Susan Lightman

Dexamethasone Intravitreal Implant for Noninfectious Intermediate or Posterior Uveitis

OBJECTIVE To evaluate the safety and efficacy of 2 doses of dexamethasone intravitreal implant (DEX implant) for treatment of noninfectious intermediate or posterior uveitis. METHODS In this 26-week trial, eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with a 0.7-mg DEX implant (n = 77), 0.35-mg DEX implant (n = 76), or sham procedure (n = 76). MAIN OUTCOME MEASURE The main outcome measure was the proportion of eyes with a vitreous haze score of 0 at week 8. RESULTS The proportion of eyes with a vitreous haze score of 0 at week 8 was 47% with the 0.7-mg DEX implant, 36% with the 0.35-mg DEX implant, and 12% with the sham (P < .001); this benefit persisted through week 26. A gain of 15 or more letters from baseline best-corrected visual acuity was seen in significantly more eyes in the DEX implant groups than the sham group at all study visits. The percentage of eyes with intraocular pressure of 25 mm Hg or more peaked at 7.1% for the 0.7-mg DEX implant, 8.7% for the 0.35-mg DEX implant, and 4.2% for the sham (P > .05 at any visit). The incidence of cataract reported in the phakic eyes was 9 of 62 (15%) with the 0.7-mg DEX implant, 6 of 51 (12%) with the 0.35-mg DEX implant, and 4 of 55 (7%) with the sham (P > .05). CONCLUSIONS In patients with noninfectious intermediate or posterior uveitis, a single DEX implant significantly improved intraocular inflammation and visual acuity persisting for 6 months. Application to Clinical Practice Dexamethasone intravitreal implant may be used safely and effectively for treatment of intermediate and posterior uveitis. Trial Registration clinicaltrials.gov Identifier: NCT00333814.

Histological features of ocular adnexal lymphoma (REAL classification) and their association with patient morbidity and survival

BACKGROUND The histological characteristics of ocular adnexal lymphomas have previously provided only a limited guide to clinical outcome for affected patients. This clinicopathological relation was re-examined using the Revised European American Lymphoma (REAL) system to classify the tumours in a large cohort of patients. METHODS The biopsies and clinical follow up data for 192 patients with ocular adnexal lymphoma were reviewed, the biopsies being regraded in accordance with the REAL classification. For each of five histological groups, logistic regression analysis was used to determine the odds ratios (OR) for the presence of systemic disease at the time of orbital diagnosis and Cox regression analysis was used to assess the hazard ratios (HR) for disseminated disease and lymphoma related death. For 108 patients in whom extraorbital spread occurred, the histological category of lymphoma was compared with the sites of dissemination. RESULTS At presentation, the frequency of previous or concurrent extraorbital disease increased from marginal zone lymphoma (OR 1.0), diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma (OR 2.3), follicle centre lymphoma (OR 3.8), diffuse large B cell lymphoma (OR 4.0) to other histological lymphoma variants (OR 26.8). For all histological types, the estimated risk of extraorbital disease and lymphoma related death continued for many years and the proportion of patients with at least one extraorbital recurrence after 5 years was 47% for MZL, 48% for LPL, 64% for FCL, 81% for DLCL, and 95% for other lymphoma variants. The corresponding estimated rates for 5 year lymphoma related mortality were 12%, 19%, 22%, 48%, and 53% respectively. CONCLUSIONS Patients with ocular adnexal lymphoma can be classified by REAL into five distinct groups, which show a progressive increase in the risks of extraorbital disease at diagnosis, of disease dissemination with time, and of tumour related death.

Posterior scleritis: Clinical features, systemic associations, and outcome in a large series of patients

OBJECTIVE To document the clinical features, systemic associations, and visual outcome in a large number of patients with posterior scleritis. DESIGN Retrospective, noncomparative case series. PARTICIPANTS There were 137 patient records showing patients with a diagnosis of posterior scleritis who were attending or had attended the scleritis clinic at Moorfields Eye Hospital between 1974 and 1996. Ninety-nine records were suitable for detailed analysis. METHODS The medical records and B-mode ultrasound examinations were reviewed. MAIN OUTCOME MEASURES The clinical features, systemic associations, treatment, and outcome of each patient were determined. RESULTS Posterior scleritis occurred at all ages. The mean age at onset was 49.3 years. Posterior scleritis began before age 40 in 30% of patients and was twice as common in women as in men. The B-mode ultrasound examination showed diffuse and nodular changes in the posterior sclera. Necrotizing posterior scleritis was not identified. Twenty-nine percent of patients had an associated systemic disease that included systemic vasculidites, autoimmune diseases, and lymphoma. Such patients more commonly had nodular changes on B-mode ultrasound examination. Early treatment controlled posterior scleral inflammation and limited visual loss. Thirty-one percent of patients lost two or more lines of vision. Statistical analysis revealed that patients older than age 50 had an increased risk of having an associated systemic disease and were more likely to experience visual loss. Patients with associated systemic disease required more aggressive immunosuppressive therapy and more frequently had accompanying anterior scleritis. There was no association between unilateral, bilateral, or recurrent disease and the presence of systemic disease or visual loss from posterior scleritis. CONCLUSIONS The B-mode ultrasound examination reveals that posterior scleritis occurs far more often than previously thought and can lead to rapid and permanent visual loss. All patients with posterior scleritis must be assumed to be at risk of visual loss. Forty percent of patients had no anterior scleral inflammation, and 9% had no detectable physical signs. All patients need to be investigated for an associated systemic disease and all require early treatment to minimize loss of vision.

T-cell cytokines in chronic allergic eye disease

BACKGROUND The pathophysiology of chronic allergic eye disease cannot be explained by type I hypersensitivity alone, and T cell-mediated inflammation has been strongly implicated as a possible additional mechanism. Previous studies suggested that T(H2)-like T cells play an important role in one form of chronic allergic eye disease. OBJECTIVES This study examined the cytokine profile of T cells in different clinical groups of subjects with chronic allergic eye disease (i.e., vernal keratoconjunctivitis [VKC], atopic keratoconjunctivitis [AKC], and giant papillary conjunctivitis [GPC]) and normal control subjects. METHODS In situ hybridization was used to identify cytokine messenger RNA (mRNA), and two-color immunohistochemical analysis was used to demonstrate cytokine immunoreactivity localizing to T cells in the conjunctiva. RESULTS Allergic tissue expressed increased levels of mRNA for IL-3, IL-4, and IL-5 when compared with normal tissue. There was significantly greater IL-2 mRNA expression in subjects with AKC than in those with VKC (p = 0.004) and those with GPC (p = 0.02). Immunoreactivity for T-cell IL-5 was present more frequently in subjects with VKC (p = 0.004), GPC (p = 0.02), and AKC (p = 0.04) than in normal control subjects. However, T-cell IFN-gamma protein expression was greater in subjects with AKC than in subjects with VKC (p = 0.01), GPC (p = 0.01), and control subjects (p = 0.005). CONCLUSIONS These results show a T(H2)-like T-cell cytokine array in subjects with VKC and GPC but a shift in cytokine profile toward a T(H1)-like pattern, potentially because of differences in chronicity of the disorders, in subjects with AKC. These important functional T-cell variations in chronic allergic eye conditions are likely to be important in understanding differences in clinical characteristics and therapeutic responses.

Mycophenolate mofetil ☆: A useful immunosuppressive in inflammatory eye disease

OBJECTIVE To assess the usefulness of mycophenolate mofetil (MMF) (Cellcept, Roche), a potent selective uncompetitive and reversible inhibitor of ionisine monophosphate dehydrogenase involved in purine synthesis, as an immunosuppressive and steroid-sparing agent in the management of ocular inflammatory disease. DESIGN Open-label, prospective, uncontrolled pilot study. PARTICIPANTS Eleven patients with uncontrolled ocular inflammation. INTERVENTION Mycophenolate mofetil, at a dosage of 1 g twice daily, was given in conjunction with steroids, as a steroid-sparing agent, or as an additional agent with cyclosporine (CsA), or instead of CsA or azathioprine. MAIN OUTCOME MEASURES The inflammatory response, side effects, and toxicity were monitored. RESULTS The addition of MMF to immunosuppressive regimens led to the improvement in symptoms and the ability to reduce the dose of prednisone in most patients. Ten of 11 patients showed a favorable response to MMF, with few side effects noted. CONCLUSION These findings suggest that MMF is a useful immunosuppressive drug for controlling ocular inflammation with minimal side effects.

Understanding uveitis: the impact of research on visual outcomes.

The term uveitis encompasses a very diverse group of inflammatory ocular diseases that cause a significant burden of legal and economic blindness. Indeed, the socioeconomic impact of uveitis is at least as significant as that of diabetic retinopathy and, in the majority of cases, those affected are young individuals of working age. Significant progress has been made in our understanding of the mechanisms underlying the inflammatory process through the use of animal models, but correlation with human disease has proved elusive and many scientific approaches which appear highly effective in animal models prove to be less effective in patients. Nevertheless, effective, targeted treatments are needed in uveitis as current treatment is based on corticosteroids and immunosuppressive drugs whose usefulness is limited by their many side-effects. The aims of this review are to summarize the state of clinical research in uveitis, to identify gaps in our knowledge, and to propose new opportunities and methodologies for future developments in all aspects of uveitis research, including epidemiology, economic impact analysis, diagnosis, therapeutics, and clinical study design. Optimal patient management and efficient drug development depend on validated structured tools, such as those that have helped to drive a rapid acceleration in the means and methods available to assess and treat patients with rheumatoid arthritis and cancer. Uveitis care should witness a similar boom as the issues discussed are resolved.

Surgically induced necrotising sclerokeratitis (SINS)--precipitating factors and response to treatment.

The clinical features, treatment, and visual outcome of 52 eyes from 43 patients who developed scleritis following surgery were reviewed. In all patients the scleral inflammation developed adjacent to a surgical wound. Ninety six per cent had necrotising disease and 23% also had evidence of secondary posterior scleritis. Many different types of ocular surgery were implicated and the majority (75%) of the patients had two or more surgical procedures before the onset of the scleritis. Although cataract extraction through a limbal incision resulted in the largest subgroup, scleritis also followed glaucoma, strabismus, and retinal detachment surgery. The latent period between surgery and the appearance of inflammation was short (mean 9 months) except for a small group in whom scleritis occurred many years after squint surgery. Sixty three per cent of patients had evidence of a systemic disease. Early diagnosis and aggressive medical treatment significantly improved the visual outcome. The precipitating factors, pathogenesis, and course of this condition are discussed.

A randomized, placebo-controlled trial of topical cyclosporin A in steroid-dependent atopic keratoconjunctivitis

OBJECTIVE This study aimed to investigate the therapeutic effect of topical cyclosporin A (CsA) 2% in maize oil as a steroid-sparing agent in steroid-dependent atopic keratoconjunctivitis. DESIGN Prospective, randomized, double-masked, placebo-controlled trial. PARTICIPANTS Twenty-one patients with steroid-dependent atopic keratoconjunctivitis were studied. INTERVENTION Patients used either topical CsA or vehicle four times daily for 3 months in addition to their usual therapy, and the clinical response was used to taper or stop topical steroids when possible. MAIN OUTCOME MEASURES Steroid drop usage per week, ability to cease steroid use, scores for symptoms and clinical signs, drop side effects, and overall subjective rating of trial drop by patients and clinician were measured. RESULTS Cyclosporin A had a greater steroid-sparing effect than did placebo. Nine of 12 CsA patients ceased steroids compared to 1 of 9 placebo patients (P = 0.01), the final steroid use was lower in the CsA group (2.6 +/- 1.4 vs. 27.7 +/- 17.7, P = 0.005), and the mean reduction in steroid use was greater for CsA (85.5 +/- 14.7 vs. 13.9 +/- 16.0, P = 0.005). Clinical signs and symptom scores were reduced to a greater level for CsA. Serious side effects were lid skin maceration in one patient using CsA and an allergic reaction in one placebo patient. Marked blurring of vision after drop instillation was common in both groups, but intense stinging was more common in CsA patients (9/12 vs. 1/9, P = 0.01), limiting frequency of drop use. The clinician rated the trial drops as good or excellent more frequently for CsA (11/12 vs. 0/9, P < 0.0001). CONCLUSIONS Topical CsA is an effective and safe steroid-sparing agent in atopic keratoconjunctivitis and, despite difficulties in patient tolerance, also improves symptoms and signs.

Assessment of visual outcome after cataract surgery in patients with uveitis

OBJECTIVE To assess the outcome of cataract surgery in eyes of patients with uveitis. DESIGN Prospective, noncomparative case series. PARTICIPANTS A total of 90 eyes of 76 patients fulfilled the enrollment criteria. INTERVENTION All patients had their surgery performed using standard cataract extraction techniques. Unless contraindicated, preoperative systemic steroids were administered to all patients with posterior disease, chronic anterior uveitis, with known macular edema, and those in whom outcome of cataract surgery on the fellow eye had been poor. RESULTS Patients were divided into those with anterior disease (n = 53) and those with posterior disease (n = 37). Overall, 81 (90%) of 90 eyes showed improvement in vision (median +4 Snellen lines). In those with anterior disease, the development of severe uveitis in the first week postsurgery was associated with a greater incidence of macular edema (P = 0.014). The single largest diagnosis in those with posterior disease was that of panuveitis (n = 24). This group showed the poorest visual outcomes in this study. The majority of patients, however, were noted to have visual loss secondary to conditions present before surgery. CONCLUSION Cataract surgery in eyes with uveitis leads to an improvement of vision in the majority of cases. Severe postoperative uveitis is the most common postoperative complication and is associated with a significant risk of macular edema in those with anterior disease. In the posterior group, poor visual outcome after surgery is most commonly the result of preoperative vision-limiting conditions.

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases

BACKGROUND The pathophysiology of chronic ocular allergic disease is not well understood. An eosinophil infiltrate is characteristic of such disease and eosinophil activity can be related to disease severity and to keratopathy, the most serious complication. Recently, eosinophils have been shown capable of cytokine production, particularly in allergic disease, although the disease-specific cytokine spectrum of tissue eosinophils is unknown. OBJECTIVES We sought to determine eosinophil numbers (absolute numbers and percentage of total leukocytes), cell surface antigen expression, and cytokine production in conjunctiva in chronic allergic eye disease and their relationship to corneal involvement. METHODS Ultrathin sections of conjunctiva were examined by tissue staining and by 1- and 2-color immunohistochemistry. RESULTS Eosinophil numbers were greater in giant papillary conjunctivitis (GPC) and vernal keratoconjunctivitis (VKC) and not related to corneal involvement. The eosinophil expression of the cell surface antigens intercellular adhesion molecule-1, CD4, IL-2R, and HLA-DR was greater in atopic keratoconjunctivitis (AKC) and VKC, the disorders with corneal disease, than in GPC, in which the cornea is not involved. For most cytokines, localization to eosinophils was greater for VKC and AKC than for GPC. RANTES, TGF-beta, and TNF-alpha localized to eosinophils in all disorders. Variations in the pattern of eosinophil-cytokine localization were found. In VKC IL-3, IL-5, IL-6, and GM-CSF were prominent; in GPC IL-5 was prominent; and in AKC IL-4, IL-8, and GM-CSF were prominent. CONCLUSIONS Chronic ocular allergic disorders affecting the cornea are distinguished from disorders that do not do so by greater expression of eosinophil surface antigens (which may imply greater cell activation) and differences in cytokine localization to eosinophils. These differences may be secondary to the variations in T-cell subsets or a primary phenomenon. Changes in eosinophil function, rather than cell numbers, may be important in clinical variations, such as keratopathy, and may allow future therapeutic exploitation.