Christina Meenken

Outcomes of HLA-B27-Positive and HLA-B27-Negative Acute Anterior Uveitis

PURPOSE Outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis were assessed after a mean follow-up of nine years. Rheumatologic complications, in particular the presence and course of ankylosing spondylitis, were examined during the same period. METHODS A hospital-based prospective study of 119 patients with HLA-B27-positive and 35 patients with HLA-B27-negative acute anterior uveitis was performed. All patients underwent a complete ophthalmologic and rheumatologic examination, including sacroiliac x-rays, and were examined again nine years later. RESULTS No statistically significant differences in ocular complications and visual outcome were found between both patient groups with acute anterior uveitis after nine years. Posterior synechiae were observed in one half of the affected eyes. Blindness was infrequent. Rheumatologic complications, including ankylosing spondylitis, originally seen in one half of the HLA-B27-positive patients, were observed in two thirds of the patients nine years later, compared to only two of 35 HLA-B27-negative patients. When ankylosing spondylitis was evident at first examination no clinically significant deterioration was observed nine years later. CONCLUSIONS After nine years we observed an ocular outcome equal for both patient groups. A small percentage of affected eyes became blind. Rheumatologic complications occurred in 55 (72%) of 76 HLA-B27-positive males and in 24 (56%) of 43 HLA-B27-positive females with acute anterior uveitis. The rheumatologic complications had a good prognosis.

Effects of protease inhibitors on the course of CMV retinitis in relation to CD4+ lymphocyte responses in HIV+ patients

AIM To gain insight into the course of CMV retinitis (CMVR) in AIDS patients receiving protease inhibitors (PI), and to evaluate whether certain patterns of CD4 response are indicative of the clinical outcome and the risk of recurrence. METHODS 15 consecutive AIDS patients receiving maintenance therapy for CMVR were included in a prospective observational cohort study at the university hospital between July and October 1996. Patients were evaluated for signs of CMVR activity and intraocular inflammation. CMVR recurrence was defined as the primary clinical endpoint. Follow up was performed until July 1997. No patient was lost to follow up. Clinical outcome was related to CD4+ lymphocyte counts, which were monitored every 6 weeks. Highly active antiretroviral treatment regimen including PI was started at study entry. RESULTS All recurrences (n=7) were in patients who failed to have a sustained increase in CD4 counts, whereas CMVR remained inactive during a follow up of 42–52 weeks in those who were able permanently to restore their CD4 values to 100×106/l or more (n=5). The remaining three patients died after 12, 16, and 50 weeks, respectively, without recurrences. All relapses of CMVR were seen after 6–16 weeks, and at CD4 counts well below 100×106/l. CONCLUSIONS The beneficial effects of PI treatment correlate with the pattern of CD4 response. Sustained increases in CD4 counts achieved in the first 16 weeks of treatment are associated with a prolonged period of CMVR quiescence. Poor initial response is associated with a high risk of CMVR recurrence.

Uveitis and Diabetes Mellitus

Of 340 patients with anterior uveitis, 20 (6%) had diabetes mellitus. This is significantly higher than the prevalence of 1.4% in the normal Dutch population (P less than .001). Of 128 patients with idiopathic anterior uveitis, 16 (12.5%) had diabetes mellitus compared to only four (1.9%) of 212 patients with anterior uveitis with an established specific ocular diagnosis (P less than .001). Of the 16 diabetic patients with idiopathic anterior uveitis, ten (63%) had type I diabetes mellitus and 12 (75%) suffered from severe diabetic complications as angiopathy, nephropathy, and neuropathy. The onset of diabetes mellitus preceded the onset of anterior uveitis in all cases. Whether or not uveitis in diabetic patients is a true inflammation rather than an ischemic phenomenon is still unknown.

Ocular immune reconstitution inflammatory syndromes

Purpose of reviewThe aim of this article is to review the current literature concerning immune reconstitution inflammatory syndrome in relation to the eye. The definition, epidemiology, pathophysiology, risk factors, clinical features, diagnosis and treatment are discussed. Recent findingsImmune reconstitution inflammatory syndrome affecting the eye has been documented in association with cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy in a large number of patients. This syndrome is referred to as immune recovery uveitis, which is presumed to be mediated by recovery of immune responses specific to residual cytomegalovirus antigen located in the eye. In addition to improved immunity itself, risk factors include a low CD4+ T count at the time of initiation of highly active antiretroviral therapy and involvement of a larger proportion of retina. Immune recovery uveitis is a major cause of visual loss and morbidity among patients with AIDS who are receiving highly active antiretroviral therapy. SummaryImmune recovery uveitis is the most common form of immune reconstitution inflammatory syndrome in HIV-infected patients with cytomegalovirus retinitis who are receiving highly active antiretroviral therapy. Clear clinical definitions are required for ocular immune reconstitution inflammatory syndromes to avoid misclassification of other inflammatory conditions. A multidisciplinary approach is important in the diagnosis and management of immune recovery uveitis.

Association of progressive outer retinal necrosis and varicella zoster encephalitis in a patient with AIDS.

BACKGROUND: A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection. METHODS: Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation. RESULTS: While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection. CONCLUSION: This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient.

Cytomegalovirus (CMV) strain differences between the eye and blood in AIDS patients with CMV retinitis.

Objective:To investigate possible differences in cytomegalovirus (CMV) strain distribution between the eye and blood in AIDS patients with CMV retinitis. Methods:CMV DNA sequences from aqueous humour and peripheral blood leukocytes (PBL), obtained from 13 AIDS patients with CMV retinitis, were compared. DNA was isolated and the CMV IE-1 sequence (part of the immediate early-1 gene) and the a-sequence (located in the a-region) were amplified by polymerase chain reaction (PCR). The PCR products of the a-sequence were analysed by Southern blotting for amplified fragment-length polymorphisms. The level of divergence between the a-sequences of aqueous humour- and PBL-derived CMV was studied in two patients by cloning these sequences followed by sequence analysis. Results:CMV DNA could be detected in all aqueous humour samples and in 10 out of 13 paired blood samples. In the 10 patients, with CMV DNA detectable in both aqueous humour and PBL, seven cases showed differences between the amplified products of both compartments. Sequence analysis in two patients revealed that the aqueous humour and PBL of the same patient can harbour both identical, similar and highly divergent CMV a-sequences. Conclusion:These results indicate that despite the haematogenous spread of CMV, the eye, being a relatively shielded organ, may contain CMV strains different from those found in the blood.

Diagnostic and therapeutic dilemmas in ocular toxoplasmosis.

Ocular toxoplasmosis, a leading cause of visual handicaps in young people, represents a late manifestation of congenital infection in the majority of cases. Ocular involvement in acquired toxoplasmosis has been repeatedly reported and shows that toxoplasmic retinitis may develop in the wake of acquired infection. The diagnosis of ocular toxoplasmosis is mainly clinical since serologic tests are positive for a considerable percentage of the general population and are not indicative for ocular involvement. The demonstration of local synthesis of toxoplasma antibodies in the eye by intraocular fluid analysis is a valuable diagnostic tool. The application of the polymerase chain reaction, in which the parasites DNA is detected, may be expected to change the diagnostic repertoire drastically in the future. The need for appropriate therapy for patients with ocular toxoplasmosis is a matter of continued debate: the majority of the medications used for treatment have potentially serious side effects and the efficacy of treatments has not been clarified in previous studies. Recently, a prospective multicenter study to evaluate the efficacy of current therapeutic strategies for ocular toxoplasmosis was performed in The Netherlands and included 106 patients with active ocular toxoplasmosis. The principal conclusion of this study is that only drug therapy with pyrimethamine had any perceptible influence on any aspect of ocular toxoplasmosis, but this effect may not be worth the risk of side effects except in fovea threatening lesions.