[Parainfectious optic neuritis with macular infiltrate in Neisseria meningitidis B meningitis]. / Parainfektiöse Optikusneuritis mit makulärem Infiltrat bei Neisseria-meningitidis-B-Meningitis.

OBJECTIVE: We report on the case of a young immunocompetent female patient with parainfectious optic neuritis and macular inflitrate due to Neisseria meningitidis B meningitis. METHOD: Case report RESULTS: A 22-year-old female patient was admitted to the emergency department for intensive care treatment with a strong suspicion of meningitis. Clinical and serological parameters were indicative of a bacterial genesis of the meningitis. By analysis of the cerebrospinal fluid (CSF) Neisseria meningitidis type B could be detected. Subjective and objective symptoms could be improved by immediate intravenous administration of antibiotics; however, 1 day before discharge the patient complained of a sudden left-sided, painful loss of vision with extreme photophobia. The ophthalmoscopic examination revealed profound ciliary injection with slight anterior uveitis and papilledema with macular infiltration and diffuse petechiae-like retinal hemorrhage. After exclusion of viral proliferation in the CSF systemic steroid therapy was carried out together with continuation of antibiotic therapy and the eye was treated with local steroids and mydriatics. This resulted in healing of the ocular inflammation and partial recovery of vision. CONCLUSION: The painful loss of vision in this patient is probably due to parainfectious optic neuritis with macular infiltrate from Neisseria meningitidis B meningitis, which is an unusual course. Despite the rarity of this disease the complication of a parainfectious inflammation of the optic nerve should be considered and appropriate steps taken when the corresponding symptoms occur.

[Epstein-Barr virus associated acute retinal necrosis]. / Epstein-Barr-Virus-assoziierte akute retinale Nekrose.

CASE REPORT: This article reports a case of an Epstein-Barr virus (EBV) associated acute retinal necrosis. A 72-year-old male patient presented in the emergency department complaining of progressive loss of vision. During patient management an acute retinal necrosis was suspected and the subsequent diagnostics from a vitreal body biopsy showed positive results only for the EBV genome. OBJECTIVE: The EBV is a rare cause of ocular inflammation. With this report we would like to draw the attention of colleagues to this unusual finding. CONCLUSION: Although EBV screening is not part of the standard diagnostic procedure, its implementation in relevant clinical situations could possibly assist the differentiation between causal relationship and morbidity.

[Unusual IOL Calcification following Vitreoretinal Surgery with Silicone Oil Endotamponade]. / Ungewöhnliche Kalzifikation intraokularer Kunstlinsen nach vitreoretinalem Eingriff mit Silikonölendotamponade.

PURPOSE: Calcification of intraocular lenses (IOL), although nowadays less frequent than in the past, is a well-documented complication that can still necessitate their explantation. Although mostly noted in hydrophilic materials it has been rarely reported in hydrophobic intraocular lenses. We wish to report on two unusual cases of intraocular lense (one hydrophobic and one hydrophilic with hydrophobic surface) calcification following vitrectomy and silicon oil endotamponade. METHODS: In the course of treatment both patients underwent multiple ocular interventions due to re-detachment/persistent macular hole including local rt-PA or triamcinolone injection due to persistent postoperative anterior chamber inflammation/macular oedema. Finally and after thorough patient examination with characteristic visual complaints and difficulty in the retinal assessment the extraction of the calcified lenses was considered necessary. The configuration as well as the elemental analysis of the opacified surface of the IOLs was performed by means of high magnification microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy (EDX). Intraocular and systemic histories of both patients were summarised. RESULTS: The scanning electron microscopy and EDX analysis demonstrated massive calcium-based deposits on the surface of the hydrophilic and a diffuse vacuolation and calcification consisting of oxygen (O), silicon (Si), magnesium (Mg), aluminium (Al), sulphur (S) and phosphorus (P) on the surface of the hydrophobic IOL. CONCLUSION: The explantation of an IOL due to calcification represents an unusual event. The careful consideration of systemic and ocular factors that promote calcification processes can help reduce the incidence of calcification. Despite all efforts in material production and risk factor analysis, it is not always possible to define or even predict the exact cause of this phenomenon and in the presence of corresponding clinical symptoms IOL exchange remains as the sole option.

Current treatment limitations in age-related macular degeneration and future approaches based on cell therapy and tissue engineering.

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.

High efficiency non-viral transfection of retinal and iris pigment epithelial cells with pigment epithelium-derived factor.

Transplantation of pigment epithelial cells in patients with age-related macular degeneration and Parkinson's disease has the potential to improve functional rehabilitation. Genetic modification of cells before transplantation may allow the delivery of neuroprotective factors to achieve functional improvement. As transplantation of cells modified using viral vectors is complicated by the possible dissemination of viral particles and severe immune reactions, we have explored non-viral methods to insert genetic material in pigment epithelial cells. Using lipofection or nucleofection ARPE-19 cells, freshly isolated and primary retinal and iris pigment epithelial (IPE) cells were transfected with plasmids encoding green fluorescent protein (GFP) and with three plasmids encoding recombinant pigment epithelium-derived factor (PEDF) and GFP. Transfection efficiency was evaluated by fluorescence microscopy and stability of protein expression by immunoblotting. Pigment epithelial cells were successfully transfected with plasmid encoding GFP. Expression of GFP in ARPE-19 was transient, but was observed for up to 1 year in IPE cells. Analysis of pigment epithelial cells transfected with PEDF plasmids revealed that PEDF fusion proteins were successfully expressed and functionally active. In conclusion, efficient transfer of genetic information in pigment epithelial cells can be achieved using non-viral transfection protocols.

[Malignant melanoma of the cornea after blunt trauma]. / Malignes Melanom der Kornea nach stumpfem Trauma.

We report the case of a 67-year-old woman who presented with a persisting corneal erosion after blunt injury. Six years later, a highly prominent corneal tumor had developed at the site of the initial erosion. Histological analysis revealed a malignant melanoma. This case provides evidence that malignant melanoma may be a long-term complication of corneal epithelial disorders.

[Non-Pharmacological Interventional Perspectives in AMD]. / Nichtmedikamentöse interventionelle Perspektiven bei der AMD.

Transplantation and translocation surgery for the treatment of AMD has been evaluated for over 25 years. More recently injections of inhibitors of vascularisation have been used with some success. Inhibitors of neovascularisation result in the recovery of vision in about 30% of patients; however, we do not understand what criteria can be used to select patients who will respond to or will not respond to treatment with antivascularisation treatment. We have to assume that successful antivascularisation treatment will require first that the retinal pigment epithelial cells be present and functional and second that the photoreceptor cells should not be degenerated. We then hypothesise that if either of these two parameters are not present, antivascular treatment will not result in vision recovery and we must then consider surgical intervention. Surgical intervention for macular degeneration encompasses procedures from simple membrane extraction to macular rotation to cell transplantation or a combination of these procedures, however these procedures must take into account that vision recovery cannot be achieved without reconstruction of the retina-choroid complex. Since in AMD degeneration of the retinal pigment epithelial cells and vascular membranes removal results in damage to the basal lamina and possibly deeper layers of Bruch's membrane, it will be necessary to reconstruct these damaged structures. In fact, transplantation of RPE cells or IPE cells has not resulted in any significant improvement in vision in AMD patients. Long-term follow-up of AMD patients following macular rotation surgery has shown that significant visual recovery is not maintained in most patients. Of the many approaches that could be used to reconstruct the damaged basal lamina and Bruch's membrane the most promising would be the introduction of a monolayer of pigment cells on a "natural" biodegradable substratum. A natural substratum consisting of extracellular matrix proteins would allow the pigment cells to retain their differentiated characteristics and functions, including the degradation the substratum and production of the normal components of the basal lamina and Bruch's membrane. In addition, the cells introduced as a monolayer can be engineered to carry specific genes to aid in the restructuring of the retina-choroid complex, such as growth factors and inhibitors of vascularisation.

[Influence of vital dyes on the function of the outer blood-retinal barrier in vitro]. / Einfluss von Vitalfarbstoffen auf die Funktion der äusseren Blut-Retina-Schranke in vitro.

BACKGROUND: The use of vital dyes in "chromovitrectomy" allows the easier removal of less recognizable structures like epiretinal membranes (EM) or the inner limiting membrane (ILM). In recent years numerous studies demonstrated the use of indocyanine green (ICG), trypan blue (TB) and patent blue (PB) for this indication. Reports of the possible risk of these dyes, i. e. especially ICG, in respect of reduced visual acuity results, possible visual field defects or alterations of the retinal pigment epithelium (RPE) resulted in limitations in their application. MATERIAL AND METHODS: Human RPE cells and choroidal endothelial cells were cultured in monolayers on semipermeable membranes representing an in vitro model of the outer blood-retinal barrier. By measurement of the transepithelial electrical resistance (TER) the stable barrier function was determined. Two different models representing an air-filled and a fluid-filled eye were tested on the one hand by addition of the dye to the culture medium and, on the other, by direct application on the cell monolayer. In these two models ICG (5 mg/ml, 0.5 mg/ml, 0.125 mg/ml), TB (1.5 mg/ml, 0.15 mg/ml) and PB (2.4 mg/ml, 0.24 mg/ml) were applied for three minutes and the influence on the barrier function was determined. RPE cell growth was also tested in these two models after the application of ICG, TB and PB. Finally, monolayers of RPE cells were evaluated by transmission electron microscopy (TEM). RESULTS: After application of TB, PB and the lowest concentration of ICG of 0.125 mg/ml, the TER remained stable in both models. In contrast, ICG in a concentration of 5 mg/ml and 0.5 mg/ml caused a significant TER decrease in the model of the air-filled eye, whereas no influence on the function of the outer blood-retinal barrier was noted in the model of the fluid-filled eye. RPE cell growth rates were not influenced by the addition of the vital dyes, with the exception of ICG in a concentration of 5 mg/ml in the model of the air-filled eye, resulting in a temporary reduction of the cell count. In good correspondence to these results also in TEM intercellular blisters were noted after application of 5 mg/mL ICG for 3 minutes in the model of the air-filled eye. However, damage to the RPE cells themselves was not obvious. No pathological changes in the TEM were noted after application of TB and PB. CONCLUSIONS: The use of PB and TB at the posterior eye segment seems to be safe concerning damage to the PRE and its barrier function. In contrast, ICG in higher concentrations and with longer application times may cause a toxic effect on RPE morphology and function.

[Bilateral anterior panuveitis as early manifestation of syphilis in a patient with HIV infection]. / Beidseitige Panuveitis als okuläre Frühmanifestation einer Lues bei einem Patienten mit HIV-1-Infektion.

INTRODUCTION: Syphilis is a dangerous sexually transmitted infection which can be effectively treated with penicillin to avoid late-onset diseases. Even if syphilis is diagnosed an HIV infection should be excluded. PATIENT: A 32-year-old homosexual man complained about a decreased bilateral visual acuity after a feverish infection with lymphadenitis colli. With slit-lamp biomicroscopy a bilateral panuveitis with papillary edema, endothelial cells and episcleritis was found. After antimycotic and antiviral therapy, his visual acuity decreased and symptoms progressed. In the lab routine we found lues and HIV infections and started an intravenous penicillin therapy immediately. A few days later the symptoms improved and visual acuity increased. CONCLUSION: Lues serology should be incorporated into routine lab diagnostics to aid the detection and to start the right therapy as soon as possible.

[Transplantation of iris pigment epithelium]. / Transplantation von Irispigmentepithel.

Transplantation of iris pigment epithelial (IPE) cells to the subretinal space has been attempted as a therapeutic modality for the treatment of age-related macular degeneration (AMD). IPE cells are used because autologous cells are readily available and because IPE and RPE cells share a common embryonic origin, possess the capacity of transdifferentiation into other ocular cells, and share common morphological and functional characteristics. Once the technique of IPE cell transplantation was established in an animal mode, several clinical studies analyzed the behavior of IPE cell suspensions transplanted to the subretinal space of patients with AMD following surgical membrane extraction. In our experience, as well as that of other investigators, transplantation of IPE cells to the subretinal space of AMD patients prevents the recurrence of the subretinal neovascularization and stabilizes but does not improve visual acuity. Since IPE cells transplanted as a cell suspension do not appear to form a cell monolayer in the subretinal space, the transplantation of preformed IPE or RPE cell monolayers is being investigated as the development of an functional cell monolayer is mandatory if functional success, i.e., recovery of vision in AMD patients, is the ultimate goal of IPE cell transplantation.

One year follow up of macular translocation with 360 degree retinotomy in patients with age related macular degeneration.

AIM: To evaluate the benefits of macular translocation with 360 degree retinotomy in patients with exudative age related macular degeneration (ARMD). METHODS: A consecutive interventional case series was performed on patients who underwent macular translocation between June 1997 and January 2000 at the department of ophthalmology, University of Aachen, Germany. A retrospective pilot study was set up with a minimum follow up of 12 months in 39 consecutive patients with subfoveal choroidal neovascularisation secondary to ARMD. The surgical technique included pars plana vitrectomy, induction of retinal detachment, 360 degree retinotomy, removal of the choroidal neovascular membranes (CNVM), macular translocation, peripheral laser retinopexy, and silicone oil endotamponade. RESULTS: 18 patients showed predominantly occult CNVM, six patients had predominantly classic CNVM, and 15 showed subretinal haemorrhage. At the 12 month follow up 13 patients (33%) showed an improvement in visual acuity of more than three lines (logMAR scale), 18 patients (46%) retained stable visual acuity with a change of equal or less than three lines (logMAR scale), and eight patients (21%) showed a decrease in visual acuity of more than three lines (logMAR scale). Recurrence of CNVM was observed in three (8%) eyes at 5-11 months postoperatively. Other complications included proliferative vitreoretinopathy with retinal detachment (n=10), peripheral epiretinal membranes (n=9), macular pucker (n=2), corneal decompensation (n=2), and hypotony (n=11). 18 patients (46%) complained about persistent diplopia. CONCLUSION: Macular translocation surgery is able to maintain or improve distant vision in the majority of patients with exudative ARMD. Proliferative vitreoretinopathy and diplopia are the two major complications. A prospective randomised controlled trial comparing macular translocation with observation for patients with the occult form of exudative ARMD may be justified.

Development and cellular functions of the iris pigment epithelium.

A number of studies have shown that transplantation of retinal pigment epithelial (RPE) cells to the subretinal space offers a promising treatment modality for retinal degenerative diseases. However, it is necessary to transplant autologous cells to avoid rejection; unfortunately, obtaining autologous RPE cells necessitates such traumatic surgical intervention as to make this approach irrelevant. It has been hypothesized that iris pigment epithelial (IPE) cells may be a possible substitute for RPE cells for transplantation into the subretinal space. The iris pigment epithelium, which has the same embryonic origin as retinal pigment epithelium, has not received much attention from visual scientists. Even though it forms a highly specialized tissue, it is not clear whether the iris pigment epithelium contributes critical functions to the health of the visual system. In vivo the IPE does not appear to have any of the functions characteristic of RPE; however, in vitro cultured IPE cells do acquire functions, such as specific phagocytosis of rod outer segments, that are characteristic of RPE cells, and have been shown to have the potential to carry out many functions characteristic of RPE cells, e.g., retinol metabolism. This review outlines the development and cellular functions of the IPE with special emphasis on the modulation of those functions that can allow the IPE cells to be transplanted to the subretinal space where they appear to acquire differentiated properties of retinal pigment epithelium (RPE).

Oxidation causes melanin fluorescence.

PURPOSE: The goal of this study is the characterization of the strong yellow fluorescence of oxidized melanin in the retinal pigment epithelium (RPE) and the choroid. METHODS: Naturally occurring melanin in the human retina and choroid was oxidized by exposing fixed and plastic-embedded sections of a human eye to light and hydrogen peroxide. Synthetic melanin was also oxidized in vitro by exposure to light and hydrogen peroxide. The fluorescence of oxidized melanin was examined by absorption spectroscopy, fluorescence spectroscopy, and fluorescence microscopy. RESULTS: Naturally occurring melanin oxidized in situ exhibited a lipofuscin-like yellow fluorescence. Oxidation of melanin in vitro degraded the melanin polymer, resulting in a fluorescent solution. Fluorescence spectroscopy gave an excitation maximum at approximately 470 nm and an emission maximum at approximately 540 nm for both natural and synthetic melanin. Increasing the time of exposure to light or hydrogen peroxide increased melanin fluorescence. CONCLUSIONS: The results indicate that the strong yellow fluorescence of melanin in the RPE and choroid in situ is a property of oxidized melanin and is not due to contamination of the melanin by proteinaceous or lipid materials. The data presented allow a reinterpretation of the results obtained from fluorescence investigations of melanin-containing tissue and suggest a link between melanin degradation and lipofuscin formation.