David Touboul

Correlations between corneal hysteresis, intraocular pressure, and corneal central pachymetry

PURPOSE: To analyze the correlation between corneal hysteresis (CH) measured with the Ocular Response Analyzer (ORA, Reichert) and ultrasonic corneal central thickness (CCT US) and intraocular pressure measured with Goldmann applanation tonometry (IOP GA). SETTING: Bordeaux 2 University, Ophthalmology Department, Bordeaux, France. METHODS: This study comprised 498 eyes of 258 patients. Corneal hysteresis, corneal resistance factor (CRF), and IOP corneal‐compensated (IOPcc) were provided by the ORA device; CCT US and IOP GA were also measured in each eye. The study population was divided into 5 groups: normal (n = 122), glaucoma (n = 159), keratoconus (n = 88), laser in situ keratomileusis (LASIK) (n = 78), and photorefractive keratectomy (n = 39). The Pearson correlation was used for statistical analysis. RESULTS: Corneal hysteresis was not strongly correlated with IOP or CCT US. The mean CH in the LASIK (8.87 mm Hg) and keratoconus (8.34 mm Hg) groups was lower than in the glaucoma (9.48 mm Hg) and normal (10.26 mm Hg) groups. The lower the CH, the lower its correlation with IOPcc and IOP GA. A CH higher than the CRF was significantly associated with the keratoconus and post‐LASIK groups. CONCLUSIONS: Corneal hysteresis, a new corneal parameter, had a moderate dependence on IOP and CCT US. Weaker corneas could be screened with ORA parameters, and low CH could be considered a risk factor for underestimation of IOP. The CCT US should continue to be considered a useful parameter.

Corneal collagen crosslinking in progressive keratoconus: multicenter results from the French National Reference Center for Keratoconus.

PURPOSE: To report refractive, topographic, and biomechanical outcomes, efficiency, and safety of corneal collagen crosslinking (CXL) 1, 3, 6, and 12 months after treatment. SETTING: National Reference Centre for Keratoconus, Bordeaux and Toulouse, France. DESIGN: Case series. METHODS: This retrospective uncontrolled double‐center study comprised eyes with progressive keratoconus. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), corneal pachymetry, endothelial cell count, and corneal hysteresis and corneal resistance factor were evaluated at baseline and at 1, 3, 6, and 12 months. RESULTS: One hundred forty‐two eyes were enrolled in the study. At 6 months, the CDVA had stabilized in 53 eyes (48.1%), improved in 36 eyes (32.7%), and decreased in 18 eyes (16.3%). At 12 months, the CDVA had stabilized in 31 eyes (47.6%), improved in 26 eyes (40.0%), and decreased in 8 eyes (12%). At 6 months, keratoconus progression had stopped in 51 eyes (49.03%) and the maximum keratometry (K) value had decreased by more than 1.0 diopter (D) in 37 eyes (35.5%); it continued to progress in 16 eyes (15.3%). At 12 months, keratoconus progression had stopped in 42 eyes (68.8%) and the maximum K value had decreased by more than 2.0 D in 13 eyes (21.3%). The complication rate with loss of vision was 3.5%. CONCLUSIONS: Ultraviolet‐A light associated with riboflavin CXL is an efficient procedure to stabilize and improve progressive keratoconus. The results reinforce previous studies highlighting the efficacy and safety of the procedure. A large prospective randomized clinical trial is needed. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Corneal confocal microscopy following conventional, transepithelial, and accelerated corneal collagen cross-linking procedures for keratoconus.

PURPOSE To compare early corneal healing following conventional, transepithelial, and accelerated corneal collagen cross-linking (CXL) protocols. METHODS Twenty-four patients with progressive keratoconus were divided into three groups to receive conventional, transepithelial, or accelerated CXL. In vivo corneal confocal microscopy was performed on each patient preoperatively and at 1, 3, and 6 months postoperatively. RESULTS Closure of the epithelial wound was complete 3 days following conventional and accelerated CXL. The subbasal nerve plexus was essentially obliterated immediately following conventional and accelerated CXL, and virtually no nerve fibers had regenerated by 6 months. The anterior stroma showed significant changes 1 month following conventional CXL; these changes were similar but more pronounced following accelerated CXL. Observed stromal changes included complete obliteration of keratocytes, increased tissue reflectivity, a honeycomb-like appearance, and circular lacunae. Some recovery of keratocyte density was noted after 6 months. These changes were less pronounced in the mid-stroma, and there were no apparent changes to the posterior stroma or endothelium. The cornea appeared to be unaltered following transepithelial CXL. CONCLUSIONS In vivo corneal confocal microscopy analysis of the postoperative impact of CXL on the cornea revealed clear differences among conventional, accelerated, and transepithelial CXL protocols. Accelerated CXL had a greater impact than conventional CXL on the anterior cornea, whereas transepithelial CXL did not appear to alter corneal morphology.

Biomechanical characteristics of the ectatic cornea

&NA; The ocular response analyzer (ORA) (Reichert, Inc.) was used in the case of a middle‐aged man who developed unilateral corneal ectasia after bilateral laser in situ keratomileusis (LASIK). The preoperative refraction was similar in the 2 eyes. Post‐LASIK ectasia was central in the left eye; topography was oblate in the right eye. The ORA values consisted of the mean of 4 measurements. Corneal hysteresis and corneal resistance factor were almost equal in the ectatic eye and the nonectatic eye. However, significant between‐eye differences in the morphology of the signals were noted, most prominently in the lower amplitude of the applanation peaks in the ectatic eye. The shape of the applanation signal yielded important information in addition to corneal hysteresis and corneal resistance factor.

Detection of Subclinical Keratoconus Using an Automated Decision Tree Classification

PURPOSE To develop a method for automatizing the detection of subclinical keratoconus based on a tree classification. DESIGN Retrospective case-control study. METHODS setting: University Hospital of Bordeaux. participants: A total of 372 eyes of 197 patients were enrolled: 177 normal eyes of 95 subjects, 47 eyes of 47 patients with forme fruste keratoconus, and 148 eyes of 102 patients with keratoconus. observation procedure: All eyes were imaged with a dual Scheimpflug analyzer. Fifty-five parameters derived from anterior and posterior corneal measurements were analyzed for each eye and a machine learning algorithm, the classification and regression tree, was used to classify the eyes into the 3 above-mentioned conditions. main outcome measures: The performance of the machine learning algorithm for classifying eye conditions was evaluated, and the curvature, elevation, pachymetric, and wavefront parameters were analyzed in each group and compared. RESULTS The discriminating rules generated with the automated decision tree classifier allowed for discrimination between normal and keratoconus with 100% sensitivity and 99.5% specificity, and between normal and forme fruste keratoconus with 93.6% sensitivity and 97.2% specificity. The algorithm selected as the most discriminant variables parameters related to posterior surface asymmetry and thickness spatial distribution. CONCLUSION The machine learning classifier showed very good performance for discriminating between normal corneas and forme fruste keratoconus and provided a tool that is closer to an automated medical reasoning. This might help in the surgical decision before refractive surgery by providing a good sensitivity in detecting ectasia-susceptible corneas.

Scalability and Severity of Keratoconus in Children

PURPOSE To assess the severity of keratoconus at diagnosis and its scalability over a period of 2 years in children compared to adults. DESIGN A retrospective monocentric study was conducted in the National Reference Center for Keratoconus, Bordeaux (France), between October 1997 and November 2010. METHODS In total, 216 patients were studied, comprising 49 patients (22.7%) aged ≤ 15 and 167 patients (77.3%) aged ≥ 27 years at diagnosis, who were seen within 2 years of diagnosis. Severity at diagnosis was assessed using Krumeichs classification, and the scalability criteria of the US Food and Drug Administration (2010) were used. Student t tests and χ(2) tests were performed to compare the 2 groups. RESULTS Keratoconus in children was significantly more severe at diagnosis, with 27.8% being stage 4 vs 7.8% of adults (P < .0001). In addition, ophthalmoscopic signs were more frequent in children (42.9% vs 29.5%, P = .05), while mean values of maximum, average, and minimum keratometry as well as simulated keratometric astigmatism were higher (P < .0001, P = .0002, P = .0005, and P = .001, respectively). After diagnosis, keratoconus did not evolve more frequently in children. However, in the case of progression, keratoconus evolved faster in children, with significant differences in the spherical equivalent and maximum and minimum keratometry (P = .03, P = .02, P = .04, respectively). CONCLUSION At diagnosis, keratoconus is often more advanced in children than in adults, with faster disease progression. Early detection and close monitoring are therefore crucial in young patients.

In Vitro Efficacy of Antifungal Treatment Using Riboflavin/UV-A (365 nm) Combination and Amphotericin B

PURPOSE To demonstrate the antimicrobial properties of riboflavin/UV-A (365 nm) against fungal pathogens. METHODS The antimicrobial properties of riboflavin/UV-A (365 nm), with or without previous treatment with amphotericin B, were tested on three groups of fungi selected from severe cases of keratomycosis: Candida albicans, Fusarium sp, and Aspergillus fumigatus. They were tested by using Kirby-Bauer discs with empty disc (control), riboflavin 0.1% alone (R), UV-A alone (UV-A), riboflavin 0.1% and additional UV-A exposure (R+UV-A), amphotericin B alone (A), amphotericin B and riboflavin 0.1% (A+R), amphotericin B and UV-A (A+UV-A), amphotericin B and riboflavin 0.1%, and additional UV-A exposure (A+R+UV-A). The mean growth inhibition zone (GIZ) was measured around the discs. RESULTS C. albicans, Fusarium sp, and A. fumigatus did not show any increased GIZ after treatment without previous amphotericin B medication. However, GIZ was significantly greater after pretreatment with amphotericin B and riboflavin/UV-A (A+R+UV-A) for C. albicans (P = 0.0005), Fusarium sp (P = 0.0023) and A. fumigatus (P = 0.0008) compared with A, A+R, and A+UV-A. CONCLUSIONS Amphotericin B is believed to interact with fungi membrane sterols to produce aggregates that form transmembrane channels. Given that collagen is one of the principal components of the cornea, it is also probable that amphotericin B may diffuse easily after cross-linking. Previous treatment with amphotericin B allowed riboflavin/UV-A effectiveness against C. albicans, Fusarium sp, and A. fumigatus. This schema might be used in the future for the treatment of keratomycosis.

Biomechanical and morphological corneal response to placement of intrastromal corneal ring segments for keratoconus

PURPOSE: To evaluate the biomechanical and morphological changes in keratoconic corneas after Intacs intrastromal corneal ring segment (ICRS) implantation. SETTING: Department of Ophthalmology, National Reference Center for Keratoconus, Bordeaux University, Bordeaux, France. METHODS: Keratoconic eyes were retrospectively analyzed after ICRS implantation; preoperative and 6‐month postoperative evaluation were done using the Ocular Response Analyzer (ORA) and the Orbscan II topographer. Biomechanical parameters included corneal hysteresis (CH), the corneal resistance factor (CRF), and other parameters extracted from the signal curves. Morphological parameters included simulated keratometry and the cone location magnitude index from the axial map (aCLMI) and tangential map (tCLMI). Parameters were extracted using software designed to read and process topographic maps. RESULTS: There were no significant differences between preoperatively and postoperatively in mean CH (7.7 mm Hg ± 1.4 [SD] versus 7.4 ± 1.4 mm Hg) or mean CRF (6.6 ± 1.8 mm Hg versus 6.1 ± 1.4 mm Hg). Only 2 ORA signal parameters were significantly different. Topographic parameters with significant decreases were minimum central keratometry (K) (mean change −5.8 ± 2.9 diopters [D]) (P<.001), minimum central K (mean change −5.8 ± 2.3 D) (P<.001), mean aCLMI (9.6 ± 2.7 preoperatively versus 7.7 ± 2.5 postoperatively) (P<.009), and mean tCLMI (18.9 ± 2.8 versus 12.9 ± 4.4) (P<.002). The only significant correlation between biomechanical and topographic parameters was postoperative ORA infrared signal peak 1 and postoperative aCLMI. CONCLUSIONS: Intrastromal corneal ring implantation significantly decreased corneal curvature, with preoperative values predicting magnitude of change. However, it did not alter the viscoelastic biomechanical parameters of CH and CRF.

Early biomechanical keratoconus pattern measured with an ocular response analyzer: Curve analysis

PURPOSE: To estimate the ability of the Ocular Response Analyzer parameters to aid in the diagnosis of keratoconus in pre‐laser in situ keratomileusis (LASIK) patients. SETTING: Department of Ophthalmology, Bordeaux 2 University, Bordeaux Cedex, France. DESIGN: Evaluation of diagnostic test. METHODS: This study compared eyes with mild stages of keratoconus (study group) with preoperative eyes that later had LASIK (control group). Corneas with a central thickness within 500 to 600 μm were targeted. The biomechanical measurements were acquired, and 12 parameters were analyzed after extraction from the signal data. RESULTS: The study group comprised 103 eyes and the control group, 97 eyes. The mean corneal hysteresis (CH) was 9.2 mm Hg in study eyes and 10.1 mm Hg in control eyes and the mean corneal resistance factor (CRF), 8.9 mm Hg and 10.6 mm Hg, respectively. For a threshold of 9.6, CH had a sensitivity of 66% with a specificity of 67%. For a threshold of 9.7, the CRF had a sensitivity of 72% and a specificity of 77%. For 6 biomechanical parameters, the probability that a patient would present with keratoconus was 3 in 1000 if 1 parameter was over the chosen threshold. CONCLUSIONS: If 1 of 6 parameters were over a chosen threshold, the probability that a patient would present with keratoconus would be almost 3 in 1000 instead of 9 in 1000 in a LASIK surgery cohort. Despite low sensitivity and specificity, some parameters provided by the corneal analyzer offered high negative likelihood ratios and deserve more study with bigger samples. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Monitoring of Cornea Elastic Properties Changes during UV-A/Riboflavin-Induced Corneal Collagen Cross-Linking using Supersonic Shear Wave Imaging: A Pilot Study

PURPOSE Keratoconus disease or post-LASIK corneal ectasia are increasingly treated using UV-A/riboflavin-induced corneal collagen cross-linking (CXL). However, this treatment suffers from a lack of techniques to provide an assessment in real-time of the CXL effects. Here, we investigated the potential interest of corneal elasticity as a biomarker of the efficacy of this treatment. METHODS For this purpose, supersonic shear wave imaging (SSI) was performed both ex vivo and in vivo on porcine eyes before and after CXL. Based on ultrasonic scanners providing ultrafast frame rates (~30 kHz), the SSI technique generates and tracks the propagation of shear waves in tissues. It provides two- and three-dimensional (2-D and 3-D) quantitative maps of the corneal elasticity. RESULTS After CXL, quantitative maps of corneal stiffness clearly depicted the cross-linked area with a typical 200-μm lateral resolution. The CXL resulted in a 56% ± 15% increase of the shear wave speed for corneas treated in vivo (n = 4). CONCLUSIONS The in vivo CXL experiments performed on pigs demonstrated that the quantitative estimation of local stiffness and the 2-D elastic maps of the corneal surface provide an efficient way to monitor the local efficacy of corneal cross-linking.