Rainer Sundmacher

Successful treatment of ocular invasive mould infection (fusariosis) with the new antifungal agent voriconazole

Editor,—Voriconazole is a new, highly potent, triazole with broad spectrum activity against fungi, including moulds as well as fluconazole resistant Candida spp.1 Like other azole antifungal agents it interferes with ergosterole biosynthesis. Its antifungal activity has been shown in several experimental as well as clinical studies.2-5 ### CASE REPORT In November 1998, a 16 year old girl was transferred to the university eye hospital in Duesseldorf with a severe ulcerative hypopyon keratitis in the left eye, from which she had been suffering for 3 months after swimming in a lake in Italy. Smears, scrapings, and serology gave no hint of the aetiology. Despite intensive topical antibacterial, anti-acanthamoebal, antifungal, and antiherpetic therapy, as well as cryoapplication, her clinical situation had deteriorated continuously before admission to our hospital. As an optical rehabilitation was unlikely, owing to the severely …

Influencing factors on chronic endothelial cell loss characterised in a homogeneous group of patients.

Background/aim: Advanced donor age, long death to excision time interval, and factors related to organ culture can trigger unfavourable intracellular processes in the graft endothelium and contribute to chronic endothelial cell loss after penetrating keratoplasty. The aim of this study was to investigate factors influencing chronic endothelial cell loss in a homogeneous group of patients. Methods: 177 patients after first normal risk keratoplasties for keratoconus were retrospectively selected from the quality control database of our clinic. For 71 of them at least four central endothelial cell density values were documented in follow up. From these patients, only those 53 without any further intraocular procedures, without glaucoma, and without graft rejection were considered. A scatter plot of logarithmised endothelial cell density values against postoperative time was drawn for each patient. The slope of the regression line then equals the constant of decay in central endothelial cell density. The influence of donor age and storage time in organ culture on this index value of cell loss was investigated by means of linear regression analysis. Results: Mean loss of central endothelial cell density was 16.7% per year. Regression analysis revealed a statistically significant negative linear effect of both postmortem time (β = –0.324; p = 0.014) and donor age (β = –0.282; p = 0.036) and a trend for storage time in organ culture (β = –0.195; p = 0.142) in a combined linear regression model. Conclusion: Increased postmortem time and advanced donor age exert a significant negative effect on chronic endothelial cell loss. Storage time in organ culture seems to be third influencing factor. These negative influences may be reduced by compensating advanced donor age with minimised postmortem and storage time.

The influence of glaucoma history on graft survival after penetrating keratoplasty

Abstract• Background: It was the purpose of this retrospective study to evaluate the effect of a preoperative history of glaucoma on graft survival after penetrating keratoplasty. • Patients and methods: Six hundred and forty-six penetrating keratoplasties with generally good prognosis were analyzed retrospectively. Indications for surgery were corneal dystrophy, degeneration and scarring. Only first keratoplasties in corneas without severe vascularization or acute inflammation were included. Surface disorders, a history of herpes or Acanthamoeba keratitis were further exclusion criteria. Keratoplasties were performed only if glaucoma seemed to be controlled preoperatively. Graft survival ratios were calculated according to Kaplan and Meier, and statistical significance was evaluated by means of the log-rank test. • Results: With a glaucoma history the estimated 3-year graft survival rate was 71%, in contrast to 89% without such a history. This difference was statistically significant (P <0.001). There was no difference between the groups with respect to immune reactions. With a glaucoma history, postoperative episodes of glaucoma decompensation were responsible for half of the graft failures. • Conclusions: A preoperative history of glaucoma affects graft prognosis negatively, presumably through a negative influence of postoperatively elevated intraocular pressure on a vulnerable graft endothelium, and not by an increase in immune reactions. Therefore, keratoplasties in eyes with glaucoma are high-risk procedures and glaucoma has to be monitored more efficiently pre- and postoperatively.

The effects of cidofovir 1% with and without cyclosporin a 1% as a topical treatment of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study

OBJECTIVE To evaluate the efficacy of cidofovir 1% eyedrops with and without cyclosporin A 1% eyedrops as a treatment of acute adenoviral keratoconjunctivitis (AKC). DESIGN Randomized, controlled trial. PARTICIPANTS Thirty-four patients with acute adenoviral keratoconjunctivitis of recent onset. METHODS Patients were divided into 4 treatment groups: 1) cidofovir four times daily, 2) cidofovir 10 times daily, 3) cidofovir four times daily and cyclosporin A four times daily, and 4) sodium chloride four times daily (control). The diagnosis was confirmed by adenoviral polymerase chain reaction from conjunctival swabs. Duration of treatment was 21 days. MAIN OUTCOME MEASURES Severity of conjunctival injection, conjunctival chemosis, punctate epithelial keratitis during the course of treatment, and presence and severity of corneal subepithelial infiltrates were evaluated by a clinical score. Duration until subjective improvement of symptoms was recorded. RESULTS The frequency of severe corneal opacities was lower with cidofovir (P = 0.048). Cidofovir was toxic locally to the skin of the eyelids and the conjunctiva in a dose-dependent manner. Symptoms of local toxicity were clinically similar to the signs of the initial viral inflammation. They first appeared 8 to 12 days after beginning of treatment and completely subsided 7 to 28 days after discontinuation of cidofovir. The outcome measures of local inflammation did not differ between the four treatment groups. Cyclosporin A did not alter the course of the infection. CONCLUSIONS Cidofovir lowers the frequency of severe corneal opacities, but its clinical use 4 to 10 times daily at a 1% concentration is limited by local toxicity. Further clinical studies to find an efficacious yet tolerable dosage regimen of cidofovir, possibly using an improved pharmaceutical preparation, are required.

Mycophenolate mofetil versus cyclosporin A in high risk keratoplasty patients: a prospectively randomised clinical trial

BACKGROUND/AIMS The requirement for an effective, minimally toxic immunosuppressive agent remains a major obstacle to performing high risk corneal transplantation. Although therapy with cyclosporin A (CSA) allows superior graft survival, its use is limited because of a wide range of side effects. Mycophenolate mofetil (MMF) has been shown to be a safe and effective immunosuppressive agent following renal transplantation. This prospective, randomised clinical trial was carried out to investigate the efficacy and safety of MMF in preventing corneal allograft rejection. METHODS Recipients of corneal transplants who were at high risk for graft failure were randomly assigned to either CSA or MMF immunosuppressive therapy. CSA was given in doses to achieve whole blood trough levels of 120–150 ng/ml. MMF was given in a daily dose of 2 g. Both therapy groups additionally received oral corticosteroids (fluocortolone 1 mg/kg) which were tapered and discontinued within the first 3 postoperative weeks. Patients were monitored closely for evidence of corneal graft rejection and adverse side effects. Drug efficacy was measured, primarily, by the number of patients who experienced at least one episode of clinical graft rejection. Safety analysis focused on reported adverse side effects and laboratory measurements. RESULTS 41 patients were enrolled in the study. There was no statistically significant difference between the two groups. 20 patients received CSA and 21 patients received MMF. Two patients in each group showed evidence of acute graft rejection which could be treated effectively by corticosteroids. All corneal grafts remained clear throughout the follow up. CONCLUSIONS In this study it was shown that MMF is just as effective as CSA in preventing acute rejection following high risk corneal transplantation. Mycophenolate mofetil represents a promising alternative therapeutic option in patients who are at high risk for corneal graft failure.

Black diaphragm aniridia intraocular lens for congenital aniridia: long-term follow-up

PURPOSE To present long-term results of implantation of a black diaphragm aniridia intraocular lens (IOL) in eyes with congenital aniridia. SETTING Eye Hospital, Heinrich-Heine-University, Düsseldorf, Germany. METHODS Cataract surgery was performed in 19 eyes of 14 patients with congenital aniridia. The black diaphragm aniridia IOL was implanted in front of the capsular bag in the ciliary sulcus. Mean patient age was 30 years (range 10 to 59 years) and mean follow-up, 46 months (range 12 to 84 months). Before surgery, corneal epithelial disorders; corneal pannus; cataract; hypoplasia of the macula, optic nerve, or both; and nystagmus were present in all 19 eyes. Clinically detectable glaucoma was present in 5 eyes. RESULTS Despite the presence of amblyopia and nystagmus, visual acuity improved in 14 of the 19 eyes. The main postoperative problems were glaucoma deterioration (4 of 19 eyes) or development (4 of 19 eyes), cystoid macular edema (2 of 11 eyes), chronic endothelial cell loss (3 of 11 eyes), and progression of corneal epithelial disorders (4 of 19 eyes). Glaucoma was controlled by medical or surgical therapy in all patients. Intraocular lens explantation was performed in 2 eyes with glaucoma. CONCLUSION Implantation of the black diaphragm aniridia IOL improved visual acuity in the majority of patients with a variety of endogenous problems in addition to aniridia.

Corneal surface reconstruction using adult mesenchymal stem cells in experimental limbal stem cell deficiency in rabbits.

Purpose:  To investigate the ability of mesenchymal stem cells (MSC) to transdifferentiate to corneal epithelial cells in experimental limbal stem cell deficiency in rabbits.

Systemic ciclosporin A in high-risk keratoplasties

Abstract• Background: It was the purpose of this study to compile the results of all high-risk keratoplasties (kp) performed in our hospital under systemic ciclosporin A (Ci A) cover from 1987 through 1994. • Methods: One hundred and thirty-one keratoplasties were performed. Ci A was administered for an average period of 9.4 months. We aimed at trough levels of 100–150 ng/ml (monoclonal RIA/TDx). The 29 kp in group A were second or third repeat kp and/or the recipient cornea had severe deep vascularization in all quadrants and/or a transplant position at the limbus was inevitable (expected risk: only immune reactions). The 40 kp in group B were threatened by severe ocular surface disorders (without severe limbal stem cell insufficiency) and by immune reactions (atopic keratopathy, keratoconus with severe endogenous eczema or chronic blepharokeratoconjunctivitis). In the 45 kp of group C resurfacing problems from severe limbal stem cell insufficiency and immune reactions were anticipated (severe burns, pseudopemphigoid or Lyell syndrome). Group D comprised 17 kp with various diagnoses (e.g. kp in newborns, rheumatic andAcanthamoeba keratitis). • Results: In group A 91% of the grafts were clear 2 years postoperatively, in group B 76%, in group C 38% and in group D 18%. In 32 of 41 failed grafts (78%), resurfacing problems were the only reason for or participated in final graft failure. Immune reactions and other causes of graft failure were of minor importance. • Conclusions: (1) Systemic Ci A cover can efficiently suppress immune reactions. (2) With the suppression of immune reactions, resurfacing disorders become the most important single cause for functional graft failure. (3) For eyes with a considerable loss of limbal stem cells, limbal stem cell transplantation should be combined with systemic Ci A cover in order to improve the long-term prognosis for penetrating keratoplasty.

Topical cyclosporin A in Thygeson's superficial punctate keratitis

Abstract · Background: Since September 1994 we have administered topical cyclosporin A 2% (CSA) in a prospective study to patients with Thygeson’s superficial punctate keratitis (TSPK). After our promising short-term results we now present medium-term data of a larger patient group. · Patients and methods: Topical CSA was administered to 52 eyes of 28 patients with TSPK. Forty-two were adult eyes (group I), 10 children’s eyes (group II). Starting with 3 drops daily during the 1st month, CSA was reduced to 1 drop every 2nd day within 4 months and stopped after 6 months. · Results: Complete suppression of the typical epithelial and supepithelial opacities could be achieved in 71.5% of cases in group I and 40% in group II as long as therapy was administered; the other patients responded only partially or not at all. Recurrences were a problem during tapering off or shortly after cessation of therapy, but they could again be treated effectively with the initial CSA regime. Thirty-one percent of all adult eyes and 20% of all pediatric eyes seemed to have completely healed during the observation time. · Conclusions: In more than two thirds of our adult patients topical CSA 2% suppresses the epithelial and subepithelial opacities for as long as this non-steroid therapy is administered. Definite healing seems to be achieved in almost one third of all adult patients. In another one third, long-term low-dose CSA therapy is necessary before complete healing may be expected. Children probably do not respond to therapy as well as adults. Whereas the only therapeutic alternative, i.e. steroid eye drops, have a significant potential for side effects in the long run, no side effects have been known from low-dose CSA eye drops. We regard CSA eye drops as a significant progress in the symptomatic treatment of TSPK.

Systemische Cyclosporin-A-Prophylaxe nach Keratoplastiken mit erhöhtem Risiko für Immunreaktionen als einzigem erhöhten Risikofaktor

Ziel: In dieser retrospektiven Studie sollte die Effektivität eines systemischen Cyclosporin-A (CsA)-Einsatzes nach Keratoplastiken mit erhöhtem Risiko für Immunreaktionen als einzigem erhöhten Risikofaktorüberprüft werden.Patienten und Methode: Zwischen November 1986 und Juni 1994 wurden 1121 perforierende Keratoplastiken, davon 646 Normalrisiko- und 475 Hochrisikokeratoplastiken, durchgeführt. Nur bei 130 dieser 475 Hochrisikokeratoplastiken stellte ein erhöhtes Risiko für Immunreaktionen den einzigen erhöhten Risikofaktor dar. Bei 26 dieser 130 Keratoplastiken wurde systemisches CsA eingesetzt.Ergebnisse: Mit systemischem CsA war in der Hochrisikogruppe Keratoplastik mit erhöhtem Risiko für Immunreaktionen als einzigem erhöhten Risikofaktor innerhalb der Nachbeobachtungszeit von bis zu 66 Monaten keine dauerhafte Transplantateintrübung zu verzeichnen (100% klare Transplantate). Ohne CsA lag der Anteil klarer Transplantate nach Kaplan-Meier 3 Jahre postoperativ in dieser Hochrisikogruppe bei nur 71,7% im Vergleich zu 86,0% bei Normalrisikokeratoplastiken. Die Unterschiede zwischen diesen 3 Gruppen waren statistisch signifikant. Mit systemischem CsA wurden in der Hochrisikogruppe Keratoplastik mit erhöhtem Risiko für Immunreaktionen als einzigem erhöhten Risikofaktor zwar mehr Immunreaktionen beobachtet als ohne diese Prophylaxe oder als bei Normalrisikokeratoplastiken. Das Verhältnis akuter und chronischer Immunreaktionen war mit CsA aber statistisch signifikant zugunsten der günstigen chronischen Verläufe verschoben.Schlußfolgerungen: Systemisches CsA verbessert die Ergebnisse von Keratoplastiken mit erhöhtem Risiko für Immunreaktionen als einzigem erhöhten Risikofaktor deutlich. Es werden zwar immer noch recht viele Immunreaktionen beobachtet, das Verhältnis akuter und chronischer Immunreaktionen ist aber deutlich zugunsten der gut zu beeinflussenden chronischen Verläufe verschoben.Background: In this retrospective study our aim was to evaluate the effectiveness of systemic cyclosporin A (CsA) after keratoplasties with an elevated risk for immune reactions as the only elevated risk factor. Patients and methods: Between November 1986 and June 1994, 1121 penetrating keratoplasties, 646 normal-risk and 475 high-risk keratoplasties were performed. In 130 out of the 475 high-risk keratoplasties an elevated risk for immune reactions was the only elevated risk factor. Twenty-six of these 130 high-risk keratoplasties were treated with systemic CsA. Results: In the high-risk group keratoplasties with an elevated risk for immune reactions as the only elevated risk factor no permanent graft failure occurred with CsA (100% clear grafts). Without CsA the percentage of clear grafts in this high risk group was only 71.7% according to Kaplan Meier 3 years postoperatively in contrast to 86.0% in normal-risk keratoplasties. The differences between these three groups were statistically significant. In the high-risk group keratoplasties with an elevated risk for immune reactions as the only elevated risk factor more immune reactions occured than without CsA or than in normal-risk keratoplasties. However, these immune reactions were mostly of the benign chronic types. Conclusions: Systemic CsA considerably improves graft prognosis after high-risk keratoplasties with an elevated risk for immune reactions as the only elevated risk factor. With CsA application we observed a significant shift from acute to chronic immune reactions, which respond much better to topical steroids.