Sl Lightman

Cytokine production and mRNA expression by conjunctival T-cell lines in chronic allergic eye disease.

Activated CD4+ T cells, mast cells and eosinophils are the main cytokine‐producing cell‐types infiltrating the conjunctiva during chronic allergic eye diseases. Interactions between these cells are thought to play an important immunopathogenic role in these disorders (giant papillary conjunctivitis; vernal keratoconjunctivitis; atopic keratoconjunctivitis).

Visual acuity following extracapsular cataract extraction in diabetes: a meta-analysis.

Although pre-operative retinopathy severity appears to be a major factor in determining the visual outcome of diabetic extracapsular cataract extraction, its precise relationship to post-operative visual acuity is ill defined. A meta-analysis was therefore carried out, and studies were included if pre-operative maculopathy and retinopathy status was sufficiently defined to permit discrimination of visual outcome between subgroups. Weighted mean proportions of eyes achieving a postoperative visual acuity ≥6/12 were as follows: no retinopathy, 87%; non-proliferative retinopathy with no maculopathy, 80%; quiescent proliferative retinopathy with no maculopathy, 57%; non-proliferative retinopathy with maculopathy, 41%; quiescent proliferative retinopathy with maculopathy, 11%; active proliferative retinopathy, 0. Differences in visual outcome between groups were significant (χ2 = 119.9, p<0.0005), attributable mostly to the trend across groups (χ2 for trend = 115.4, p<0.0005). Logistic regression indicated that maculopathy was a more potent predictor of post-operative visual acuity ≤6/12 (odds ratio 6.4, 95% CI 4.13-9.94, p<0.0005) than quiescent proliferative retinopathy (odds ratio 3.33, 95% CI 2.04-5.42, p<0.0005). The severity of retinopathy and maculopathy prior to cataract surgery in diabetics are the major determinants of post-operative visual acuity. Further study of the relationship between pre-operative retinopathy severity and the incidence of post-operative complications, progression of retinopathy and maculopathy is required to optimise the management of cataract in diabetes.

Behçet's disease in Japan and in Great Britain: a comparative study.

Behçets disease (BD) is an important cause of visual morbidity throughout the world, but shows striking differences in racial predilection. Despite important advances in the therapeutic management of acute intraocular inflammation, the long-term impact of these new strategies on visual outcome of BD and their efficacy in different ethnic groups is unknown. A comparative study of patient characteristics, clinical ocular features and inflammatory score, and current therapy was undertaken on all patients fulfilling the International Study Group criteria for Behçets disease and the Behçets Disease Research Committee of Japan, who attended the Uveitis Clinics of Moorfields Eye Hospital (n=19) and Kurume University School of Medicine (KUS) (n=35) during a continuous consecutive four-week period. Japanese patients were significantly older (43.2+/-11.8 years) than the patients seen in London (35.4+/-8. 9 years). There was a predominance of male patients in both groups. All patients seen in KUS were Japanese, while the patients in London included 12 Caucasians, five Middle Eastern, one African, and one Asian. No significant differences were seen between the two populations in the duration of systemic disease or systems affected by the disease, such as mouth ulcers, genital ulcers, skin lesions including erythema nodosum, or arthritis. The duration of ocular disease was similar in both centres: around seven years. There was, however, a significant difference in the number of eyes with active anterior uveitis (59.7% KUS vs 18.4% London (chi-square: 5.4; p=0.006)) and/or posterior uveitis (31.3% KUS vs 18.4% London (chi-square: 5.42; p<0.02)). No significant differences were found in the number of eyes with optic disc swelling or optic atrophy and in each centre the number of eyes with vision greater than 6/9 or worse than 6/60 were the same. The treatment schedules were very different between the two centres. More patients were treated with topical steroids in Japan (68.7% KUS vs 10.5% London (chi-square: 30.5; p=0.001), but a similar number used concomitant intraocular pressure-lowering agents. More patients received systemic steroids in London (84.2% London vs 17% KUS (chi-square: 20.25; p<0.001)). Three patients received systemic steroids alone, five had prednisolone and cyclosporin, four had prednisolone and azathioprine, and four had triple therapy with prednisolone, cyclosporin, and azathioprine. Only one patient used colchicine. Cyclosporin use was similar in London and KUS (47.4% and 42.8%, respectively). In Japan, three patients used prednisolone alone and three tacrolimus (FK506). In addition, two patients, who were on steroids alone, took colchicine as well. More patients in Japan had undergone surgery for cataract and glaucoma (chi-square: 4.0; p=0.045). In KUS, seven of 67 eyes had cataract surgery. A further three eyes had visually significant cataract and two eyes had undergone glaucoma surgery. In contrast, no patients in London had undergone any surgery up to and including this period.

PROGRESSIVE OUTER RETINAL NECROSIS (PORN) IN AIDS PATIENTS: A DIFFERENT APPEARANCE OF VARICELLA-ZOSTER RETINITIS

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmato-genous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

Uveitis presenting de novo in the elderly

Seventy-one consecutive patients presenting with their first episode of uveitis at the age of 60 or more years, were studied retrospectively. The majority were found to have idiopathic uveitides on investigation. In those who did have associated systemic disease, the commonest finding was non-insulin-dependent diabetes mellitus or an autoimmune disease. There were no cases of ocular lymphoma in this series. We conclude that, contrary to some previous reports, idiopathic uveitis may occur in the elderly, and that the relative frequencies of acute anterior, chronic anterior, intermediate and posterior uveitides are similar to those seen in young patients.

Distribution of IL-2R and CD45Ro expression on CD4+ and CD8+ T-lymphocytes in the peripheral blood of patients with posterior uveitis

Different lines of evidence support a major role for activated T-lymphocytes in the pathogenesis of posterior uveitis. The initial site of activation of these autoreactive T-cells, either locally in the eye or in the peripheral immune compartment, is still unknown. This study was undertaken to investigate whether with currently available techniques, it is possible to detect alterations in the levels and subsets of activated T-cells in the peripheral blood of patients with posterior uveitis. For this reason, 3-colour immunofluorescent staining was performed to assess the distribution of IL-2 receptors (IL-2R) and the CD45RO-antigen on CD4+ and CD8+ subsets of peripheral blood lymphocytes (PBLs) from patients with posterior uveitis (n = 29). Only the subgroup of patients with posterior uveitis as part of a systemic immune-mediated disease (sarcoidosis, Behçets disease) (n = 9) showed a significant increase in IL-2R expression on peripheral blood lymphocytes (p less than 0.005) when compared to normals (n = 12). This increased expression was reflected much more significantly in the CD4+ (p less than 0.0005) rather than in the CD8+ subset (p less than 0.05) of lymphocytes. In contrast, no significant increase in CD45RO expression on either subset of T lymphocytes was found in any subgroup of posterior uveitis in comparison with normals.

Vision-related functioning outcomes of dexamethasone intravitreal implant in noninfectious intermediate or posterior uveitis.

PURPOSE To evaluate the effect of a single treatment with dexamethasone intravitreal implant (DEX implant) on patient-reported visual functioning in patients with noninfectious intermediate or posterior uveitis. METHODS Patient eyes with noninfectious intermediate or posterior uveitis were randomized to a single treatment with DEX implant 0.70 mg (n=77), DEX implant 0.35 mg (n=76), or a sham procedure (n=76) and followed for 26 weeks. Vision-related functioning was measured using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) assessed at baseline and at weeks 8, 16, and 26 or early exit. Analysis of covariance and mixed model analysis of covariance were used to compare vision-related functioning between the DEX implant 0.70 and 0.35 mg groups and the sham group. RESULTS By 8 weeks, the DEX implant 0.70 mg group demonstrated significant improvements in NEI VFQ-25 subscales near vision (P=0.031), distance vision (P=0.023), peripheral vision (P=0.045), vision-specific social functioning (P=0.019), and the NEI VFQ-25 composite score (P=0.007) compared with sham. After 26 weeks, the DEX implant 0.70 mg group reported significant improvements in NEI VFQ-25 subscales distance vision (P=0.003), vision-specific role difficulties (P=0.038), vision-specific dependency (P=0.017), vision-specific social functioning (P=0.009), vision-specific mental health (P=0.036), and the composite score (P=0.001) compared with sham. CONCLUSIONS In patients with noninfectious intermediate or posterior uveitis receiving a single treatment of DEX implant 0.70 mg, significant and clinically meaningful improvements in patient-reported visual functioning were observed as early as week 8 and were maintained over 26 weeks. (ClinicalTrials.gov number, NCT00333814.).

Intracellular cytokine profiles and T cell activation in pulmonary sarcoidosis.

In granulomatous inflammatory lung diseases such as sarcoidosis, the balance of cytokine production by activated T cells in the lungs may influence clinical disease outcome. To investigate the potential of T lymphocytes to produce cytokines and contribute to this process, T cells from bronchoalveolar lavage (BAL) and PB from 19 patients with active lung disease were stimulated, stained, and analysed by flow cytometry for intracellular production of cytokines and expression of the activation marker CD69. Higher proportions of BAL cells expressed CD69 compared with PB, in the absence of in vitro stimulation. The expression of IFN-gamma was similar in unstimulated BAL and PB T cells, and there was no association between the expression of CD69 and IFN-gamma. Following stimulation, there were increased numbers of IFN-gamma(+) T cells. A similar trend was found with IL-2(+) T cells, but there were lower levels of IL-4(+) T cells in BAL compared with PB, and similar levels of IL-10(+) T cells. The presence of activated T lymphocytes in BAL samples from patients with sarcoidosis, with the potential to produce Th1 type 1 cytokines may contribute to the inflammatory processes in this granulomatous lung disease. The use of intracellular flow cytometry to investigate cytokine production by BAL T cells could help to indicate potential targets for future therapy.

Combined orbital floor betamethasone and depot methylprednisolone in uveitis.

Purpose: To evaluate the outcome of orbital floor injection of betamethasone and methylprednisolone in the management of uveitis, with particular reference to its efficacy in avoiding increase in systemic immunosuppressive drugs. Methods: A sample of all patients attending the Uveitis Service at Moorfields Eye Hospital was carried out over a three-month period. All patients who had received one or more orbital floor injections of betamethasone (4 mg) and methylprednisolone (Depo-Medrone; 40 mg) in the management of their uveitis were identified and the case notes reviewed. Results: A total of 48 patients who had received 75 orbital floor injections were identified during the sample period. Most patients had either panuveitis (n = 24) or pars planitis (n = 14). One-month post-injection visual acuity (VA) had improved by at least one Snellen line after 33/75 injections (44%) and at least two lines after 11/75 (15%), was unchanged after 25 (33%), but had deteriorated in 14 (19%). VA was not recorded after 3/75 injections. The only complications recorded were periorbital haemorrhage (n = 1) and complaints of persistent pain after an injection (n = 1). Symptoms (pain and subjective vision) improved after 36/75 injections (47%), were unchanged after 24 (32%), and were reported as worse after five (7%). Additionally, three patients reported an improvement in symptoms which lasted less than one month. Signs other than VA were improved after 28/75 (37%), were unchanged after 38 (51%), and deteriorated after only one injection. Of the 31 patients given orbital floor injections to avoid systemic therapy, seven (23%) subsequently went on to require it, and the clinical course then improved in 45%. Conclusions: Combined orbital floor injection of betamethasone and methylprednisolone can result in improved visual acuity, symptoms, and signs of inflammation in uveitis, and may therefore avoid the necessity for increased systemic medication.