Pierre Fournié

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.

A randomized paired eye comparison of two techniques for treating moderately high myopia: LASIK and artisan phakic lens.

OBJECTIVE To compare refractive performance and safety of laser in situ keratomileusis (LASIK) and Artisan phakic intraocular lens (PIOL) for moderately high myopia. DESIGN A prospective, randomized trial with paired eye control. PARTICIPANTS Twenty-five patients with myopia ranging from -8.00 to -12.00 diopters (D). INTERVENTION For each patient, one eye received LASIK and the other one was implanted with an Artisan phakic intraocular lens. The treated eye and the surgical technique were randomized. MAIN OUTCOME MEASURES Primary outcome measure was spherical equivalent refraction. Main secondary outcome measures were the change of two or more lines and safety index (ratio postoperative to preoperative best-corrected visual acuity). RESULTS One year after surgery, the mean spherical equivalent refraction was -0.74 +/- 0.67 D for LASIK-treated eyes and -0.95 +/- 0.45 D for Artisan-treated eyes, and the majority of LASIK-treated eyes (64%) and Artisan-treated eyes (60%) were within +/-1.00 D of the intended result. At 1 month, the mean spherical equivalent refraction was -0.28 +/- 0.71 D for LASIK and -1.07 +/- 0.59 D for Artisan (P < 0.01). The changes of two or more lines were in favor of Artisan (P < 0.05). The safety index was significantly better for Artisan (1.12 +/- 0.21) than for LASIK (0.99 +/- 0.17) at 1 year (P < 0.02). CONCLUSIONS In cases of moderately high myopia, LASIK and Artisan phakic intraocular lenses seemed to produce a similar predictability. The best-corrected visual acuity and subjective evaluation of quality of vision were better for Artisan.

Iontophoresis Transcorneal Delivery Technique for Transepithelial Corneal Collagen Crosslinking With Riboflavin in a Rabbit Model.

PURPOSE We compared an iontophoresis riboflavin delivery technique for transepithelial corneal collagen crosslinking (I-CXL) with a conventional CXL (C-CXL). METHODS We designed three experimental sets using 152 New Zealand rabbits to study riboflavin application by iontophoresis using charged riboflavin solution (Ricrolin+) with a 1-mA current for 5 minutes. The first set was to compare riboflavin concentration measured by 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 2-fold less riboflavin concentration than conventional application (936.2 ± 312.5 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 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.

Descemet stripping automated endothelial keratoplasty in a child with descemet membrane breaks after forceps delivery.

Purpose: To report the use of Descemet stripping automated endothelial keratoplasty (DSAEK) and to treat visual loss in Descemet membrane (DM) breaks after forceps delivery. Methods: An 8-year-old boy presented with unilateral DM ruptures secondary to forceps delivery. Central, vertically oriented DM breaks significantly decreased visual acuity. Preoperative visual acuity was 20/80. A DSAEK was performed, the DM and endothelium were stripped from the recipient, and an 8.5-mm-diameter donor button consisting of posterior stroma and healthy endothelium was folded and implanted through a 5-mm incision. An air bubble was used to press the donor tissue against the recipient cornea, allowing it to attach without sutures. Results: Graft dislocation in the early postoperative period required surgical repositioning of the donor lenticule, which led to excellent anatomic and functional outcomes. There was a significant and rapid improvement of the best-corrected visual acuity, which was 20/50 at the first month and 20/32 at the seventh month postoperatively. Conclusions: To our knowledge, this is the first report of a DSAEK in a child with DM tears after forceps delivery. Selective replacement of posterior corneal layers with DSAEK might be a promising alternative to penetrating keratoplasty to successfully treat endothelial or DM lesions during childhood.

Fixed dilated pupil (urrets-zavalia syndrome) and anterior subcapsular cataract formation after descemet stripping endothelial keratoplasty.

Purpose: To report a fixed dilated pupil and anterior subcapsular cataract formation following Descemet stripping endothelial keratoplasty (DSAEK). Methods: A 47-year-old man with Fuchs endothelial dystrophy underwent DSAEK of the right eye. The preoperative slit lamp examination was normal. Mydriatic drops were used at the end of procedure. Results: Postoperatively, the pupil remained fixed and dilated with no right direct or consensual response to light, or constriction during accommodation throughout a 1-year follow-up period. Slit lamp examination after air resorption revealed a transient anterior subcapsular cataract and posterior synechiae. Based on these findings, a diagnosis of Urrets-Zavalia syndrome was made. Conclusion: To our knowledge, this is the first report of Urrets-Zavalia syndrome after DSAEK.

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the probands mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases.

Severe endothelial cell loss following uneventful angle-supported phakic intraocular lens implantation for high myopia

&NA; Endothelial decompensation is a serious complication of phakic intraocular lens (pIOL) implantation and is a major concern during the postoperative period. We report 3 eyes in which the same foldable angle‐supported pIOL was implanted to correct high myopia. Rapid and severe postoperative endothelial cell loss occurred in all 3 eyes. An over‐sized pIOL that induced excessive vaulting into the anterior chamber was the main risk factor. In 2 eyes, the pIOL was explanted uneventfully; 1 eye required Descemets stripping automated endothelial keratoplasty because of total endothelial decompensation. These cases illustrate the importance of accurate sizing of foldable angle‐supported anterior chamber pIOLs to avoid excessive vaulting. They also highlight the importance of regular follow‐up and preventive pIOL explantation as soon as significant endothelial cell loss is detected.

Esotropias that totally resolve under general anesthesia treated exclusively with bilateral fadenoperation.

Purpose: Fadenoperation has been proven to be an efficient method to treat convergence excess because it treats medial rectus (MR) overaction. We wanted to evaluate its efficiency in esotropias that totally disappear under anesthesia, regardless of the amount of deviation in waking hours. Methods: Included were 122 successive cases of children of ages 3 to 16 years with esotropia that completely disappears under general anesthesia (GA), representing 26.25% of all patients with esotropia that had surgery between August 2002 and July 2004. They all received a fadenoperation (retroequatorial strapping) of both MR without recession with a 5/0 nylon suture. Results: Patients were evaluated between 27 and 51 months postoperatively. Mean initial deviation was 21 prism dioptres (PD) at distance and 31 PD at near fixation. Of the 122 cases, 102 (83.6%) showed stable postoperative deviation between +8 and –8 PD, 7 showed exotropias (< 20 PD), and 13 showed esotropias (< 20 PD). These results were found without correlation to preoperative angle of deviation, ametropia, age at surgery, or association with vertical surgery. Conclusion: Our results suggest that fadenoperation of MR is an option to treat esotropias that disappear under anesthesia. The retroequatorial strapping we use seems safer than classical fadenoperation. We believe that the position of the eyes under GA should be considered for the surgical approach of esotropias.

Correlation Between Epithelial Ingrowth and Basement Membrane Remodeling in Human Corneas After Laser-Assisted In Situ Keratomileusis

OBJECTIVE To further investigate the hypothesis that epithelial ingrowth in human corneas after laser-assisted in situ keratomileusis (LASIK) correlates with basement membrane remodeling, as suggested by the presence of matrix metalloproteinase 9 around epithelial cells in the lamellar scar. METHODS Immunohistochemical analysis and transmission electron microscopy were applied to human postmortem corneas with post-LASIK epithelial ingrowth. RESULTS Epithelial ingrowth into the flap margin was observed in 8 of 18 corneas (44%). Matrix metalloproteinase 9 immunolocalized around ingrown epithelium in 6 of these 8 corneas (75%). There was a positive correlation between the presence of matrix metalloproteinase 9 at the wound margin and discontinuities in the basement membrane, as determined by laminin and beta(4) integrin immunofluorescence. Transforming growth factor beta2 was present into the stroma of some corneas with epithelial ingrowth and interrupted basement membrane, suggesting some degree of epithelial-stromal interaction. Transmission electron microscopy confirmed large areas of remodeled basement membrane along ingrown epithelial cells. CONCLUSIONS The neo-basement membrane components underlying the ingrown cells in human corneas with epithelial ingrowth after LASIK appear to be partially disassembled. Epithelial-stromal interaction over time may be related to prolonged wound healing remodeling, which calls into question the stability of the flap.

Customized Topography-Guided Corneal Collagen Cross-linking for Keratoconus

PURPOSE To compare the efficacy and safety of topography-guided corneal collagen cross-linking (TG-CXL) to conventional corneal CXL (C-CXL) in progressive keratoconus. METHODS In this prospective, nonrandomized clinical trial, 60 eyes of 60 patients were scheduled to receive either TG-CXL (30 eyes with deepithelialization focused on the cone, riboflavin application for 10 minutes, and 30 mW/cm2 pulsed ultraviolet-A irradiance pattern according to topography) or C-CXL (30 eyes treated in accordance with the Dresden protocol). Patients were observed for 1 year postoperatively. Maximum keratometry (Kmax), mean keratometry in the inferior part of the cornea (I index), corrected distance visual acuity (CDVA), demarcation line observed in optical coherence tomography, and nerves and cell densities analyzed by confocal microscopy were compared preoperatively and at 1 year postoperatively. RESULTS The difference was significant for both Kmax (P < .01) and I index (P < .01) between the two groups. CDVA improved significantly in the TG-CXL (0.2162 ± 0.2495 logMAR, P < .05) versus the C-CXL (0.2648 ± 0.2574 logMAR, P = .104) group. A stromal demarcation line was observed in both treatment groups, with similar depth at the top of the cone (P = .391), but it was shallower at the surrounding area in the TG-CXL group (P < .0001). Stromal evaluation by confocal microscopy showed less damage and faster healing in the surrounding area than on the cone area in the TG-CXL group. CONCLUSIONS At 1 year postoperatively, TG-CXL seems to be as safe as C-CXL with stronger flattening in Kmax and I index and better improvement in CDVA. TG-CXL induces a biological gradient between the cone and the surrounding area that facilitates nerve and cell recovery. [J Refract Surg. 2017;33(5):290-297.].