P.T.V.M. de Jong

Serologic and Polymerase Chain Reaction Analysis of Intraocular Fluids in the Diagnosis of Infectious Uveitis

PURPOSEnInfectious uveitis entities are usually rapidly progressive blinding diseases that can be prevented by prompt administration of specific antimicrobial therapy. With the aim of improving early diagnosis in patients with infectious uveitis, intraocular fluid samples from patients with sight-threatening posterior uveitis were investigated to determine the causative agent.nnnMETHODSnThirty-eight patients with acquired immunodeficiency syndrome (AIDS) and retinitis, eight immunosuppressed patients with retinitis, 16 immunocompetent patients with acute retinal necrosis, and 22 immunocompetent patients with toxoplasmic retinochoroiditis were analyzed by polymerase chain reaction for the presence of herpesviruses and Toxoplasma gondii DNA and for local antibody production against these microorganisms.nnnRESULTSnIn patients with AIDS and retinitis, polymerase chain reaction was positive for cytomegalovirus DNA in 21 (91%) of the 23 ocular fluid samples obtained during active cytomegalovirus retinitis, whereas local antibody production analysis was negative in all cases. In acute retinal necrosis, varicella-zoster virus or herpes simplex virus could be established as the inciting agent in 81% of the cases, using the combination of both techniques. Polymerase chain reaction was positive in all samples obtained within two weeks after the onset of disease. Toxoplasma gondii DNA was detected in 4 of 13 samples (31%) from immuno-competent patients with active toxoplasmic retinochoroiditis; in each case, local antibody production was also detected. In contrast, no local antibody production was observed in two of three samples from transplant recipients that were positive for T. gondii DNA. All the control samples tested were negative for the above-mentioned tests.nnnCONCLUSIONSnIn patients with AIDS, polymerase chain reaction analysis is preferable above local antibody production in detecting the inciting agent of retinitis. In other cases, the combination of both techniques can make a valuable contribution to the diagnosis.

Clinical Features of Acute Anterior Uveitis

We studied the clinical features and prognosis of 73 patients with HLA-B27 positive and 71 patients with HLA-B27 negative acute anterior uveitis using computer analysis of more than 50 variables per patient. The patients with HLA-B27 positive acute anterior uveitis showed the following characteristics which were significantly different from patients with HLA-B27 negative acute anterior uveitis: younger age at onset; high male to female ratio; frequent unilateral alternating eye involvement; severe ocular symptoms during activity, such as presence of fibrin in the anterior chamber; absence of mutton fat keratic precipitates; high incidence of ocular complications; and frequent association with seronegative spondyloarthropathies. Despite the difference of disease severity and incidence of complications, the long-term visual outcome did not differ significantly between the two groups. No distinctions were observed when patients with HLA-B27 positive acute anterior uveitis were subdivided according to sex or the presence of ankylosing spondylitis. HLA-B27 positive acute anterior uveitis formed a distinct clinical entity associated with serious prognosis as compared to HLA-B27 negative acute anterior uveitis.

Therapy for ocular toxoplasmosis.

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

The Proteinaceous Coating and Cytology of Implant Lenses in Rabbits

We performed extracapsular lens extraction with implantation of a J-loop posterior chamber lens in 14 rabbit eyes. Postoperatively, the animals were examined by slit lamp. They were killed after varying survival times of up to 12 weeks, and the implants were examined by scanning electron microscopy. Three days after the operation a thin amorphous coating that did not consist of collagen was found covering all implants. Three cell types were present on the coating: macrophages, leukocytes, and flattened giant cells. This coating resembled morphologically the fibronectin coating on intraocular lenses in vitro.

Fuchs' heterochromic cyclitis: review of the literature on the pathogenetic mechanisms.

Fuchs theory Ernst Fuchs, who first described this disease in 1906, assumed that the syndrome was caused by a noxious factor of unknown origin, which was active from fetal or early postnatal life. First, the normal development of uveal pigmentation would be inhibited, resulting in heterochromia (Fig 1). Later, the eye would respond to this pathological agent by a low grade inflammation. Many objections were raised against Fuchs theory. The heterochromia was not always congenital and there were no signs of overt ocular inflammation.

Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes

Several studies suggest a role for IL-6 in the pathogenesis of uveitis. Earlier we have shown that aqueous humour obtained from patients with uveitis contained raised levels of IL-6. In the study described here we investigated the IL-6 levels in vitreous fluid samples obtained from 75 uveitis patients with different uveitis entities. Vitreous samples from 14 patients with proliferative intraocular disorders (PID) and 29 eye bank eyes were used as controls. All the samples were tested in the IL-6 B9 bioassay as well as in a sensitive ELISA for IL-6. Raised IL-6 levels were detected in the vitreous fluid of uveitis patients as well as patients with PID, implicating IL-6 as a common inflammatory mediator. The highest mean level of IL-6 was found in the vitreous fluid of patients with acute retinal necrosis. The mean IL-6 levels measured by the ELISA were higher compared to the levels measured by the B9 bioassay. This may be caused by the presence of B9 bioassay inhibitory factors in the vitreous fluid of these patients.

An Ultrastructural Study of Elsehnig's Pearls in the Pseudophakic Eye

In two pseudophakic human eyes, obtained post mortem, Elschnigs pearls were visible biomicroscopically. One eye contained a medallion lens and the other an iridocapsular lens (implanted for 53 months and 39 months, respectively). The medallion lens was fixed to the iris but was not attached to the Soemmerrings ring. Elschnigs pearls and star-shaped cells were found on the posterior capsule in the pupillary space. One loop of the iridocapsular lens was encased in the Soemmerrings ring whereas the other was located between the iris and the lens remnants. The Elschnigs pearls were on the anterior side of the ring; only a few were in the pupillary space. Two other pseudophakic eyes with clear posterior capsules also contained small numbers of Elschnigs pearls on or just near the peripheral lens remnants.

Therapy of ocular toxoplasmosis

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n=106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n=29); group 2. clindamycin, sulphadiazine and corticosteroids (n=37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n=8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n=32). Patients from group 1 received leucovorin 5 mg twice a week.No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P<0.05).We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis.

Using immunohistochemical techniques, we analyzed iris biopsy specimens from eight patients with Fuchs heterochromic cyclitis, seven patients with various other types of uveitis, and eight glaucoma patients without uveitis. No specific abnormalities related to Fuchs heterochromic cyclitis could be detected. Four of the patients with Fuchs heterochromic cyclitis and four of the patients with uveitis showed evidence of an inflammatory cell infiltrate, which was a mixture of interleukin-2 receptor-negative T helper and suppressor cells, B lymphocytes, and plasma cells. Only an occasional T lymphocyte could be seen in two of the patients without uveitis. The class II antigen HLA-DR was expressed on iris stromal cells in every patient in the Fuchs heterochromic cyclitis group and uveitis group and in six of the patients in the nonuveitis group. In six of the Fuchs heterochromic cyclitis patients, including two without immunohistochemical evidence of inflammatory cell infiltrate, histologic abnormalities were present on hematoxylin and eosin sections.

Immune Deposits in Iris Biopsy Specimens From Patients With Fuchs' Heterochromic Iridocyclitis

To investigate whether Fuchs heterochromic iridocyclitis may be an immune complex vasculitis, we used an immunofluorescence technique to detect immunoglobulins and complement in iris biopsy specimens from nine patients with Fuchs heterochromic iridocyclitis, 12 patients with other types of uveitis, and nine patients with glaucoma but without uveitis. No specific immune deposits were observed in the irises of the patients with Fuchs heterochromic iridocyclitis. Immunoglobulin G, IgA, IgM, and complement were detected in patients with Fuchs heterochromic iridocyclitis and patients with uveitis, and these results differed significantly (P less than .05) from the group without uveitis. The immune deposits were found only in the iris vessel walls. No light-microscopic evidence of an inflammatory vascular process could be detected. Further studies are necessary to investigate whether the immune reactants originate from the circulation or result from local formation.