Selezione di Lavori su CXL

J Refract Surg. 2015 Jan 1;31(1):36-40.

Demarcation Line Evaluation of Iontophoresis-Assisted Transepithelial Corneal Collagen Cross-linking for Keratoconus.

Bonnel S, Berguiga M, De Rivoyre B, Bedubourg G, Sendon D, Froussart-Maille F, Rigal-Sastourne JC.

Abstract

PURPOSE:
To evaluate the visualization and depth of the demarcation line with anterior segment optical coherence tomography (AS-OCT) after iontophoresis-assisted transepithelial corneal collagen cross-linking (CXL).

METHODS:
This prospective, consecutive, single center, non-randomized clinical study involved 15 eyes of 12 patients with keratoconus who underwent an AS-OCT scan (Spectralis; Heidelberg Engineering, Inc., Carlsbad, CA) to search for a demarcation line and its depth at 1 month after iontophoresis-assisted transepithelial CXL. AS-OCT scan measurements were performed by two independent examiners.

RESULTS:
No intraoperative or postoperative complications were observed. Kappa coefficient estimation for operator agreement in demarcation line visualization (whether it was visualized) was 70.6%. The corneal stromal demarcation line was identified in 9 eyes (60%) by both examiners. Mean depth of the corneal stromal demarcation line was 246.67 ± 50.72 µm (range: 183 to 339 µm) for the first examiner and 241.89 ± 62.52 µm (range: 163 to 358 µm) for the second examiner. There were no statistically significant differences for the measurements of the paired comparisons between the two examiners (P = .61). The Pearson correlation coefficient between the measurements was 0.910.

CONCLUSIONS:
Iontophoresis-assisted transepithelial CXL creates a demarcation line that can be visualized with AS-OCT, which seems less easily distinguishable and shallower than in conventional CXL. However, its depth and visualization seems to be more similar to conventional CXL than transepithelial CXL. [J Refract Surg. 2015;31(1):36-40.].

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J Refract Surg. 2014 Nov;30(11):746-53.

Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes.

Vinciguerra P, Randleman JB, Romano V, Legrottaglie EF, Rosetta P, Camesasca FI, Piscopo R, Azzolini C, Vinciguerra R.
 
Abstract

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.  

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Graefes Arch Clin Exp Ophthalmol. 2014 Nov 4.

Early effects of corneal collagen cross-linking by iontophoresis in ex vivo human corneas.

Mencucci R, Ambrosini S, Paladini I, Favuzza E, Boccalini C, Raugei G, Vannelli GB, Marini M.

Abstract

PURPOSE:
The purpose was to investigate the early modifications induced by collagen cross-linking by iontophoresis of riboflavin (ionto-CXL) in ex vivo human corneas by evaluating different protocols of UVA irradiation.

METHODS:
In this experimental study 46 ex vivo human corneas obtained from the Eye Bank of Mestre (Italy) were divided in different groups: six were utilized as control (CTL); eight were treated with ionto-CXL at 3 mW/cm2 power for 30 min (I-3); eight were treated with ionto-CXL at 10 mW/cm2 for 9 min (I-10); eight were treated with iontophoretic delivery of riboflavin only (I-0); eight were treated with the standard CXL at 3 mW/cm2 for 30 min (S-3); and eight were treated with CXL at 10 mW/cm2 for 9 min (S-10). All samples were evaluated by haematoxylin-eosin staining and immunohistochemical analysis using different markers (Connexin 43, CD34, Collagen I, TUNEL assay). Western blot analysis, utilizing Bax and Ki67 primary antibodies, for detection of keratocyte apoptosis and proliferation, respectively, was also performed.


RESULTS:
No endothelial damage was evidenced in the treated groups. In I-10 corneas the epithelial layers were not always well-preserved. Anterior stroma showed an uneven distribution and numerical reduction of keratocytes as well as increased apoptosis; a reduced subepithelial interweaving of collagen I fibers was observed. In S-3 and S-10 the changes induced by treatments were similar to I-10. I-3 and I-0 showed no significant changes with respect to the control group. 

CONCLUSIONS:
In the ionto-CXL at 10 mW/cm2 group occurred the main morphological and biomolecular changes. This experimental study suggests that iontophoresis can be considered a non-invasive potential delivery tool for riboflavin penetration in corneal stroma during CXL.

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J Cataract Refract Surg. 2014 Oct;40(10):1706-15.

Biomechanical changes in the human cornea after transepithelial corneal crosslinking using iontophoresis.


Lombardo M1, Serrao S2, Rosati M2, Ducoli P2, Lombardo G2.

Abstract 

PURPOSE:
To evaluate the corneal response to variable intraocular pressure (IOP) in human eye globes after ultraviolet-A (UVA) transepithelial corneal crosslinking using iontophoresis.

SETTING:

Fondazione G.B. Bietti IRCCS, Rome, Italy.

DESIGN:
Experimental study.

METHODS:
Four human donor eye globes were treated with transepithelial crosslinking using iontophoresis and rapid UVA corneal irradiation, and 4 globes had standard crosslinking. Inflation experiments were performed on the globes before and after crosslinking. Topographic maps of the anterior and posterior cornea were acquired using Scheimpflug topography. Images were obtained using a mechanical regimen to analyze corneal strain in response to cyclic stress. Corneal shape changes were analyzed as a function of IOP, and corneal stress-strain curves were generated.

RESULTS:
Before crosslinking, instillation of hypotonic riboflavin-5-phosphate sodium 0.1% solution using iontophoresis increased corneal thickness by 5% and instillation of dextran-enriched riboflavin 0.1% solution decreased corneal thickness by 13%. Five minutes after treatment, both crosslinking procedures reduced corneal thickness by 2%. Young's modulus (E) of the anterior cornea increased by a mean of 1.8 times (from 1.6 to 2.9 MPa) and 1.9 times (from 1.3 to 2.5 MPa) after transepithelial crosslinking using iontophoresis and standard crosslinking, respectively. The E value of the posterior cornea also increased after both procedures (mean 1.7 times versus 3.1 times). 

CONCLUSIONS:
Transepithelial crosslinking using iontophoresis increased the biomechanical strength of human corneal tissue in inflation testing of donor eye globes. The effect on corneal stiffness was almost comparable to that of standard crosslinking. 

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Invest Ophthalmol Vis Sci. 2014 Apr 17;55(4):2526-33.

Structural modifications and tissue response after standard epi-off and iontophoretic corneal crosslinking with different irradiation procedures.

Mastropasqua L, Lanzini M, Curcio C, Calienno R, Mastropasqua R, Colasante M, Mastropasqua A, Nubile M.

PURPOSE: 
The aim of this study is to investigate modifications in human cadaver corneas after different crosslinking procedures, including standard epi-off treatment, iontophoresis imbibition, and different exposure to ultraviolet A (UVA) sources (30 minutes at 3 mW and 9 minutes at 10 mW). 

METHODS:
A total of 12 human cadaver corneas was examined and divided as follows: 3 served as control (group 1), 3 were treated with a standard epi-off procedure (group 2), 6 underwent iontophoresis imbibition for 5 minutes, and then 3 were irradiated for 30 minutes with 3 mW UVA (group 3), and 3 for 9 minutes at 10 mW UVA (group 4). Deformation amplitude index was measured before and after the corneas underwent treatment. After treatment, corneas were prepared for hematoxylin-eosin and immunohistochemistry evaluation. The expression of TUNEL, matrix metalloproteinase-1 (MMP-1), collagen type I, and CD34 was investigate in all samples. 

RESULTS: 
The deformation amplitude index decreased in all groups, in particular in group 4, indicating an improvement of corneal biomechanical properties. Immunohistochemical staining showed a significant stromal alteration in group 2, mild damage in group 3, and no modifications in corneal morphology in group 4. The TUNEL (P < 0.001) and MMP-1 (P = 0.002) positivity was more evident in group 4. Collagen type I positivity significantly increased in groups 3 (P = 0.002) and 4 (P = 0.002). The CD34 expression was more evident in groups 2 (P = 0.003) and 3 (P = 0.003). 

CONCLUSIONS:
Iontophoresis imbibition followed by UVA irradiation for 9 minutes at 10 mW determined less tissue damage and better stromal remodeling. 

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Invest Ophthalmol Vis Sci. 2014 Mar 18.

Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. 

Cassagne M1, Laurent C, Rodrigues M, Galinier A, Spoerl E, Galiacy SD, Soler V, Fournié P, Malecaze F.   

Abstract

PURPOSE: 
To compare an iontophoresis riboflavin delivery technique for transepithelial corneal collagen crosslinking (I-CXL) with a conventional CXL (C-CXL).

METHODS:
We designed 3 experimental sets using 152 New Zealand rabbits to study riboflavin application by iontophoresis using charged riboflavin solution (Ricrolin+®) with a 1mA current for 5 min. The first set was to compare riboflavin concentration measured by High-Performance Liquid Chromatography (HPLC) in corneas after iontophoresis or conventional riboflavin application. The second set was to analyze autofluorescence and stromal collagen modification immediately and 14 days after I-CXL or C-CXL, by using nonlinear two-photon microscopy (TP) and second harmonic generation (SHG). In the third set, physical modifications after I-CXL and C-CXL were evaluated by stress-strain measurements and by studying corneal resistance against collagenase digestion.

RESULTS: 
Based on HPLC analysis, we found that iontophoresis allowed riboflavin diffusion with two-fold less riboflavin concentration than conventional application (936.2 ± 312.5 ng/ml and 1708 ± 908.3 ng/ml, respectively, p<0.05).
Corneal TP and SHG imaging revealed that I-CXL and C-CXL resulted in a comparable increased anterior and median stromal autofluorescence and collagen packing. The stress at 10% strain showed a similar stiffness of corneas treated by I-CXL or C-CXL (631.9 ±241.5 kPa and 680.3 ±216.4 kPa, respectively, p=0.908). Moreover, we observed an increased resistance against corneal collagenase digestion after I-CXL and C-CXL (61.90 ±5.28 % and 72.21 ±4.32 % of remaining surface, respectively, p=0.154).

CONCLUSIONS:
This experimental study suggests that I-CXL is a promising alternative methodology for riboflavin delivery in crosslinking treatments, preserving the epithelium. 

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 Acta Ophthalmol. 2014 Feb;92(1):e30-4.

Transepithelial corneal collagen cross-linking by iontophoresis of riboflavin. 

Bikbova G, Bikbov M.

PURPOSE:
To evaluate the effectiveness of transepithelial cornea impregnation with riboflavin 0.1% by iontophoresis for collagen cross-linking.


MATERIAL AND METHODS:
Transepithelial collagen cross-linking by iontophoresis of riboflavin was performed in a series of 22 eyes of 19 patients with progressive keratoconus I-II of Amsler classification. The riboflavin solution was administered by iontophoresis for 10 min in total, after which standard surface UVA irradiation (370 nm, 3 mW/cm(2) ) was performed at a 5-cm distance for 30 min.

RESULTS:
The riboflavin/UVA treatment resulted in a decrease in the average keratometry level from 46.47 ± 1.03 to 44.12 ± 1.12 D 1 year after the procedure. Corneal astigmatism decreased from 3.44 ± 0.48 to 2.95 ± 0.23 D. Uncorrected distance visual acuity improved from 0.61 ± 0.44 up to 0.48 ± 0.41 (LogMAR). Preoperative and postoperative endothelial cell density remained unchanged at 2765 ± 21.15 cells/mm(2).

CONCLUSION:
Transepithelial collagen cross-linking by iontophoresis might become an effective method for riboflavin impregnation of the corneal stroma reducing the duration of the procedure and being more comfortable for the patients. Further long-term studies are necessary to complete the evaluation of the efficacy and risk spectrum of the modified cross-linking technique.