Low power vs standard power transpupillary thermotherapy in patients with age-related macular degeneration and subfoveal choroidal neovascularization ineligible for photodynamic therapy.

AIM: To assess the effect of standard power vs low power transpupillary thermotherapy (TTT) in patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration ineligible for photodynamic therapy (PDT) by original treatment of age-related macular degeneration with photodynamic therapy (TAP) study group recommendations. METHODS: Retrospective review of 79 patients with active predominantly occult subfoveal choroidal neovascularization or predominantly classic subfoveal choroidal neovascularization but Snellen visual acuity <20/200. All patients were treated with TTT administered via a Mainster wide field fundus contact lens with a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27) and 181 mW/mm in the low power group (n=52). The primary outcome was stabilization (<1 Snellen line change) or improvement (two or more Snellen lines) in visual acuity. Clinical and fluorescein angiographic resolution of overlying exudation was documented. RESULTS: At 24 month follow-up, 17 patients (63%) in the standard power and 36 patients (69%) in the low power group achieved stable or improved vision. Improved vision (mean three lines) was observed in 22% of the standard power and 23% of the low power group. Overlying exudation was reduced clinically with minimal or no leakage on fluorescein angiogram in 85% of standard power and 90% of low power group. Subgroup analysis in the low power group demonstrated a visual benefit in patients with subfoveal lesions, which had any classic component. CONCLUSIONS: Low power TTT is as effective as standard power in stabilizing or improving vision and reducing overlying exudation in patients with active subfoveal choroidal neovascularization ineligible for PDT.

Outcomes after combination photodynamic therapy and immunosuppression for inflammatory subfoveal choroidal neovascularisation.

AIM: To report the visual and angiographic outcomes after combination photodynamic therapy (PDT) and immunosuppression for inflammatory subfoveal choroidal neovascularisation (CNV). METHODS: Retrospective review of six consecutive patients, five female and one male, aged 23-40 years with active subfoveal CNV secondary to posterior uveitis. Patients received either intravitreal triamcinolone or systemic immunosuppression (mycophenolate mofetil, tacrolimus) and PDT. Five patients had intravitreal triamcinolone injections and two patients were on systemic immunosuppression; all patients underwent PDT (mean two treatments). Visual acuity was measured on a 2 metre ETDRS chart and fluorescein angiograms were performed at each visit. RESULTS: Median follow up was 15 months (range 10-31). Vision improved by a median of 13 letters in five patients and remained stable (+/-1 letter) in one patient. Median visual acuity improved from 20/160 at presentation to 20/40 at latest follow up (p=0.03). There was a reduction in clinical exudation and cessation of angiographic leakage in all six patients. All interventions were well tolerated. CONCLUSION: Combination PDT and immunosuppression may be a useful therapeutic option for young patients with active inflammatory subfoveal CNV.

Genetic polymorphism of HLA DR in a Scottish population of patients with pars planitis.

PURPOSE: Human leucocyte antigen (HLA) class II influences the immunological susceptibility for a variety of diseases including many types of non-infectious intraocular inflammation. Previous studies on North American patients with pars planitis, a subtype of intermediate uveitis, reported an increased prevalence of HLA DR15 in this population. In contrast, two European studies could not find an association between HLA DR2 or its allelic subtype DR15 and various forms of intermediate uveitis. We therefore investigated the genotype frequency of HLA DR alleles in a Scottish population of patients with typical pars planitis. METHODS: Twenty patients with pars planitis were identified from the uveitis database of Grampian University Hospitals. Only patients with bilateral vitritis and snowbanks in at least one eye in the absence of systemic disease were included in the study. Fifteen patients and 34 healthy controls underwent HLA DR genotyping for all DRB genes using PCR sequence specific primers. RESULTS: HLA DR15 was found in 13% of patients with pars planitis and in 24% of controls. There was no statistically significant difference between these two groups. Furthermore, the frequencies of HLA DR 1, 3-14, and 16 did not differ significantly between patients and controls. CONCLUSIONS: There appears to be no association between the occurrence of pars planitis and the HLA DR15 or other known HLA DR genotypes in Scottish patients. However, the small sample size limits the power of this study.

CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis.

PURPOSE: To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis. METHODS: Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity. RESULTS: Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of CD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity. CONCLUSIONS: Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.

Immunogenetics and clinical phenotype of sympathetic ophthalmia in British and Irish patients.

BACKGROUND/AIMS: Sympathetic ophthalmia (SO) is a classic example of autoimmune disease where human leucocyte antigen (HLA) genomic associations could provide further understanding of mechanisms of disease. This study sought to assess HLA genetic polymorphism in British and Irish patients with SO, and to assess whether HLA gene variants are associated with clinical phenotype or disease severity. METHODS: High resolution DNA based HLA typing using polymerase chain reaction sequence specific primers was performed in 27 patients with SO and 51 matched healthy controls. Clinical phenotype and markers of disease severity were determined prospectively in 17 newly diagnosed patients and from medical record review and repeat clinical examination in 10 previously diagnosed patients. RESULTS: HLA-Cw*03 (p=0.008), DRB1*04 (p=0.017), and DQA1*03 (p=0.014) were significantly associated with SO. For class II alleles at higher resolution, only HLA-DRB1*0404 (relative risk (RR) = 5.6, p = 0.045) was significantly associated with SO. The highest relative risk for any of the associated haplotypes was with HLA-DRB1*0404-DQA1*0301 (RR=10.9, p=0.019). Patients with the DRB1*04-DQA1*03 associated haplotype were significantly more likely to develop SO earlier, with fewer inciting ocular trauma events, and to require more systemic steroid therapy to control inflammatory activity. CONCLUSIONS: Sympathetic ophthalmia is associated with HLA-DRB1*04 and DQA1*03 genotypes in white patients, similar to Japanese patients. Differences in DRB1*04 gene variant associations (-0404 in Britain and Ireland and -0405 in Japan) may have implications for HLA peptide binding in disease initiation. The DRB1*04-DQA1*03 haplotype is a marker of increased SO susceptibility and severity, as in Vogt-Koyanagi-Harada disease, which also has similar clinicopathological and HLA associations.

Prospective surveillance of sympathetic ophthalmia in the UK and Republic of Ireland.

AIMS: To establish current epidemiological data, risks, and interventional outcomes of newly diagnosed sympathetic ophthalmia (SO). METHODS: Prospective surveillance took place of all permanently employed ophthalmologists in the UK and Republic of Ireland by a monthly reporting card through the British Ophthalmological Surveillance Unit. Case ascertainment was made of newly diagnosed SO from July 1997 and questionnaire data were returned at baseline, 6 months, and 1 year after diagnosis. RESULTS: 23 patients with newly diagnosed SO were recruited over 15 months, corresponding to a minimum estimated incidence of 0.03/100 000. Baseline data were available on 18 patients, in whom SO occurred after surgery in 11 patients, after retinal surgery alone in six patients, and after accidental trauma in seven patients. 12 of the 16 patients with 1 year follow up had a visual acuity of 6/12 or better. Good visual outcome was related to prompt and adequate systemic immunosuppressive therapy. CONCLUSIONS: The incidence of sympathetic ophthalmia is very low. The main current risk is surgery, particularly retinal surgery, but visual prognosis is good if early diagnosis is made and rapid, adequate immunotherapy is commenced.

Tacrolimus (FK506) in failed cyclosporin A therapy in endogenous posterior uveitis.

Tacrolimus (FK506) is effective in Japanese endogenous posterior uveitis (EPU), but there is limited data on its role in refractory EPU where cyclosporin A (CsA) toxicity/resistance develops. This open prospective clinical study aimed to assess the efficacy and adverse effects of low-dose FK506 therapy in western patients with refractory EPU where CsA resistance or toxicity has developed. Patients with CsA resistant/toxic EPU were started on low-dose (< 0.10 mg/kg/day) FK506 therapy. Immunosuppressive efficacy was assessed by visual acuity, binocular indirect ophthalmoscopy (BIO) scores, and change in clinical features. Adverse effects were assessed by routine biochemical tests (including serum creatinine) and symptoms. Seven patients (13 eyes), aged (mean +/- SD) 37.5 +/- 14.8 years, were recruited with previous CsA nephrotoxicity as the main indication and prior duration of EPU of (mean +/- SD) 13.1 +/- 7.3 years. Behçet's disease was the commonest diagnosis. FK506 therapy was maintained at 0.06 +/- 0.02 mg/kg/day, trough level of 8.7 +/- 1.8 ng/ml, in combination with low-dose prednisolone (0.11 +/- 0.04 mg/kg/day) in all patients for a mean duration of 8.7 months (range 1.0-17.7). From baseline (for 11 eyes with meaningful follow-up), visual acuity was maintained in nine eyes and BIO score improved in nine eyes. No major adverse effects developed, with only a 7.5 +/- 6.5% maximum increase in serum creatinine in patients with previous CsA-induced nephrotoxicity. Minor adverse effects (especially mild hyperglycaemia and neurological symptoms) were common and usually well tolerated, except for two patients in whom drug withdrawal was necessary, thus producing therapeutic failure. Low-dose FK506 is effective in refractory EPU as CsA-rescue therapy, and should be considered earlier in the evolution of refractory EPU.

Cyclosporin A therapy in refractory non-infectious childhood uveitis.

AIMS: To assess the immunosuppressive efficacy, steroid sparing effect and adverse effects of cyclosporin A (CsA) therapy in refractory non-infectious childhood uveitis. METHODS: A retrospective case series review of the medical records of children on CsA therapy attending a tertiary referral centre for refractory endogenous uveitis was performed. Low dose (< or = 5.0 mg/kg/day) CsA therapy was started either as monotherapy or in combination with other agents. The CsA immunosuppressive efficacy was assessed by visual acuity and binocular indirect ophthalmoscopy (BIO) score outcomes and steroid sparing effect by growth charts and ability to withdraw or maintain a low steroid dose. Possible CsA adverse effects were monitored by routine biochemistry (including serum creatinine) and haematological tests, blood pressure recordings, and symptoms. RESULTS: 14 patients (25 eyes, 10 males, four females) were recruited with steroid failure as the most common CsA indication. Age (mean (SD)) at start of CsA therapy was 8.7 (4.1) years with a duration of CsA therapy of 20.9 (range 3.5-88.3) months at a maintenance CsA dose of 4.0 (1.0) mg/kg/day. From baseline, visual acuity improved or was maintained in 23 (92%) eyes and BIO score improved in 19 (76%) eyes. Height centiles were preserved and the maintenance prednisolone dose was 6.3 (3.3) mg/day, where required, in 10 (71%) patients. Nephrotoxicity was not observed, with transient systemic hypertension developing in one patient. Minor adverse effects were more common but were well tolerated. CONCLUSIONS: Cyclosporin A therapy is effective and safe in the medium term, if closely monitored, in refractory non-infectious childhood uveitis.

Acute intraoperative suprachoroidal haemorrhage in ocular surgery.

PURPOSE/BACKGROUND: Acute intraoperative suprachoroidal haemorrhage (AISH) is the most sight-threatening complication of ocular surgery. We investigated the visual outcomes following this intraoperative event, patient characteristics that may predispose to it and the clinical features that may be of prognostic significance. METHODS: The records of 45 cases of AISH collected from ophthalmic centres in the United Kingdom, Republic of Ireland and Switzerland were reviewed. Two satisfactory controls in terms of operative procedure, surgeon, age (+/- 5 years) and gender were found for each of 33 of our cases. Systemic and ocular characteristics were compared for cases and controls, and the visual results of all cases of AISH are analysed. RESULTS: Cases and controls differed only in terms of axial length and pre-operative intraocular pressure, both of which were significantly greater for eyes that experienced an AISH (p < 0.05). Ten eyes (22.2%) achieved a final Snellen acuity of 6/12 or better. Statistically significant associations with a final acuity of counting fingers or worse included spontaneous nuclear expression (p = 0.02), retinal detachment (p < 0.0001), four-quadrant suprachoroidal haemorrhage (p = 0.007) and vision of perception of light or worse at the first dressing (p = 0.0001). Four of the 6 eyes that experienced an AISH during phacoemulsification surgery had a visual outcome of 6/12 or better, and this was significantly greater than for cases involving extracapsular cataract surgery (p = 0.004). CONCLUSION: The results indicate that longer axial length and higher pre-operative intraocular pressure are associated with increased risk of AISH. Poor visual results are more likely following spontaneous nuclear expression, retinal detachment, four-quadrant suprachoroidal haemorrhage or vision of perception of light or worse at the first dressing. The results also suggest that AISH complicating a phacoemulsification procedure has a more favourable visual prognosis than AISH that occurs during extracapsular cataract surgery.

Primary association of HLA-B51 with Behçet's disease in Ireland.

AIMS/BACKGROUND: While a primary association of HLA-B51 with Behçet's disease (BD) in Japanese and Mediterranean patients supports an immunogenetic predisposition, this link is unclear in north western Europe. This study assessed HLA associations with BD, and HLA-B51 with certain clinical characteristics, in the Republic of Ireland, which has an ethnically homogeneous population. METHODS: HLA-A, HLA-B, and HLA-DR typing was performed in 24 BD patients, conforming to International Study Group criteria, and in blood donors, as controls. Patient records were retrospectively reviewed and patients reassessed clinically. RESULTS: A highly significant HLA-B51 association (corrected exact p value = 0.002, relative risk = 6.3) with BD was determined, despite a low B51 prevalence (25%) in patients. No other HLA type was associated. There was a significant B51 link with male sex in BD patients but no association with age at first manifestation/diagnosis, eye involvement, cyclosporin A therapy, or poor visual acuity was determined. CONCLUSIONS: This study supports a HLA-B51 immunogenetic predisposition, similar to Japanese patients, in Irish BD in an ethnically homogeneous population in north western Europe. However, owing to a low prevalence of B51 positivity in BD patients in Ireland, a multifactorial pathogenesis is suggested.