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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.

We have attempted in this article to summarise the present literature on the risks of virus transmission via corneal transplantation, with special emphasize on Herpes simplex virus (HSV).We conducted a literature search from Medline.HSV is now acknowledged as a cause of primary graft failure, and this entity has been attributed to donor-to-host HSV infection. HSV is the primary cause of graft failure, and may induce reactivation in the recipient in the dendritic form, or in atypical forms.Corneal transplantation is a potential route for HSV infection as a possible transmittable disease which now has to be taken into consideration in eye banks.

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.

One of the most common complications after mechanical penetrating keratoplasty is the occurrence of irregular astigmatism. We developed a method to prepare donor grafts for transplantation applying excimer laser techniques. The quality of the cut edges and exposure time were evaluated.The beam of an experimental excimer laser (OPTex, Lambda Physik) was homogenized and guided by an optical system including lenses and scanner mirrors. A special software was used to conduct the laser beam in a circular mode over the surface of the cornea. Corneas from porcine eyes were stabilized in an artificial anterior chamber. Twenty in vitro explants were trephinated applying our method and subsequently investigated by electron microscopy and histology.All experiments provided regular and smooth cut edges. The average exposure time until perforation was 10.5 min (SD 2.7 min), the diameter of the grafts was 8.0 mm.The experiments showed the possibility of non-contact trephination and generation of smooth cut edges with a rotating focussed excimer laser beam in a porcine cornea model. A major advantage of the system is the possibility of customized "tailored" grafts.

Different strategies are currently used for prophylaxis and therapy of immunological transplant reactions. The aim of the present study was to evaluate clinical practice in planning and treatment of perforating keratoplasty (KPL) in Germany.A questionnaire was sent out to 148 members of the cornea section of the German Ophthalmological Society. The return consisted of 69 (47%) questionnaires representing 69% of institutions, 39% of responses returned from institutions performing50 KPL/year, 15% from institutions operating100 KPL and 4% from centres performing300 KPL/year.Of the responders 13% currently never use HLA-matched grafts, 22% choose matched grafts in every risk KPL and 1.5% always use matched grafts. In normal risk situations 1.5% treat less than 2 weeks with topical steroids, 66% 3-12 months, 6.5%1 year, 35% additionally treat with systemic steroids. Cyclosporine A (CsA) (92%) is besides steroids (80%) the most common systemic immunomodulatory agent in high risk situations, while methotrexate is used by only 9.5%. The duration of immunosuppressive therapy varies from3 months (9%) up to12 months (14%). The postoperative therapy after KPL in herpes includes topical (51%) and systemic aciclovir3 (26%) and3 weeks (67%) and additional systemic immunomodulatory agents (37%). The acute immune reaction is treated predominantly with steroids: topical (95%), subconjunctival (29%), intracameral (1.5%). Systemic steroids are given orally (48%) and intravenously (42%), 12% treat with topical CsA.Besides therapeutic options that are accepted as common practice (e.g. systemic CsA) clinical practice varies widely. This may reflect the lack of evidence-based clinical observations.

The immune privileged nature of the cornea contributes to the favourable outcome in corneal grafts. However, preventive measures are necessary to reduce allograft rejection particular in "high-risk" cases. Although corticosteroids are still a major component of our immunopharmacological armentarium, they might be supplemented by other more specific immunomodulating agents. The spectrum includes agents such as azathioprin, methotrexate or more specific calcineurin inhibitors affecting T-cells (cyclosporin A, FK506) and highly selective monoclonal antibodies directed against T-cell subpopulations and other targets. In order to better evaluate the risks and benefit of these agents, the properties of established and forthcoming agents are presented. In addition, this review attempts to address some new concepts of tolerance induction following penetrating keratoplasty.

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.

Topically applied drugs can penetrate transcorneally or paracorneally (transsclerally). There are only few studies to demonstrate the relationship of both penetration routes. The immuno-modulator mycophenolate mofetil (MMF), ester and pro-drug of mycophenolic acid (MPA), is a promising substance for such studies.Rabbit eyes were treated with different preparations of MMF as a cyclodextrin complex (MM-CD) and as a suspension (MMF-SP) and MPA as a cyclodextrin complex (MPA-CD). The concentrations of both compounds were measured in the cornea, conjunctiva, aqueous humor, vitreous body and iris-ciliary body.Only MPA is detectable in the cornea after application of MMF-CD and MMF-SP. In the aqueous humor high concentrations of MPA are detectable after 60 min. In the iris-ciliary body both MMF and MPA can be found.The intraocularly detected mycophenolate mofetil represents the paracorneally penetrated fraction. After topical application of mycophenolate mofetil in suitable preparations high concentrations of the active substance can be achieved intraocularly. These favourable pharmacokinetic characteristics are promising for new therapeutic strategies in immune-mediated diseases of the anterior part of the eye.

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.

Corticosteroids are, even 50 years after introduction in ophthalmology, the best, and often only choice of treatment for acute inflammatory eye disorders. Their broad spectrum of actions may not only explain the greater potency compared with other anti-inflammatory agents but also be responsible for multiple serious side effects. For future developments, several directions may be chosen including development of safer drugs with high therapeutic index and application of long-term drug-release systems.

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.

RGD peptides competitively inihibit adhesion molecules of the lens epithelial cells (LEC). The purpose of our study was to investigate whether this peptide is capable of detaching adherent cells and preventing posterior capsule opacification (PCO).Cultures of bovine and human LECs on culture dishes and discs of bovine anterior lens capsules were used. The inhibition of adhesion and the detachment of confluent LEC layers by the cyclic RGD peptide cRGDdFV were studied (incubation time was 3 days and 1 h and concentrations of 10(-4) and 10(-3) M were used).A dose-dependent inhibition of adhesion (48% and 42%, respectively) was obtained. There was a significant difference between the control peptide group and cRGDdFV (p0.0001). Cell detachment from lens capsules was not achieved but complete detachment from the culture dish occurred after 37 min.Short-term incubation of LECs by cRGDdFV did not lead to a sufficient inhibition of adhesion in vitro. A detachment of adherent LECs by cRGDdFV was not achieved.

Wegener's disease, an immune vasculitis, is characterized by granulomata and vasculitis of small and large vessels. Ocular manifestations are observed in approximately half of all cases.We report on a 58-year-old male with severe generalized Wegener's disease which was first diagnosed in 1986. The involvement of the central nervous system became clinically manifest by a stroke, of the kidneys by incipient renal insufficiency, and of the larynx by recurrent subglottic stenosis of the trachea. The first ocular involvement, a conjunctivitis, was observed in 1988. Despite systemic immuno-suppressive therapy, local conservative therapy and repeated surgical procedures, his vision decreased bilaterally from 60/60 to hand movement (OD) and light perception only (OS) during the following years because of a massive bilateral symblepharon. Transplantation of autologous oral mucosa to the conjunctiva led to a persistent increase of vision and a good cosmetic result.We conclude that in patients with Wegener's disease, who have developed a symblepharon despite intensive therapy, the transplantation of oral mucosa can produce a sufficient functional and cosmetic result.

Allograft rejection remains the single largest impediment to success in corneal transplantation. This article briefly reviews our current understanding of some fundamental aspects of corneal immunology and the pathogenetic mechanisms underlying corneal graft rejection. As knowledge increases, it is hoped that a better understanding of the immunobiology may result in improved preventive and therapeutic measures.

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.

Gene therapy has gained increasing attention and a number of ongoing clinical trials have been initiated. This article provides current perspectives and limitations on gene therapy in ophthalmology. Since a number of comprehensive studies on gene therapy for retinal diseases already exist, we focus attention to the treatment of anterior segment disorders of the eye.We undertook a reference search (DIMDI, PubMed) of articles published between (1989-2000) using the key words cornea, conjunctiva, eye, gene therapy, and keratoplasty. The search was restricted to publications in English, French and German. In addition, we incorporated some results of our recent experiments on cytokine gene transfer to the cornea.Attention to gene therapy in ophthalmology is currently focused on retina and choroidea (40 articles) however, an increasing number of publications includes the cornea (12 articles). The majority of these contributions deals with improvements in the design of gene therapy vectors in particular for targeted application.Gene therapy to the cornea may offer interesting new venues. Currently, insufficient gene transfer technologies and safety concerns prevent the broad application in humans. However, a broad spectrum of applications can be supposed.

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.

Inhibition of protein kinase C (PKC) and rho-kinase (ROCK) may represent a new way of influencing outflow facility through isolated relaxation of the trabecular meshwork (TM). This work was performed to investigate the existence of calcium-independent contraction in this smooth-muscle-like tissue and its modulation by targeting the rho-guanosine triphosphatase (GTPase)-mediated pathway.Isometric tension measurements of bovine TM and ciliary muscle (CM) were performed. Intra- and extracellular calcium buffering was accomplished with EGTA and 1, 2-bis(2-aminophenoxy)-ethane-N,N:,N:,N:',N:'-tetra-acetic acid tetrakis/acetoxymethhyl ester (BAPTA-AM) followed by stimulation of PKC with phorbolester (PMA) or 4alpha-phorbol. Calcium-independent contraction was blocked using the highly specific ROCK inhibitor Y-27632. Western blot analysis and immunoprecipitation was performed using human TM cells.In TM, carbachol induced partial contraction under conditions of extracellular calcium depletion (22. 1% +/- 2.3% versus 100%, n = 9). The membrane-permeable calcium chelator BAPTA-AM completely blocked this response (1.1% +/- 1.4% versus 100%, n = 9). When calcium was completely blocked, PMA induced contraction in TM (16.7% +/- 5.9% versus 100%, n = 9) but not in CM (1.8% +/- 2.5% versus 100%, n = 6). The inactive PMA analogue 4alpha-phorbol did not induce contraction, indicating that activation of PKC is involved in this contractile response. The ROCK inhibitor Y-27632 completely blocked the calcium-independent PMA-induced contraction in TM. Western blot analysis and immunoprecipitation revealed the expression of the rho-A protein in human TM cells.The data indicate that contrary to CM, the TM features calcium-independent contractile mechanisms linked to rho-A and PKC isoforms that do not require calcium for activation. ROCK inhibitors may allow specific modulation of the TM to enhance outflow facility, thus lowering intraocular pressure.

Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX.OFLX was incorporated into multilamellar large vesicles. 0.1 ml of this suspension (= 180.2 microg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 microg, 500 microg and 1,000 microg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy.The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 microg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 microg free OFLX. Three days after injection of 1,000 microg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation.This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 microg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage.

The eye is the target of a variety of immune mediated diseases. Advances in the field of immunology have permitted a better understanding of these challenges. This progress has been accompanied by the development of more specific immunomodulating agents. Corticosteroids are still a major agent in the management of ocular immunomediated diseases, but are now supplemented by other potent immunomodulating agents. The excitement in pharmacological research has in turn provided more insight in immune mechanisms and some of the newer agents have been used as "probes" for a better understanding of basic mechanisms. In order to better evaluate the indications of certain agents, the properties of established and forthcoming agents are presented. The field of immunopharmacology includes a multitude of preclinical areas related to the development of immunotherapy and immunotoxicology. This review attempts to address some topics of the current knowledge of the use of immunomodulating agents in ophthalmology.

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.

Ciprofloxacin (CIP) is a fluoroquinolone-antibiotic with a high antimicrobial activity against all pathogens causing bacterial endophthalmitis. After intravitreal injection, however, elimination half-life of this antibiotic is only 2.2 hours. To prolong intraocular bioavailability this study was performed to incorporate CIP into liposomes and to determine its clearance from the vitreous after intravitreal injection.CIP was incorporated into multilamellar vesicles by mechanical dispersion. 0.1 ml of this suspension (equiv. 273.6 micrograms CIP) was injected into the midvitreous of pigmented rabbit eyes (Chinchilla-bastards). One day, 3 and 14 days after the injection intravitreal concentration of CIP was determined by means of high-pressure-liquid-chromatography after dissolution of the liposomes by ultrasound. At the same intervals serum concentration of the antibiotic was examined as well.Within 24 hours intravitreal concentration fell to 18.0 micrograms/ml. Three days after the injection the concentration of CIP was 6.9 micrograms/ml. This is still above the minimal inhibitory concentration (MIC90) of the most common ocular pathogens. At 14 days CIP was not detectable in the vitreous any more. The serum concentration was between 0.04 microgram/ml and 0.07 microgram/ml. 3 and 14 days after injection no CIP could be detected.This study shows that the incorporation of CIP into liposomes can be achieved in sufficient doses by mechanical dispersion method. After intravitreal application the bioavailability of the antibiotic can be markedly improved. Even after 3 days the intravitreal levels were above the MIC90 of the most common endophthalmitis pathogens.