M. S. A. Suttorp-Schulten

A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis.

OBJECTIVE To compare the effects of two treatment regimens, one of which included azithromycin, for the treatment of sight-threatening (near optic disk or fovea) ocular toxoplasmosis. DESIGN Prospective, randomized open-labeled multicenter study, masked in part with regard to evaluation. METHODS PARTICIPANTS TOTAL ENROLLMENT: 46 patients with sight-threatening ocular toxoplasmosis; pyrimethamine and azithromycin group: 24 patients; pyrimethamine and sulfadiazine group: 22 patients. INTERVENTION Patients were randomized into two treatment regimens. Group 1 was treated with pyrimethamine and azithromycin complemented with folinic acid and the addition of prednisone from day 3. Group 2 was treated with pyrimethamine and sulfadiazine complemented with folinic acid and the addition of prednisone from day 3. Patients used study medications daily for 4 weeks. Ocular and laboratory examinations were performed at least weekly during the observation period. The study was masked in part with regard to evaluation. MAIN OUTCOME MEASURES An assessment was made of the time to resolution of the intraocular inflammatory activity, the size of the retinochoroidal lesion, and visual acuity before and after the treatment as well as all adverse effects of treatments. RESULTS Adverse effects were more frequent in the pyrimethamine/sulfadiazine group (P <.04), and three patients in this group had to discontinue treatment. The time to resolution of inflammatory activity, decrease in size of retinochoroidal lesions, and optimal visual acuity did not differ between the two treatment groups. The number of patients who developed recurrences during the first year after treatment was similar for both groups. CONCLUSIONS The efficacy of the multidrug regimen with pyrimethamine and azithromycin was similar to the standard treatment with pyrimethamine and sulfadiazine. However, the frequency and severity of adverse effects was significantly lower with a regimen containing pyrimethamine and azithromycin. Multidrug therapy with the combination of pyrimethamine and azithromycin appears to be an acceptable alternative for treatment of sight-threatening ocular toxoplasmosis.

A new ultrasonographic method to detect disease activity and predict response to immunosuppressive treatment in Graves ophthalmopathy

Purpose: To determine whether the internal reflectivity of the eye muscles on Amode ultrasonography serves as indicator for disease activity in Graves ophthalmopathy, thereby predicting response to immunosuppressive treatment. Methods: Eye muscle reflectivity, expressed as percentage of the initial scleral spike, was measured in the superior, medial, and lateral recti, and normal values were determined in 23 healthy controls. These were compared with values in 16 consecutive patients with untreated, moderately severe Graves ophthalmopathy. The accuracy of the measurement was assessed by calculating the intra- and interobserver coefficient of repeatability. Baseline eye muscle reflectivity in the 16 patients was correlated to the therapeutic outcome 24 weeks after start of immunosuppressive therapy. The response to treatment served as indicator for pretreatment disease activity. Results: Eye muscle reflectivity could be measured reliably, with an intraobserver coefficient of repeatability of 8.2% in controls and 10.2% in patients. Patients had lower reflectivity than controls (54.6 ± 17.4% versus 70.7 ± 6.6%; P P = 0.02). From the individual data, a cut-off value of 40% was derived, which appeared as an accurate predictor of outcome (positive predictive value 73%; 95% confidence interval 39%–94%). Conclusions: Measuring eye muscle reflectivity in Graves ophthalmopathy appears to be a reliable new method to determine disease activity, with a promising accuracy in predicting therapeutic outcome of immunosuppressive treatment.

Presumed Ocular Histoplasmosis in the Netherlands - an area without histoplasmosis

AIMS/BACKGROUND The syndrome of ocular histoplasmosis is usually prefaced by ‘presumed’ as the aetiology is not yet clear. The aim of this study was to evaluate the clinical features of a similar ocular syndrome in the Netherlands where the fungus Histoplasma capsulatum is not endemic. METHODS A retrospective multicentre study in which all patients were included who were diagnosed with a syndrome similar to presumed ocular histoplasmosis and in whom both fluorescein angiogram and all complete patient data were available. Fluorescein angiograms were examined by three authors in a masked fashion. Eighty one patients were selected who fulfilled the ophthalmic criteria for presumed ocular histoplasmosis. Fifty one patients showed the classic clinical picture, while 30 patients had an incomplete form as they did not show numerous histospots. RESULTS No major difference in clinical characteristics could be identified when comparing the group of patients with the classic syndrome with the one with the incomplete syndrome. Final visual outcome of patients with macular subretinal neovascularisation after laser treatment was better when compared with untreated patients (p<0.01). CONCLUSIONS Since the fungus Histoplasma capsulatum is absent in the Netherlands, other aetiological agents must have led to this clinical entity similar to the presumed ocular histoplasmosis syndrome seen in the USA.

Detection of locally produced antibodies to herpes viruses in the aqueous of patients with acquired immune deficiency syndrome (AIDS) or acute retinal necrosis syndrome (ARN)

Intraocular synthesis of IgG antibodies against HSV (herpes simplex virus), CMV (cytomegalovirus) and VZV (varicella zoster virus) is considered as an indirect proof of uveoretinal infection. Paired serum and aqueous samples obtained from 16 patients with retinitis associated with AIDS, 3 patients with ARN, 8 patients with posterior uveitis not related to AIDS or ARN and 5 patients with senile cataract were tested for total immunoglobulin G levels and antibodies to HSV, CMV and VZV by the fixed cell immunofluorescence technique. Since therapy must often be started before results of cultures are available, rapid detection of locally produced anti-Herpes Virus antibodies can be a precious tool in the diagnosis of ocular viral infection. Using this technique we were able to confirm the clinically suspected diagnosis in more than 50% of AIDS patients with retinitis and in two out of three patients with ARN.

Macular grid laser photocoagulation in uveitis.

AIMS/BACKGROUND--The aim of this study was to evaluate whether grid laser photocoagulation of the macula is beneficial in the treatment of cystoid macular oedema in patients with uveitis. METHODS--Six eyes of five patients with long standing cystoid macular oedema due to chronic uveitis were treated by grid laser photocoagulation of the macula. RESULTS--In the first weeks after treatment a temporary increase of oedema and paracentral scotomas were observed. At the long term follow up of more than 18 months in all patients, macular oedema had been reduced significantly or disappeared in all eyes treated. One eye had a significant increase in Snellen acuity, three eyes more or less stabilised, and two eyes deteriorated. CONCLUSION--The beneficial effect of laser treatment on visual acuity in patients with uveitis might be more favourable if performed at an earlier stage of the disease.

Long-term Effects of Ceftriaxone Treatment on Intraocular Lyme Borreliosis

Twelve patients with intraocular Lyme borreliosis suffering from vitreitis were treated with ceftriaxone intravenously. Eight patients had definitive Lyme borreliosis, and tentative diagnosis was made in four patients. After treatment with ceftriaxone, all 12 patients were followed up for more than one year. Vitreitis diminished in all patients and visual acuity improved in six patients. The best results were achieved in patients with definitive Lyme borreliosis.

Contrast sensitivity and the diagnosis dysthyroid optic neuropathy.

Contrast sensitivity function (CSF) was investigated in 19 patients (34 eyes) with clinical signs and symptoms of dysthyroid optic neuropathy (DON). CSF was disturbed in 33 eyes and was shown to improve after orbital decompression. These results indicate that the CSF may be a useful supplementary test of visual function in patients with DON.

HPLC analysis of tear proteins in giant papillary conjunctivitis

Giant papillary conjunctivitis (GPC) is a well defined entity seen in patients with deposits on their lenses. High performance liquid chromatography (HPLC) tear protein analysis was performed on 17 GPC patients and compared with healthy controls with and without contact lenses. The IgA levels are somewhat lower in GPC patients as compared with healthy controls not wearing lenses (P < 0.05). A similar decrease was also seen in the control group wearing contact lenses. We were not able to identify a specific HPLC tear protein profile in GPC patients as compared with controls. The HPLC profile therefore gives no explanation for the lens deposits and is not suitable as a diagnostic or prognostic tool.

Recent Developments in the Treatment of Posterior Uveitis

Uveitis is an intraocular inflammation that can be caused by infection, autoimmune disease, trauma or malignancy. It is a serious cause of visual handicap and therapy is targeted at: removal of possible infectious agents, the immunological processes that lead to or sustain the inflammation and finally to prevent or treat the destructive effects of the inflammation on the delicate ocular structures. In this review the latest developments concerning the treatment of posterior uveitis are illuminated, e. g., new approaches concerning the treatment of infectious uveitis including the therapy of herpes virus (VZV, HSV and CMV), bacterial and toxoplasma infections of the eye. Several new ways to influence the immune response and inflammation are described including the use of interferons, modulation of cytokines, soft steroids, other new immunosuppressive drugs and treatment of autoimmune uveitis by oral tolerization. An overview is given to illustrate new ways to administer drugs into eyes, such as intravitreal devices. Finally new developments in the field of the treatment of the various complications of uveitis (cystoid macular edema) are described.