[Show abstract][Hide abstract] ABSTRACT: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness. Topical as well as systemic immunosuppressants are administered for prophylaxis. However, severe adverse effects limit long-term usage. By contrast, matching for transplantation antigens might be effective for a long time.
FANCY is a prospective, controlled, randomised, double-blind, multi-centre clinical trial with two parallel arms. The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint 'time to first endothelial graft rejection'. Relevant inclusion criteria are age over 18 years and waiting for penetrating or endothelial lamellar keratoplasty. The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6 months. After randomisation, patients either receive a HLA-matched graft (experimental intervention) or a random graft (control intervention). The calculated sample size is 620 patients. The trial started in 2009 with a recruitment period of 24 months. A total of 654 patients were included during this time.
The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine. However, during the course of the trial, the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty (DMEK). Nowadays, immune reactions are confined mostly to the 'high-risk' subgroups. If we would design FANCY in 2014, we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here.Trial registration: The unique identifying number of the FANCY trial is NCT00810472.
[Show abstract][Hide abstract] ABSTRACT: To compare combined trabectome-cataract surgery with cataract-alone surgery regarding their refractive and visual outcomes and complications.
In 137 eyes that underwent combined trabectome-cataract surgery, the postoperative refraction error and best visual acuity after at least 2 months postoperatively were compared to those of an in-house control group of 1,704 eyes that underwent outpatient cataract surgery.
Combined trabectome-cataract surgery showed no significant differences regarding the biometry prediction error (BPE, mean 0.53 D vs. 0.48 D, p = 0.24) or visual outcome (BCVA, 0.81 vs. 0.78, p = 0.06). The rate of postoperative cystoid macular edema was slightly higher in the combined surgery group (2.2 % vs. 1.9 %).
Refractive and visual outcomes were similar in both groups. Despite the slightly higher rate of postoperative macula edema, we were able to observe that the combination of these two procedures is a feasible method in glaucoma and cataract surgeries.
[Show abstract][Hide abstract] ABSTRACT: The German Ophthalmological Society (GOS) recently proposed surgical entry criteria, i.e. 300 cataract surgeries. We herein correlate the surgical hands-on experience with the risk of posterior capsule ruptures in order to assess whether this number is appropriate.
PLoS ONE 11/2014; 9(11):e112819. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recently, novel techniques introduced to the field of corneal surgery, e.g. Descemet membrane endothelial keratoplasty (DMEK) and corneal crosslinking, extended the therapeutic options. Additionally contact lens fitting has developed new alternatives. We herein investigated, whether these techniques have affected volume and spectrum of indications of keratoplasties in both a center more specialized in treating Fuchs' dystrophy (center 1) and a second center that is more specialized in treating keratoconus (center 2).
PLoS ONE 11/2014; 9(11):e112696. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The limbal stem cell niche is a structure of the ocular surface that is characterized by high specification, organization, and clinical significance. Harboring the limbal epithelial stem cells, which are the progenitor cells of the corneal epithelium, it provides a niche environment that guarantees the self-renewal of the corneal epithelium stem cells throughout life. Growth factors, stromal niche cells, and specific extracellular matrix compositions provide this environment. In recent years, another important component has been added to this list: the biomechanical aspect of the niche. This review focuses on this new and still underestimated aspect, which exhibits a direct effect on cells and can also influence growth and differentiation. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background: Cataract is one of the most common diseases in ophthalmology. Up to now the only way to estimate the total number of carried out surgeries in Germany were the surveys done by DOG, BVA, DGII and BDOC or reports of the federal statistical office. Objectives: Objective of this paper is to evaluate the annual quality reports of the Federal Joint Committee with a view to how the hospitals are participating in the nationwide comprehensive coverage concerning cataract surgery and if there is a continuing trend to more outpatient cataract surgeries in German eye hospitals. Material and Methods: The number of outpatient and inpatient cataract surgeries included in the annual quality reports of 2006, 2008 and 2010 were put into relation with population density for every provincial state. Results: In 2006, 2008 and 2010 a total of 765,179 cataract surgeries were recorded. Median number of cataract surgeries per 1000 inhabitants showed an only slight increase (2006: 2.8; 2008 and 2010: 3.0; p = 0.82). The ratio of outpatient to inpatient surgeries showed only a slight increase from 0.84 (2006) to 0.86 (2010). Conclusions: Lack of spatial and temporal variations imply that hospitals take a part in supplying the population with cataract surgery. There is no trend to more outpatient cataract surgeries at the moment. This implies that there might be a stable patient population that is not suitable for outpatient care.
[Show abstract][Hide abstract] ABSTRACT: Purpose
To analyse the willingness for postmortem cornea donation in Germany.
Employees in two cities (UKM, UKS), and university hospitals (STM, STE), members of the German Ophthalmological Society (DOG), and employees of an automobile company (BO) participated in a questionnaire about postmortem cornea donation attitudes. The questionnaire consisted of demographic items, motives concerning postmortem cornea donation, general attitudes toward donation, and questions concerning the perceived needs for information about donation. The statistical analyses included logistic regression with the target parameter of 'willingness to donate cornea postmortem'.
Of the participants, 67.7 % (UKM, UKS), 70.9 % (STM, STE), 70.8 % (BO), and 79.4 % (DOG) declared their intention to donate their corneas postmortem. Younger age (p < 0.001), poorer general health (p < 0.05), faith in an eternal life (p < 0.05), disagreement with brain death diagnostics (p < 0.001), fear of receiving worse medical treatment (p < 0.001), and fear of the commercialization of organs (p < 0.001) were found to be risk factors for a negative attitude toward postmortem cornea. The majority of participants (57.4 %) indicated that additional information about donation would be appreciated, and the internet (69.9 %) was considered the most appropriate means for conveying this information.
Emotional items were revealed to be the most relevant factors influencing the willingness to donate cornea postmortem, which may be counteracted by means of public education. The relatively low willingness among the medical staff contrasts with previous observations in a professional ophthalmologic society.
Albrecht von Graæes Archiv für Ophthalmologie 09/2014; · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To test whether subconjunctival cyclosporine A (CsA) implants affect the incidence and the degree of corneal neovascularization occurring after penetrating keratoplasty.
Prospective, randomized, multicenter, controlled phase 2/3 clinical trial. The study comprised 43 trial sites in Germany, India, and the United States.
Enrolled patients (n = 97) were randomized to 1 of 3 groups: treatment group A (n = 36), treatment group B (n = 40), and the control group (n = 21).
Patients from each group received either of 2 doses of subconjunctival CsA (group A, low-dose CsA; group B, high-dose CsA) or placebo (carrier only) implants at the time of high-risk penetrating keratoplasty.
Main Outcome Measures
The incidence and degree of corneal neovascularization occurring after penetrating keratoplasty were evaluated in a substudy (LX201-01 study: NCT00447187). A web-based image upload system was developed. Standardized digital slit-lamp pictures were quantitatively and objectively evaluated using CellˆF morphometry software.
No statistically significant difference in incidence and degree of corneal neovascularization developing after penetrating keratoplasty was found between treatment groups and placebo group. Mean corneal neovascularization area at week 52 (visit 12) was 2.32±1.79% in treatment group A versus placebo (2.79±2.11%; P = 0.45) and 2.74±2.22% in treatment group B versus placebo (2.79±2.11%; P = 0.94).
High-dose subconjunctival CsA implants do not significantly affect corneal neovascularization after high-risk penetrating keratoplasty. This suggests that local CsA has negligible antiangiogenic effects in the human cornea, at least in the transplant setting.
[Show abstract][Hide abstract] ABSTRACT: To determine the incidence and potential risk factors of cystoid macular oedema (CMO) following Descemet membrane endothelial keratoplasty (DMEK) with or without simultaneous cataract surgery.
British Journal of Ophthalmology 08/2014; · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: ReLEx®flex is a corneal refractive procedure performed by removing corneal lenticules
with a femtosecond (fs) laser system. Using electron microscopy, tissue parameters of extracted
lenticules were analysed for potential correlations to the refractive results. Furthermore,
the effect of previous contact lens (CL) wear on refractive stability (regression) was tested.
Patients and Methods: 19 lenticules from 11 patients (age 24–56 years, 8 f, 3 m) were prepared
for EM. The central areas of the samples were photographed and the distance between the collagen
fibres and their diameters were digitally measured. ANOVA analysis was used to correlate
postoperative refractional stability with time of preoperative CL use, fibre diameter and the coefficient
of variation (CV) of fibre distance.
Results: 14 of 19 lenticules were from patients who had worn CL preoperatively. The cumulative
duration of CL wear averaged around 31.2 ± 35.5 thousand hours. Preoperative CL use significantly
influenced the postoperative regression: the longer time patients had worn CL, the greater was
the regression towards myopia (p = 0.01). Additionally, the morphological parameters collagen
fibre diameter (p = 0.09) and CV of fibre distance (p = 0.07) had an impact on regression.
Conclusions: Prolonged CL use and alterations in ultrastructural patterns affected the refractive
stability after ReLExflex. Although the pathophysiological relationships between CL use, corneal
morphological parameters, and refractive stability are still poorly understood, these findings
could potentially be used as prognostic markers for postoperative refraction after ReLExflex.
Klinische Monatsblätter für Augenheilkunde 07/2014; · 0.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this review we summarise the new insights into corneal dystrophies following publication of the IC3D classification in 2008. Topics covered are new mutations, new clinical/histological phenotypes, first descriptions of known mutations in previously not mentioned ethnic groups, new dystrophic entities after modern corneal surgery and potentially new types of conservative therapy.
[Show abstract][Hide abstract] ABSTRACT: PurposeWe retrospectively studied the efficacy and safety of different surgical approaches to treating pediatric limbal dermoids with regard to intra and postoperative complications.Methods
The data of 12 consecutive patients (14 eyes), who underwent monocentric surgery of a limbal demoid in the past 9 years, were retrospectively analyzed for intra and postoperative complications. Group one consists of eleven eyes: seven eyes with a bare-sclera deep lamellar excision of the dermoid and four eyes with an additional amniotic membrane transplantation subsequent to excision. Group two consists of three eyes: two eyes treated with Mitomycin C 0.02% over 2 min following the excision, and one eye treated with Mitomycin C and amniotic membrane transplantation after removal of the dermoid. Follow-up ranged from 2 to 53 months (median 17 months).ResultsIntraoperative complications did not occur in any of the patients. Postoperatively, all patients showed corneal reepithelialization within a week. Limbal stem cell deficiency with a pseudopterygium developed in four eyes, one treated with bare-sclera excision and the others with amniotic membrane transplantation. One pseudopterygium had to be removed surgically because of visual acuity deterioration. Not a single eye treated with Mitomycin C developed a pseudopterygium.Conclusions
The transplantation of amniotic membrane following removal of a limbal dermoid cannot prevent the occurrence of a pseudopterygium. However, the use of Mitomycin C seems to have a protective effect.Eye advance online publication, 23 May 2014; doi:10.1038/eye.2014.112.
[Show abstract][Hide abstract] ABSTRACT: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation.
Multicenter, double-masked, randomized, placebo-controlled phase III study.
Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180.
The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL.
Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related.
This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.
[Show abstract][Hide abstract] ABSTRACT: Penetrating keratoplasty is being replaced by posterior lamellar techniques like Descemet stripping automated endothelial keratoplasty or Descemet membrane endothelial keratoplasty (DMEK) for the surgical treatment of patients with endothelial insufficiency. Although DMEK leads to the best visual results, Descemet stripping automated endothelial keratoplasty is still the standard procedure for many surgeons because it is technically more standardized. Here, we investigated how donor characteristics may influence DMEK surgery.
After in vitro preparation of DMEK grafts (n = 28), we measured the width of the graft roll, which we correlated to various donor characteristics. In 31 DMEK cases, we measured the intraoperative time from implantation to attachment of the graft, which we correlated to the respective donor characteristics and endothelial cell loss. We used Pearson's method and a multifactorial linear model for the statistical assessments.
We found a statistically significant correlation between donor age (P < 0.001) and endothelial cell density (P < 0.05), and the width of the DMEK rolls. That is, older donors and grafts with higher endothelial cell densities formed broader graft rolls. Donor age also showed a trend to directly influence the unfolding time that took longer using younger grafts. Furthermore, the relative endothelial cell loss increased with longer unfolding times.
We found that donor age and endothelial cell density influence the properties of DMEK grafts, and thereby the duration of the surgical procedure. Increased unfolding times result in higher endothelial cell loss. Therefore, it seems reasonable to accept preferably older donors with high endothelial cell densities for DMEK, which may be particularly true for inexperienced surgeons or complex clinical situations.
[Show abstract][Hide abstract] ABSTRACT: In order to prevent rejection of an allogeneic corneal transplant after perforating (high risk) keratoplasty, active agents from different classes of pharmacological substances are used, as with solid organ transplantation. In addition to glucocorticoids, antiproliferative agents, small molecule inhibitors and antibodies, those belonging to the group of macrolides with their many derivatives represent an interesting class of substances in this context. As a supplement to cyclosporin A (CSA) the most successful macrolide in transplantation medicine, animal experiments are currently being carried out to test newer macrolide derivatives, such as sanglifehrin A (SFA). This overview describes the classes of drugs and modes of action of currently administered standard medications in the clinical routine and new developments are presented.
Der Ophthalmologe 03/2014; 111(3):270-82. · 0.72 Impact Factor