Leila I. Kump

Intravitreal clindamycin for toxoplasmic retinochoroiditis.

Purpose: To report outcomes of off-label use of intravitreal clindamycin in the treatment of toxoplasmic retinochoroiditis. Methods: In a noncomparative, retrospective, interventional case series, we reviewed the charts of six consecutive patients with toxoplasmic retinochoroiditis who were treated with intravitreal injection of clindamycin (1.0 mg/0.1 mL) because of intolerance to or disease progression despite oral microbial treatment. The primary outcome measures were change in Snellen visual acuity, resolution of inflammation, and adverse events. Results: Injection of intravitreal clindamycin was associated with control of toxoplasmic retinochoroiditis and resolution of vitreous inflammation in all six patients. Five patients had improvement in visual acuity. One patients vision was limited because of macular scarring. Four patients underwent concomitant pars plana vitrectomy (PPV) at the time of injection. One patient who had concomitant clindamycin injection and PPV developed a retinal detachment postoperatively. Conclusion: Intravitreal clindamycin injection, alone or in conjunction with PPV, was associated with resolution of toxoplasmic retinochoroiditis in six patients.

Interferon-β and adhesion molecules (E-selectin and s-intracellular adhesion molecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling

Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behçets disease. Here we show that type 1 interferons (IFN α/β) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN‐β, which was detected in 39% of Behçets disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN‐β were monitored prospectively. IFN‐β was shown to be present for 6–12u2003months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behçets and uveitis patient sera were compared to sera from normal controls. Sera from Behçets disease patients contained significantly elevated levels of the soluble adhesion molecules, sE‐selectin and s‐intracellular adhesion molecule‐1 (sICAM‐1), whereas sera from patients with idiopathic uveitis contained significantly increased sE‐selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE‐selectin, sICAM‐1 and IFN‐β. Production of these molecules was inhibited by pretreatment with anti‐Toll‐like receptor 3 (TLR‐3) antibody. In conclusion, IFN‐β, sE‐selectin and sICAM‐1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR‐3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis.

Retinal vasculitis in rheumatic diseases: an unseen burden

Retinal vascular inflammation, a potentially blinding condition (herein: retinal vasculitis (RV)) is commonly associated with a heterogeneous group of diseases characterized by systemic inflammatory cell infiltration and/or necrosis of blood vessel walls. RV may arise as an isolated ocular disorder, as part of systemic vasculitis (Wegener’s granulomatosis and Adamantiadis–Behcet Disease), or it can be secondary to an underlying connective tissue disease (systemic lupus erythematosus, sarcoidosis, and rheumatoid arthritis), systemic infection, or malignancy. Depending on the type of RV, it can be a potentially disabling condition, in the short or long term. Early diagnosis is the key to successful treatment and better prognosis. However, early diagnosis can be difficult, because these conditions usually present with nonspecific visual symptoms for a long period before diagnostic manifestations occur. The retina should be examined in warranted patients with verified rheumatic disease, since retinal vasculitis may be asymptomatic at the beginning (peripheral retinal disease). RV can be detected clinically (often accompanied by uveitis, scleritis, or macular edema) or revealed on fluorescein fundus angiography, even if minimal signs of retinal vessel inflammation are present. RV may also represent one of the possible extra-articular manifestations of the rheumatic disease. Rheumatologists should be familiar with the ocular manifestations of these disorders, since they may not only be sight-threatening, but more importantly, could be the presenting or even the very first manifestations of active, potentially lethal systemic disease in a patient with nonspecific rheumatologic presentation.

Behçet's disease: comparing 3 decades of treatment response at the National Eye Institute

BACKGROUNDnThe goal of the present study was to analyze differences in response to the treatment of ocular Behçets disease (BD) in the 1960s, 1980s, and 1990s.nnnMETHODSnMedical records of 120 patients with uveitis due to BD followed at the National Eye Institute, National Institutes of Health, from 1962 to 2004, were reviewed.nnnRESULTSnThe patients were categorized into 3 groups according to the time of follow-up: the first group was followed from 1962 until 1972, the second group from 1983 until 1992, and the third group from 1992 through 2004. Snellen visual acuity was converted to logMAR values. The range of values for inflammation was 0.5 (trace), 1 (mild), 2 (moderate), and 3 (severe). There were 45 patients (89 affected eyes) in the 1960s group, 26 patients (52 eyes) in the 1980s group, and 49 patients (94 eyes) in the most recent group. Statistical analysis showed that the mean logMAR score decreased with each decade. Mean visual acuity in the 1990s group was significantly better than in the previous decades (p < 0.001 for the 1960s group and p = 0.019 for the 1980s). The mean inflammation score was significantly higher in the 1960s than in the subsequent decades (p < 0.001 both for the 1980s and for the 1990s).nnnINTERPRETATIONnBD is a severe, blinding disorder. There was a definitive trend toward improvement in clinical outcome from the 1960s to 1990s. We attribute this trend to the introduction of newer, more potent corticosteroid-sparing agents and targeted therapy.

Patterns of Exacerbations of Chronic Non-Infectious Uveitis in Pregnancy and Puerperium

Purpose: To determine patterns of exacerbations of recurrent non-infectious uveitis during pregnancy and puerperium. Design: Retrospective cohort study. Methods: The medical records of 32 women with a history of chronic non-infectious uveitis, who were pregnant during their follow-up at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary, from 1983 through 2003, were reviewed. The uveitis relapse rate during pregnancy was compared to the relapse rate during pregnancy-free periods in these women and to the relapse rate in a control group of women of childbearing age with recurrent non-infectious uveitis. Results: Among the 32 women who were pregnant during follow-up (40 pregnancies), the rate of flare-ups during pregnancy (1.0 recurrence per year) was lower than that observed during non-pregnant periods (2.4 per year; p < 0.001) and lower than that observed in the non-pregnant control group (3.1 per year; p < 0.001). Flare-ups were most frequent in the first trimester of pregnancy and decreased markedly in the second and third trimesters (2.3, 0.5, and 0.4 recurrences per year, respectively; p < 0.001). Conclusions: Pregnancy is associated with lower numbers of flare-ups of non-infectious uveitis compared to the non-pregnant state. If flare-ups do occur during pregnancy, they happen predominantly in the first trimester.

Ocular toxoplasmosis in pregnancy

Purpose:u2002 To describe the course of ocular toxoplasmosis during pregnancy.

OCT-3 Study of Serous Retinal Detachment in a Preeclamptic Patient

We report optical coherence tomography-3 (OCT-3) of retinal disorders in acute preeclampsia. A 33-year-old woman developed mind hypertension (170/90 mm Hg) and proteinuria in the 28th week of pregnancy. The patient complained of sudden and severe visual acuity decrease. Fundus exam showed bilateral serous retinal detachment at the macula area. OCT-3 exam demonstrated subretinal and intraretinal fluid. Bilateral serous retinal detachment is an unusual finding of preeclampsia of unknown aetiology. Intense arteriolar vasospasm has been implicated in the pathogenesis of the serous retinal detachment. OCT-3 showed the presence of both subretinal and intraretinal fluid during the acute phase of preeclampsia.

CHAPTER 49 – Ocular Disease

Publisher Summary nThe presence of uveitogenic antigens in the eye that are capable of inducing disease is a well-established concept. Several antigens have been isolated that are capable of inducing ocular inflammatory disease similar to that seen in humans. Retinal S-antigen or arrestin is one of the most potent uveitogenic antigens defined to date. It causes an immune-mediated, bilateral inflammatory response in the eye, or experimental autoimmune uveitis (EAU), when injected in microgram quantities at a site far from the globe. Several other uveitogenic antigens have since been identified, such as interphotoreceptor retinoid-binding protein (IRBP), recoverin, bovine melanin protein, rhodopsin, phosducin, RPE 65, and tyrosinase proteins. Furthermore, the establishment of and extensive studies using experimental autoimmune uveitis (EAU) models have greatly facilitated the understanding of autoimmune uveitis. Despite some evidence of the involvement of humoral immunity, cellular immunity is primarily responsible for the disease. Finally, the chapter discusses various treatment regimes for ocular diseases.