Thomas Reinhard

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.

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.

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.

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.

Central corneolimbal transplantation under systemic ciclosporin A cover for severe limbal stem cell insufficiency

Abstract• Background: Severe stem cell deficiencies uniformly lead to superficial conjunctivalization of corneal grafts with subsequent functional failure. We sought better long-term results by transplanting central corneolimbal grafts and simultaneously protecting the graft and its stem cells from immunological destruction by means of systemic administration of ciclosporin A. • Patients and methods: In an ongoing pilot study, up to April 1995 20 eyes with stem cell dysfunctions of various etiology (e.g. chemical burn, ocular pseudopemphigoid, congenital aniridia) received eccentrically trephined fresh corneal grafts of 7.7–10.0 mm diameter. About one third of the circumference of the grafts contained limbal area. The mean age of the patients was 46.2 years (range 9–84 years). All patients received systemic ciclosporin A for at least 12 months. At present, the mean follow-up period is 9.6 months (mean 1–20.6 months). • Results: Fourteen of 20 grafts (70%) have remained clear so far. Reasons for six graft failures were surface disorders in four eyes, immune reactions in one eye and surface disorders in combination with immune reactions in another eye. Ten of 20 grafts (50%) experienced severe surface disorders. In six eyes surface disorders were coincident with endothelial immune reactions, in four eyes they were not. In four of 20 grafts (20%) conjunctivalization was observed in front of the transplanted limbal area; in seven of 20 grafts (35%) conjunctivalization occurred only distant from the transplanted limbal stem cells. • Conclusions: Our method of central corneolimbal transplantation with simultaneous protection of the transplanted stem cell population from immunological destruction by means of systemic ciclosporin A has been successful for 14 eyes with severe stem cell deficiencies up to 20.6 months postoperatively. This new treatment principle promises — for the first time — long-term rehabilitation for a majority of eyes with severe limbal stem cell deficiencies.

Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching

AbstractBackground Owing to contradictory results, HLA matching in penetrating keratoplasty still is equivocal. Different surgical techniques in multicentre studies, missing risk differentiation in high-risk situations, and faulty HLA typing can be identified as main reasons for these contradictory results. In this monocentre study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogeneous group of 418 normal-risk keratoplasty patients using serological typing techniques for HLA class I and immuno-genetic typing techniques for class II.Methods Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0–2, group II with 3–6 mismatches in the A/B/DR loci). All surgery was carried out by three experienced surgeons according to a standardized scheme. Furthermore, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups with regard to the number of ABO or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft, and endothelial cell density of the graft at the end of organ culture. All HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and immunogenetically for HLA class II (DR locus).Results At 4 years postoperatively, the ratio of clear and rejection-free graft survival was 92% in group I and 66% in group II (Kaplan–Meier estimation, log rank test, P=0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (P=0.03).Conclusions In this monocentre study with proper typing techniques, the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogeneous group of normal-risk keratoplasty patients.

Organ-cultured corneal grafts from septic donors: a retrospective study

Purpose To evaluate the quality of corneal grafts from donors, who have died from septic multi-organ failure and who are called septic donors in the following.Methods One hundred and eighty-two corneal grafts from septic donors were stored in organ culture for 10–14 days. Graft evaluation was performed according to the criteria of the European Eye Bank Association. Only donor corneas with cell density values above 2000 cells/mm2 were transplanted. Ninety-one patients who received these transplanted corneas were examined retrospectively with special emphasis on endophthalmitis, graft failure and incidence of immune reactions.Results Ninety-one of 182 donor corneas (50%) from septic donors were discarded mainly due to endothelial damage (61; 67%). Only seven (8%) were discarded due to medium contamination. In contrast, 452 of 1261 donor corneas (36%) from non-septic donors during the same period were discarded, again mainly due to endothelial damage (264; 58%). In this group, 48 donor corneas (11%) were discarded due to medium contamination. No patient who had received a graft from a septic donor has experienced endophthalmitis. The rate of immune reactions and graft failure was in the same range when compared to a larger group who received grafts from non-septic donors.Conclusion Our data reveal no contraindication against the use of corneal grafts derived from septic donors, critical graft assessment in organ culture provided.

HLA class I and II matching improves prognosis in penetrating normal-risk keratoplasty.

BACKGROUND HLA matching in penetrating keratoplasty is still neglected in most eye clinics. This is due to contradictory results of studies performed in the past. Different surgical techniques in multicenter studies, missing risk differentiation in high-risk situations and faulty HLA typing can be identified as the main reasons for these contradictory results. In this monocenter study, the value of HLA class I and II matching (A, B, DR loci) was examined in a homogenous group of 398 normal-risk keratoplasty patients using modern typing techniques. METHODS Penetrating normal-risk keratoplasty was performed in two groups of patients (group I with 0-2, group II with 3-6 mismatches in the A/B/DR loci). Surgery was done by 3 experienced surgeons according to a standardized scheme. Also, postoperative therapy and controls were standardized. There were no statistically significant differences between the two study groups as regards number of AB0 or H-Y compatibilities, patient age, patient gender, ratio of previous intraocular surgery, ratio of triple procedures, indication for surgery, follow-up period, donor age, donor gender, post-mortem time of the graft and endothelial cell density of the graft at the end of organ culture. HLA typing was performed in a quality-controlled laboratory, serologically for HLA class I (A and B loci) and moleculargenetically for HLA class II (DR locus). RESULTS Four years postoperatively, the ratio of clear and rejection-free graft survival was 91% in group I and 67% in group II (Kaplan-Meier estimation, log rank test, p = 0.03). Monovariate analysis in the Cox model gave no influence of solitary HLA class I or II matching, but only an influence of combined HLA class I and II matching (p = 0.03). CONCLUSIONS In this monocenter study with proper typing techniques the beneficial effect of HLA class I plus II matching on clear and rejection-free graft survival could be demonstrated in a homogenous group of normal-risk keratoplasty patients.

A comparative investigation of FK506 and cyclosporin A in murine corneal transplantation

Abstract · Background: Acute rejection is the cause of over 50% of transplant opacifications in some immunological high-risk groups. More potent immunomodulating substances must be found in order to allow extended or individualised therapeutic options for combating rejection. · Methods: Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients, respectively. FK506 (Prograf) was administered intraperitoneally for 14 days in a dosage of 0.3 mg/kg bw, and cyclosporin A (CSA; Sandimmun) was administered, likewise for 14 days, in an intramuscular dosage of 10 mg/kg bw. The transplants were examined every 3rd day by slit-lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation. · Results: The average transplant survival period in the allogeneic strain combination was 7.9 days (SEM=1.1). Therapy with FK506 led to a statistically significant prolongation of transplant survival to 17.1 days (SEM=1.5, P<0.05). Therapy with CSA delayed transplant rejection to 21 days (SEM=0.0, P<0.05). No statistically significant difference was found between the two therapeutic regimens. There were no significant histomorphologic differences in rejected grafts in the FK506- and CSA-treated animals. · Conclusions: In this study we have shown that FK506 is able to delay corneal allograft rejection at a much lower dosage than CSA without a higher incidence of side effects related to toxicity or overimmunosuppression.