Gabriel van Rij

The IC3D Classification of the Corneal Dystrophies

BACKGROUND The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.

A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14

Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10−14). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16–1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42–2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.

Implantation of Artisan toric phakic intraocular lenses for the correction of astigmatism and spherical errors in patients with keratoconus.

PURPOSE To evaluate the correction of astigmatism and spherical ametropia in patients with keratoconus through implantation of an Artisan toric phakic intraocular lens (PIOL) (Ophtec, Groningen, The Netherlands). METHODS Artisan toric PIOLs were implanted uneventfully in both eyes of three patients with keratoconus with clear central corneas and contact lens intolerance. RESULTS Best spectacle-corrected subjective visual acuity after lens implantation was unchanged in one eye and improved in five eyes. Spherical equivalent refraction was significantly reduced in all eyes (P=.03). The safety index was 1.49. CONCLUSIONS The implantation of an Artisan toric PIOL may be an alternative for treating astigmatism and myopia in contact lens intolerant patients with keratoconus with clear central corneas. Especially in patients with associated myopia, this procedure is worth considering before planning a penetrating keratoplasty.

Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty

OBJECTIVE To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

Changes in Corneal Curvature Induced by Sutures and Incisions

To clarify the mechanisms by which incisions and sutures produce corneal astigmatism, we made incisions and wedge resections closed by sutures in the corneoscleral limbus of human eye bank eyes, studying the changes in corneal curvature by shadowgraph photography of the corneal contour, by central keratometry, and by measurement of corneal diameter. The compression of tissue within the sutures or the closure of an excision of a wedge of tissue by sutures induced astigmatism in the meridian of surgery regardless of changes in the sagittal depth of the anterior chamber. Sutures and wedge resections closed by sutures in the anterior part of the cornea compressed or removed more tissue from the anterior part than the posterior part, producing a depression of the limbal cornea toward the anterior chamber and steepening the central cornea in the meridian of surgery. The corneal diameter decreased in that meridian. In the opposite meridian, the cornea flattened, the corneal diameter increased, and the sagittal depth decreased.

Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas.

In this study we investigated the properties of corneal aldehyde dehydrogenase (ALDH) in keratoconus corneas using various electrophoretic techniques combined with immunochemical and zymographic identification. Normal corneas and other pathologic corneal buttons obtained during keratoplastic surgery were used as a control. A significant (p<0.001) lower enzymatic activity was found in keratoconus epithelial extracts (3.1 ± 2.1 IU/mg protein) compared with normal controls (5.5 ± 2.6 IU/mg protein), whereas no significant differences were observed in the stromal and endothelial extracts. No significant differences were observed for the corneal ALDH thermolability behavior, nor did any marked changes occur in the position of the 54- and 88-kDa species when comparing the pathologic corneas and normal controls. On the other hand, isoelectric focusing analysis showed a different pattern for the pathologic corneas as compared with controls. Moreover, native-polyacrylamide gel electrophoresis analysis showed that normal corneas exhibit three bands, whereas keratoconus and other pathologic corneas only show two bands. The shift from the three-band pattern to the two-band pattern could be reproduced in vitro using reducing agents, such as glutathione

Refractive, topographic, and visual outcomes of same-day corneal cross-linking with Ferrara intracorneal ring segments in patients with progressive keratoconus.

Purpose: To report refractive, topographic, and visual outcomes 12 months after same-day treatment with corneal cross-linking (CXL) and Ferrara intracorneal ring segments (ICRS) in eyes with progressive keratoconus (KC) and contact lens intolerance. Methods: This was a case series of 7 eyes (7 patients) with progressive mild to moderate keratoconus and contact lens intolerance undergoing implantation of Ferrara ICRS immediately followed by corneal cross-linking. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refractive error, pachymetry, and keratometry were evaluated at 3, 6, and 12 months of follow-up. Results: Mean follow-up was 11.7 ± 3.6 months (range, 5–17 months). Mean preoperative UCVA and BSCVA were 0.10 ± 0.07 (range, 0.05–0.2) and 0.56 ± 0.08 (range, 0.5–0.7), respectively. One year after the treatment, mean UCVA and BSCVA measured 0.60 ± 0.24 (range, 0.32–0.9) and 0.82 ± 0.25 (range, 0.5–1.2), respectively. The mean spherical equivalent decreased significantly (P < 0.05) with 3.5 diopters (D). Mean K values (average keratometry of the cornea) decreased from 46.81 ± 2.13 D (range, 44–51 D) to 43.97 ± 2.22 D (range, 42–47.5 D) 1 year after the treatment. The average preoperative thinnest pachymetry measured 462 ± 46 μm (range, 410 ± 546 μm) and did not change significantly after the treatment. In patient 1, the inferior ICRS was removed 5 months postoperatively because of implant migration. Conclusions: The combined treatment of corneal cross-linking and Ferrara ICRS is a safe procedure that may be considered in patients with progressive mild to moderate KC and contact lens intolerance.

Toric phakic intraocular lens for the correction of hyperopia and astigmatism

PURPOSE: To evaluate the Artisan toric phakic intraocular lens (pIOL) for the correction of hyperopia and astigmatism. SETTING: Department of Ophthalmology, Erasmus MC, Rotterdam, The Netherlands, and Department of Ophthalmology, Sint Truiden, Belgium. METHODS: In this prospective study of 47 eyes of 28 patients with hyperopia and astigmatism, Artisan toric pIOLs were implanted between April 1999 and June 2004. Uncorrected visual acuity (UCVA), best corrected visual acuity, refraction, astigmatism, safety, and predictability were analyzed. Change in astigmatism was analyzed with vector analysis. Refractive cylinders are expressed in minus form. RESULTS: Mean preoperative spherical equivalent was +4.33 diopters (D) ± 2.26 (SD). Mean follow‐up was 11.1 months (range 6 to 36 months). A gain of 1 or more lines in best spectacle‐corrected visual acuity (BSCVA) was seen in 36.2%. Safety index and efficacy index after 6 months were 1.06 and 0.87, respectively. The mean postoperative astigmatism at 6 months was 0.19 D at an axis of 144 degrees. At 6 months, about three quarters (76.6%) of the eyes had a UCVA of 20/40 or better. One eye lost 2 lines of BSCVA. In 1 eye, the lens position had to be changed because of a large axis misalignment. No serious complications developed in any of the treated eyes during follow‐up. CONCLUSIONS: Artisan toric pIOLs can correct moderate to high hyperopia combined with astigmatism with good refractive results. In this study, there were no serious complications. However, the predictability of the refractive results appeared to be lower than those in the correction of myopia and astigmatism with toric Artisan lenses.

Introduction of Epithelial Cells in the Flap-Graft Interface During Descemet Stripping Automated Endothelial Keratoplasty

M icrokeratome-assisted Descemet stripping automated endothelial keratoplasty (DSAEK) is a form of lamellar corneal surgery that allows for the selective replacement of diseased endothelium. The DSAEK procedure is relatively new. So far, few complications have been described; these include graft detachment and graft failure. Recently, epithelial ingrowth in the flap-graft interface after DSAEK has been reported. We report a case of introduction of epithelial cells, originating from the donor tissue, in the flap-graft interface.

Prospective clinical evaluation of McCarey-Kaufman and organ culture cornea preservation media: 14-year follow-up.

Purpose: To compare the outcome of corneal grafts preserved in McCarey-Kaufman (MK) medium versus organ culture after penetrating keratoplasties. Methods: Paired corneas were stored in McCarey medium for 2-44 hours (mean 21 hours) and in organ culture (OC) for 144 -240 hours (mean 192 hours). Penetrating keratoplasties were performed by 2 surgeons in 2 groups of patients with keratoconus, matched for age. Each pair was transplanted by the same surgeon using the same technique. Visual acuity, central corneal thickness, and central endothelial cell density were assessed at 166 ± 7.8 months postoperatively. Results: Nine pairs of patients were recovered for a long-term follow-up. The mean endothelial cell densities for the MK and OC groups were 611 ± 155 and 683 ± 168 cells/mm2, respectively, which were not significantly different. A first rapid cell loss rate of 2.07% and 2.52% per month and a second slow of 0.78% and 0.69% per month were observed in the respective groups. Individual values of best corrected visual acuity were all the same (value 1.00) for both groups. Corneal thicknesses were, respectively, 571 ± 52 and 540 ± 35 μm and were significantly different (P = 0.013). Conclusions: After 14 years of penetrating keratoplasties performed with corneas stored in MK versus OC, no significant differences were observed in visual acuity, endothelial cell density, and cell loss. The observed thinner grafts after OC compared with MK could not be explained.