Giant Cell Arteritis. / Riesenzellarteriitis.

Giant cell arteritis (GCA) is the most common primary vasculitis and is associated with potential bilateral blindness. Neither clinical nor laboratory evidence is simple and unequivocal for this disease, which usually requires rapid and reliable diagnosis and therapy. The ophthalmologist should consider GCA with the following ocular symptoms: visual loss or visual field defects, transient visual disturbances (amaurosis fugax), diplopia, eye pain, or new onset head or jaw claudication. An immediate ophthalmological examination with slit lamp, ophthalmoscopy, and visual field, as well as color duplex ultrasound of the temporal artery should be performed. If there is sufficient clinical suspicion of GCA, corticosteroid therapy should be initiated immediately, with prompt referral to a rheumatologist/internist and, if necessary, temporal artery biopsy should be arranged. Numerous developments in modern imaging with colour duplex ultrasonography, MRI, and PET-CT have the potential to compete with the classical, well-established biopsy of a temporal artery. Early determination of ESR and CRP may support RZA diagnosis. Therapeutically, steroid-sparing immunosuppression with IL-6 blockade or methotrexate can be considered. These developments have led to a revision of both the classification criteria and the diagnostic and therapeutic recommendations of the American College of Rheumatologists and the European League against Rheumatism, which are summarised here for ophthalmology.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Clinicopathological Correlation of Microbial Keratitis and Ahead: Is There a Corneal Sepsis? / Zur klinisch-pathologischen Korrelation der mikrobiellen Keratitis und darüber hinaus: Gibt es eine korneale Sepsis?

Microbial, infectious keratitis is a relevant indication for penetrating keratoplasty. The requirement for transplantation results in histopathological examination of the entire thickness of the cornea. Although the clinical diagnosis is not always possible to confirm, pathology can support diagnostic evidence of clinical presentation and pathogenesis. This is achieved with multiple methods from cytology, histochemistry, immunohistology, molecular pathology and in rare cases electron microscopy. These allow tissue-based detection of previous and parallel diseases and the responsible pathogens. The failure of satisfactory clinicopathological correlation raises the question whether a suspected pathogen was not ultimately responsible for destroyed corneal tissue. The pathogenesis of keratitis requiring transplantation is not yet completely understood, also on the experimental level. The development of such a keratitis can lead to a clinical symptomatology which can be described as "threatening organ dysfunction", a term used in sepsis research. Considering recent literature, possible correlations between sepsis and microbial keratitis and their relation to histopathology are discussed.

Ten-Year Outcome of Glaucoma Drainage Device Surgery After Penetrating Keratoplasty.

PRECIS: In eyes with intractable glaucoma, drainage devices provide long-term control of intraocular pressure also after penetrating keratoplasty (PK). There is a high incidence of corneal graft failure. PURPOSE: To compare very long-term results of eyes with glaucoma drainage device (GDD) after PK. METHODS: We retrospectively reviewed medical records of all patients who underwent GDD placement after PK at our institution between 2001 and 2017. Forty eyes of 40 patients were studied. Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Corneal outcome was assessed by graft rejection, failure, and visual acuity. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean follow-up was 125.0±52.3 (median, 116.5) months. Twenty of 40 eyes had a follow-up of at least 10 years. The mean preoperative IOP was 34.0±8.3 (median, 32.0) mm Hg with 3.2±1.3 (median, 3.5) glaucoma medications. At last postoperative follow-up, the mean IOP decreased to 12.7±4.9 (median, 14.0) mm Hg with 1.0±1.2 (median, 0.0) glaucoma medications. GDD implantation successfully controlled glaucoma in 88%, 88%, 85%, 80%, 78%, 75%, and 70% of eyes, at 1, 2, 3, 4, 5, 7, and 10 years, respectively. At last follow-up 68% showed glaucoma success. The corneal grafts remained clear in 74%, 63%, 45%, 45%, 37%, 32%, and 26% of eyes at 1, 2, 3, 4, 5, 7, and 10 years, respectively. Only 7 corneal grafts (17.5%) remained clear at last follow-up. CONCLUSIONS: A GDD can successfully control intractable glaucoma even after a very long period of time also after PK. However, the survival of the corneal grafts is low.

SARS-CoV-2: Impact on, Risk Assessment and Countermeasures in German Eye Banks.

INTRODUCTION: Since the beginning of the COVID-19 pandemic there has been some debate regarding the risk of transmission through tissue transplantation and tissue banking processes. AIM OF THE STUDY: To analyze the changes that SARS-CoV-2 has caused regarding the harvesting of corneal donor tissue and eye bank activities in Germany. METHODS: A questionnaire was provided to 26 eye banks in Germany, consisting of questions about adaptations made in the screening of potential donors and the harvesting of corneal tissue following the pandemic spread of SARS-CoV-2. RESULTS: Eighteen eye banks actively reduced recruitment of donors and two banks ceased all activity. Additional diagnostic screening was performed in eight banks, using conjunctival swabs and/or nasopharyngeal swabs. In six eye banks, additional protective measures, such as FFP2 masks and/or facial shields, were implemented. Overall, a mean reduction in the number of obtained donor tissues of 17% was observed. DISCUSSION: Conjunctival and/or nasopharyngeal swabs of donors have been implemented by a minority. Reasons for not performing additional tests may be moderate sensitivity and lack of validation for postmortem use of RT-PCR testing. Also, the hazard of SARS-CoV-2 entering the corneal donor pool with subsequent transmission might be perceived as theoretical. Face shields provide a sufficient barrier against splash and splatter contamination but may be insufficient against aerosols. Additional face masks would provide support against aerosols, but it remains debatable if corneal harvesting can be considered an aerosol-producing procedure. In the future we expect to see changes in current guidelines because of a surge in scientific activities to improve our understanding of the risks involved with cornea donation in the COVID-19 pandemic, and because current practice may reduce the availability of donor corneas due to new exclusion criteria while the demand remains unchanged.

Long-term results of glaucoma drainage device surgery.

BACKGROUND: To evaluate long-term results of eyes with glaucoma drainage device (GDD). METHODS: We retrospectively reviewed medical records of all patients who underwent GDD placement at our institution between 2001 and 2014. A total of 110 eyes of 90 patients were studied. Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean follow-up was 78.3 ± 44.0 months. The mean preoperative intraocular pressure was 30.8 ± 6.9 mmHg with 3.5 ± 1.1 glaucoma medications. At last postoperative follow-up, the mean IOP decreased to 14.3 ± 5.4 mmHg with 1.6 ± 1.5 glaucoma medications. GDD implantation successfully controlled glaucoma in 86, 85, 81, 78, 79, 76 and 73% of eyes at 1, 2, 3, 4, 5, 7 and 10 years, respectively. At last follow-up IOP was successfully controlled in 67% of eyes. Clinical complications occurred in 56.4% of eyes during the follow-up period. CONCLUSIONS: A glaucoma drainage device can successfully control intractable glaucoma even after a very long period of time.

Open globe and penetrating eyelid injuries from fish hooks.

BACKGROUND: A few case reports have described accidental eye injuries caused by fish hooks. The severity of ocular injuries is dependent on the involved ocular structures. Severe ocular injuries due to fish hooks are rare. We describe open globe and penetrating eyelid injuries from fish hooks at the Baltic Sea. METHODS: Nine patients with traumatic ocular injuries caused by fish hooks were included. The following parameters were evaluated: severity of injury, best corrected visual acuity at admission and last follow-up, and surgical treatment. RESULTS: All nine patients were male. Age ranged between 7 and 51 years with a median of 13 years. Sixty-seven percent of the patients were children. Four of the nine patients were 9 years or younger. In 5 eyes (55%) the injury was limited to the eyelid. An open globe injury was found in 4 patients (45%). The mean follow-up was 16.7 ± 32.8 months. All patients required surgical treatment. The number of operations ranged from 1 to 3, with a mean of 1.4. At admission and last follow-up, patients with eyelid injuries showed a median best corrected visual acuity (BCVA) of logMAR 0.0. Patients with open globe injuries showed a median best corrected visual acuity of logMAR 1.5 at admission, and of logMAR 0.6 at last follow-up. CONCLUSIONS: Nearly half of the patients suffered severe penetrating injuries. Especially children misjudge the risk potential of fishing due to their lack of experience. Fishing glasses should be worn not only for UV protection, but also as injury prevention strategy.

Intravitreal injection of anti-Interleukin (IL)-6 antibody attenuates experimental autoimmune uveitis in mice.

PURPOSE: To evaluate the effect of an intravitreally applied anti-IL-6 antibody for the treatment of experimental autoimmune uveitis (EAU). METHODS: EAU was induced in female B10.RIII mice by Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund's adjuvant, boosted by Pertussis toxin. Single blinded intravitreal injections of anti-IL-6 antibody were applied 5-7days as well as 8-10days (3day interval) after EAU induction into the randomized treatment eye and phosphate buffered saline (PBS) into the fellow control eye. Clinical and fluorescein angiography scoring (6 EAU grades) was done at each injection day and at enucleation day 14. Enucleated eyes were either scored histologically (6 EAU grades) or examined by ELISA for levels of IL-6, IL-17 and IL-6 soluble Receptor (sIL-6R). RESULTS: Uveitis developed in all 12 mice. Clinical uveitis score was significantly reduced (p=0.035) in treated eyes (median 2.0, range 0-4.0, n=12) compared to the fellow control eyes (median 3.0, range 1.0-4.0, n=12). Angiography scores were reduced in 9/12 treated eyes and histological scores in 3/4 treated eyes compared to the fellow control eyes. Cytokine levels were determined in 8 mice, of which 4 responded to anti-IL-6 treatment and 4 did not respond. All mice responding to treatment had a significant reduction of IL-6 (p<0.01) and IL-17 (p=0.01) levels in treated eyes compared to the fellow control eyes. This difference was not seen in non-responding mice. CONCLUSIONS: Intravitreal anti-IL-6 treatment significantly attenuates experimental autoimmune uveitis in mice. EAU activity correlates with ocular IL-6 and IL-17 levels.

Reduction of GAPDH in lenses of Parkinson's disease patients: A possible new biomarker.

BACKGROUND: We previously showed that the protein pattern of lenses removed in cataract surgery differs between patients with Parkinson's disease and age-matched controls. In this study, we identified the protein reduced in abundance in the 34- to 37-kDa gel band. METHODS: During cataract surgery (phacoemulsification), we collected the rinsing fluid and lens particles from the eyes of PD patients and controls. Residual lens fragments in the supernatant of 3 PD patients and aged-matched controls were studied for protein profiles using liquid chromatography-mass spectrometry and Western blots. RESULTS: We identified glyceraldehyde-3-phosphate dehydrogenase by mass spectrometry as the protein reduced in abundance and verified this finding in Western blots. CONCLUSIONS: Glyceraldehyde-3-phosphate dehydrogenase has been implicated in PD development. The reduction of glyceraldehyde-3-phosphate dehydrogenase in the lenses of PD patients may be a new biomarker for PD and might also indicate an important role for this protein in PD development. © 2016 International Parkinson and Movement Disorder Society.

Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive Granulomatosis With Polyangiitis (Wegener's) Is a Clinically Distinct Subset of ANCA-Associated Vasculitis: A Retrospective Analysis of 315 Patients From a German Vasculitis Referral Center.

OBJECTIVE: To compare the phenotype, clinical course, and outcome of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-positive granulomatosis with polyangiitis (Wegener's) (GPA) to proteinase 3 (PR3)-ANCA-positive GPA and to MPO-ANCA-positive microscopic polyangiitis (MPA). METHODS: We characterized all MPO-ANCA-positive patients classified as having GPA by the European Medicines Agency algorithm who attended our center, in a retrospective chart review. A second cohort of patients with PR3-ANCA-positive GPA matched for age and sex was characterized. Patients with MPO-ANCA-positive MPA from a recently published cohort were also included in the analysis. All patients were diagnosed and treated according to a standardized interdisciplinary approach at a vasculitis referral center. RESULTS: Comprehensive data were available for 59 patients with MPO-ANCA-positive GPA, and they were compared to 118 patients with PR3-ANCA-positive GPA and 138 patients with MPO-ANCA-positive MPA. We observed a distinct phenotype in MPO-ANCA-positive GPA as compared to the other 2 cohorts. Patients with MPO-ANCA-positive GPA frequently had limited disease without severe organ involvement, had a high prevalence of subglottic stenosis, and had less need for aggressive immunosuppressive therapy (cyclophosphamide/rituximab). The patients with MPO-ANCA-positive GPA were also younger than the MPA patients and were predominantly female (significantly different than the MPA cohort). While GPA patients had higher survival rates compared to MPA patients (due to a high prevalence of pulmonary fibrosis in MPA), patients with MPO-ANCA had significantly lower relapse rates than those with PR3-ANCA. CONCLUSION: Patients with MPO-ANCA-positive GPA show significantly different clinical courses compared to those with PR3-ANCA-positive GPA or MPO-ANCA-positive MPA, which should be considered in their clinical management. Classification according to ANCA specificity may improve the evaluation of relapse risk.

Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort.

OBJECTIVE: To evaluate the clinical presentation and long-term outcome of a vasculitis centre cohort of patients with microscopic polyangiitis (MPA) with respect to organ manifestations, treatment, chronic damage and mortality. METHODS: We performed a retrospective chart review at our vasculitis referral centre. MPA patients admitted between 1991 and 2013 classified by a modified European Medicines Agency algorithm were diagnosed and treated according to a standardized interdisciplinary approach. RESULTS: Comprehensive data from standardized interdisciplinary workups was available for 144 patients (median follow-up 72 months). The overall standardized mortality ratio was 1.40 (95% CI 0.91, 2.07; P = 0.13). We observed a higher mortality [hazard ratio (HR) 4.04 (95% CI 1.21, 13.45), P = 0.02] in 17 patients with MPA-associated fibrosing interstitial lung disease (ILD) and 56 patients with peripheral nervous system involvement [HR 5.26 (95% CI 1.10, 25.14), P = 0.04] at disease onset. One hundred and fifteen patients (79.9%) responded to the initial treatment. Sixty-one (42.3%) achieved complete remission and 54 (37.5%) achieved partial remission. Twenty (13.9%) showed a refractory disease course. CONCLUSION: MPA patients at our tertiary rheumatology referral centre seemed to have a less severe phenotype resulting in a less severe disease course and better outcome than reported in other cohorts. Fibrosing ILD was significantly associated with mortality in this cohort.

Laser suture lysis after trabeculectomy with mitomycin C: analysis of suture selection.

OBJECTIVE: This paper analyses to what extent positioning and timing influences the degree of intraocular pressure (IOP) reduction by laser suture lysis (LSL) after trabeculectomy with mitomycin C. METHODS: The IOP reduction following LSL was assessed in a consecutive case series of 168 eyes (120 patients) after trabeculectomy with mitomycin C. Scleral flap sutures of 3.3±0.6 were placed on average. The IOP reduction was assessed in terms of suture positioning and the time of LSL. RESULTS: LSL was performed early (<7 d) on 48 of 168 eyes (29%). The mean IOP before trabeculectomy was 22.1±5.9 and 20.3±6.2 mm Hg on the first postoperative day. LSL additionally reduced the IOP by 6.3±6.9 mm Hg. LSL was performed late (>7 d) on 27 of 168 eyes (16%). The mean preoperative IOP was 20.7±6.0 mm Hg, 12.1±7.8 mm Hg on the first postoperative day, and increased again to 21.7±4.5 mm Hg by the time of LSL. The IOP reduction achieved by LSL was 7.0±5.1 mm Hg. In a subgroup of 54 eyes with 3 scleral flap sutures, there was no significant difference in IOP reduction in a comparison of corner and central sutures (P=0.4). The reduction of IOP after LSL was not significantly correlated with the number of respectively remaining scleral flap sutures (P=0.17). There was no correlation between the time of LSL and IOP reduction (P=0.96). CONCLUSION: The reduction of IOP after LSL is not related to suture selection or the number of remaining scleral flap sutures.

Orbital masses in granulomatosis with polyangiitis are associated with a refractory course and a high burden of local damage.

OBJECTIVES: To identify and characterize patients with orbital masses in a monocentric cohort of 1142 GPA patients followed up from 1990 until the end of 2010 with regard to disease stage, local orbital inflammation, course of disease and outcome and to assess the efficacy of immunosuppressive treatment. METHODS: All GPA patients fulfilling ACR criteria or Chapel Hill Consensus Conference definitions or who had localized GPA and who developed orbital masses were evaluated regarding the course and outcome of the orbital masses (assessed by MRI, ophthalmologist and ENT specialist), all other clinical manifestations, disease stages, ANCA status, immunosuppression and its side effects and surgical procedures. RESULTS: Of 1142 GPA patients 58 developed orbital masses during a median follow-up of 101.5 months (range 23-255 months). Forty patients fulfilled the inclusion criteria and had complete clinical assessments [44% females, median age 43 (20-74) years, 85% ANCA positive]. Seventy-five per cent (29/40) had systemic disease when orbital masses occurred; both orbits were affected in 30%. Seventy-two per cent had evidence of infiltration from paranasal sinuses. Under highly potent immunosuppression (mostly CYC and glucocorticoids), 41% were refractory, 24% had unchanged activity, 24% showed a response and 8.1% had complete remission. Forty-four per cent had relapses of orbital masses. Seventy-two per cent developed visual impairment, 19% suffered blindness. Blindness was associated with a longer time to remission and a relapsing and refractory course. CONCLUSION: Orbital masses are a rare manifestation of GPA and are characterized by a refractory course and by a high rate of local damage. Patients with a refractory or relapsing course are at higher risk of developing blindness.

A vasculitis centre based management strategy leads to improved outcome in eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA): monocentric experiences in 150 patients.

OBJECTIVE: To evaluate a vasculitis centre based management strategy for eosinophilic granulomatosis and polyangiitis (Churg-Strauss, EGPA). METHODS: A retrospective cohort study at a vasculitis referral centre was performed. All EGPA patients admitted from 1990 to 2009 were included. A structured interdisciplinary work-up for proof of diagnosis, Disease Extent Index and Birmingham Vasculitis Activity Score was performed. Immunosuppressive therapy was initiated and regularly adapted. Treatment targets were induction and maintenance of remission according to definitions given by the European League Against Rheumatism and the European Vasculitis Study Group. Outcomes were mortality, rate of remission, relapses, adverse events and prednisolone-dose. RESULTS: Out of 269 patients with suspected EGPA 150 fulfilled the inclusion criteria. Of those, 104 had more than one follow-up visit resulting in a mean follow up of 53±4.9 months. By using additional data sources the follow-up concerning survival was extended to 92±5 month. Severe organ manifestations occurred at heart (46%), kidney (18%) and lungs (10%). Cyclophosphamide was used in 107 patients (71%). The prednisolone-doses of all patients were within the targeted range (i.e. ≤7.5 mg) in 69% of the total follow-up time; the median dose at end of follow-up was 5mg/d. The 10-year survival rate was 89% resulting in mortality comparable to the general population (SMR 1.29). Only patients with cardiac failure associated with EGPA had an increased mortality (SMR 3.06). CONCLUSIONS: Regular re-evaluation and target-orientated adaption of therapy may lead to normalization of life expectancy and attenuation of disease progression. Continued centre based interdisciplinary treatment should be standard of care.

Correlation of fundus autofluorescence, spectral-domain optical coherence tomography, and microperimetry in late deferoxamine maculopathy.

PURPOSE: To describe long-term functional and morphologic retinal changes by deferoxamine, a chelating agent used to treat systemic iron overload. METHODS: Ophthalmologic examination of acute deferoxamine maculopathy and follow-up of 5 years, using ophthalmologic examination, fluorescence angiography, electrophysiology, color vision testing, fundus image-correlated microperimetry, time-domain and spectral-domain optical coherence tomographies. The patient is a 53-year old woman who presented with acute visual deterioration to 20/50 in the right eye, 20/60 in the left eye, and reduced color vision. She had been treated with deferoxamine for 6 months. The diagnosis of deferoxamine maculopathy was made, and the drug discontinued immediately. RESULTS: After 5 months, visual acuity was 20/25 bilaterally, but mottling of the retinal pigment epithelium (RPE) had developed. Five years later, visual acuity was 20/20 in both eyes. Fundus autofluorescence showed progressively clumped hyper- and hypofluorescence with larger areas of total RPE atrophy in the left eye. Spectral-domain optical coherence tomography visualized areas of RPE thickening, photoreceptor outer segment elongation, outer retinal tubulation, and outer retinal and RPE atrophy. Fundus image-correlated microperimetry showed relative central scotomas at the beginning, some of which recovered to normal light sensitivity, while others deteriorated to absolute scotomas. CONCLUSION: Although visual acuity had recovered after cessation of deferoxamine, functional and morphologic residues remained, which included disturbed color vision, central microscotomas, and progressive RPE and outer retinal degeneration.

Multilayered Gore-Tex patch for temporary coverage of deep noninfectious corneal defects: surgical procedure and clinical experience.

PURPOSE: To evaluate the multilayer Gore-Tex patch as temporary coverage of deep, noninfectious corneal defects. DESIGN: Retrospective, interventional case series. SETTING: University Medical Center Schleswig-Holstein, Kiel, Germany. PATIENT POPULATION: Thirty-nine eyes of 38 patients with noninfectious, deep corneal defects. Underlying disorders included neurotrophic or immunologic ulcers in 37 eyes (94.9%) and traumatic defects in 2 eyes (5.1%). Intervention procedures: Corneal defects were covered with multiple Gore-Tex layers, of which the uppermost was sutured to the cornea. The Gore-Tex patch was kept in place until an appropriate corneal transplant was obtained and effective systemic immunosuppression was initiated. MAIN OUTCOME MEASURES: Long-term preservation of the eye, frequency of resuturing of the Gore-Tex patch, and best-corrected visual acuity. RESULTS: In 38 cases, the eye could be preserved. In 10 eyes, additional sutures were required. Before surgery, the mean best-corrected visual acuity (logMAR) was 1.14 ± 0.45 (20/250), and that at final follow-up was 1.13 ± 0.41 (20/250). The Gore-Tex patch remained in place 4 days to 32 months (mean, 6.4 ± 8.3 months) until corneal transplantation (27 eyes) or until an alternative way of defect coverage could be performed. Three eyes did not require further coverage after explantation of the Gore-Tex patch. In 6 eyes, either the Gore-Tex patch was kept in place or the patients died. CONCLUSIONS: Temporary coverage of deep corneal defects with multilayer Gore-Tex patches allows time until an appropriate corneal transplant is obtained. The technique is particularly useful in patients with underlying autoimmune disorders, because an effective systemic immunosuppression can be initiated before corneal transplantation.

Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades.

OBJECTIVE: To determine the long-term outcome in patients with Wegener's granulomatosis (WG) over 4 decades in an academic hospital unit specializing in rheumatology. METHODS: We included 290 patients, divided them into 2 cohorts, and compared them with the historical cohort of 155 patients. Comparisons were retrospective regarding disease manifestations, therapy, mortality, and incidence of malignancies. The historical cohort (cohort 1) included 155 patients diagnosed between 1966 and 1993, cohort 2 included 123 patients diagnosed between 1994 and 1998, and cohort 3 included 167 patients diagnosed between 1999 and 2002. RESULTS: Over time, the interval between first symptoms and diagnosis was reduced by half (from 8 months to 4 months). Organ manifestations were similar in the 3 cohorts, and more than 80% of patients still required cyclophosphamide (CYC); however, the median cumulative dose was reduced significantly (from 67 gm in cohort 1 to 36 gm in cohort 2 and to 24 gm in cohort 3). The standardized mortality ratios (SMRs) declined (from 2.1 in cohort 1 to 1.41 in cohort 2 and to 1.03 in cohort 3), with fewer deaths related to WG and/or therapy (86.4% in cohort 1, 76.9% in cohort 2, 50% in cohort 3), decreasing relapse rates (63.9% in cohort 1, 51.2% in cohort 2, 35.3% in cohort 3), and no increased rate of malignancies. Compared with young females, young males had a considerably higher SMR (8.87 [95% confidence interval 4.05-16.8]) and more frequent renal manifestations (54.4% versus 33.8%). CONCLUSION: Mortality of WG patients declined over the last 4 decades, probably due to improved diagnostic and therapeutic procedures and increased awareness of WG, which led to earlier diagnosis and therapy, reduction in relapse rates, and lower cumulative CYC dose with fewer deaths related to therapy.