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Considerations on the evolution of research on uveitis in the last thirty years. In the sixties, one was mainly looking for the etiology of the disease. Simultaneous serological investigations in serum and aqueous humor allowed in positive cases to conclude on a local antibody production, and thus certify the role of a given microbiological agent, for instance a virus. In the same time however, the importance of autantigens such as lens or uvea tissues was recognized. Even more important was the discovery of the s-antigen (soluble antigen) from the outer segments of the retinal photoreceptors, and with it the development of the model EAU (experimental autoimmune uveitis). Since 1970, multiple pathogenetical, for instance genetic, processes of uveitis could be studied on molecular-biological level, among them the mechanisms of antigen presentation or the role of the various lymphocyte subpopulations during the immune response. There was also an evolution about therapy of uveitis during these 30 years. Main drugs were in the sixties steroids and classical cytostatics, later came cyclosporin-A and other immune modulatory drugs such as FK-506. Finally, still only experimental, new methods of modulation of the disease are studied, such as changes in the presentation of the antigen or modulation of the immune response through monoclonal antibodies.

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Screening by immune disease is useful for one part in the various ocular inflammatory processes, uveitis, vasculitis, (epi)scleritis and myositis, for the other in collagen diseases with possible eye complications. The various forms of uveitis can be related either to rheumatic disease, to some HLA antigen, to a microbiological agent, sometimes to sarcoidosis. Retinal vasculitis remains almost always of unknown origin, while scleritis and myositis are often related to rheumatic disease, eventually to Wegener's granulomatosis. On the other side, in collagen disease (SLE, polymyositis, sclerodermia a.s.o.) the eye can participate either with fundus, scleral or orbital changes. Concerning therapy, steroids and immunosuppressive cytostatic drugs are the most useful; since most cases remain with unknown etiology, they cannot take benefit from specific therapy, except for instance the retinochoroiditis due to toxoplasmosis.

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Presentation is made of the ocular complications of AIDS which were observed in the ophthalmologic clinic of the University Hospital in Zurich from 1986 to 1991. Besides cotton-wool spots, CMV-retinitis is the most frequent and best known infectious complication. In all other infections, diagnosis is most difficult, because it could never be supported by histological examination. Presentation is made of some cases of acute retinal necrosis, toxoplasmosis, cryptococcosis, candida, and of some cases of uveitis with unknown etiology. Furthermore we present one intraocular non-Hodgkin lymphoma, some suspicions of Kaposi's sarcoma and some neurologic disturbances of central origin.

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The presumptive diagnosis of Candida endophthalmitis was made in 11 intravenous (i.v.) drug addicts, seven surgical patients and five individuals with no established risk factors. It was based on the clinical symptoms with partial to total visual loss and the findings of a retinohyalitic lesion eventually affecting the entire eye. Empiric antimycotic treatment consisted of i.v. amphotericin B (average cumulative dose 1,580 mg) and i.v. or oral flucytosine (mean cumulative dose 231 g). This treatment resulted in a significant mean improvement of visual acuity from 0.15 to 0.275 during treatment and 0.55 after completion of therapy. Long-term results showed stable scar healing of the inflammatory lesions and stable to improved visual acuity. Transient side effects of treatment included anemia, thrombocytopenia and a rise of serum creatinine. Empiric antimycotic treatment of presumptive Candida endophthalmitis favourably influences the course of this infection. Regular ophthalmological examination of these patients is mandatory.

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Presentation of 5 patients with acquired immune deficiency syndrome and unusual ocular complications. The first case appears as a non-specific, intermediate uveitis, the others as complications due to various infectious agents.

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Hopeless glaucoma cases fluctuate between excessive pressures and phthisis. Due to the underlying disease (neovascularization in the chamber angle, chronic inflammation, dysgenesis, aphakia) the customary surgical pressure-lowering operations often fail and medication is also useless. As a "last-ditch" measure, there remains only destruction of the ciliary body. In the Zurich eye department, noninvasive cyclophotocoagulation has been performed since 1987. The present paper reports on the first cases with long-term follow-up.

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The involvement of the retina in the inflammation being one important factor in severe uveitis, the authors have tested the "ganzfeld" electroretinogram (ERG) in various forms of uveitis, especially in cases having opaque media. In Fuchs' syndrome and chronic anterior uveitis, the ERG is normal or only slightly altered, while important reduction of the potentials can occur even in case of good vision in intermediate uveitis, probably indicating concomitant retinal vasculitis. In Behçet's disease, ERG is mostly useful in testing the efficacy of therapy. ERG can be rather deceiving in idiopathic vasculitis, where the potentials are not always as reduced as expected. On the contrary, this test seems to allow differential diagnosis between Harada's disease and acute multifocal placoid pigment epitheliopathy. However, one must bear in mind that concurrent steroid treatment can elevate the amplitude of the potentials, a phenomenon which has to be taken into account when interpreting ERG results.

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Diagnosis of intraocular inflammations can be difficult, particularly if the patient is suffering from immunodeficiency. Among the endogenous inflammations this applies mainly to cases of hyaloretinitis caused by Candida or other fungi, often presenting as an acute hyalitis with sudden onset; the various ocular complications of AIDS, especially those due to toxoplasmosis (rare) and cytomegalovirus, and lyme disease, which can occasionally cause chronic panuveitis. Among the exogenous cases it applies to postoperative and posttraumatic endophthalmitis. In all these cases the diagnosis has to be established clinically if possible, since, as a consequence of the immunodeficiency, serology is hardly helpful, and only biopsy (of the vitreous) may provide additional information. Rapid diagnosis is very important because of the urgent need for therapy.

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Immunodepressive or immunoregulatory drugs might be indicated among the therapeutic possibilities in uveitis and associated diseases, especially in those cases, which resist to specific treatment and steroids, and in those in which disorders of the immune system play a pathogenetic role. Classical cytostatic drugs mainly act by a reduction of the amount of circulating lymphocytes. The most useful seem to be the alkylating drugs (chlorambucil, cyclophosphamide) and antimitotics (procarbazine, colchicine), or antifolic (methotrexate), while the antipurines (azathioprine) seem to us less effective. Such therapy requires the full consent of the patient. The dosage of the drug has to be well established in order to keep the total amount of leucocytes between 4,000-5,000/mm3. Side effects can be hair loss, sterility, rarely hemorrhagic cystitis, and, mostly only in the initial therapy period, nausea and vomiting. Teratogenic risks seem non-existent. Since the therapeutical effect comes rather slowly, a local steroid therapy can be added. Absolute indications for such therapy are Behçet and sympathetic ophthalmitis, while all severe chronic uveitis forms are relative indications. Acute iritis and chorioretinitis are contraindications. The results with procarbazine and cyclophosphamide run around 40% full successes (healing of inflammation and improvement of function) and 30% satisfactory results (healing of inflammatory signs, without improvement of function). Failures amount to 17% and 13% of the patients cannot be thoroughly controlled. With regard to the failures, alternative treatment might be attempted with cyclosporin A, plasmapheresis or perhaps immunostimulation.

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Intermediate uveitis defines the group of diseases formerly called pars planitis or chronic cyclitis. Its frequency amounts to 10-20% of all uveitis cases. The anamnesis is vague. The clinical symptoms mainly involve the vitreous. The visual acuity is variable, depending of the involvement of the retina. A slight inflammation of the anterior chamber is possible, but no synechiae are present. The vitreous shows a positive Tyndall and cells, snow balls, eventual plaques on the pars plana. Serious cases are complicated by a retinal vasculitis, which often leads to cystic macular edema and papillary edema. Schisis and retinal holes are more seldom. A complicated cataract can develop. The most valuable complementary tests are fluorescein angiography and electroretinography, useful to detect retinal damage. Aetiological investigations give mostly poor results and are not very useful. Differential diagnosis has to be made, among others, from Fuchs' heterochromic cyclitis and from acute cellular infiltration of the vitreous in case of retinochoroiditis or candida endophthalmitis. Treatment of intermediate uveitis can be only local and discrete when only the vitreous is involved. If the retina is damaged, systemic steroids or immunodepressive cytostatic drugs might be indicated. Despite the duration of the disease, its prognosis remains rather good. Only about 15% of the cases end up with visual impairment to 1/10 or less, while more than half of the cases maintain a visual acuity higher than 0.6, even after three years of disease progress.

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We present middle and long-term results of cyclophosphamide and procarbazine therapy of Behçet's uveitis. Of 45 patients, 20 were followed for 1-4 years (14 successful cases, 5 satisfactory results with regression of inflammatory signs but no functional improvement, 1 failure), 17 for 5-10 years (9 successes, 5 satisfactory results, 3 failures), and 8 for 11-16 years (2 successes, 2 satisfactory results, 4 failures). The high percentage of success (over 55%) could be attributed partly to the early onset of therapy and may be partly to the choice of drugs.

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This paper presents a short review of some inflammatory diseases which involve both the nervous system and the uvea, and of some forms of uveitis whose onset could be neurogenic. Multiple sclerosis and reticulum cell sarcoma are examples of systemic neurologic diseases which can be accompanied by uveitis or pseudo-uveitis. Syndromes such as Behçet's or Vogt-Koyanagi-Harada are characterized not only by a highly severe panuveitis but also by the participation of optic nerve, meningeal, and brain tissues in the inflammatory process. The occurrence of sympathetic ophthalmia and herpetic uveitis could to a certain extent be due to a neurogenic transmission of the antigen. For Fuchs' heterochromic cyclitis, however, the old theory of sympathetic nerve dysfunction at its origin is no longer widely accepted.

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The beta-blocking agent carteolol hydrochloride differs slightly from other beta-blockers by its intrinsic sympathomimetic activity. Its effect on intraocular pressure and heart rate was tested in a comparison with timolol maleate, as was subjective tolerance of it, in 28 eyes (14 subjects) with either ocular hypertension or simple chronic open-angle glaucoma. The two drugs had a similar effect on intraocular pressure; both were well tolerated subjectively. Carteolol lowered heart rate more in patients with higher heart rates, while timolol lowered it more in patients with lower heart rates.

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