Allegonda Van der Lelij

Uveitis masquerade syndromes

BACKGROUND Incorrect diagnosis of the uveitic masquerade syndromes (UMS) may have severe consequences. In this study, the frequency, clinical manifestations, and informative diagnostic tests for UMS are described. DESIGN Retrospective observational case series. PARTICIPANTS Forty patients with UMS were identified in a cohort of 828 consecutive patients with uveitis. The mean follow-up was 4.5 years. METHODS A review of clinical, laboratory, photographic, and angiographic records was performed. MAIN OUTCOME MEASURES Clinical features, associated systemic diseases, diagnostic procedures and their role in the diagnostic process, and systemic and visual outcomes. RESULTS Nineteen patients had intraocular malignancy (48% of all with UMS; 2.3% of all with uveitis), mainly intraocular lymphoma (n = 13) and leukemia (n = 3). The ophthalmologist was the first to recognize malignant disease in 11 of 19 patients (58%). Of 21 patients with nonmalignant UMS, 10 had an ocular vascular disease and 5 a hereditary ocular disorder. The patients with malignant UMS were older than those with nonmalignant UMS (average age, 50 vs 44 years, P: < 0.05). During follow-up, 9 of 19 patients with malignant UMS died. The most informative diagnostic procedure for malignant UMS was intraocular fluid analysis; for nonmalignant UMS, fluorescein angiography. The cytologic analysis of intraocular fluids yielded the best results for diagnosing intraocular malignancies (7 of 11 patients, 64%); the association of negative cytologic results with the recent administration of systemic corticosteroids was noted. Immunophenotyping of the aqueous confirmed the diagnosis of hematologic malignancy for 3 of 5 patients examined. Panuveitis was the most frequent manifestation of malignant UMS. Intraocular lymphomas presented with isolated vitreitis (n = 6), chorioretinal lesions (n = 5) and iris infiltration (n = 2). Clinical presentation of nonmalignant UMS was diverse but consisted mainly of abnormalities of the retinal vasculature. CONCLUSIONS UMS was diagnosed in 5% of the patients with uveitis at a tertiary center. Despite the variety of underlying disorders and different clinical presentations, a high frequency of malignant and vascular diseases was found. Awareness of the clinical manifestations of UMS and application of the correct diagnostic procedures should promote timely diagnosis and treatment, which are essential not only for visual acuity but also for the life of the patient.

Anterior uveitis with sectoral iris atrophy in the absence of keratitis: a distinct clinical entity among herpetic eye diseases.

OBJECTIVE To determine the cause and describe the clinical features of unilateral anterior uveitis with sectoral atrophy of the iris in the absence of associated keratitis. DESIGN Retrospective, observational case series. PARTICIPANTS Thirty-one patients with unilateral anterior uveitis with sectoral iris atrophy and without (previous) keratitis. METHODS The patients were selected from our database of 592 patients with anterior uveitis. MAIN OUTCOME MEASURES We reviewed the clinical data on the 31 patients and the results of diagnostic anterior chamber fluid analysis for 24 of the 31 patients. Specifically, production of local antibodies against herpes simplex virus (HSV) and varicella zoster virus (VZV) was determined and the polymerase chain reaction was performed to demonstrate the DNA of HSV, VZV, and cytomegalovirus (CMV) in the aqueous samples. RESULTS Main clinical characteristics of anterior uveitis with iris atrophy included unilateral involvement with a prolonged course and recurrent exacerbations in all cases. Elevated intraocular pressure during intraocular inflammation occurred in 90% of patients (28 of 31). Visual outcome was favorable because 29 of 31 patients (94%) retained a visual acuity of 20/32 or more. The causal agent was identified as HSV in 83% (20 of 24) and VZV in 13% (3 of 24) and was inconclusive in one case. The patients with HSV uveitis were younger than those with VZV uveitis (mean age at onset 34 and 65 years, respectively; P = 0.0056). CONCLUSIONS Unilateral anterior uveitis with sectoral atrophy of the iris without associated (previous) keratitis is a distinct entity among herpetic eye diseases. Recurrent unilateral anterior uveitis with iris atrophy and/or elevated intraocular pressure has most likely been caused by HSV.

Detection of intraocular antibody production to herpesviruses in acute retinal necrosis syndrome

In order to improve the determination of the causative agent in acute retinal necrosis syndrome, we evaluated the detection of intraocular antibody production to herpesviruses in 28 patients with this disease. Intraocular antibody production was determined by calculation of the Goldmann-Witmer coefficient whereby specific antibody titers in the inflamed eye and circulation are related to the total IgG content in ocular fluid and serum. Specific antibody titers to herpesviruses and Toxoplasma were determined by the indirect immunofluorescence technique. Thirty-five patients with ocular toxoplasmosis, cataract, or proliferative vitreoretinal disorders were tested as controls. By this technique, intraocular antibody production to varicella zoster virus or herpes simplex virus could be established in 16 (57%) of the patients with the typical clinical features of acute retinal necrosis, compared to none of the controls. Of the 33 affected eyes, 21 (64%) had a visual outcome of less than 20/200. We concluded that detection of intraocular antibody production to herpesviruses may be a useful diagnostic tool in establishing the causative agents in acute retinal necrosis.

Peripheral Multifocal Chorioretinitis: A Distinct Clinical Entity?

OBJECTIVE The purpose of the study is to delineate the clinical features, complications, visual prognosis, and associated systemic diseases of peripheral multifocal chorioretinitis. DESIGN The study design was a retrospective study. PARTICIPANTS Of 828 patients with uveitis, 53 patients (6.4%) fulfilled all 3 of the following criteria: (1) the presence of multiple (>10), small, round, punched-out lesions in the peripheral retina; (2) the absence of central chorioretinal lesions; and (3) an associated intraocular inflammatory reaction. RESULTS The majority of patients were elderly white females with bilateral ocular involvement. The presenting symptoms consisted of vitreitis and/or iritis, papillitis, and numerous retinal punched-out lesions in the periphery. On initial examination, the complications included cystoid macular edema (CME) (48%), glaucoma (25%), and cataracts (19%), resulting in a mean visual acuity of 20/80. After more than 2 years of follow-up, CME was found in 72% and cataract in 62% of the affected eyes. Submacular neovascularization never developed. The final mean visual acuity was 20/60; this was mainly dependent on the presence of CME (eyes with CME; visual acuity was 20/80, eyes without CME; visual acuity was 20/50). In 25% of patients, an association with sarcoidosis was observed (histologic and radiologic diagnoses), and an additional 29% of patients had elevated serum angiotensin-converting enzyme levels. CONCLUSIONS Within the spectrum of multifocal chorioretinitis, the authors have defined a distinct clinical entity of peripheral multifocal chorioretinitis. The recognition of this clinical entity may be valuable because of its specific symptoms, prognosis, and association with sarcoidosis.

SIDE-EFFECTS OF IVERMECTIN IN TREATMENT OF ONCHOCERCIASIS

In a prospective study to determine the tolerance for and safety of ivermectin therapy for onchocerciasis in a hyperendemic area in Sierra Leone, 28 (32%) of 87 patients had adverse reactions that required treatment with acetylsalicylic acid and antihistamines, but none of the observed adverse reactions were considered life-threatening. A significant relation was found between the frequency and severity of side-effects and the degree of parasite infestation, as quantified by the skin-snip counts. Free administration of ivermectin to severely infected onchocerciasis patients is not recommended without some form of medical supervision.

Reactivations of ocular toxoplasmosis after cataract extraction.

PURPOSE To determine the risk of reactivation of ocular toxoplasmosis following cataract extraction. DESIGN Retrospective case-control study. PARTICIPANTS Out of 154 patients with ocular toxoplasmosis, 14 patients (15 eyes) who had undergone a cataract extraction and 45 age- and sex- matched controls without cataract were selected. INTERVENTION A review of the medical records of 14 patients with ocular toxoplasmosis and cataract and 45 control patients with ocular toxoplasmosis but without cataract. The clinical records of the controls and patients were assessed for an identical 4-month period following the date of the cataract extraction in the index patients. MAIN OUTCOME MEASURES Development of a new active retinal lesion within 4 months after cataract surgery in patients and age -and sex matched-controls. The presence of risk factors such as sex, congenital or postnatal acquisition of ocular toxoplasmosis, age at first clinical manifestation of ocular toxoplasmosis, total number of attacks per affected eye, type of cataract, age at the time of cataract surgery and the intervals between surgery and first clinical manifestation of ocular toxoplasmosis and between surgery and the last recurrence of ocular toxoplasmosis, as well as the use of antiparasitic medication during surgery, type and complications of surgery and optimal visual acuity before and after cataract surgery. RESULTS Reactivations of ocular toxoplasmosis following cataract extraction occurred in 5/14 patients (5/15 eyes), which was higher than the incidence of recurrences in age -and sex-matched controls (p < 0.001). No additional risk factors for the development of recurrences of ocular toxoplasmosis after cataract surgery were found. Incidence of recurrences preceding surgery did not differ between patients and controls. CONCLUSION We identified an increased risk of reactivation of ocular toxoplasmosis following cataract extraction which implies that prophylactic treatment with antiparasitic drugs during and after the cataract surgery might be worthwhile for patients at risk of visual loss.

Detection of herpes simplex virus type 1, 2 and varicella zoster virus DNA in recipient corneal buttons

AIM To study the value of polymerase chain reaction (PCR) analysis, to detect viral DNA in recipient corneal buttons taken at the time of penetrating keratoplasty (PKP) in patients with an initial diagnosis of herpetic stromal keratitis (HSK). Since HSK has a tendency to recur, an accurate diagnosis of previous HSK could be the reason to start antiviral treatment immediately, thereby possibly decreasing the number of graft failures due to recurrent herpetic keratitis. METHODS Recipient corneal buttons and aqueous humour (AH) samples were obtained at the time of PKP from HSK patients (n=31) and from other patients (n=78). Eye bank corneas were also used (n=23). Herpes simplex virus type 1 (HSV-1), type 2 (HSV-2), and varicella zoster virus (VZV) infection were assessed by PCR and antibody detection. RESULTS The clinical diagnosis HSK could be confirmed by PCR for HSV-1 in 10/31 (32%). In these corneal buttons HSV-2 DNA was detected in 1/31 (3%) and VZV DNA in 6/31 (19%). Intraocular anti-HSV antibody production was detected in 9/28 AH samples tested (32%). In the other patient derived corneas HSV-1 DNA was detected in 13/78 (17%), including eight failed corneal grafts without clinically obvious herpetic keratitis in the medical history. In clear eye bank corneas HSV-1 was detected in 1/23 (4%). CONCLUSIONS PCR of HSV-1 on corneal buttons can be a useful diagnostic tool in addition to detection of intraocular anti-HSV antibody production. Furthermore, the results were suggestive for the involvement of corneal HSV infection during allograft failure of corneas without previous clinical characteristic signs of herpetic keratitis.

Herpes simplex virus type 1 (HSV‐1)–induced retinitis following herpes simplex encephalitis: Indications for brain‐to‐eye transmission of HSV‐1

Herpes simplex encephalitis is a severe neurological disease with high mortality and morbidity rates. Reactivated herpes simplex virus type 1 (HSV‐1) can cause relapses and might even spread to the retina, where it can induce a potentially blinding eye disease, known as acute retinal necrosis. In the present study, the HSV‐1 strains in the brain and eye of 2 patients with acute retinal necrosis following an episode of herpes simplex encephalitis were genotyped. The HSV‐1 strains in both the brain and eye were identical in each patient, but they differed interindividually. The data suggest brain‐to‐eye transmission of HSV‐1 in these patients. Ann Neurol 2001;49:104–106

T Cells Specific for the Triggering Virus Infiltrate the Eye in Patients with Herpes Simplex Virus-Mediated Acute Retinal Necrosis

Acute retinal necrosis (ARN) is a rare, potentially blinding retinal disease resulting from ocular infections with herpes simplex virus (HSV) or varicella-zoster virus (VZV). To determine the antigen specificity and functional characteristics of ocular infiltrating T cells in ARN, T cells were isolated and expanded nonspecifically from intraocular fluid (IOF) samples from 2 patients with HSV-1- and 3 with VZV-mediated ARN. HSV-specific T cell reactivity could be detected only in the IOF-derived T cell lines (TCLs) of the 2 patients with HSV-mediated ARN. These TCLs consisted of both HSV type-common and type-specific CD4+ and CD8+ T cell clones (TCCs) with differential T cell receptor usage. Irrespective of their phenotype, the TCCs were cytolytic and secreted interferon-gamma, tumor necrosis factor-alpha, interleukin-4, and interleukin-5. In both patients, the antigen specificity of a substantial number of HSV-1-specific TCCs could be mapped to approximately 0.67-0.73 HSV-1 map units. The data presented suggest the contribution of T cells, specific for the triggering virus, to the pathogenesis of ARN.

Characteristics of soluble immune complexes prepared from oligovalent DNP conjugates and anti-DNP antibodies

The stability of soluble immune complexes was investigated after isolation by gel filtration and sucrose gradient ultracentrifugation. Soluble immune complexes were formed between specific goat anti-dinitrophenol (DNP) antibodies and DNP conjugated to a large (19 S) carrier, namely bovine thyroglobulin. The composition and molecular weight of these complexes were determined by ultracentrifugation on calibrated sucrose density gradients and the use of different isotopic markers for antigen and antibody. A good separation of immune complexes containing one, two, or three antigen molecules per complex was obtained by ultracentrifugation while gel filtration was less effective. Ultracentrifugational analysis of fractions isolated by these two procedures showed that large immune complexes containing more than one antigen were relatively labile, whereas small immune complexes containing one antigen were stable. The stability of large immune complexes was dependent on dilution. Because dilution affects the size and composition of soluble immune complexes, it is important to emphasize that for the investigation of a causal relationship between the biological properties and the size and composition of immune complexes, analysis of the immune complexes should be performed in the same dilutions in which they will be used experimentally.