Intracorneal bovine albumin: an immunologic model of corneal angiogenesis.

BACKGROUND: We characterized the neovascularization that follows the intracorneal injection of bovine albumin (BA) in rabbits as a model of corneal angiogenesis. METHODS: New Zealand white rabbits received intracorneal injections of phosphate-buffered saline with and without various amounts of BA. The rabbits were co-sensitized or pre-sensitized by intramuscular BA or were not sensitized. The corneal vascular response was quantified by ranking photographs taken periodically after the injection. RESULTS: In pre-sensitized animals, blood vessels were apparent within 4 days and reached maximum intensity 14 days after the intracorneal injection. Corneas also vascularized in non-sensitized rabbits, but a larger dose (> 0.2 mg BA) was required than in pre-sensitized animals (> 0.02 mg BA). Vascularization began later in non-sensitized animals and was less extensive than in pre-sensitized animals. CONCLUSION: The intracorneal injection of BA is a reproducible model of corneal angiogenesis in rabbits and should allow the involved immunological mechanisms to be elucidated.

Endothelial metaplasia in the iridocorneal endothelial syndrome.

PURPOSE: To test the hypothesis that the aberrant, cytokeratin-expressing cells that replace endothelium in the iridocorneal endothelial (ICE) syndrome are of endothelial origin. METHODS: Corneas from four patients with Chandler's syndrome and three with essential iris atrophy were examined by two-color immunofluorescence for simultaneous expression of cytokeratins and two markers of endothelial lineage: vimentin and the antigen recognized by the antiendothelial monoclonal antibody 2B4.14.1. RESULTS: In six corneas, unequivocal endothelial staining for cytokeratins was present; in each of these, cells coexpressing cytokeratins and the two endothelial markers were clearly identifiable. In the remaining cornea, weak cytokeratin staining that colocalized with vimentin was present. CONCLUSIONS: These results lend strong support to the hypothesis that the "epithelial-like" endothelial cells in ICE syndrome are cells of endothelial lineage rather than heterotopia of epithelial cells; these cells probably arise via a metaplastic transformation of preexisting endothelium.

Corneal dystrophies and keratoconus.

Knowledge about keratoconus (KC) and the corneal dystrophies continues to advance at a steady pace in view of the wide interest in these topics to basic scientists and clinical ophthalmologists. As in the past the articles on KC outnumber those on all of the other corneal dystrophies combined. Major advances have been made mainly regarding several specific corneal dystrophies, but KC remains a perplexing disorder with many unanswered questions. As we learn more and more about the corneal dystrophies from genetic linkage analyses and molecular biological techniques it will eventually be possible to understand the fundamental defect that causes these conditions.

Correlation of histological tumor vascularization and Doppler sonography in patients with malignant melanoma of the choroid.

BACKGROUND: In previous studies Doppler sonography was proven to the useful for diagnostics and follow-up of malignant melanomas of the choroid. METHODS: To evaluate the correlation between Doppler sonographical findings and the histological tumor vascularization, we examined five eyes of five patients with malignant melanoma of the choroid before enucleation with an ATL Ultramark-8 Duplex scanner and compared these results with computerized planimetry of histological tumor vascularization after immunohistochemical staining of vascular endothelium with anti-factor-VIII antibodies. RESULTS: We found no definite correlation of flow velocities with histological parameters of tumor vascularization. The tendency was for a decrease in maximum flow velocities as histological vascularization increased. CONCLUSIONS: Due to (1) the usual lack of sensitivity parameters of the used Duplex device for the clinical user and (2) the unpredictable branching pattern within a melanoma resulting in an unknown angle of incidence of the Doppler beam, we conclude that the quantitative results of Doppler sonography require cautious interpretation. Nevertheless, presence or absence of Doppler shifts is a valuable parameter for the follow-up of irradiated tumors.

[Problems in perforating keratoplasty with large diameter]. / Probleme bei perforierenden Keratoplastiken mit grossem Durchmesser.

The follow-up of 52 perforating corneal grafts with a diameter of more than 9 mm is presented. The indications for surgery in this series were different from those in a control group. In the 3-year follow-up time most transplants were clear and had a good final visual outcome. Secondary glaucomas were not significant, but a high endothelial cell density decrease could be demonstrated.

[Pseudo-esotropia caused by nasal dislocation of the macula in patients with high infantile myopia]. / Pseudoesotropie durch Verlagerung der Makula nach nasal bei Patienten mit infantiler hoher Myopie.

Pseudostrabismus due to dislocation of the macula is a well-known clinical entity mostly reported in the outward, upward and downward directions. This heterotopia is thought to be caused by changes in the growth rate in different areas of the retina or mechanically by retinal traction due to abortive ROP, vascular abnormalities, chorioiditis or other peripheral retinal disorders. In this paper we demonstrate four cases of macular dislocation in the direction of the optic disc associated with high myopia in infants and toddlers without signs of other retinal abnormalities. These children had myopia had myopia ranging from -17 to -20 D and esotropia superimposed by pseudostrabismus. In all four cases, strabismus surgery was performed. Postoperatively, these children showed signs of some binocular interaction. This case report may indicate that in children with strabismus associated with high myopia macular dislocation should be considered as a further characteristic affecting diagnosis and therapy.

[Results of therapy in ocular toxoplasmosis. Comparison of various forms of therapy]. / Ergebnisse der Therapie bei okulärer Toxoplasmose. Ein Vergleich unterschiedlicher Therapieformen.

We performed a retrospective non-random study to evaluate the effectiveness of different therapeutical concepts in the treatment of retinal toxoplasmosis. Visual acuity after therapy and at the end of the observation period as well as the recurrence frequency were used to determine the success of treatment. The protocols of 75 patients treated for retinal toxoplasmosis at the University of Hamburg were evaluated for this study. The mean observation period was 220 weeks with a standard deviation of 110 weeks. Concerning the visual outcome, a therapeutic effect was statistically shown for monotherapy with antibiotics and for their combination with corticosteroids. Steroid therapy was demonstrated to be helpful, especially in cases of extramacular localization of fundus lesions. This was probably caused by steroid-induced improvement of vitreous infiltration. As for the different antibiotics used, the combination of clindamycin with sulfmethoxydiazine and/or pyrimethamine showed the best results. Monotherapy with clindamycine alone had statistically no effect on the final visual outcome. The relapse frequency was not influenced by any therapeutic concept used. According to these results, a combination of clindamycine and pyrimethamine should be the therapy of choice for treatment of retinal toxoplasmosis.

Sensitivity and specificity of optic disc parameters in chronic glaucoma.

PURPOSE: Optic disc parameters are commonly used for the early detection of glaucomatous optic discs. We used receiver operating characteristics (ROC) curves to illustrate the separation characteristics of different disc parameters for this purpose. METHODS: We performed computer perimetry and computerized optic disc topometry on 93 eyes of 53 subjects with glaucoma and glaucoma-related diseases. The optic disc parameters were correlated with visual field indexes, and ROC curves for the detection of glaucomatous disc changes were calculated. RESULTS: According to clinical experience, the vertical cup/disc ratio was able to identify the glaucomatous eyes the most easily, whereas the neuroretinal rim area was less helpful in this regard. In terms of the correlation of optic disc parameters with visual field indexes, the rim area was the more powerful of the two. The cup volume showed neither separation of glaucomatous from normal eyes nor correlation with visual field indexes. CONCLUSIONS: The vertical cup-to-disc ratio is the most suitable for screening purposes, whereas the rim area is more valuable for follow-up evaluation.

Visual field indices for the nasal step: different calculation procedures and their correlation with the clinical classification of visual field defects.

We calculated normal values for the normal population of the Octopus G1 program (n = 836) and values for defective fields due to glaucoma and other diseases (n = 147) to determine indices for a nasal step in the interpretation of glaucomatous visual fields. We used different calculation procedures and correlated the results with the clinical evaluation of the visual field. All indices tested were able to detect and quantify nasal steps in defective fields and to separate them from normal findings (area under curve of Receiver Operating Characteristic curves 0.963 to 0.999). Indices calculated excluding sensitivity values of positions with the greatest distance from the horizontal meridian or weighting of sensitivity values according to their closeness to the horizontal meridian showed the best results (auc = 0.999). We can thus conclude that the calculation of an index for nasal step is a simple and effective adjunct to any interpretation system for visual fields.

[Unusual course of hypernephroma metastasis]. / Ungewöhnlicher Verlauf einer Hypernephrommetastase.

11 years after removal of a kidney because of hypernephroma a choroidal metastasis of this tumor grew. Clinically an inflammatory process had been suspected, thus leading to late correct diagnosis. The clinical and histological findings are presented. In the overall statistic of ocular metastasis seen in the university-eye-hospital in Hamburg, hypernephromas hold the 3rd place in the rank-list of the most common primary tumors. Thus, in case of a suspected ocular metastasis, in differential diagnosis a hypernephroma should be excluded.

[Antibody titer to Toxoplasma gondii in uveitis of toxoplasmosis and other origin]. / Antikörpertiter gegen Toxoplasma gondii bei Uveitiden toxoplasmotischer und anderer Genese.

The diagnostic value of toxoplasma serology in ocular toxoplasmosis is a controversial issue. Some authors feel that a positive titer indicates nothing more than that the patient had been exposed to Toxoplasma gondii at some stage. Even if in most cases the diagnosis is based on the morphological findings on the fundus, it might sometimes be useful to have an additional serologic evaluation. In a retrospective study we compared the level of antitoxoplasmosis antibodies (measured in a complement fixation test and an immunofluorescence test) in 75 patients with clinically proven ocular toxoplasmosis and 146 patients with uveitis of other origin. In our results we showed that the incidence of positive titers and antibody levels are significantly higher in patient with ocular toxoplasmosis than in other uveitis patient (chi 2-test, Mann-Whitney Willcoxon test, p = 0.05). There was no significant difference between antibody levels in patients with anterior uveitis, posterior uveitis or panuveitis of nontoxoplasmotic origin. No correlation between the antibody levels and amount of retinochorioidal fundus lesions could be found. Based on our results, we conclude that in cases where fundus findings are compatible with ocular toxoplasmosis and a complement fixation or immunefluorescence test is positive, specific antitoxoplasmotic therapy should be started.

[Humoral immune response to retinal S-antigen in patients with uveitis]. / Humorale Immunantwort gegen retinales S-Antigen bei Patienten mit Uveitis.

Experimental autoimmune uveoretinitis (EAU) is a predominantly T-cell-mediated autoimmune inflammatory disease of the retina and uveal tract of the eye. Retinal S-antigen, a protein found in retinal photoreceptor cells, is a potent agent for the induction of EAU in susceptible species and strains. Elevated titers of antibody to S-antigen have been reported in patients with different forms of uveitis. Serum samples from 166 patients and 87 healthy blood donors were tested by immunoblotting against human retinal abstract for IgG, IgM and IgA antibodies to S-antigen. Compared to the controls the patient sera showed a higher incidence of S-specific antibodies (17.5% vs 9.2%). No specific correlation between the presence of any type of uveitis and anti-S antibodies has been found (anterior uveitis 15.1%, posterior 19.6%, panuveitis 18.9%). There was a higher incidence especially with IgG antibodies during active disease (19.7% vs 9.2% in controls). The results suggest that since EAU is T-cell mediated, antibodies in humans may be most important as indicators of autoimmunity rather than mediators of the inflammation. As these anti-S antibodies might be induced by disruption and nonspecific inflammation of the retina and uvea alone, an important and difficult question in patients is whether or not these secondary autoimmune response can contribute to the induction of uveitis.

[Serologic diagnosis and follow-up in patients with uveitis. Antibodies to virulence antigens of Yersinia enterocolitica]. / Serologische Diagnostik und Verlaufskontrollen bei Patienten mit Uveitis. Antikörper gegen Virulenzantigene von Yersinia enterocolitica.

Sera from 72 patients with uveitis and sera from 93 healthy blood donors were analyzed by an immunoblot technique for antibodies to plasmid-encoded virulence associated antigens of Yersinia enterocolitica. In the group of patients with acute anterior uveitis (n = 16), antibodies of the classes IgA, IgG, IgM were significantly increased in comparison to the healthy blood donors. The presence of IgA antibodies is a sign of acute or persistent Yersinia infection. For the other forms of uveitis these antibodies were not identifiable in such a significant number of patients. After 2 years, clinical and serological investigations were carried out again in these patients. At the time of the second investigation, 25/72 (34.7%) of these patients showed intraocular inflammatory activity (group 1), but in 47/72 (65.3%) ophthalmological inflammation was no longer present (group 2). The serological investigation of group 1 and group 2 showed no significant difference in the antibody response to Y. enterocolitica. From these results we conclude that a persistent or acute Yersinia infection is a possible trigger for acute anterior uveitis. To investigate an infection with Yersinia enterocolitica, a method demonstrating antibodies to the plasmid encoded antigens of Y. enterocolitica must be employed, because the virulence and the persistence of infection can only be analyzed by this technique.

[Specificity of the humoral immune response to Candida albicans in patients with panuveitis]. / Spezifität der humoralen Immunantwort gegen Candida albicans bei Patienten mit Panuveitis.

Sera from 54 patients with panuveitis and 99 healthy blood donors were tested with an immunoblot assay for antibodies to 11 cytoplasmatic antigens of Candida albicans. In patients with panuveitis, IgG and IgM antibodies to a greater variety of Candida antigens were detected than in blood donors (t test, p = 0.005). Additionally, IgG antibodies to a 160-kDa protein and a 43-kDa protein, as well as IgM antibodies to the 160-kDa protein and a 67-kDa protein, were recognized more frequently in the sera of patients with panuveitis than in the sera of blood donors (U test, p = 0.05). These results suggest that in comparison to blood donors, patients with panuveitis have an altered immune response to Candida albicans.