Riccardo 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.

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.

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.

Detection of Keratoconus With a New Biomechanical Index.

PURPOSE To evaluate the ability of a new combined biomechanical index called the Corvis Biomechanical Index (CBI) based on corneal thickness profile and deformation parameters to separate normal from keratoconic patients. METHODS Six hundred fifty-eight patients (329 eyes in each database) were included in this multicenter retrospective study. Patients from two clinics located on different continents were selected to test the capability of the CBI to separate healthy and keratoconic eyes in more than one ethnic group using the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). Logistic regression was employed to determine, based on Database 1 as the development dataset, the optimal combination of parameters to accurately separate normal from keratoconic eyes. The CBI was subsequently independently validated on Database 2. RESULTS The CBI included several dynamic corneal response parameters: deformation amplitude ratio at 1 and 2 mm, applanation 1 velocity, standard deviation of deformation amplitude at highest concavity, Ambrósios Relational Thickness to the horizontal profile, and a novel stiffness parameter. The receiver operating characteristic curve analysis of the training database showed an area under the curve of 0.983. With a cut-off value of 0.5, 98.2% of the cases were correctly classified with 100% specificity and 94.1% sensitivity. In the validation dataset, the same cut-off point correctly classified 98.8% of the cases with 98.4% specificity and 100% sensitivity. CONCLUSIONS The CBI was shown to be highly sensitive and specific to separate healthy from keratoconic eyes. The presence of an external validation dataset confirms this finding and suggests the possible use of the CBI in everyday clinical practice to aid in the diagnosis of keratoconus. [J Refract Surg. 2016;32(12):803-810.].

Vitreous Substitutes: The Present and the Future.

Vitreoretinal surgery has advanced in numerous directions during recent years. The removal of the vitreous body is one of the main characteristics of this surgical procedure. Several molecules have been tested in the past to fill the vitreous cavity and to mimic its functions. We here review the currently available vitreous substitutes, focusing on their molecular properties and functions, together with their adverse effects. Afterwards we describe the characteristics of the ideal vitreous substitute. The challenges facing every ophthalmology researcher are to reach a long-term intraocular permanence of vitreous substitute with total inertness of the molecule injected and the control of inflammatory reactions. We report new polymers with gelification characteristics and smart hydrogels representing the future of vitreoretinal surgery. Finally, we describe the current studies on vitreous regeneration and cell cultures to create new intraocular gels with optimal biocompatibility and rheological properties.

Influence of Pachymetry and Intraocular Pressure on Dynamic Corneal Response Parameters in Healthy Patients

PURPOSE To evaluate the influence of pachymetry, age, and intraocular pressure in normal patients and to provide normative values for all dynamic corneal response parameters (DCRs) provided by dynamic Scheimpflug analysis. METHODS Seven hundred five healthy patients were included in this multicenter retrospective study. The biomechanical response data were analyzed to obtain normative values with their dependence on corrected and clinically validated intraocular pressure estimates developed using the finite element method (bIOP), central corneal thickness (CCT), and age, and to evaluate the influence of bIOP, CCT, and age. RESULTS The results showed that all DCRs were correlated with bIOP except deflection amplitude (DefA) ratio, highest concavity (HC) radius, and inverse concave radius. The analysis of the relationship of DCRs with CCT indicated that HC radius, inverse concave radius, deformation amplitude (DA) ratio, and DefA ratio were correlated with CCT (rho values of 0.343, -0.407, -0.444, and -0.406, respectively). The age group subanalysis revealed that primarily whole eye movement followed by DA ratio and inverse concave radius were the parameters that were most influenced by age. Finally, custom software was created to compare normative values to imported examinations. CONCLUSIONS HC radius, inverse concave radius, DA ratio, and DefA ratio were shown to be suitable parameters to evaluate in vivo corneal biomechanics due to their independence from IOP and their correlation with pachymetry and age. The creation of normative values allows the interpretation of an abnormal examination without the need to match every case with another normal patient matched for CCT and IOP. [J Refract Surg. 2016;32(8):550-561.].

Imaging Mass Spectrometry by Matrix-Assisted Laser Desorption/Ionization and Stress-Strain Measurements in Iontophoresis Transepithelial Corneal Collagen Cross-Linking

Purpose. To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL), with standard cross linking (S-CXL) and current transepithelial protocol (TE-CXL). Materials and Methods. The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS) and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated. Results. MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% and P = 0.05) in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups. Conclusions. In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium.

High fluence iontophoretic corneal collagen cross-linking: in vivo OCT imaging of riboflavin penetration.

To the Editor: We read with interest the excellent article by Malhotra et al.1 regarding in vivo estimation of ribofl avin penetration using anterior segment optical coherence tomography (OCT). The article evaluates the effect of complete versus grid-like epithelial removal on ribofl avin penetration during collagen cross-linking (CXL) in vivo using hand-held OCT. Twenty eyes of 20 patients were imaged intraoperatively at 30 and 60 minutes after starting the procedure. Results showed a homogeneous hyperrefl ective band extending to a mean depth of 54.2 μm after 30 minutes. In the gridlike removal group, the band was reported uneven in the epi-on areas. We agree with the authors on the use of OCT for in vivo evaluation of ribofl avin’s penetration inside the stroma. Moreover, we agree that grid removal of the epithelium is not able to soak the corneal stroma evenly like the epi-off procedure.2 In our study, we report the in vivo ribofl avin penetration during CXL performed with iontophoresis versus conventional epithelium-off protocol using high-resolution OCT. Six eyes (6 patients) undergoing CXL were measured preoperatively, intraoperatively, and postoperatively using high-resolution OCT. The epithelium was removed completely in the central 9-mm zone in 3 eyes (epi-off group), whereas ribofl avin penetration through intact epithelium was promoted by an iontophoresis device in the remaining 3 eyes (iontophoresis group). The iontophoresis device for corneal application (8 mm in diameter) is placed on the cornea using an annular suction ring (low suction created by a syringe connected on the suction annulus). The device is fi lled with approximately 0.5 mL solution from the open proximal side, until the electrode (stainless steel mesh) is covered (Figure 1A). The device is connected to a constant current generator (I-ON XL, Sooft, Italy) set at 1 mA (the total dose of 5 mA min is monitored by the generator). During the irradiation phase (10mW/cm2 for 9 minutes), a good fl uorescence is clearly detectable (Figure 1B) even after washing with balanced salt solution. The depth of the hyperrefl ective band (representing penetration of ribofl avin) in the anterior corneal stroma was measured. In the conventional epi-off group, after 30 minutes of passive impregnation, a homogeneous hyperrefl ective band without fading effect was measured at mean depth of 80 μm (Figure 1C). In the iontophoresis group, we observed a less homogeneous but deeper hyperrefl ective band with a fading effect extending through the anterior 200 μm of the cornea (Figure 1D). This band was not visible until the end of irradiation time. Intraoperative OCT imaging could be a useful technique to evaluate in vivo penetration of ribofl avin in-

Corneal collagen cross-linking window absorption.

Purpose: To evaluate the safety and efficacy of treatment of severe infectious corneal ulcers with hypoosmolar riboflavin solution and UV-A collagen cross-linking (CXL) without deepithelizing the cornea. Methods: Four eyes of 3 patients with severe keratitis and associated corneal melting, were treated with a new protocol of corneal CXL for infectious keratitis, named cross-linking window absorption (CXL-WA). CXL-WA was performed when the infection did not respond to systemic and topical antibiotic therapy. The protocol entails the use of hypoosmolar riboflavin before the irradiation with UV-A, and the penetration is obtained through the epithelial defect overlying the ulcer. Results: In all cases, CXL halted the progression of the ulcer. After a minimum follow-up of 3 months, none of the patients had recurrence of the infection. Conclusion: CXL-WA is a promising technique of treatment of infectious corneal ulcers, delaying or preventing more invasive approaches.

Macular Hypotrophy After Internal Limiting Membrane Removal For Diabetic Macular Edema

Purpose: To compare the anatomic and functional effects of three different approaches to nontractional diabetic macular edema. Methods: Retrospective comparative study. Sixty eyes of 60 patients diagnosed with cystoid diabetic macular edema and treated with 1.25 mg/mL intravitreal bevacizumab (Group A), laser photocoagulation (Group B), or vitrectomy with inner limiting membrane peeling (Group C) were included in the study. Changes in number of Early Treatment Diabetic Retinopathy Study letters, central macular thickness, largest diameter of the intraretinal cysts (IC), and choroidal thickness were investigated. Analyses were performed during follow-up visits at Months 1, 3, 6, 9, and 12. Results: Visual acuity only significantly improved in Group A at the last follow-up (P = 0.004). Central macular thickness significantly decreased in every group throughout the follow-up period. Differences in central macular thickness between Groups A and B (P < 0.01), A and C (P < 0.01), and B and C (P < 0.01) were significant. Intraretinal cysts also significantly decreased in each group throughout the follow-up period. Differences in IC size between Groups A and B (P = 0.8), A and C (P = 0.1), and B and C (P = 0.1) were not significant. Choroidal thickness did not undergo any significant change in any group throughout the follow-up period. A significant correlation was also found in Group A between best-corrected visual acuity at month 12 and baseline central macular thickness (R = 0.3; P = 0.006), and in Group B between postoperative best-corrected visual acuity at month 12 and baseline IC size (R = 0.8; P < 0.01, negatively correlated at 92.4%). Conclusion: According to our retrospective data, diabetic macular edema with intraretinal cysts larger than 390 &mgr;m should not be treated with vitrectomy with ILM peeling, because this may induce subfoveal atrophy, defined as the “Floor Effect,” and subsequent visual deterioration.