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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.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.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.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.

Objective and design: To examine the effects of the nitric oxide synthase (NOS) inhibitors aminoguanidine (AG) and L-NAME on leukocyte adhesion in endotoxin-induced uveitis (EIU).¶Material: Uveitis was induced in Lewis rats (n = 124) by LPS injection (Salmonella typhimurium).¶Treatment: Rats either (1) did not receive any LPS or other treatments (controls), received (2) only subcutaneous saline injections with LPS administration, (3) a single s.c. dose of AG (100 mg/kg body weight) at the time of LPS administration, (4) a single s.c. injection of AG 8 h after LPS injection, (5) s.c. injections of AG at the time of LPS administration and 8 h after LPS injection or (6) received a single dose of L-NAME (75 mg/kg body weight) at the time of LPS administration.¶Methods: Intravital microscopy (IVM) of iris vessels was performed at 2, 4, 8, 16, 24 and 48 h after endotoxin injection. Aqueous humor analysis for protein concentration and cell count was performed after IVM.¶Results: At 2 h after the induction of uveitis, significantly more rolling leukocytes were detected in the AG and L-NAME-treated group than in untreated EIU (4.8 ± 0.31 and 9.83 ± 0.64 vs. 2.85 ± 0.37 %, mean ± SEM, p < 0.01). However, at 16 h the percentage of rolling leukocytes was significantly reduced in all groups which had received AG (LPS: 8.08 ± 0.37 %; LPS/AG 0h: 3.78 ± 0.25 %; LPS/AG 8 h: 5.34 ± 0.3 %; LPS/AG 0 + 8 h: 3.86 ± 0.31 %). L-NAME enhanced leukocyte rolling even at 24 h after LPS (12.38 ± 0.64 %). Early treatment of EIU with AG significantly reduced the number of sticking leukocytes at 4, 8 and 24 h (306 ± 13 vs. 571 ± 41, 228 ± 12 vs. 345 ± 19 and 240 ± 14 vs. 469 ± 23 cells/mm2, respectively). L-NAME inhibited LPS-induced sticking of leukocytes at all observed time points and this effect was most pronounced at 24 h (147 ± 10 vs. 469 ± 23 cells/mm2).¶Conclusions: In EIU, administration of AG or L-NAME causes enhanced leukocyte rolling in the early inflammatory response. However, firm adhesion of leukocytes to the vascular endothelium decreases and this effect prevails, ameliorating leukocyte infiltration.

The commercially available interferon gamma release assays T-SPOT.TB and QuantiFERON-TB Gold/QuantiFERON-TB Gold In-Tube may be important, besides the direct detection with culturing, PCR or the Mantoux skin test, for the diagnosis of tuberculosis as a possible cause of uveitis. It is important to know the limitations of these tests to get a fast and reliable diagnosis which may necessitate initiation of causative treatment of the tuberculosis to prevent further damage to the eye and to avoid multi-drug resistant tuberculosis strains.

Eye involvement is a frequent finding in patients with rheumatoid arthritis and may represent the leading clinical manifestation of disease. In this context, all components of the visual organ might be affected. The main spectrum of eye involvement comprises keratoconjunctivitis sicca, episcleritis and scleritis as well as ulcerative keratitis. As with the underlying disease, autoimmune reactions based on a patient's genetic predisposition are assumed to be of significance in disease pathogenesis. Emerging evidence also points to additional morphological and physiological ocular characteristics in the pathogenesis of the various ocular pathologies. This article gives an overview of clinical aspects, pathogenetic background as well as therapeutic options for ocular involvement in rheumatoid arthritis.

Several studies investigating the antibiotic prophylaxis of acute postoperative endophthalmitis provide very different results concerning the incidence and prophylaxis of this very severe complication of cataract surgery. For a long time the preoperative use of povidione-iodine had been the only procedure with overall acceptance and proven benefit. Following findings in Sweden that supported the advantages of the use of intracameral cefuroxime, the European Society of Cataract and Refractive Surgeons (ESCRS) performed a study to confirm the Swedish results and to lead to a revision of ESCRS guidelines.In a randomised, partially masked and placebo-controlled study 16,211 patients undergoing phacoemulsification cataract surgery were included. 25 ophthalmological units in 9 European countries took part in this study. The study consists of a 2 x 2 factorial design, dividing patients into 4 treatment groups. Two out of the 4 groups were treated with 1 mg intracameral cefuroxime (in 0.1 mL isotonic NaCl solution). In parallel, two groups (one treated with cefuroxime, one untreated) received topical levofloxacin 0.5% in a standard regimen. If clinical signs like pain or loss of vision indicated a postoperative endophthalmitis, suspicious results were confirmed by culture, Gram stain and PCR. In a follow-on study, Sundelin (Sweden) and colleagues included 30 patients who received topically-applied levofloxacin 0.5% following the ESCRS dosing scheme, in addition to intracameral administration of cefuroxime. Aqueous humour samples were taken at the end of surgery and at a second time point postoperatively. The levofloxacin concentration was measured by HPLC. The median maximal concentration (Cmax) was compared with the MIC90-values of relevant bacterial isolates.29 patients developed a postoperative endophthalmitis, of whom 20 were classified as having a proven infectious cause. The absence of a prophylactic intracameral cefuroxime administration at 1 mg in 0.1 mL isotonic NaCl was associated with a 4.92-fold increase in the risk of postoperative endophthalmitis (95% CI 1.87-12.9). A clear corneal incision (CCI) or the use of silicon based IOL optic material accounted as additional risk factors for postoperative endophthalmitis. While the use of CCI was associated with a 5.88-fold higher risk of infection compared to STI (scleral tunnel incision), the implantation of silicon based IOL was associated with a 3.13-fold higher risk. Intraoperative complications were also associated with a higher risk of postoperative endophthalmitis (4.95-fold higher risk).Intracameral injection of cefuroxime reduces the risk of postoperative infectious endophthalmitis following phacoemulsification cataract surgery. Additional risk factors are the use of CCI and silicon based IOL implants.

Mycophenolate mofetil (MMF) has gained acceptance as an immune modulatory agent in the treatment of autoimmune disorders such as uveitis. It represented a major advance, although optimal use may be limited, in particular, by gastrointestinal (GI) side effects in up to 50 % patients. This prospective study was undertaken to evaluate the effect of conversion from mycophenolate mofetil (MMF) to an enteric-coated mycophenolate sodium (EC-MPS).Within a cohort of 143 patients treated with MMF we prospectively followed 19 individuals who developed gastrointestinal side effects. Because of limited treatment alternatives, conversion to an enteric-coated mycophenolate sodium (EC-MPS) was undertaken. A standardised questionnaire (GSRS) was completed by each patient regarding GI adverse events, at predefined intervals during the study.The spectrum of underlying disorders included uveitis (n = 16) and ocular cicatricial pemphigoid (n = 3) that were initially treated with MMF (1000 mg BID). All patients could be kept on EC-MPS treatment and followed with a mean follow-up of 44 weeks (median +/- 12). The maximum of scores on GSRS was reached at baseline (conversion to EC-MPS) in all but 3 patients. However, GSRS scores improved significantly between baseline and visit 4 (3 months) and remained stable further on (p0.03). In all but one (uveitis) patient the underlying disorders were under control demonstrating the similar efficacies of MMF and EC-MPS treatments.The use of EC-MPS appears to be a valid treatment option in ocular autoimmune disorders. In particular. patients with gastrointestinal problems may profit from a significantly reduced frequency of adverse events.

The object of this work was a comparison of confocal images of corneal dystrophies made by a slit scanning microscope versus a laser scanning microscope.Using the Rostock Cornea Modul-HRT II as a confocal laser scanning microscope the images of five patients with some epithelial, stromal and endothelial corneal dystrophies were acquired. The pictures were compared qualitatively with those taken by the slit scanning microscope "ConfoScan P2" from corresponding pathologies. Also, the images of normal corneas of ten healthy persons were acquired for a qualitative comparison.Confocal images from both devices were able to provide significant helpful diagnostic findings about the corneal microstructure. Essential qualitative differences between the images of both devices used were not observed. Due to the additional hardware components and the software module for image acquisition, analysis and archiving, the RCM-HRT II is favoured over the "ConfoScan P2". Nevertheless, the evaluation in favour of the RCM-HRT II has to be confined because an optimised, user-friendly enhancement, the "ConfoScan 4" is currently available.Evaluating corneal dystrophies in vivo, an equivalent utility of both technical approaches has been observed.

Uveitis is a frequent and potentially vision-threatening manifestation of juvenile idiopathic arthritis (JIA). There are only a few population-based studies providing data on the frequency and severity of uveitis.Documentation of patients with JIA was collected in a national database. An analysis of the paediatric rheumatologic and ophthalmologic data collected from all patients that were included in 2002 was performed.Uveitis was documented in 12 % of a total of 3271 JIA patients: extended oligoarthritis (25 %), persistent oligoarthritis (16 %), seronegative polyarthritis (4 %), seropositive polyarthritis (2 %), psoriatic arthritis (10 %), enthesitis-related arthritis (ERA) (7 %), systemic arthritis (1 %), other arthritis forms (11 %). Ophthalmologic data were available from 115 uveitis patients (28 %). Mean age at onset of uveitis was 5.2 (SD 3.2) years. JIA patients with uveitis were significantly younger at onset of arthritis (3.8 vs. 7.0 years), and were more often girls (74 vs. 63 %) or ANA-positive (86 vs. 42 %) than the patients without uveitis. Uveitis complications were present in 45 % at initial presentation of uveitis. After a mean duration of 5.6 years, complications were noted in 56 %, and included band keratopathy (29 %), posterior synechiae (27 %), cataract (26 %), glaucoma (8 %), and macula oedema (6 %). Final visual acuity was less than 20/50 in 31 % and less than 20/200 in 12 % of eyes. In patients with uveitis, immunosuppressive or immunomodulatory drugs were used significantly more often than in patients without uveitis (75 % vs. 43 %).The nationwide data documents the spectrum of uveitis in patients with JIA, the complications and the therapy for uveitis. The high rate of uveitis complications at the time of diagnosis points out the need for early ophthalmologic screening and therapy, and for a close collaboration between ophthalmologist and paediatric rheumatologist.

Interferons are a complex group of glycoproteins with antiviral, antiproliferative and immunomodulatory activity. They are used to treat different types of human neoplasms and chronic hepatitis C. Several case reports have described interferon-induced ocular side effects since the first case in 1990.We report about a 61-year-old female undergoing interferon 2alpha treatment who developed bilateral retinopathy during systemic therapy and provide a summary about ocular side effects and their consequences.Patients should be monitored by ophthalmologists before, during and after interferon therapy in order to avoid side effects like retinal neovascularisation and to prevent potential serious side effects.

The diagnosis of the multisystemic Vogt-Koyanagi-Harada (VKH) syndrome including ocular, neurological and dermatological manifestations is difficult due to the absence of diagnostic serological parameters and the variable onset of clinical signs and symptoms in the course of the disease.A 12 year old female patient was admitted to our clinic , presenting with bilateral choroiditis, vitiligo and episodes of headache. After having ruled out an underlying rheumatological or infectious disease, a VKH syndrome was suspected and effectively treated with systemic steroids. The initial diagnosis of VKH syndrome would not have been possible, if the existing diagnostic criteria had been applied.As can be seen in the case of our patient, the existing diagnostic criteria of VKH syndrome may prove to be inadequate in diagnosing VKH syndrome, particularly at the onset of the disease. Considering, that early diagnosis and treatment is crucial in improving the outcome of the disease, current diagnostic criteria have been revised. Recent retrospective data suggest a higher sensitivity for the revised diagnostic criteria.

Children with juvenile chronic arthritis are at risk to develop intraocular inflammation depending on the type of arthritis. The pathogenic mechanisms are unclear; however, an association with antinuclear antibodies is well known. In particular young girls with oligoarticular onset of arthritis are affected most often. Regular ophthalmologic examinations should allow early diagnosis and effective therapy. Complications such as synechiae, cataract, or macula edema are seen especially in uveitis patients with late diagnosis and insufficient anti-inflammatory therapy. Better therapeutic regimens have led to a better overall prognosis of intraocular inflammation in recent years.

Cyclosporine (CsA) is a widely used drug in the treatment of posterior uveitis. Whereas treatment with CsA has considerably improved the visual prognosis of uveitis patients, the therapeutic benefits of CsA are partially outweighed by its adverse effects, most notably nephrotoxicity and hypertension. Recently, monitoring the CsA 2-h postdose level (C(2)) has been recommended as the most sensitive assay and predictor of clinical outcome in transplantation.This prospective clinical trial included 15 patients with posterior uveitis who received oral CsA (5 mg/kg BW b.i.d.). The relationship of C(2) to C0 blood levels was analyzed and correlated with clinical safety and efficacy.A high intrapatient and interpatient variability was observed regarding the C0 values depending on several factors including comedication and intestinal resorption. C(2) values corresponded to control measurements of intraocular inflammation.C(2) monitoring offers a simple and accurate alternative for clinical monitoring of CsA. It allows the dose of CsA to be individualized effectively for each patient.

The diagnosis of ocular toxocariasis can be difficult and the aim of this study was to evaluate the benefit of ELISA testing of vitreous body fluid.We present five consecutively treated patients with ocular symptoms of toxocariasis, three of these patients presenting with epiretinal membranes and subretinal granulomas were vitrectomized. Vitreous and body fluid and serum were tested for toxocara antibodies by ELISA. Moreover vitreous body fluid of 10 patients with epiretinal membranes of other origins were examined by the same ELISA.In all three operated patients toxocara antibodies were detected in the vitreous fluid but ELISA testing of serum samples was negative in two of the three patients. Visual acuity increased or remained stable in the operated patients. The ELISA test was negative in all vitreous fluid samples of the control group.ELISA testing of vitreous body fluid can prove the presence of toxocara infection when no systemic signs of infection are present and no antibodies are detectable in the serum. Well-timed vitrectomy is a suitable therapy for vitreo-retinal complications in ocular toxocariasis to improve prognosis and to confirm the diagnosis.

In corneal recipients with herpes infection, acyclovir given for 1 year postoperatively prevents viral reactivation and improves graft outcome. The indication for prophylactic antiviral therapy relies on the preoperative diagnosis of herpes. However, many patients present with corneal scars featuring sequelae of herpes without a proven history of herpes. Here we report the results of a prospective study of anti-herpes simplex virus (anti-HSV) and varicella zoster virus (VZV) antibody testing in the aqueous humor at the time of corneal transplantation to refine the indication of the antiviral treatment.The study involved 33 keratitis corneal graft recipients, 21 of whom had documented herpes keratitis. A control group was made with 11 cataract patients. An anterior chamber puncture was performed just before surgery. The micro-ELISA test was done on both aqueous humor and serum, and local anti-HSV or VZV antibody synthesis was acknowledged if the ratio of antibody concentrations was above 4.Local antibody synthesis to HSV was detected in 22 cases, to VZV in 9 cases, to both HSV and VZV in 6 cases, and no synthesis in 8 cases. The sensitivity of the test was 65% in patients with a documented history of herpes (14 cases out of 21). Among non-herpetic patients, the test was positive in 9 patients, who thus benefited from postoperative antiviral therapy. No viral reactivation was encountered after a minimum follow-up of 1 year.Antibody testing in the aqueous humor at the time of keratoplasty is a convenient, inexpensive diagnostic tool in corneal recipients. It provides useful information before prescribing a long and expensive postoperative antiviral therapy.

Objective: To compare the efficacy, tolerability and local tolerance of diclofenac sodium 0.1% containing hydroxypropylgamma cyclodextrin preserved with benzalkonium chloride 0.005% (Voltaren® Ophtha CD),1 with that of diclofenac sodium 0.1% preserved with thiomersal 0.004% (Voltaren® Ophtha) in the treatment of inflammation after cataract-intraocular lens surgery. Design and setting: Randomised 2 : 1, double-masked, parallel-group study in six centres in Germany. Study participants: 299 patients scheduled to undergo phacoemulsification with posterior chamber intraocular lens implantation. Interventions: Study medications were instilled four times in the 30 minutes before surgery and four times daily from the first postoperative day. Main outcomemeasures: The key efficacy variable was the reduction in anterior chamber flare (photons/millisecond) from day 1 to day 6 to 8. Patients underwent comprehensive ocular examinations, including laser flaremetry (KOWA), preoperatively and postoperatively at days 1, 6 to 8 and 24 to 32. Results: 268 patients (Voltaren® Ophtha CD 177, Voltaren® Ophtha 91) completed the day 6 to 8 visit without any protocol violations. Reduction in the degree of intraocular inflammation with Voltaren® Ophtha CD was equivalent to that achieved with Voltaren® Ophtha at the day 6 to 8 [95% confidence interval (CI) −3.07 to +0.54] and day 24 to 32 (95% CI −1.44 to +1.40) visits. Although there was no significant (p = 0.464) difference between the two study groups in patients’ global assessment of local tolerance at day 24 to 32, ocular discomfort was significantly (p = 0.023) less with Voltaren® Ophtha CD compared with Voltaren® Ophtha. Conclusions: Voltaren® Ophtha CD was as effective and well tolerated but had less ocular discomfort compared with Voltaren® Ophtha in the treatment of ocular inflammation after phacoemulsification with intraocular lens implantation. This new formulation of diclofenac sodium 0.1% may be used as an alternative to the existing formulations of ophthalmic diclofenac sodium 0.1%.

To study the role of macrophages in experimental melanin-induced uveitis (EMIU), we used the method of intravital microscopy to analyse changes in leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with liposomal clodronate.EMIU was induced in Lewis rats (n = 48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated with liposomal clodronate (DMDP-lip) or empty liposomes on days -2, +1, 4, 6 and 8. Using IVM, postcapillary iris venules of rats were examined to quantify leukocyte rolling and firm adhesion to the vascular endothelium.Depletion of macrophages caused a decreased percentage of rolling leukocytes on day 8 (2 +/- 1.1% vs 15.2 +/- 1.6%, DMDP-lip vs EMIU, mean +/- SEM, ANOVA, p0.05) and day 10 (2.6 +/- 0.3% vs 14.2 +/- 1.6%). A significant decline in the number of firmly adherent leukocytes was detected on days 8 and 10 (88 +/- 13/mm2 vs 175 +/- 18/mm2 and 129 +/- 13/mm2 vs 372 +/- 31/mm2, DMDP-lip vs EMIU). Treatment with empty liposomes showed no changes in leukocyte firm adhesion.Elimination of macrophages prevents the induction of EMIU. In autoimmune-mediated uveitis, macrophages play a crucial role in the initiation of leukocyte-endothelium interaction.

The diagnosis of ocular toxoplasmosis is mainly based on ophthalmological examination but might be difficult to establish in some cases. The purpose of our study was to evaluate the value of aqueous humor and serum analysis in ocular toxoplasmosis.We analyzed the avidity of toxoplasma-specific IgG in aqueous humor and serum samples from 50 patients with toxoplasmic retinochoroiditis, with 25 patients with uveitis posterior or panuveitis serving as controls.Specific intraocular antibody synthesis could be confirmed in 49 patients (98%). In two patients (8%) of the control group, antibody synthesis was detected (false positive). Forty-nine patients with diagnoses of ocular toxoplasmosis were positive for serum anti-T. gondii IgG, but only three patients had increased IgM levels.Analysis of local antibody production is a reliable method for confirming or excluding a suspected clinical diagnosis of toxoplasma retinochoroiditis. The determination of toxoplasma antibodies in the patients' serum is of limited value.

Herpetic keratitis is a common indication for corneal transplantation. In this patient group especially, there is a relatively high risk of graft failure, partly because of viral recurrence. It can be difficult to clinically distinguish stromal herpetic recurrence from early endothelial allograft rejection. Also a perioperative observation of viral activity seems advisable because of therapeutic consequences. For these reasons we use aqueous humor analysis in certain corneal transplant patients to determine intraocular antibody production. The aim of this study was to evaluate the diagnostic value of such an analysis of aqueous humor.A total of 28 samples of aqueous humor were obtained from 24 eyes and all samples were tested for antibodies against herpes simplex virus (HSV), most samples (26/28) were tested for antibodies against varizella zoster virus (VZV) and some samples (6/28) for antibodies against cytomegalovirus. We used a modified micro-ELISA technique to detect intraocular IgG production.In 14 samples (50%) we found antibodies against HSV, in 7 samples (25%) against HSV and VZV, in 1 sample (3.6%) against VZV and 6 samples (21.4%) were negative for all antibodies tested.The results of aqueous humor analysis led to a specific local or systemic antiviral therapy perioperatively or in the case of postoperative recurrence of herpetic keratitis in most patients. Some patients could be spared long-term treatment with antiviral agents because of negative results in the aqueous humor analysis.

Acute retinal necrosis syndrome (ARN) might be complicated by retinal detachment, vasculopathy and optic neuropathy and has a poor prognosis despite intensive medical and surgical therapy.A series of 10 consecutive patients (14 eyes) with ARN were followed for 36 months (average of 20 months +/- 10). We present the results of the clinical evaluation for diagnostic and therapeutic modalities.Viral etiology was confirmed in 9 of 10 aqueous-humor samples. Intraocular antibody synthesis against Varicella-Zoster Virus was found in 7, against Herpes-Simplex Virus in 5 and against Cytomegalovirus in 2 samples. Three eyes had a mild clinical course with a visual acuity of 0.6 or better. Vitrectomy and silicone-oil tamponade preserved visual acuity from 0.3 to 0.1. ARN lead to blindness in 5 eyes due to vasculopathy, optic neuropathy or retinal detachment. An arterial branch occlusion was successfully overcome with i.v. heparin treatment in one patient.Aqueous-humor analysis supports clinical diagnosis. Early vitrectomy and silicone oil tamponade stabilizes retinal structure and preserves visual acuity. Occlusive vasculopathy and optic neuropathy are the main causes leading to blindness.

Confocal microscopy represents a methodology that allows in vivo examination of corneal morphology, particularly of the epithelium and stroma.Using the confocal microscope "ConfoScan Modell P2" epithelial, stromal and endothelial changes were evaluated in 11 patients with corneal dystrophies. All findings were compared with data from healthy individuals.Confocal images could be correlated to conventional (slitlamp) biomicroscopic findings in all patients with corneal dystrophies. In addition, confocal microscopy provided more detailed images particularly of epithelial and stromal changes.Our data indicate that confocal microscopy provides information on living tissue that correlates with that obtained with conventional techniques on fixed and sectioned tissue.

Inflammatory stimuli induce the expression of adhesion molecules on leukocytes and endothelial cells. The adhesive forces between leukocytes and the vascular endothelium are antagonized by the shear stress of the flowing blood. The aim of this study was to examine how differences in the apparent wall shear rate measured in iris venules with varying caliber affect leukocyte-endothelium interaction.The microvasculature of the iris in Lewis rats (n = 6) was examined using intravital fluorescence microscopy [2]. Blood flow was visualized with FITC-HES and leukocytes were stained with rhodamine 6G. Venules (n = 110) ranging in diameter from 20-60 microns were analysed with regard to the following parameters: Flux of leukocytes, velocity of leukocytes in the center stream, number of rolling and adherent leukocytes. The apparent wall shear rate was calculated from the center stream velocity and the vessel diameter. Animals were examined 4 h after administration of endotoxin from S. typhimurium (500 mg/kg body wt i.p.), when leukocyte-endothelium interaction is strongly enhanced.The flux of leukocytes, the absolute number of rolling leukocytes and the velocity of leukocytes in the center stream was higher in larger than in smaller venules. The apparent wall shear rate decreased with increasing vessel diameter. Calculated values were 806 +/- 59 s-1 for vessels 20-30 microns in diameter and 483 +/- 34 s-1 for vessels of 50-60 microns (mean +/- SEM). The number of adherent leukocytes per mm2 endothelial surface and the rolling fraction did not show significant differences between vessels with varying caliber.Although the shear rate declined with increasing vessel diameter, we could not observe an increase in rolling and adherent leukocytes. The effects of vessel diameter on leukocyte adhesion to the vascular endothelium in postcapillary iris venules are minimal.

We report clinical experiences with six patients treated at the University of Tübingen between 1982 and 1994 for symptoms of typical and atypical ocular manifestations of Cogan's syndrome. All cases had systemic symptoms in addition to involvement of the cochleovestibular system. Otologic symptoms were the initial presentation in four cases. Vestibular dysfunction often preceded hearing loss. Five patients had keratitis and also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids. Three patients were diagnosed early, allowing corticosteroid treatment to begin early with stabilization of hearing. Total bilateral deafness could not be prevented in the remaining patients. The importance of being aware of auditory-vestibular dysfunction occurring in patients with ocular inflammation and the role of early immunotherapy in preventing deafness has to be emphasized.

Erythema exudativum multiforme major (EEMM), also know as Stevens-Johnson syndrome, may cause severe conjunctival and corneal alterations. The etiology remains unknown. The aim of are study was to evaluate the clinical course, therapy and prognosis of ocular involvement.In a retrospective study, we evaluated ten patients with EEMM who were treated between 1986 and 1994 at the University Eye Clinic Tübingen.The age of the four female and six male patients varied between 5 and 70 years. Drugs as a possible precipitating factor were found in all cases (acetylsalicylicacid, sulfonamide, erythromycin, cotrimoxazole, Valproinicacid, paracetamol). Eight patients experienced an infection at the same time. Clinically, we were able to differentiate two groups regarding severity of the disease. Seven patients were characterized by ocular alterations that only involved the conjunctiva, leading to conjunctival scars. In those cases local treatment with antibiotics and corticosteroids was effective. In the second group severe ocular damage occurred, with symblephara, keratinization and consecutive perforating keratoplasty. Secondary infections became evident in a total of six cases from the two groups.Drugs as a possible precipitating factor could be identified in all cases. In eight of ten patients previous infection was known. This agrees with literatures reports of viral infections (e.g. herpes simplex) as cofactors causing EEMM, especially for the aggressive form, remains unresolved. The danger of possible superinfection should always be taken into consideration.

To analyze leukocyte-endothelium interaction in iris venules of living rats and to quantify changes of leukocyte dynamics in endotoxin-induced uveitis (EIU).Lewis rats received an intraperitoneal injection of 100 micrograms of lipopolysaccharide (LPS; Salmonella typhimurium). Using intravital fluorescence microscopy, the iris vessels were examined, 2, 4, 6, 10, 14, 24, and 72 hours after LPS injection. A setup for intravital fluorescence microscopy of iris venules in the rat is described. Images are recorded with a video camera and stored on S-VHS videotape for off-line analysis. For contrast enhancement, erythrocytes and plasma were stained with fluorescein isothiocyanate (FITC) and FITC-hydroxyethylstarch, respectively. Rhodamine 6G was used for intravital staining of leukocytes. Resolution and magnification (x850) of the system facilitates observation of individual cells in the bloodstream in real time. Leukocytes were either flowing in the center stream, rolling along the endothelium, or firmly adherent. Image analysis provided data on microvascular leukocyte flux and leukocyte velocity.The percentage of leukocytes rolling on postcapillary venular endothelium increased significantly (P0.05) 4 hours after endotoxin administration, as did the number of firmly adherent cells. Leukocyte-endothelium interaction reached its maximum 6 to 10 hours before an increase of inflammatory cells in the aqueous humor. The response to endotoxin was reversible, subsiding to near-normal values after 72 hours.Intravital fluorescence microscopy provides data on microvascular parameters, including the number of rolling and sticking leukocytes on vascular endothelium. Inflammation of the anterior uvea was characterized with regard to leukocyte recruitment from blood to the vessel wall.

Monoclonal antibodies (mAb) have generated interest as therapeutic agents. Limited data are available on the treatment of corneal graft rejection. The purpose of this study was to assess the use of topically applied mAb on experimental corneal grafts.W 3/25, an IgG 1 mouse antirat mAb that recognizes a CD4+ cell subset, was used to treat Lewis recipient rats that received orthotopic corneal grafts of Wistar-Furth donors. Recipients were randomly assigned to receive topically applied drops of liposome-incorporated anti-CD4 mAb (LIP-anti-CD4 mAb), an equivalent amount of free anti-CD4 mAb, an isotype-matched control mAb encapsulated in liposomes (LIP-control mAb), or empty liposomes (emp-LIP) 5 times daily for 10 days. To investigate the immunologic effect of mAb treatment, flow cytometry of the targeted cells and cytotoxic activity of lymphocytes were analyzed.Application of LIP-anti-CD4 mAb was effective in reducing the rejection rate (P.05) and in prolonging the mean survival time of corneal grafts that underwent rejection (P.05). In contrast, no significant effect on graft outcome was observed after the application of control agents. Flow cytometry analysis did not reveal systemic depletion of the targeted lymphocyte subset in any anti-CD4 mAb treated animals. Rejected grafts elicited a cellular cytotoxic immune response in a cell-mediated lymphocytotoxic assay independent of the treatment given.The results suggest that treatment with topically applied LIP-anti-CD4 mAb prolongs graft survival in orthotopic corneal grafts in a rat model. The beneficial effect of LIP-anti-CD4 mAb, probably due to enhanced intraocular delivery, was achieved by using relatively low doses of mAb.

To investigate the use of topically applied FK506, a new immunosuppressive compound, systemic and ocular absorption was determined in serum and various ocular tissues.Two drops of 20 microliters FK506 were applied using oil dissolved (OD-FK506) or liposome-bound (LIP-FK506) drug. FK506 concentrations were measured at intervals of 30, 60, and 120 minutes by immunoassay.After application of OD-FK506, the highest concentrations of FK506 were found in the cornea and the conjunctiva (200-1200 ng/g) with substantial drug also present in anterior and posterior sclera. Relatively low concentrations were measured in the aqueous and vitreous humors (0.2-1.0 ng/g) of these animals. Using the same treatment regimen, LIP-FK506 was effective in delivering significantly higher drug concentrations (P0.05) to all ocular tissues and particularly aqueous humor (5-28 ng/g) and vitreous humor (12-22 ng/g) at all time points. During the observation period drug concentrations produced by LIP-FK506 remained well above the therapeutic range. FK506 levels were not detectable in serum (0.2 ng/ml) with either drug formulation.These findings indicate that liposomes may be a promising formulation for topical use of FK506 in ocular immune-mediated diseases.

Over a 5-year period, a consecutive series of 52 eyes in 46 patients with uveitis underwent extracapsular cataract extraction. Twenty-eight of these cases received a posterior chamber intraocular lens (IOL). During an average follow-up of 25 months (range 7 to 58 months) 71% of eyes receiving an IOL achieved postoperatively a visual acuity of 0.5 or better; 54% of aphakic eyes reached this level. Persistent cystoid macular edema limited the visual improvement to 20/200 in 6 patients; none of the patients developed cystoid macular edema postoperatively on clinical observation. Intraocular hypertension occurred postoperatively in 12 eyes, but was limited to a 4-week postoperative period in 9 cases. YAG laser capsulotomy was performed in 2 eyes with opacification of the posterior lens capsule without any further complications. The results suggest that uveitis patients benefit from cataract extraction and in selected cases can tolerate IOL implantation without major complications.

Although Staphylococcus epidermidis is the most common cause of postoperative pseudophakic endophthalmitis, little is known about the immune response to S. epidermidis-induced endophthalmitis. Using a rabbit model, the immune response to an intravitreal injection of 7000 S. epidermidis (group 1) or 30,000 S. epidermidis (group 2) organisms was investigated. Clinical evaluations showed that rabbits in group 2 had a more severe inflammatory reaction in the conjunctiva, cornea, iris, and vitreous than those in group 1. The inflammatory reaction in group 1 largely resolved by day 30; group 2 continued to show a severe inflammatory response. Histopathologic findings correlated with clinical findings, with rabbits in group 2 showing a more severe inflammatory reaction in both the anterior and posterior segments of the globe. Positive vitreous cultures for S. epidermidis were present in rabbits in group 1 on days 3, 7, 10, 14, and 21 but not thereafter. However, group 2 had higher vitreous colony counts at days 3, 7, and 14 and negative vitreous cultures thereafter. Neither group showed delayed hypersensitivity to S. epidermidis antigens (evaluated by skin tests). Serum immunoglobulin (Ig) G antibody levels to phenol-inactivated S. epidermidis and glycerol teichoic acid (GTA) increased progressively, reached a peak at days 10-14, and then declined in both groups. Serum IgA antibody levels to these antigens were not detected. Group 2 had a more prolonged IgG antibody response in vitreous and aqueous than group 1. Tear fluid showed the weakest IgG and IgA antibody response to S. epidermidis and GTA. S. epidermidis-induced endophthalmitis was associated with a humoral but not a delayed hypersensitivity response to this organism.

In animal studies, bromocriptine (Pravidel) has demonstrated immunosuppression because of inhibition of prolactin. After publication of positive results in the treatment of uveitis in a few case reports and in an uncontrolled study we conducted a double-blind placebo-controlled study in 13 patients with chronic recurrent anterior uveitis who had experienced three or more recurrences during the previous year. Therapy was started gradually during the symptom-free interval and continued for 1 year with 2.5 mg twice daily. Two recurrences or relevant side effects led to discontinuation of the therapy. In the bromocriptine group, 2 of 7 patients had no recurrences during the study period. Two patients had to stop because of two recurrences but, in contrast to earlier recurrences, they responded to local corticosteriod treatment within a few days. The remaining 3 patients (1 with one recurrence, 2 without) had to stop because of the side effects (arterial hypotension, arthritic complaints). In 5 of 6 patients in the placebo group treatment was stopped because of recurrences and in 1 patients because she believed she was experiencing a side effect from bromocriptine (breast atrophy). In summary, bromocriptine seems to have a prophylactic effect on anterior uveitis. Side effects were frequent but mild compared to other immunosuppressives. In case of arterial hypotension, additional therapy could make this drug more tolerable.

Chronic recurrent uveitis still responds unsatisfactorily to therapy. Prolactin, a pituitary hormone that attains high blood levels physiologically in stress situations, has an immune modulating effect. The prolactin antagonist bromocriptine (2 x 2.5 mg/day) was administered prophylactically to prevent recurrence in seven patients with chronic iritis/iridocyclitis or panuveitis (Group A). On this therapy two patients suffered a mild recurrence (in one case in the first month). Another patient developed rebound uveitis after discontinuing bromocriptine medication. Tolerance appears to vary considerably, and in three patients the therapy had to be discontinued because of arterial hypotension and congestive rhinopathy, respectively. The three patients in Group B (with iritis, sympathetic ophthalmia, and intermediate uveitis) received bromocriptine in addition to cyclosporin A after plasmapheresis. This combination resulted in an elevated cyclosporin A plasma level, and the dosage was reduced by 30-50% (plasma level 70-120 ng/ml). With this lower dosage of cyclosporin A, the creatinine level of one of the patients returned to normal. Viewed on the basis of these initial results bromocriptine would appear to reduce the number of recurrences of chronic uveitis. Moreover, the synergism with cyclosporin A, described both theoretically and in an animal model in the literature, appears attainable in therapy.