, 'power-typing' of donor corneas appears to be of limited clinical use.

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The regional mechanical performance of the cornea and limbus was studied in vitro by pressure loading of 18 intact human eyes. The pressure-induced (2-100 mmHg) meridional and circumferential tangential mechanical strains of the epi-and endothelial side of the cornea were measured at the centre, the para-centre, the periphery and the limbus. Strains were computed from digital measures of distances between tiny mercury droplet markers fixed on the corneal surfaces. Corresponding in-plane membrane stresses were calculated from measurements of the regional meridional and circumferential radius of curvature and from measurements of the corneal thickness of the four regions. Young's moduli of elasticity were computed for each region in the meridional and circumferential direction assuming orthotropic elastic behaviour of the corneal stroma. A power function was used to fit the non-linear elastic stress-strain relationships. The pressure-induced meridional strains were smallest at the corneal paracentre and periphery, and largest at the limbus. The circumferential strains varied less between regions with the para-centre straining most. In the meridional direction, Young's modulus of elasticity was highest at the central and para-central corneal regions, whereas the highest circumferential elastic modulus was found at the limbus. This study supports the notation of circumferentially orientated reinforcing structures in human limbal tissue. The para-central region of the human cornea was found stiffer in the meridional direction compared with the circumferential direction, suggesting a meridionally orientated reinforcement of the para-central parts of the human cornea. These findings may have important implications for mechanical modelling of keratorefractive procedures.

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The effect of 193 nm excimer laser radiation on human corneal endothelial cell density was examined. Fifty-five eyes from 35 patients underwent photorefractive keratectomy for myopia. Photomicrographs of the endothelium were taken a short time before the operation and on an average of 7 months postoperatively with a specular microscope. The average endothelial cell densities were preoperatively 3375 +/- 266 cell/mm2 (mean +/- SD) and postoperatively 3348 +/- 287 cells/mm2, corresponding to a fall of 27 cells/mm2 (N = 55). This fall in endothelial cell density was not statistically significant. A significant correlation between the change in cell density and age of the patient was found, with older patients losing more cells (N = 35, 2p < 0.05). The magnification of the specular microscope was found to change with corneal thickness. The importance of correcting the endothelial cell densities for corneal thickness is discussed.

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BACKGROUND: Corneal refractive surgical procedures alter the shape and structure of the tissue, possibly compromising its mechanical stability. METHODS: One or both eyes of 87 subjects were studied: 26 of these 87 had been treated for myopia by excimer laser ablation and 36 by radial keratotomy; 25 without previous corneal surgery functioned as controls. Corneal topography was evaluated by TMS-1 videophotokeratography before and after 180 degrees tilting of the patient, and the pressure-induced ring-wise changes in spherical equivalent power (axial power) were calculated. Changes in corneal shape also were evaluated by computing the instantaneous radius of curvature. The intraocular pressure was measured before and after tilting by a hand-held applanation tonometer. RESULTS: The mean intraocular pressure increased from 13.9 +/- 2.3 mm Hg before tilting to 30.0 +/- 3.8 mm Hg during tilting. In the control eyes, the mean power of the central cornea during tilting decreased 0.187 +/- 0.045 diopters (D) (p < .05); in the excimer-laser-ablated eyes, 0.038 +/- 0.056 D (not statistically significant); and in those treated with radial keratotomy, 0.523 +/- 0.054 D (p < .01). After radial keratotomy, the cornea steepened outside the clear zone in response to pressure loading, whereas it did not change significantly in the laser-ablated or control eyes. CONCLUSIONS: Pressure-induced deformation of normal and excimer laser-ablated human cornea is small, whereas radially incised corneas have significantly decreased mechanical stability.

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