Paolo Vinciguerra

Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking.

PURPOSE To report refractive, topographic, tomographic, and aberrometric outcomes 12 months after corneal cross-linking (CXL) in eyes with progressive advanced keratoconus. DESIGN Prospective, nonrandomized, single-center clinical study. PARTICIPANTS Twenty-eight eyes undergoing CXL between April and June 2006. INTERVENTION Riboflavin-ultraviolet A (UVA)-induced CXL included instillation of 0.1% riboflavin-20% dextrane solution 30 minutes before UVA irradiation and every 5 minutes for an additional 30 minutes during irradiation. MAIN OUTCOME MEASURES Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count were evaluated at baseline and at 1, 3, 6, and 12 months follow-up. RESULTS Mean baseline UCVA and BSCVA were 0.17+/-0.09 and 0.52+/-0.17, respectively; 12-month mean UCVA and BSCVA were 0.27+/-0.08 and 0.72+/-0.16, a statistically significant difference (P<0.05). Mean spherical equivalent refraction showed a significant decrease of 0.41 diopters (D). Mean baseline simulated keratometry (SIM K) flattest and steepest meridians and SIM K average were 46.10, 50.37, and 48.08 D, respectively; at 12 months, 40.22, 44.21, and 42.01 D, respectively, were recorded, a difference that was significant for all 3 indices (P<0.05). Mean average pupillary power (APP) changed significantly from 47.50 to 41.04 D at 12 months (P<0.05) and apical keratometry (AK) from 58.94 to 55.18 D (P<0.05). The treated eyes showed no deterioration of the Klyce indices at 6 months postoperatively, whereas the untreated (contralateral) eyes did show deterioration. For a 3-mm pupil, there was a significant reduction (P<0.05) in whole eye (total), corneal, higher order, and astigmatic wavefront aberrations. A significant difference (P<0.05) in total coma and total spherical aberration after CXL was also observed. Mean baseline pupil center pachymetry and total corneal volume decreased significantly (P<0.05) to 470.09+/-29.01 microm and 57.17+/-3.21 mm(3) from baseline values of 490.68+/-30.69 microm and 59.37+/-4.36 mm(3), respectively. Endothelial cell counts did not changed significantly (P=0.13). CONCLUSIONS Corneal cross-linking seems to be effective in improving UCVA and BSCVA in eyes with progressive keratoconus by significantly reducing corneal APP, AK, and corneal and total wavefront aberrations at 1 year postoperatively.

Intraoperative and Postoperative Effects of Corneal Collagen Cross-linking on Progressive Keratoconus

OBJECTIVES To report intraoperative and 24-month refractive, topographic, tomographic, and aberrometric outcomes after corneal collagen cross-linking in progressive advanced keratoconus. METHODS Prospective, nonrandomized single-center clinical study involving 28 eyes. Main outcome measures included uncorrected and best spectacle-corrected visual acuities, sphere and cylinder refraction, topography, tomography, aberrometry, and endothelial cell count evaluated at baseline and follow-up at 1, 3, 6, 12, and 24 months after treatment. Topography was also recorded intraoperatively. RESULTS Two years after treatment, mean baseline uncorrected and best spectacle-corrected visual acuities improved significantly (P = .048 and <.001, respectively) and mean spherical equivalent refraction decreased significantly (P = .03). Mean baseline flattest and steepest meridians on simulated keratometry, simulated keratometry average, mean average pupillary power, and apical keratometry all decreased significantly (P < .03). Deterioration of the Klyce indices was observed in the untreated contralateral eyes but not in treated eyes. Total corneal wavefront aberrations Z(0) (piston), Z(2) (defocus), and Z(7) (III coma) decreased significantly (P < or = .046). Mean 12-month baseline pupil center pachymetry and total corneal volume decreased significantly (P = .045). Endothelial cell counts did not change significantly (P = .13). CONCLUSIONS Two years postoperatively, corneal collagen cross-linking appears to be effective in improving uncorrected and best spectacle-corrected visual acuities in eyes with progressive keratoconus by significantly reducing corneal average pupillary power, apical keratometry, and total corneal wavefront aberrations.

Two-Year Corneal Cross-Linking Results in Patients Younger Than 18 Years With Documented Progressive Keratoconus

PURPOSE To report refractive, topographic, aberrometric, and tomographic outcomes 24 months after corneal cross-linking (CXL) in patients up to 18 years of age with progressive keratoconus. DESIGN Prospective, interventional case series. METHODS Forty eyes underwent riboflavin-ultraviolet A-induced CXL. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), sphere and cylinder, topography, aberrometry, tomography, and endothelial cell counts were evaluated at baseline and at 1, 3, 6, 12, and 24 months. RESULTS Mean logarithm of the minimum angle of resolution baseline UCVA and BSCVA were 0.79 ± 0.21 and 0.39 ± 0.10, respectively. Mean UCVA and BSCVA at 2 years were 0.58 ± 0.18 and 0.20 ± 0.09, respectively. The improvement in UCVA and BSCVA was significant throughout the postoperative follow-up (P < .05). Mean spherical equivalent refraction showed a significant decrease of 1.57 diopters (D) at 24 months (P = .02). Mean baseline simulated keratometry was 46.32 D in the flattest meridian and 51.48 D in the steepest meridian; at 2 years, the values were 45.30 D (P = .04) and 50.21 D (P = .07), respectively. For a 3-mm pupil, there was a significant reduction (P < .05) in whole eye (total), corneal, higher-order, and astigmatic wavefront aberrations at 24 months. A significant difference (P < .05) in total coma and total spherical aberration 2 years after CXL also was observed. Mean baseline pupil center pachymetry decreased significantly (P = .04) at 6 months, but recovered by 12 months and remained stable thereafter through the 2-year follow-up. Endothelial cell counts did not change significantly (P = .32). CONCLUSIONS CXL improved UCVA and BSCVA in the study patients, most likely by significantly reducing corneal asymmetry and corneal as well as total wavefront aberrations.

Scheimpflug imaging of corneas after collagen cross-linking.

Purpose: To compare geometrical shape factors of keratoconus corneas after cross-linking (CXL) by means of Scheimpflug imaging with those of untreated fellow eyes. Setting: Institut für Refraktive und Ophthalmo-Chirurgie, Zürich, Switzerland. Methods: Scheimpflug imaging of the anterior segments was performed with the Pentacam (Oculus, Wetzlar, Germany) in 21 patients with progressive keratectasia before and after CXL. Only 1 eye per patient was treated with corneal cross-linking using the riboflavin/UV-A approach, the fellow eye serving as control. The following corneal parameters and their postoperative evolution during 1 year after treatment have been evaluated: minimal curvature radius and its location, thickness at the thinnest point, location of the thinnest point, anterior and posterior elevation, conoid asphericity constants of the anterior and posterior surface, and 7 keratoconus indices. Statistical comparison was performed by means of the Wilcoxon test. Results: None of the treated eyes showed topographic progression in contrast to the untreated group where 8 eyes experienced significant progression. Minimal curvature radius increased significantly after 1 year compared with preoperative (6.14-6.21 mm), whereas in the untreated fellow eye, it significantly decreased (6.94-6.86 mm). Minimal corneal thickness was significantly reduced after treatment (P < 0.002 at 12 months). The cornea showed an evolution toward a more regular shape as indicated by a significant reduction in 4 of 7 keratoconus indices. No complications of CXL occurred in this small study group. Conclusions: After cross-linking, the corneal shape undergoes a process of regularization. This process is active during the first year after treatment and may continue. Longer follow-up is warranted to estimate the full amount of regression of the keratectasia after CXL.

Flattening of the cornea after collagen crosslinking for keratoconus

PURPOSE: To identify preoperative parameters that may predict flattening of the keratoconic cornea after collagen crosslinking (CXL). SETTING: Institut für Refraktive und Ophthalmo‐Chirurgie (IROC), Zurich, Switzerland. DESIGN: Cohort study. METHODS: Patients with verified progressive primary keratectasia received standard corneal CXL. Factors such as corrected distance visual acuity (CDVA) and Scheimpflug tomography (Pentacam) were used to follow the evolution from preoperatively to 12 months after CXL. Statistical analysis included U tests and Spearman rank correlation tests to detect risk factors for flattening of the keratoconus. RESULTS: The study enrolled 151 eyes of 151 patients; more than 80% completed the 12‐month follow‐up. The flattening rate (flattening of the maximum curvature >1.00 diopter [D]) was 37.7%. A preoperative maximum keratometry (K) reading of more than 54.00 D was identified as the only significant risk factor for this effect (odds ratio, 1.88; 95% confidence interval, 1.01‐3.51). A restriction to corneas with a maximum K value greater than 54.00 D would have resulted in a significant flattening in 51% of the cases. CONCLUSIONS: Statistically significant flattening occurred during 1 year after CXL in more than 50% of cases when the preoperative maximum K reading was more than 54.00 D. None of the other preoperative parameters evaluated (eg, age, sex, diagnosis, CDVA, corneal shape factors) had a statistically significant impact on corneal flattening after CXL. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Intra- and postoperative variation in ocular response analyzer parameters in keratoconic eyes after corneal cross-linking.

PURPOSE To analyze intra- and postoperative variation in Ocular Response Analyzer (ORA, Reichert Ophthalmic Instruments) parameters in 24 keratoconic eyes undergoing corneal cross-linking (CXL). METHODS In a prospective clinical study, corneal hysteresis (CH), corneal resistance factor (CRF), peak 1 and peak 2 amplitude, corneal-compensated and Goldmann-correlated intraocular pressure (IOP) were evaluated using the ORA. The thinnest cornea point was measured with the Pentacam (Oculus Inc). Corneal topography and endothelial cell count were performed. Measurements were recorded at baseline; intraoperatively after epithelium removal, riboflavin impregnation, and ultraviolet A irradiation; and postoperatively after corneal re-epithelialization and at 1, 6, and 12 months. RESULTS A statistically significant reduction of the thinnest cornea point from 462±23.24 μm was observed at the end of the CXL procedure intraoperatively and at 1- and 6-month follow-up (P<.05). A significant increase in the thinnest cornea point to 624±31.72 μm was found after re-epithelialization (P<.05), and no significant changes were observed at 1 year postoperatively. Mean CH and CRF did not change significantly after de-epithelialization, but were noted to significantly increase after CXL intraoperatively and postoperatively at 1-month follow-up. At 6 and 12 months postoperatively, CH and CRF were not statistically significantly different from pre-operatively. Peak 1 and peak 2 decreased intraoperatively from 276±52 and 228±47 to 172±42 and 131±42, respectively, at the conclusion of CXL (P<.05), and were noted to increase to 493±41 and 444±51, respectively, at 6-month follow-up. Corneal-compensated IOP and Goldmann-correlated IOP increased at 1 month after CXL (P>.05). CONCLUSIONS The results showed a significant change in ORA parameters and the thinnest cornea point during and after the CXL procedure and a high correlation between peak amplitudes and corneal asymmetry, providing insight to the bioelastic and biomechanical behavior of the cornea during and after CXL.

Corneal collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results

PURPOSE To evaluate the 1-year results of corneal collagen cross-linking (CXL) in eyes with postoperative excimer laser refractive surgery corneal ectasia. METHODS Thirteen eyes of 9 consecutive patients who had undergone excimer laser refractive surgery (photorefractive keratectomy [n = 3], LASIK [n = 10]) with resultant unstable corneal ectasia underwent CXL with photosensitizing riboflavin 0.1% solution and subsequent exposure to ultraviolet radiation. Study eyes underwent complete ophthalmologic examination, endothelial specular microscopy, corneal topography, and aberrometry as well as central pachymetry and Scheimpflug-based topo/tomography preoperatively and at 3-, 6-, and 12-month intervals. RESULTS Best spectacle-corrected visual acuity (BSCVA) improvement was statistically significant (P < .05) beyond 6 months after surgery (improvement of 0.1 logMAR at 1 year). Mean spherical equivalent refraction and mean refractive sphere reduction (improvement of 1.40 and 1.44 diopters [D], respectively) were statistically significant (P < .05) at 6 months postoperatively. At 1 year after CXL, mean endothelial cell count and keratometry (average SimK decrease of 2.02 D) as well as Klyce and Ambrósio indices did not deteriorate. Coma and spherical aberration did not change significantly. Mean pupil center pachymetry and corneal thickness at 0 and 2 mm from the thinnest corneal point decreased significantly. CONCLUSIONS One year after surgery, CXL appears to stabilize eyes with ectasia consequent to excimer laser refractive surgery and improve BSCVA.

Corneal cross-linking as a treatment for keratoconus: Four-year morphologic and clinical outcomes with respect to patient age

PURPOSE To report the 4-year outcomes of corneal cross-linking (CXL) for progressive keratoconus in a population of different age groups. DESIGN Retrospective, single-center, nonrandomized clinical study. PARTICIPANTS Four hundred consecutive eyes treated with corneal CXL for progressive keratoconus from April 2006 through April 2010. INTERVENTION After removal of the epithelium, the cornea was irrigated for 30 minutes with a solution of 0.1% riboflavin and 20% dextran, followed by irradiation with an ultraviolet A light of 3 mW/cm(2) for 30 minutes. MAIN OUTCOME MEASURES Best-corrected visual acuity (BCVA), sphere and cylinder refraction, corneal topography, Scheimpflug tomography, and aberrometry were assessed at baseline and at 1, 6, 12, 24, 36, and 48 months after corneal CXL treatment. The compiled data were stratified according to age (group A, younger than 18 years; group B, 18-29 years; group C, 30-39 years; and group D, older than 40 years). RESULTS Comparative analysis included 400 eyes of 301 patients. Functional results showed a significant increase in BCVA in group A by a mean reduction of -0.11 logarithm of the minimum angle of resolution (logMAR) after 12 months, in group B by a mean reduction of -0.31 logMAR after 36 months, in group C by a mean reduction of -0.33 logMAR after 36 months, and in group D by a mean reduction of -0.26 logMAR after 36 months. Morphologic results showed an analogous regularization of corneal shape with a significant reduction of opposite sector index by a mean value of -0.53 at 12 months in group A, -1.14 at 36 months in group B, -1.10 at 36 months in group C, and -0.55 at 12 months for group D. Optical quality improvement was demonstrated by a mean significant reduction of coma -1.52 μm after 12 months in group A, -1.58 μm after 24 months in group B, -2.57 μm after 36 months for group C, and -0.25 μm after 36 months in group D. CONCLUSIONS Outcomes stratified by age indicate the efficacy of corneal CXL in stabilizing the progression of ectatic disease in all age groups and improving the functional and morphologic parameters in select groups. Results indicated better functional and morphologic results in the population between 18 and 39 years of age. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells

AIM Limbal cultures restore the corneal epithelium in patients with ocular burns. We investigated the biological parameters instrumental for their clinical success. METHODS We report a long-term multicenter prospective study on 152 patients carrying corneal destruction due to severe ocular burns, treated with autologous limbal cells cultured on fibrin and clinical-grade 3T3-J2 feeder cells. Clinical results were statistically evaluated both by parametric and nonparametric methods. RESULTS Clinical outcomes were scored as full success, partial success and failure in 66.05, 19.14 and 14.81% of eyes, respectively. The total number of clonogenic cells, colony size, growth rate and presence of conjunctival cells could not predict clinical results. Instead, the clinical data provided conclusive evidence that graft quality and likelihood of a successful outcome rely on an accurate evaluation of the number of stem cells detected before transplantation as holoclones expressing high levels of the p63 transcription factor. No adverse effects related to the feeder layer have been observed and the regenerated epithelium was completely devoid of any 3T3-J2 contamination. CONCLUSION Cultures of limbal stem cells can be safely used to successfully treat massive destruction of the human cornea. We emphasize the importance of a discipline for defining the suitability and the quality of cultured epithelial grafts, which are relevant to the future clinical use of any cultured cell type.

Transepithelial Iontophoresis Corneal Collagen Cross-linking for Progressive Keratoconus: Initial Clinical Outcomes

PURPOSE To report initial clinical results of transepithelial corneal collagen cross-linking with iontophoresis (I-CXL). METHODS Twenty eyes of 20 patients diagnosed as having progressive keratoconus who underwent I-CXL were included in this prospective non-randomized clinical study. Corrected distance visual acuity (CDVA), spherical equivalent and cylinder refraction, various corneal topography and Scheimpflug tomography parameters, aberrometry, anterior segment optical coherence tomography, and endothelial cell count were assessed at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS CDVA improved significantly at 3, 6, and 12 months postoperatively (logMAR difference of -0.07 ± 0.01, -0.09 ± 0.03, and -0.12 ± 0.06, respectively; P < .05). Aberrometry remained stable during follow-up and a trend toward improvement was noted. All topographic parameters (including maximum keratometry) were stable during the follow-up, but exhibited a positive non-significant trend toward improvement. Minimum corneal thickness values were stable for up to 12 months postoperatively. None of the patients showed a progression of keratoconus. Endothelial cell counts did not change significantly (P > .05). CONCLUSIONS Preliminary results up to 1 year postoperatively indicate the efficacy of I-CXL in stabilizing the progression of this degenerative disease combined with significant improvement of CDVA. I-CXL, which spares the corneal epithelium, has the potential to become a valid alternative for halting the progression of keratoconus while reducing postoperative patient pain, risk of infection, and treatment time in select patients; however, the relative efficacy of this technique compared to standard epithelium-off techniques remains to be determined.