Aldo Caporossi

Long-term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study

PURPOSE To report the long-term results of 44 keratoconic eyes treated by combined riboflavin ultraviolet A collagen cross-linking in the first Italian open, nonrandomized phase II clinical trial, the Siena Eye Cross Study. DESIGN Perspective, nonrandomized, open trial. METHODS After Siena University Institutional Review Board approval, from September 2004 through September 2008, 363 eyes with progressive keratoconus were treated with riboflavin ultraviolet A collagen cross-linking. Forty-four eyes with a minimum follow-up of 48 months (mean, 52.4 months; range, 48 to 60 months) were evaluated before and after surgery. Examinations comprised uncorrected visual acuity, best spectacle-corrected visual acuity, spherical spectacle-corrected visual acuity, endothelial cells count (I Konan, Non Con Robo; Konan Medical, Inc., Hyogo, Japan), optical (Visante OCT; Zeiss, Jena, Germany) and ultrasound (DGH; Pachette, Exton, Pennsylvania, USA) pachymetry, corneal topography and surface aberrometry (CSO EyeTop, Florence, Italy), tomography (Orbscan IIz; Bausch & Lomb Inc., Rochester, New York, USA), posterior segment optical coherence tomography (Stratus OCT; Zeiss, Jena, Germany), and in vivo confocal microscopy (HRT II; Heidelberg Engineering, Rostock, Germany). RESULTS Keratoconus stability was detected in 44 eyes after 48 months of minimum follow-up; fellow eyes showed a mean progression of 1.5 diopters in more than 65% after 24 months, then were treated. The mean K value was reduced by a mean of 2 diopters, and coma aberration reduction with corneal symmetry improvement was observed in more than 85%. The mean best spectacle-corrected visual acuity improved by 1.9 Snellen lines, and the uncorrected visual acuity improved by 2.7 Snellen lines. CONCLUSIONS The results of the Siena Eye Cross Study showed a long-term stability of keratoconus after cross-linking without relevant side effects. The uncorrected visual acuity and best spectacle-corrected visual acuity improvements were supported by clinical, topographic, and wavefront modifications induced by the treatment.

Parasurgical therapy for keratoconus by riboflavin–ultraviolet type A rays induced cross-linking of corneal collagen : Preliminary refractive results in an Italian study

PURPOSE: To assess the effectiveness of riboflavin–ultraviolet type A rays induced cross‐linking of corneal collagen in reducing progression of keratoconus and in improving visual acuity in patients with progressive keratoconus. SETTING: Department of Ophthalmology, Siena University, Siena, Italy. METHODS: This was a second‐phase prospective nonrandomized open study. Starting in September 2004, 10 eyes of 10 patients (mean age 31.4 years) with bilateral keratoconus were treated by combined riboflavin–ultraviolet type A rays (UVA) collagen cross‐linking. Radiant energy was 3 mW/cm2 or 5.4 joule/cm2 for a 30‐minute exposure at 1 cm from the corneal apex. A complete ophthalmologic examination (uncorrected visual acuity [UCVA], sphere spectacles corrected visual acuity (SSCVA), best spectacle‐corrected visual acuity [BSCVA]) was performed. Patients had corneal computerized topographic examination, linear scan optical tomography, endothelial cell count, ultrasound pachometry, intraocular pressure (IOP) evaluation, and HRT II system confocal microscopy at 1, 2, 3, and 6 months. After treatment, eyes were medicated and dressed with a soft contact lens. RESULTS: Comparative preoperative and postoperative results showed increases of 3.6 lines for UCVA (P = .0000112), 1.85 lines for SSCVA (P = .00065), and 1.66 lines for BSCVA (P = .00071). Topographic analysis showed a mean K reduction of 2.1 ± 0.13 diopters (D) in the central 3.0 mm. Statistical analysis of IOP and endothelial cell count did not show significant differences. Topo‐aberrometric analysis findings of corneal symmetry showed a trend toward increasing corneal symmetry with a major reduction in asymmetry between vertical hemimeridians. CONCLUSIONS: Refractive results showed a reduction of about 2.5 D in the mean spherical equivalent, topographically confirmed by the reduction in mean K. Results of surface aberrometric analysis showed improvement in morphologic symmetry with a significant reduction in comatic aberrations.

Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in vivo confocal microscopy in humans.

Purpose: To assess ultrastructural stromal modifications after riboflavin-UVA-induced cross-linking of corneal collagen in patients with progressive keratoconus. Methods: This was a second-phase prospective nonrandomized open study in 10 patients with progressive keratoconus treated by riboflavin-UVA-induced cross-linking of corneal collagen and assessed by means of Heidelberg Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal microscopy. The eye in the worst clinical condition was treated for each patient. Treatment under topical anesthesia included corneal deepithelization (9-mm diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500 solution at 5 minutes before UVA irradiation and every 5 minutes for a total of 30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment. Results: Rarefaction of keratocytes in the anterior and intermediate stroma, associated with stromal edema, was observed immediately after treatment. The observation at 3 months after the operation detected keratocyte repopulation in the central treated area, whereas the edema had disappeared. Cell density increased progressively over the postoperative period. At ∼6 months, keratocyte repopulation was complete, accompanied by increased density of stromal fibers. No endothelial damage was observed at any time. Conclusions: Reduction in anterior and intermediate stromal keratocytes followed by gradual repopulation has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy after riboflavin-UVA-induced corneal collagen cross-linking.

Corneal Healing After Riboflavin Ultraviolet-A Collagen Cross-Linking Determined by Confocal Laser Scanning Microscopy In Vivo: Early and Late Modifications

PURPOSE To assess early and late micromorphological modifications of cross-linked corneas in vivo by means of Heidelberg Retinal Tomography (HRT) II confocal microscopy. DESIGN Prospective nonrandomized open trial. METHODS Micromorphological examination of 44 cross-linked keratoconic corneas was performed in vivo by HRT II confocal laser scanning microscopy. Riboflavin ultraviolet (UV)-A-induced corneal collagen cross-linking (CXL) was performed according to the Siena protocol: pilocarpin 1% drops 30 minutes before, topical anesthesia with lidocaine 4% drops 15 minutes before irradiation, mechanical scraping of epithelium (9-mm-diameter area), preirradiation soaking for 10 minutes in riboflavin solution 0.1% (Ricrolin, Sooft, Italy) applied every 2.5 minutes for 30 minutes, 30 minutes exposure to solid-state UVA illuminator (Caporossi; Baiocchi; Mazzotta, X-linker, CSO, Italy), 8-mm-diameter irradiated area, energy delivered 3 mW/cm(2). All patients were examined by confocal scans preoperatively and at the following times after treatment: one, three, and six months, and one, two, and three years. RESULTS No damage to the limbal region was observed. Epithelial regrowth was complete after four days of soft contact lens bandage. The anatomy of the subepithelial plexus was restored one year after the operation with full corneal sensitivity. Increased density of extracellular matrix in late postoperative period indicated cross-linked collagen to a depth of 340 microm expressed by a late demarcation line. CONCLUSION In vivo confocal microscopy showed early and late modification of corneal microstructure after the treatment. The three-year stability of CXL recorded could be related to increased cross-links formation, synthesis of well-structured collagen and new lamellar interconnections.

Stromal haze after combined riboflavin-UVA corneal collagen cross-linking in keratoconus : in vivo confocal microscopic evaluation

The technique of corneal collagen cross‐linking consists of photopolymerization of stromal fibres by the combined action of a photosensitizing substance (riboflavin or vitamin B2) and ultraviolet light from a solid state UVA source. Photopolymerization increases the rigidity of corneal collagen and its resistance to keratectasia. In this report we present two cases, studied through in vivo confocal microscopy, with stage III keratoconus that developed stromal haze after the cross‐linking treatment.

Corneal crosslinking: Riboflavin concentration in corneal stroma exposed with and without epithelium

PURPOSE: To evaluate intrastromal concentrations of riboflavin with and without epithelium to ensure the efficacy and safety of corneal crosslinking (CXL) by the standard and transepithelial procedures. SETTING: Department of Ophthalmology and Department of Pharmacology G. Segre, Siena University, Siena, Italy. METHODS: This study comprised keratoconic patients enrolled for penetrating keratoplasty (PKP) and warm‐stored sclerocorneal rings unsuitable for transplantation. Half the PKP specimens were debrided, and half were left with the epithelium in situ. One of the latter and 1 debrided sample were not exposed to riboflavin (controls). Samples in both groups were soaked with 0.1% riboflavin–dextran 20% solution instilled every 2 minutes for 5, 15, and 30 minutes. Riboflavin concentrations were determined by high‐performance liquid chromatography (HPLC). RESULTS: The study evaluated 14 PKP specimens and 16 sclerocorneal rings. Control samples did not show a riboflavin emission peak. In exposed samples with epithelium, the mean riboflavin concentration was 91.88 ng/g after 5 minutes of exposure, 95.60 ng/g after 15 minutes, and 94.92 ng/g after 30 minutes. In the debrided samples, the mean riboflavin concentration was 14.42 μg/g, 20.92 μg/g, and 24.06 μg/g, respectively. No differences were seen between the in vivo samples and the ex vivo samples. CONCLUSIONS: The HPLC quantitative study showed that stromal concentrations of riboflavin increased with exposure time only if the epithelium was removed. A theoretically safe and effective riboflavin concentration of 15 μg/g was obtained for ultraviolet A‐induced CXL only after the epithelium was removed and after at least 10 minutes of riboflavin application every 2 minutes.

Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results

Purpose To assess the clinical results of transepithelial collagen crosslinking (CXL) in patients 26 years and younger with progressive keratoconus suitable for epithelium‐off (epi‐off) CXL. Setting Department of Ophthalmology, Siena University Hospital, Siena, Italy. Design Prospective case series. Methods The study included 26 eyes (26 patients) treated by transepithelial (epithelium‐on) CXL. The mean age was 22 years (range 11 to 26 years) (10 younger than 18 years; 16 between 19 years and 26 years). Preoperative and postoperative examinations included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, simulated maximum keratometry (K), coma and spherical aberration, and corneal optical coherence tomography optical pachymetry. The solution for transepithelial CXL (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet‐A treatment was performed with the Caporossi Baiocchi Mazzotta X Linker Vega at 3 mW/cm2. Results After relative improvement in the first 3 to 6 months, the UDVA and CDVA gradually returned to baseline preoperative values. After 12 months of stability, the simulated maximum K value worsened at 24 months. Coma aberration showed no statistically significant change. Spherical aberration increased at 24 months. Pachymetry showed a progressive, statistically significant decrease at 24 months. Fifty percent of pediatric patients were retreated with epi‐off CXL due to significant deterioration of all parameters after 12 months of follow‐up. Conclusions Functional results after transepithelial CXL showed keratoconus instability, in particular in pediatric patients 18 years old and younger; there was also functional regression in patients between 19 years and 26 years old after 24 months of follow‐up. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Pathogenesis of posterior capsular opacification. Part I. Epidemiological and clinico-statistical data.

ABSTRACT We examined 895 eves having extracapsular cataract surgery; 403 had an intraocular lens (IOL) implanted and 492 did not. The incidence of posterior capsular opacification was 7.69% in the eyes with an IOL and 14.23% in the eyes without an IOL. If we exclude complicated cataracts from the cases that did not have an IOL, the incidence of posterior capsular opacification decreases to 9.06%. Various models of implanted IOLs showed different incidences of posterior capsular opacification: For J‐looped lenses the incidence was 11.02%; for Frezzotti‐Caporossi lenses, 7.35%. The follow‐up Nvas too short for soft lenses. The Frezzotti‐Caporossi lens can he inserted with the convex side either anterior or posterior. A statistical evaluation shows that the reverse optic or posterior convex orientation in the bag caused a lower incidence of posterior capsular opacification (3.01%).

Riboflavin-UVA-induced corneal collagen cross-linking in pediatric patients

Purpose: Evaluation of stability and functional response after riboflavin-UVA–induced cross-linking in a population of patients younger than 18 years with progressive keratoconus after 36 months of follow-up. Methods: Prospective nonrandomized phase II open trial conducted at the Department of Ophthalmology, Siena University, Italy. The “Siena CXL Pediatrics” trial involved 152 patients aged 18 years or younger (10–18 years) with clinical and instrumental evidence of keratoconus progression. The population was divided into 2 groups according to corneal thickness (>450 and <450 μm) at the time of enrollment. The riboflavin-UVA–induced corneal cross-linking was performed in all patients according to the standard epi-off protocol. Parameters recorded preoperatively and postoperatively were as follows: uncorrected visual acuity, best spectacle–corrected visual acuity, corneal topography and surface aberrometry (CSO Eye Top topographer; Florence, Italy), optical pachometry (Visante OCT; Zeiss Meditec, Jena, Germany), and HRT II confocal microscopy (Rostock Cornea Module, Heidelberg, Germany). Results: Functional data at 36 months showed an increase of +0.18 and +0.16 Snellen lines for uncorrected visual acuity and best spectacle-corrected visual acuity, respectively, in the thicker group (corneal thickness >450 μm) and +0.14 and +0.15 Snellen lines, respectively, in the thinner group (corneal thickness <450 μm). Patients in the latter group already showed a better and faster functional recovery than the thicker group at 3-month follow-up. Topographic results showed statistically significant improvement in K readings and asymmetry index values. Coma reduction was also statistically significant. Conclusions: The study demonstrated significant and rapid functional improvement in pediatric patients younger than 18 years with progressive keratoconus, undergoing riboflavin-UVA–induced cross-linking. In pediatric age, a good functional response and keratoconus stability was obtained after corneal cross-linking in a 36-month follow-up.

Morphological and functional correlations in riboflavin UV A corneal collagen cross‐linking for keratoconus

Purpose:  To investigate the correlations between corneal structural modifications assessed by in vivo corneal confocal microscopy with visual function [uncorrected visual acuity (UCVA), best spectacle‐corrected visual acuity (BSCVA)] and morphological data (corneal topography, pachymetry, elevation analysis) after riboflavin UV A corneal collagen cross‐linking (CXL) for the stabilization of progressive keratoconus.