[Ligneous conjunctivitis]. / Conjunctivitis lignosa.

CASE REPORT: We report the case of a 3-year-old female patient with therapy refractive recurrent conjunctivitis and membrane formation of the upper eyelid. After surgical removal the histological examination showed an image compatible with ligneous conjunctivitis. A manifest serum plasminogen deficiency (22 %) supported the diagnosis. TREATMENT: The treatment with corticosteroids, heparin-containing and fresh frozen plasma (FFP) eye drops, renewed surgical ablation with perioperative intravenous FFP administration and local cyclosporine A eye drops achieved a stable condition with low disease activity. CONCLUSION: The combination of these therapy approaches has been performed here for the first time and has not been described in the literature so far.

[The German Acanthamoeba keratitis register: Initial results of a multicenter study]. / Das Deutsche Akanthamöbenkeratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. PATIENTS AND METHODS: Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. RESULTS: Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 ± 4.0 months (range 0-23 months). A triple therapy with Brolene® Lavasept® and antibiotic eye drops at least 5 ×/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 ± 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 ± 5/25) and without (5/32 ± 5/25) keratoplasty. CONCLUSION: Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases (berthold.seitz@uks.eu), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease.

[Expression of matrix metalloproteinase-19 in the human cornea. Wound healing in the MMP-19 knock-out mouse model]. / Expression von Matrixmetalloproteinase-19 in der humanen Kornea. Untersuchungen zur kornealen Wundheilung im MMP-19-knock-out-Mausmodell.

BACKGROUND: At present there are no data in the literature on the expression of matrix metalloprotein-19 in the human cornea. The aim of this study was to analyze the expression of matrix metalloproteinase-19 in the human cornea and to investigate its potential role in corneal wound healing using a MMP-19 knock-out mouse model. METHODS: A method with Western blotting and immunohistological staining for MMP-19 was performed using paraffin embedded human corneas. Excimer laser keratectomy was performed in wild type (wt) and MMP-19 knock-out (ko) mice and the rate of re-epithelialization was analyzed after 8 h and 18 h. RESULTS: MMP-19 was strongly expressed in the human corneal epithelium mainly in the basal cell layer. MMP-19 was not expressed in the corneal stroma. In the mouse model the size of the corneal lesion after 8 h was 83% (wt) and 89.9% (ko) of the initial area (p=0.09). After 18 h the lesion was 17% (wt) and 13.3% (ko) of the initial area (p=0.01). Laminin-5 was expressed in the migrating epithelial cells with no differences between wild type and knock-out mouse. CONCLUSION: MMP-19 showed a strong expression in the basal cells of the human corneal epithelium. Corneal re-epithelialization was slightly faster in the MMP-19 knock-out mouse. No differences in the expression of laminin-5 could be detected.

[Imaging techniques in the evaluation of primary large vessel vasculitides: Part 2: duplex ultrasound, positron emission tomography, computed tomography, and ophthalmological methods]. / Bildgebende Techniken zur Diagnostik primärer Grossgefässvaskulitiden : Teil 2: Duplexsonographie, Positronenemissionstomographie, Computertomographie und ophthalmologische Diagnostik.

This article focuses on the clinical application and technical aspects of imaging methods which are used alternatively or additionally to angiography or magnetic resonance imaging in patients with Takayasu's arteritis or giant cell arteritis. Providing a high spatial resolution, duplex ultrasound is particularly suitable for the evaluation of peripheral arteries. With the exception of cranial arteries, positron emission tomography as a whole body examination is the best imaging modality for the assessment of inflammatory activity. Computed tomography is used for angiographic examinations and enables evaluation of wall thickening in large arteries. It is the method of choice in the case of emergencies due to aortic aneurysm or dissection. In addition to angiographic and ultrasound techniques, ophthalmological methods comprise biomicroscopy, including funduscopy and optical coherence tomography.

[Acute retinal necrosis: Clinical features and therapy options]. / Akute retinale Nekrose : Klinik und Therapieoptionen.

Varicella zoster virus is the most frequent cause of acute retinal necrosis (ARN) followed by herpes simplex virus. Retinal ischemia and optic nerve atrophy are the main causes of the frequently poor final visual outcome in severe cases of ARN. The clinical diagnosis of ARN should be made as early as possible. Acyclovir should be administered intravenously due to its unreliable oral bioavailability. Systemic corticosteroids should be applied to suppress tissue damage caused by the host's inflammatory response. Severe cases of ARN should be treated by early vitrectomy with diagnostic vitreous biopsy, intravitreal aciclovir lavage, intraoperative laser retinopexy and silicone oil tamponade. The role of prophylactic laser retinopexy for prevention of secondary retinal detachment remains to be determined. The cause of different degrees of severity of ARN is unknown. The degree of severity of ARN is probably an independent predictor of the functional outcome.

[Acute retinal necrosis from the virologist's perspective]. / Akute retinale Nekrose aus Virologensicht.

Acute retinal necrosis occurs in approximately one per million persons per year and is caused in approximately 70% of the cases by the varicella zoster virus or in about 30% of the cases by herpes simplex virus. The early diagnosis is primarily based on virus-specific polymerase chain reaction in fluid from the anterior chamber or vitreous humor and can be supported by the determination of specific antibody titers from fluid and serum. Virus detection provides the basis for early causative therapy which limits disease progression and risk of complications. Retinal infections by varicella zoster virus or herpes simplex virus are treated with aciclovir, ganciclovir, or famciclovir. Ganciclovir and valganciclovir are used for the therapy of retinal cytomegalovirus infections. In the case of resistance development, foscarnet or cidofovir are available as second line antiviral drugs. The early use of specific antiviral agents is a crucial prerequisite for optimized therapy of acute retinal necrosis.

[Imaging techniques in the evaluation of primary large vessel vasculitides: part 1: angiography, interventional therapy, and magnetic resonance imaging]. / Bildgebende Techniken zur Diagnostik primärer Grossgefässvaskulitiden: Teil 1: Angiographie, interventionelle Therapie und Magnetresonanztomographie.

Imaging methods have become indispensable for the diagnosis and follow-up of giant cell arteritis and Takayasu's arterititis, in addition to physical examination and laboratory parameters. The choice of method is predominantly determined by clinical presentation and localization of the vascular territory to be examined. Furthermore, aspects of radiation protection, contrast media intolerance and other contraindications, as well as the varying costs of the different procedures need to be considered. This article reviews the clinical and morphological features of primary large vessel vasculitides which are fundamental to the identification of the disease and the assessment of inflammatory activity using imaging modalities. Angiography is the gold standard for the evaluation of stenotic lesions and can be combined with interventional treatment. Vessel wall thickening as a defining diagnostic criterion is outlined only by cross-sectional imaging. In addition to MR angiography, MRI techniques in particular enable vizualization of inflammatory processes in central as well as in peripheral arteries.

[Typical questions from the rheumatologist to the ophthalmologist and cooperating radiologist]. / Typische Fragen aus der Rheumatologie an den Augenarzt und den kooperierenden Radiologen.

Patients with rheumatic disorders may suffer from various acute or chronic ocular symptoms. In addition to pain and motility disorders, loss of vision, and irreversible deterioration of the eye may occur. Red eye, a symptom easily identified, can be a sign of rheumatic involvement, but can also have a variety of other causes. Dry eye is frequently present in rheumatic patients. It is always important that infections and masquerade syndromes are ruled out in the differential diagnoses of any ocular inflammation. In cases of ocular inflammation the ophthalmologist should determine the diagnostic procedure on the basis of his clinical experience. Uveitis is a common complication of juvenile idiopathic arthritis depending on the subtype of arthritis. Patients with episcleritis rarely suffer from systemic inflammation, while inflammation is found in half of all cases of scleritis. Corneal ulceration should always be managed as an emergency case and, in addition to systemic medication, surgical intervention is often indicated. The degree of orbital or ocular involvement can be objectively monitored using modern imaging techniques. Medications against rheumatic inflammation may rarely result in ocular side effects, which should be detected early by the eye specialist.

[Atypical ocular toxoplasmosis with concomitant ocular reactivation of varicella-zoster virus and cytomegalovirus in an immunocompromised host]. / Atypische Toxoplasmose-Chorioretinitis mit begleitender Varizella-Zoster-Virus und Zytomegalovirus-Reaktivierung bei einem immunsupprimierten Patienten.

BACKGROUND: Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical. HISTORY AND SIGNS: A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia. THERAPY AND OUTCOME: Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy. CONCLUSIONS: The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.

Detection of Treponema pallidum in the vitreous by PCR.

BACKGROUND: Ocular involvement of syphilis still poses a clinical challenge due to the chameleonic behaviour of the disease. As the serodiagnosis has significant limitations, the direct detection of Treponema pallidum (TP) in the vitreous represents a desirable diagnostic tool. METHODS: Real-time polymerase chain reaction (PCR) for the detection of TP was applied in diagnostic vitrectomies of two patients with acute chorioretinitis. Qualitative verification of TP by real-time PCR and melting point analysis according to a modified protocol was ruled out. Patients underwent complete ophthalmological examination with fundus photographs, fluorescein angiography, serological examination, antibiotic treatment and follow-up. RESULTS: In two cases of acute chorioretinitis of unknown origin, real-time PCR of vitreous specimens of both patients provided evidence of TP and was 100% specific. Initial diagnosis of presumed viral retinitis was ruled out by PCR of vitreous specimen. Patients were treated with systemic antibiotics and showed prompt improvement in visual function and resolution of fundus lesions. CONCLUSIONS: With real-time PCR, detection of TP in the vitreous was possible and delivered a sensitive, quick and inexpensive answer to a disease rather difficult to assess. In cases of acute chorioretinitis, the use of PCR-based assays of vitreous specimens in the diagnostic evaluation of patients is advisable. Although syphilitic chorioretinitis is a rare disease, PCR should include search for TP, as diagnostic dilemmas prolong definitive treatment in a sight-threatening disease.

Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations.

OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) in patients with refractory Wegener's granulomatosis (WG). PATIENTS AND METHODS: Eight consecutive patients with active refractory WG were included. In all patients disease activity had persisted despite standard treatment with cyclophosphamide and prednisolone, as well as tumour necrosis factor alpha blockade 3 months before inclusion in the study. Patients had particular granulomatous manifestations like retro-orbital granulomata (n=5), nodules of the lungs (n=1), and subglottic stenosis (n=2). RTX was given intravenously every 4th week in combination with the standard treatment in five patients and with methotrexate in two others. Disease extent and activity were monitored clinically by interdisciplinary care, immunodiagnostics (ANCA serology, B cells by flow cytometry), and magnetic resonance imaging. RESULTS: Beneficial response and a reduction in disease activity were seen in three patients, two of whom went into complete remission. In three other patients, disease activity remained unchanged while the disease progressed in the remaining two patients. In all patients peripheral blood B cells fell to zero during treatment with RTX. cANCA titres remained unchanged in all except one patient. CONCLUSION: In this pilot study, B lymphocyte depletion was not associated with a change of the ANCA titres or obvious clinical improvement of refractory granulomatous disease in patients with WG. Further studies are needed to evaluate the role of RTX in WG.

[Prognosis of corneal transplantation after penetrating eye injury]. / Prognose von Korneatransplantationen nach Bulbusperforation.

BACKGROUND: The success of penetrating keratoplasty (PKP) after penetrating eye injuries is often worse than in keratoplasty with Fuchs' endothelial dystrophy. However, comparable investigations are rare. Therefore, we have retrospectively analyzed the results and complication rates of PKPs in patients who experienced penetrating eye injuries. PATIENTS AND METHODS: Between 1990 and 1997 forty-four patients who received a corneal transplant at Kiel University Eye Hospital after penetrating eye injury (study group S) were analyzed. 29 patients were re-examined (visual acuity testing, slit lamp microscopy, applanation tonometry, stereo testing, corneal TMS topography, keratometry, endothelial microscopy, perimetry, indirect retinoscopy, testing of the retinal visual acuity and probatory contact lens fitting). Postoperative follow-up ranged between 1 and 6 years (median 3 years). The results were compared to a group of corneal grafts performed in patients with Fuchs' endothelial dystrophy (K, n = 18 patients, 25 eyes, median follow-up 2.8 years). RESULTS: 38males and 6 women had had a bilateral visual acuity of 0.8 or better before the accident, except for three cases. At the time of eye injury the patients' age ranged from 4 to 76 years. The eye trauma was caused by splinters of metal (45 %), glass (20 %), wood (16 %) or stone (11 %). In 73 % of the cases the injury was confined to the anterior segment of the eye (S1). The posterior part of the eye was involved in 27 % (S2). BCVA of S before keratoplasty (KP) was 1/15 on average (K 0.2), at least one year after KP 0.25 (K 0.4); post KP S1 was better than S2 (p = 0.0234), and K better than S (p = 0.0009). In group S 29 patients received a graft at random because of a central corneal scar, 14 patients received an HLA-typed graft with 2.3 mismatches on average. 93 % of the grafts (41 patients) were clear at the last examination, 8 patients showed rejection episodes, half of them were reversible. 5 patients received a second graft because of an irreversible rejection or endothelial decompensation. BCVA improved by at least one line in 84 % in S (K 92 %). BCVA was unchanged after KP in 6.8 % (K 8 %). In 9.1 % of S BCVA after KP was worse (K 0 %). 32 out of 44 patients had a BCVA of 0.1 or better after the last check-up, 13 out of 44 patients presented with a BCVA of 0.5 or better (K40 %). 15 out of 29 patients separately tested showed stereopsis compared to 8 preoperatively in S. In 48 % of the patients studied stereovision could not be restored. 82 % of the patients suffered from topographical irregular astigmatism in S, the superficial geometry of recipient's cornea seems relevant for astigmatism of the graft. Frequent postsurgical complications consisted of secondary glaucoma (S 27 %, K 4 %), immunological rejections (S 18 %, K 0 %), and amblyopia (S 14 %, K 0 %). CONCLUSION: Compared to patients with Fuchs' dystrophy the results of grafting after eye injuries are significantly worse. This relates to BCVA, astigmatism, frequency of secondary glaucoma and graft rejection.

Distribution of TFF peptides in corneal disease and pterygium.

The central cornea of 10 cadavers and 33 patients suffering from keratoconus, herpetic keratitis, Fuchs' dystrophy and pterygium were analysed focusing on the expression of TFF peptides by means of reverse transcription polymerase chain reaction and immunohistochemistry. TFF1 and TFF3 transcripts were detected in healthy corneae as well as in pterygia. Only TFF3 mRNA was transcribed in keratoconus, Fuchs' dystrophy and herpetic keratitis. Immunohistochemistry revealed absence of all three TFF peptides in healthy corneae but production of TFF3 in each of the diseased corneae. In pterygia both TFF1 and TFF3 synthesis was detectable in goblet cells. The absence of TFF peptide production in the healthy cornea indicates that TFF3 secretion is induced in different corneal diseases by yet unknown stimuli. Here TFF3 synthesis can be interpreted as a protection mechanism, because all corneal diseases analysed are characterized by progressive tissue destruction. TFF1 and TFF3 production by goblet cells in pterygia is comparable to the healthy conjunctiva suggesting that TFF peptides do not play a significant role in the pathogenesis of pterygia.

[Pars plana vitrectomy in cystoid macular edema of different forms of chronic uveitis]. / Pars-plana-Vitrektomie bei zystoidem Makulaödem bei verschiedenen Formen der chronischen Uveitis.

BACKGROUND: Cystoid macular edema (CME) is a common complication in different forms of chronic uveitis. In spite of immunosuppressive and anti-inflammatory therapy, chronic or relapsing courses can occur which may have a negative impact on visual prognosis. Pars plana vitrectomy (PPV) is known to positively influence chronic uveitis. This retrospective study was performed to investigate the role of PPV in the therapy refractive uveitic CME. PATIENTS AND METHODS: PPV for CME was performed in eyes with CME in intermediate uveitis (IMU, n=42), chronic iridocyclitis in juvenile rheumatoid arthritis (CIC, n=14) and multifocal chorioretinitis (MFC, n=12). In none of the eyes had immunosuppressive and/or anti-inflammatory therapy or anti-edema treatment (e.g.acetazolamide) led to regression of the CME. After a postoperative follow-up period of 7 and 106 months all patients were re-examined. RESULTS: Postoperative complete or partial regression of CME was observed as follows: IMU: 25/42 (59.5%), CIC: 8/14 (57.1%),MFC: 5/12 (41.7%). A significant increase in visual acuity of 2 lines and more was observed in 50%,71.4% and 41.7% of eyes, respectively. In the long-term follow-up best functional results were achieved in eyes with IMU. CONCLUSIONS: Response to PPV was variable according to the type of underlying form of uveitis. The lowest success rate could be observed in eyes with MFC. Although the postoperative regression rate of CME was satisfactory in eyes with CIC, long-term visual acuity results were disappointing due to secondary complications of CIC in this young age group. Best results were achieved in patients with IMU (statistically not significant). A multicenter study in a larger series of patients is needed to investigate the exact role of PPV in different forms of chronic uveitis.