Carina Koppen

Keratitis and corneal scarring after UVA/riboflavin cross-linking for keratoconus.

PURPOSE To report four cases of severe keratitis after standard corneal collagen cross-linking (CXL) treatment for keratoconus. METHODS Four patients with progressive keratoconus from two different centers were treated by ultraviolet A (UVA) CXL, using riboflavin as a photosensitizer. The epithelium was removed over the central 8 to 9 mm of the cornea. Riboflavin 0.1% in dextran 20% was instilled every 2 minutes for 30 minutes before UVA exposure. The UV-X light source (IROC), calibrated at 3 mW/cm(2), was applied for 30 minutes while instillation was continued every 2 minutes. At the end of the treatment, a bandage contact lens was applied and topical treatment consisting of a combination of antibiotics and/or anti-inflammatory drops was initiated. RESULTS Patients experienced delayed (after more than 24 hours) symptoms and signs of inflammation. The eyes showed pronounced ciliary redness with cells in the anterior chamber and central keratic precipitates; multiple white infiltrates had developed at the edge and within the area of CXL. High-dose topical or subconjunctival corticosteroids led to rapid initial improvement of symptoms and signs. Herpes virus could not be detected on the ocular surface or on the anterior chamber tap of one patient. CONCLUSIONS We report four cases of keratitis and corneal scarring from a total of 117 eyes treated with CXL. The location of the scarring determined the amount of loss of visual acuity: in two eyes, there was a persistent decrease in best spectacle-corrected visual acuity.

Refractive and topographic results of benzalkonium chloride–assisted transepithelial crosslinking

PURPOSE: To evaluate the effect of benzalkonium chloride–assisted (BAC) transepithelial collagen crosslinking (CXL) in eyes with progressive keratoconus and a minimum follow‐up of 6 months. SETTING: Department of Ophthalmology, Antwerp University Hospital, Antwerp, Belgium. DESIGN: Cohort study. METHODS: Eyes with progressive keratoconus had CXL treatment without epithelial debridement. The standard CXL irradiation was preceded by instillation of proparacaine drops 0.5% preserved with BAC 0.005% every 5 minutes for 30 minutes. Selected parameters of refraction assessed by Placido disk (Eyesys) and Scheimpflug (Pentacam) examinations were compared before CXL and after CXL at 6, 12, and 18 months. RESULTS: The study enrolled 53 eyes of 38 patients. Sphere, cylinder, as well as maximum keratometry (K max) simulated K values (steep, flat, astigmatism), and refractive power values (steep, flat, astigmatism) measured using the Placido disk device remained stable over the 18‐month follow‐up. Only corrected distance visual acuity showed a statistically significant improvement at 6 months and 12 months. The Scheimpflug device measurements of maximum K and pachymetry at the thinnest point showed statistically significant progression throughout the study. No patient developed corneal haze or other complications. CONCLUSION: Transepithelial CXL using proparacaine drops 0.5% preserved with BAC 0.005% was less effective than standard CXL in stabilizing progressive keratoconus. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Limbal Stem Cell Deficiency: Current Treatment Options and Emerging Therapies.

Severe ocular surface disease can result in limbal stem cell deficiency (LSCD), a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due to removal of large limbal grafts has been significantly reduced by the optimization of cultivated limbal epithelial transplantation (CLET). Despite the great successes of CLET, there still is room for improvement as overall success rate is 70% and visual acuity often remains suboptimal after successful transplantation. Simple limbal epithelial transplantation reports higher success rates but has not been performed in as many patients yet. This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and evolving techniques in ocular surface regeneration are being discussed, in particular, advantages and disadvantages of alternative cell scaffolds and cell sources for cell based ocular surface reconstruction.

Human Tears Reveal Insights into Corneal Neovascularization

Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

The absorption characteristics of the human cornea in ultraviolet-a crosslinking.

Objectives: With respect to the safety of ultraviolet-A (UVA) crosslinking for the corneal endothelium, an absorption coefficient is used that has been calculated in riboflavin soaked porcine corneas. We aim to validate this value for clinical use by measuring the absorption coefficient for UVA 365 nm in postmortem human corneas after instilling riboflavin on the corneal surface. Methods: Corneal thickness was measured in nine pairs of human donor eyes of which one eye was subjected to manual removal of the epithelium, whereas the epithelium of the fellow eye was left intact. Both eyes were instilled with riboflavin 0.1% in dextran 20% on the intact globe. After 20 min, the corneas were rinsed, and a corneoscleral button was trephined. The transmission of the cornea for UVA 365 nm was measured by transillumination, which allows calculation of the absorption coefficient. Results: Measurement of average corneal thickness was 658.5 ± 51.5 &mgr;m when the epithelium was removed, and 758.3 ± 98.8 &mgr;m without epithelial removal. The average transmittance for UVA 365 nm was 12.89 ± 4.10% with epithelial debridement and 28.52 ± 4.39% without (P<0.05). The resultant average absorption coefficient is 32 ± 5 cm−1 when the epithelium is removed and 17 ± 2 cm−1 when it is left intact (P<0.05). Conclusions: Our results show an absorption coefficient for human corneas that is much lower than the values reported in the literature. This finding may be relevant when considering endothelial safety of the clinical crosslinking treatment.

Repeatability and Inter-device Agreement for Three Different Methods of Keratometry: Placido, Scheimpflug, and Color LED Corneal Topography

PURPOSE To determine the repeatability of a color LED corneal topographer (Cassini; iOptics, The Hague, The Netherlands) and compare it with Placido and Scheimpflug based devices (EyeSys 2000; EyeSys Laboratories, Houston, TX, and Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany). METHODS This prospective study involved 20 healthy volunteers (20 eyes) recruited from the staff of the Antwerp University Hospital. For each eye, three measurements were taken using each device, from which eight parameters describing keratometry and astigmatism were derived. Repeatability was assessed using intrasession, within-subject analysis of variance. Agreement was evaluated between pairs of devices with Bland- Altman plots and 95% confidence intervals. RESULTS The repeatability values were good for all three devices, although slightly worse for the Cassini than for the other two devices for steep, flat, and mean keratometry. The EyeSys showed worse repeatability for the astigmatism axis. EyeSys and Pentacam agreed well with each other in terms of mean keratometry, whereas the Cassini gave consistently higher values by 0.52 diopters (D) when compared with the EyeSys (P < .05, paired t test) and by 0.38 D when compared with the Pentacam (P < .05, paired t test). The Cassini provided similar repeatability values (2.31°) for the astigmatism axis to the Pentacam (2.22°), in contrast to the EyeSys, which produced much more variable axes (9.0°) (P < .05, paired t test). CONCLUSIONS Overall, the three devices display comparable repeatability. The one exception is the astigmatism axis measurement of the EyeSys. The Cassini provides higher keratometry values than the other two devices, but the astigmatism axis agrees well with that provided by the Pentacam.

Influence of contact lens wear on the results of ultraviolet A/riboflavin cross-linking for progressive keratoconus

Aims To report on the influence of rigid gas permeable contact lens (CL) wear on the results of ultraviolet A/riboflavin cross-linking (CXL) for stabilisation of progressive keratoconus. Methods Prospective non-comparative study of 15 eyes without CL and 12 eyes fitted with CL from 1 to 10 weeks post-CXL. None of the patients had been wearing CL before CXL. The effect of the CXL treatment was measured by the change from the baseline of best spectacle corrected visual acuity (BSCVA), refractive sphere and cylinder, maximal keratometry value (K max), simulated keratometry steep, flat, astigmatism, refractive power (RP) steep, flat and astigmatism, I-S value on EyeSys (EyeSys Vision Inc, Houston, Texas, USA) and K max on Pentacam (Oculus Optikgeräte, Wetzlar, Germany). The results of these measurements are reported pre-CXL and at 6-month intervals up to 18 months post-CXL. Results In the eyes without CL, none of the study parameters showed a significant change from baseline. Only in the group of eyes fitted with CL post-CXL, several parameters showed a significant improvement: I-S value and K max on EyeSys (all time points), RP steep and simulated astigmatism (6 and 12 months) and RP flat (12 months). Conclusion CL can be a confounding factor in interpreting the results of CXL: lens wear itself leads to improved topographic parameters.

Visual acuity after penetrating keratoplasty for pseudophakic and aphakic bullous keratopathy

Purpose: To identify prognostic factors that determine the visual acuity after penetrating keratoplasty (PKP) for bullous keratopathy secondary to cataract surgery. Setting: Department of Ophthalmology, University Hospital Antwerp, Antwerp, Belgium. Methods: Twenty‐six patients who had PKP for bullous keratopathy were examined before and after surgery. The patients were divided into 3 groups: pseudophakic bullous keratopathy (PBK) after cataract extraction with implantation of a posterior chamber intraocular lens (PC IOL) (Group 1) or an anterior chamber IOL (AC IOL) (Group 2); aphakic bullous keratopathy (ABK) (Group 3). The following parameters were recorded: preoperative and postoperative visual acuity, age at the time of surgery, interval between cataract surgery and development of bullous keratopathy, presence of an AC IOL or a PC IOL, aphakia, and presence of concomitant ocular pathology. Results: Visual acuity improved in Group 1 (0.02 to 0.26); no visual improvement was observed in the other groups. Posterior segment damage occurred in one third of the patients in Group 1 and in all patients in the other groups. Patients with an intact posterior segment had a significantly better visual outcome. In eyes without posterior segment pathology, visual acuity improved from a mean of 0.03 (range 0 to 0.20) to a mean of 0.37 (range 0.03 to 0.90). In eyes with posterior segment pathology, no visual acuity improvement could be obtained. Conclusion: The most important negative prognostic factors affecting visual acuity were the presence of concomitant ocular pathology, an AC IOL, and a long interval between surgery and the development of bullous keratopathy.

Influence of neodymium:YAG laser capsulotomy on ocular wavefront aberrations in pseudophakic eyes with hydrophilic and hydrophobic intraocular lenses.

PURPOSE: To study the influence of neodymium:YAG (Nd:YAG) laser capsulotomy on ocular wavefront aberrations. SETTING: Department of Ophthalmology, Antwerp University Hospital, Edegem, Belgium. METHODS: The wavefront aberrations in pseudophakic eyes with posterior capsule opacification (PCO) were measured with an iTrace aberrometer before and after Nd:YAG laser capsulotomy. These results were analyzed using Zernike coefficients, the total and higher‐order root‐mean‐square (RMS) values, and the wavefront peak–valley difference. In addition, a separate evaluation was performed of 2 intraocular lens (IOL) types: the hydrophilic 92S (hydrophilic IOL subgroup) and the hydrophobic AcrySof SA60AT (hydrophobic IOL subgroup). RESULTS: The study evaluated 62 pseudophakic eyes (56 patients). The RMS values in all eyes decreased significantly after Nd:YAG laser capsulotomy; the mean decrease in total RMS was 0.186 μm ± 0.445 (SD) and in higher‐order RMS, 0.138 ± 0.223 μm. The decrease in total RMS (mean 0.325 ± 0.372 μm) was significant in the hydrophobic IOL subgroup (n = 14) but not in the hydrophilic IOL subgroup. Before capsulotomy, there was a statistically significant difference between the 2 subgroups in the higher‐order astigmatism coefficient C(4,−2). After laser capsulotomy, the difference was significantly less. CONCLUSION: Neodymium:YAG laser capsulotomy significantly reduced the wavefront RMS in the hydrophobic IOL subgroup but not in the hydrophilic IOL subgroup. The difference in the wavefront before capsulotomy may originate from a difference in the healing response of the capsular bag between the 2 IOL types.

Safety of Cultivated Limbal Epithelial Stem Cell Transplantation for Human Corneal Regeneration

Ex vivo cultivated limbal stem cell transplantation is a promising technique for the treatment of limbal stem cell deficiency. While the results of the clinical trials have been extensively reported since the introduction of the technique in 1997, little has been reported regarding the potential health risks associated with production processes and transplantation techniques. Culture procedures require the use of animal and/or human-derived products, which carry the potential of introducing toxic or infectious agents through contamination with known or unknown additives. Protocols vary widely, and the risks depend on the local institutional methods. Good manufacturing practice and xeno-free culture protocols could reduce potential health risks but are not yet a common practice worldwide. In this review, we focus on the safety of both autologous- and allogeneic-cultivated limbal stem cell transplantation, with respect to culture processes, surgical approaches, and postoperative strategies.