[Adenoviral keratoconjunctivitis]. / Adenovirus-Keratokonjunktivitis.

Keratoconjunctivitis caused by adenoviruses (epidemic keratoconjunctivitis, EKC, ICD-10 B30.0+) is common, can be severe and may cause significant morbidity. In the early stages of adenoviral infections it is often difficult to differentiate the clinical presentation from other causes of a red eye. Because of its highly contagious nature that can rapidly lead to epidemic outbreaks, prompt viral identification and prevention of further spread are major challenges. Even today the diagnosis is still mainly clinical, with laboratory tests only rarely contributing. New diagnostic tests, such as the Rapid Pathogen Detector (RPS, Sarasota FL) AdenoPlus detection kit, that are practical, rapid and inexpensive to use in the general practice may obviate these problems. Because of its highly resistant properties to desiccation and highly developed escape mechanisms which protect the virus from the host's immune response, long-term problems often remain. Remnants of viral proteins often persist on the corneal surface of Bowman's layer for a long time and may lead to the formation of subepithelial infiltrates. No treatment other than symptomatic eye drops is available. The major sequelae are subepithelial infiltrates, which are difficult to treat. Cyclosporin A eye drops are a good option with a low risk profile. The use of topical steroids can possibly be disadvantageous but can be discussed at all stages of the disease. As nosocomial spread of adenoviruses is relatively common, preventive measures remain a major responsibility for ophthalmologists.

[Immunosuppressives to prevent rejection reactions after allogeneic corneal transplantation]. / Immunsuppressiva zur Verhinderung von Abstoßungsreaktionen nach allogenen Hornhauttransplantationen.

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.

[Corneal tumour following anterior chamber lens implantation in a patient with Marfan syndrome. Case study of a 57-year-old patient]. / Kornealer Tumor nach Vorderkammerlinsenimplantation bei Marfan-Syndrom. Kasuistik eines 57-jährigen Patienten.

A 57-year-old male patient with Marfan syndrome presented at our clinic with a whitish gelatinous corneal tumour in the right eye. The initial examination revealed pronounced corneal oedema, bullous keratopathy, as well as an iris-fixed anterior chamber lens implanted 7 years previously. After the tumour was removed, the anterior chamber lens was explanted and keratoplasty was explanted and a two stage keratoplasty was performed. Histological analysis of the tumour and the cornea revealed vimentin and a number of smooth muscle actin (SMA)-positive tumour cells. The cornea below the tumour displayed a partially absent Bowman's layer and extensive pannus tissue. The characteristics of the corneal tumour and the subjacent cornea as described above are typical of secondary corneal myxoma. The influence of Marfan syndrome, a systemic connective tissue disorder present in the patient, on the etiopathogenesis of the corneal myxoma could not be fully determined.

[Perspectives of femtosecond laser-assisted keratoplasty]. / Perspektiven der Femtosekundenlaser-assistierten Keratoplastik.

The femtosecond laser technique allows completely new trephination procedures in penetrating and lamellar keratoplasty. With femtosecond laser-assisted penetrating keratoplasty it is possible to perform profiled trephination, such as top hat and mushroom profiles. Thus, it is easier to get a watertight wound closure intraoperatively and due to the larger wound surface wound healing is faster and allows early complete suture removal. In lamellar keratoplasty the femtosecond laser enables the surgeon to cut to any depth in the corneas resulting in thin corneal donor buttons, e.g. for DSAEK. In this manuscript an overview is given of the state of the art and of the perspectives of femtosecond laser keratoplasty.

[Therapeutic applications of the femtosecond laser in corneal surgery]. / Therapeutischer Einsatz des Femtosekundenlasers in der Hornhautchirurgie.

Since 2001 the femtosecond laser has primarily been used in refractive surgery, e. g., for lasik, implantation of intracorneal ring segments or antiastigmatic corneal incisions. However, the femtosecond laser is more and more used for therapeutic reasons in corneal surgery. In this context it is used for profiled trephinations in penetrating keratoplasty where various profiles of the cutting edge can be designed (e. g., top-hat profile, mushroom profile, zig-zag profile). The potential advantages of these profiles include improved graft adaptation, better and more stable wound healing leading to earlier suture removal and eventually prolonged graft survival. However, none of these potential advantages has been demonstrated by reliable study results until now. First clinical experiences show that much earlier suture removal is possible without significant complications. However, with sutures in there seems to be no advantage of the femtosecond laser compared to mechanically guided trephination systems regarding visual acuity and postoperative astigmatism. Besides penetrating profiles, the femtosecond laser also allows for lamellar cuts. As deep anterior lamellar keratoplasty can only be supported by the femtosecond laser, it is mostly used for posterior lamellar grafts in this context. However, first clinical results using the femtosecond laser for DSAEK (descemet stripping automated endothelial keratoplasty) are poorer than those using microkeratome-prepared lamellar grafts for DSAEK.

[Penetrating keratoplasty in corneal infections with herpes simplex virus and varicella zoster virus]. / Perforierende Keratoplastik bei Hornhautinfektionen durch Herpes-simplex-Virus und Varizella-zoster-Virus.

Penetrating keratoplasties due to herpetic corneal scars are more often performed compared to persisting Varicella zoster virus infections, which are quite seldom. Penetrating keratoplasties in herpetic corneas are risk keratoplasties due to the vascularisation and the risk of recurrent virus replication. The prognosis in these corneal transplantations has been improved in recent years due to better postoperative medical treatment with virustatics and systemic immunosuppression. Indications for and treatment following penetrating keratoplasty in herpetic eyes are the topics of this review.

[Femtosecond laser-assisted penetrating keratoplasty]. / Femtosekundenlaserassistierte perforierende Keratoplastik.

The femtosecond laser technique allows completely new trephination methods in penetrating keratoplasty with profiles in the graft and the host cornea. The most common so-called profiled trephinations are the top hat and mushroom profiles. Due to the profile it is easier to get a watertight wound closure intraoperatively and due to the larger wound surface the wound healing is faster and more stable. This will possibly allow an earlier suture removal with final visual rehabilitation. First clinical results show that femtosecond laser-assisted penetrating keratoplasty is a safe surgical procedure. The long term results after complete suture removal will show whether the astigmatism results are better than those of conventional trephination techniques.

Mycophenolate mofetil (MMF) following penetrating high-risk keratoplasty: long-term results of a prospective, randomised, multicentre study.

BACKGROUND: The purpose of this prospective, randomised, multicentre study was to prove the efficacy and safety of mycophenolate mofetil (MMF) in preventing graft rejection and in improving clear graft survival following high-risk keratoplasty. METHODS: In all, 98 of 140 scheduled patients were included in this study (57 MMF, 41 control). Recruitment was stopped prematurely due to a statistically significant result. The patients in the MMF group received MMF orally 2 x 1 g daily for 6 months. All of the patients received fluocortolone 1 mg/kg/day tapered over 3 weeks and topical prednisolone acetate 5 x /day tapered over 5 months. Main criteria were immune reaction-free and clear graft survival, and the occurrence of side effects. RESULTS: The mean follow-up time was 34.9+/-16.3 (mean+/-SD) months. Eleven patients withdrew from the study (nine patients due to protocol deviation, two because of side effects). Six reversible and two irreversible graft rejections occurred in the MMF group, and five reversible and seven irreversible rejections in the control group. The Kaplan-Meier analysis revealed an immune reaction-free graft survival after the mean follow-up time of 83% in the MMF group and 64.5% in the control group (P=0.044). Graft failure occurred in 10 MMF-treated patients (two due to rejection) and in nine patients in the control group (seven due to rejection). A total of 36 of 57 MMF-treated patients experienced mostly reversible adverse events. CONCLUSIONS: Systemic immunosuppression with MMF over 6 months is relatively well tolerated and improves rejection-free graft survival following high-risk keratoplasty statistically significant, even in the long run.

[Cyclosporin A eyedrops for keratitis nummularis after adenovirus keratoconjunctivitis]. / Cyclosporin-A-Augentropfen bei Nummuli nach Adenovirus-Keratokonjunktivitis.

Keratoconjunctivitis is a common infectious disease of the eye surface, which is caused by adenovirus. The chronic form is keratitis nummularis. Cyclosporin A is a calcineurin inhibitor which has been used in ophthalmology for approximately 15 years for local therapy of chronic inflammation of the eye surface. Since the 1990s this medication has proven effective for the treatment of keratitis nummularis. The indications for treatment with cyclosporin A eyedrops are given when a reduction in vision due to keratitis nummularis has not shown any improvement within 6 weeks after acute inflammation.

[Long-term results of FK 506 eye drops following corneal transplantation]. / Langzeitergebnisse mit FK 506-Augentropfen nach Hornhaut-Transplantation.

BACKGROUND: Immunological graft rejection is the main reason for graft failure following corneal transplantation despite the use of topical and systemic steroids. As steroids are associated with side effects, alternative therapeutic strategies are needed. PATIENTS AND METHODS: In this clinical trial patients undergoing corneal transplantation have been prospectively randomised to receive either prednisolone acetate 1 % eye drops 5 x /day, tapering off by one drop every month (n = 20), or to receive FK 506 eye drops 3 x /day for six months (n = 20). Patients in both groups received additionally systemic steroids for three weeks (fluocortolon 1 mg/kg body weight). Primary endpoints were the number of immune reactions and the clear graft survival, the secondary endpoint was the number of side effects. RESULTS: Three immune reactions in the steroid group and one immune reaction in the FK 506 group were seen within the follow-up time of three years. No irreversible graft rejections occurred in either group. Eight patients in the FK 506 group concluded the study early due to local side effects. CONCLUSIONS: In this long-term follow-up the use of FK 506 eye drops following corneal transplantation resulted in a lower number of immune reactions when compared to topical steroids. With a change in the galenic formulation FK 506 might be a powerful therapeutic option for preventing immunological graft rejection.

[Basiliximab following penetrating risk-keratoplasty--a prospective randomized pilot study]. / Basiliximab als Monotherapie nach perforierender Risikokeratoplastik--eine prospektive randomisierte Pilotstudie.

BACKGROUND: Until now cyclosporin A (CSA) and mycophenolate mofetil (MMF) are the only available systemic immunosuppressants for patients undergoing risk keratoplasty. Basiliximab is a chimeric monoclonal interleukin 2-receptor antibody, which inhibits T-cell proliferation. Basiliximab is approved for the treatment in patients after kidney transplantation. The aim of this study was to prove the efficacy and safety of Basiliximab after penetrating risk keratoplasty. PATIENTS AND METHODS: 20 patients undergoing risk keratoplasty received as postoperative medication fluocortolon 1 mg/kg/d (tapered off within three weeks) and prednisolone acetate eye-drops 5x/d (tapered off within five months). In addition, 10 patients received 20 mg basiliximab immediately following surgery and four days postoperatively. 10 patients in the control group received oral CSA adapted to the blood-trough level (120-150 ng/mL) for six months. RESULTS: After a mean follow-up time of 477 +/- 263 days 4 patients of the basiliximab group showed corneal immune reactions (2 irreversible), while no side effects were observed. In the CSA group 2 immune reactions occurred (1 irreversible). In 2 CSA-treated patients the CSA administration had to be stopped due to side effects. CONCLUSIONS: Basiliximab has a lower efficacy in preventing immune reactions after risk keratoplasty than CSA. However, the side effect profile of basiliximab is more favourable than that of CSA.

[Corneal melting after cross-linking and deep lamellar keratoplasty in a keratoconus patient]. / Hornhauteinschmelzung nach Cross-Linking und tiefer lamellärer Keratoplastik ("DALK") bei Keratokonus.

We present the case of a 45-year-old patient with severe atopic disease and keratoconus who suffered from corneal melting following cross-linking and deep anterior lamellar keratoplasty (DALK) due to subclinical infection with Herpes simplex virus (HSV). Penetrating keratoplasty and intensive antiviral and immunosuppressive medical treatment were necessary to control the infection. The case demonstrates the difficulties in the treatment of keratoconus in patients with severe atopic disease.

[Steam cautery of the cornea in microbial keratitis]. / Dampfkauterisation der Hornhaut bei mikrobieller Keratitis.

In some cases topical antimicrobial treatment of microbial keratitis or corneal ulcers remains unsuccessful, with increasing infiltration of the corneal stroma. In this situation the steam cautery procedure developed by Karl Wessely in 1911 can lead to rapid healing of the inflammatory process, avoiding further corneal surgery. In this article we describe the steam cautery technique and discuss its indications for microbial keratitis.

[Penetrating keratoplasty with intrastromal corneal ring. A prospective randomized study]. / Perforierende Keratoplastik mit intrastromalem Hornhautring. Eine prospektive randomisierte Studie.

BACKGROUND: The purpose of the study was to evaluate the efficacy and safety of Krumeichs' intrastromal corneal ring following penetrating keratoplasty. Postoperative astigmatism and occurrence of complications were the main criteria of this study. MATERIAL AND METHODS: A total of 20 patients were included in this prospectively randomized study (10 patients with and 10 patients without corneal ring). Follow-up examinations were performed 6 weeks, 4, 12, and 18 months postoperatively, including best corrected visual acuity and Orbscan corneal topography. RESULTS: The mean follow-up time is currently 18.9+/-2.8 months. The mean astigmatism (Orbscan) is 3.9 D in the group with ring and 4.0 D in the group without a ring. Spontaneous suture rupture occurred in five patients with corneal ring. CONCLUSIONS: The use of the intrastromal corneal ring following penetrating keratoplasty caused no reduction of postoperative astigmatism. The reason for the spontaneous suture ruptures is unclear.

[Intracameral application of corticosteroids for treating severe endothelial rejection after penetrating keratoplasty]. / Intrakamerale Applikation von Kortikosteroiden zur Therapie der schweren endothelialen Abstossung nach perforierender Keratoplastik.

Immune reaction is the main cause for graft failure following penetrating keratoplasty. Endothelial immune reaction is the most frequent and most dangerous subtype of rejection because destruction of the graft endothelium can lead to graft failure. "Acute" endothelial rejection is treated by administration of topical and systemic steroids. Intracameral application of corticosteroids by means of an anterior chamber flush is an adjunctive measure that can stop the immune reaction immediately. This measure is thus recommended in all intermediate and severe endothelial rejections.

The new malononitrilamide immunosuppressant FK778 prolongs corneal allograft survival in the rat keratoplasty model.

PURPOSE: Aim of this study was to prove the efficacy and safety of the new malononitrilamide immunosuppressive FK778 in prolonging clear graft survival following allogeneic orthotopic keratoplasty in rats. METHODS: Sixty-seven penetrating keratoplasties were performed using Fisher and Lewis rats as donors and recipients, respectively: group 1 (n=11), allogeneic control without therapy; group 2 (n=12), syngeneic control; group 3 (n=11), mycophenolate mofetil (MMF) 40 mg/kg bodyweight; group 4 (n=12), FK778 5 mg/kg bodyweight; group 5 (n=12), FK778 10 mg/kg bodyweight; and group 6 (n=9), FK778 20 mg/kg bodyweight. Four animals in each group were killed for immunohistological evaluation on day 14. Therapy was administered orally for 18 days. The grafts were evaluated every three days by means of a scoring system including opacity, oedema, and vascularization. Time to rejection was analysed with the Kaplan-Meier survival analysis and compared with the log-rank test. The densities of infiltrating immune cells were compared statistically using the non-parametric Mann-Whitney test. RESULTS: Mean rejection-free graft survival was 11.4 days in group 1 (allogeneic control), 100 days (total follow-up time) in group 2 (syngeneic control), 24.0 days in group 3 (MMF 40 mg/kg), 15.7 days in group 4 (FK778 5 mg/kg), 19.1 days in group 5 (FK778 10 mg/kg), and 25.4 days in group 6 (FK778 20 mg/kg) (P<0.005). CONCLUSIONS: Systemic immunosuppression with FK778 prolongs graft survival in the rat keratoplasty model. FK778's efficacy is comparable with that of MMF in preventing immunologic graft rejection.

[Systemic immunosuppressives after penetrating keratoplasty]. / Systemische Immunsuppressiva nach perforierender Keratoplastik.

Immunologic rejection is the main cause of corneal graft failure. If corneal transplantation is performed in a high-risk situation without the use of systemic immunosuppression, corneal graft failure has to be expected in over 50% of patients within the first postoperative year. The clonal expansion of graft-specific lymphocytes occurs in lymphoid tissues. As topical steroids do not reach the secondary lymphoid organs, and even systemic steroids do not interfere sufficiently with the clonal expansion of activated T cells, it is essential to administer systemic immunosuppressives in order to achieve clear graft survival. As corneal transplantation is not a life-saving procedure, the profile of side-effects is a central issue when choosing an immunosuppressive medication.

[Topical immunosuppressives after penetrating keratoplasty]. / Lokale Immunsuppressiva nach perforierender Keratoplastik.

Topical steroids are routinely used in the postoperative treatment following penetrating keratoplasty. Due to the known side effects such as steroid-response glaucoma, cataract, and surface disorders, a broader armamentarium of topical immunomodulating drugs with comparable efficacy, better tolerance and less side effects is desirable. Cyclosporine A and FK506 eye drops are a promising alternative. A new approach involves subconjunctival drug delivering implants and locally applied antiangiogenic substances, which still have to be tested in clinical studies.