Dara J Kilmartin

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.

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 (⩽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.

Risk factors for endothelial cell loss after phacoemulsification surgery by a junior resident

Purpose: To assess the risk factors for endothelial cell loss after phacoemulsification cataract surgery performed by a junior resident. Setting: Ophthalmic teaching hospital, Dublin, Ireland. Methods: This prospective study included 40 eyes having divide‐and‐conquer phacoemulsification cataract surgery by a junior resident under the supervision of an experienced surgeon. Nine variables were examined to assess the risk for corneal endothelial cell loss postoperatively. Results: The mean overall endothelial cell loss was 11.6%. Longer surgery time, longer absolute and effective phaco time, higher mean ultrasound power, and higher cataract density were significantly associated with endothelial cell loss on univariate analysis. Multivariate analysis identified a grade 3 nucleus (severely dense) and long absolute phaco time as independent predictors for endothelial cell loss, with longer absolute phaco time the stronger predictor. Conclusions: Divide‐and‐conquer phacoemulsification cataract surgery was a safe technique in the hands of an ophthalmic trainee. This study supports advice to junior surgeons to choose cases with less dense cataracts as this will help reduce the absolute phaco time and thus minimize endothelial cell loss.

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.

Cytokine polymorphism in noninfectious uveitis.

PURPOSE Noninfectious uveitis is a sight-threatening immune-mediated intraocular inflammatory disorder. The inheritance of uveitis in multiplex families and its association with known monogenic and polygenic immunologic disorders suggests that common genetic variants underlie susceptibility to uveitis as well as to other immunologic disorders. TNFA and IL10 are strong candidate genes, given the influence of these cytokines on inflammation, immune tolerance, and apoptosis. METHODS The role of 12 polymorphisms spanning the TNFA and IL10 genomic regions was investigated in 192 uveitis patients and 92 population control subjects from four regional centers in the United Kingdom and Republic of Ireland. RESULTS The results demonstrate that uveitis is associated with three haplotype-tagging SNPs (htSNPs) in the IL10 gene: htSNP2 (rs6703630), htSNP5 (rs2222202), and htSNP6 (rs3024490). IL10htSNP2AG/htSNP5TC was the most significantly associated haplotype (P = 0.00085), whereas the LTA+252AA/TNFhtSNP2GG haplotype was protective (P = 0.00031). Furthermore, subgroup analysis showed that the frequency of the TNFd4 allele was higher in patients with nonremitting ocular disease and/or those requiring higher levels of maintenance immunosuppression. Although these associations lost significance after Bonferroni correction, they infer a relationship that may be validated by a larger study. CONCLUSIONS Since these variants are implicated in the susceptibility and severity of several immunologic disorders, the results support the hypothesis that common genetic determinants influence shared mechanisms of autoimmunity.

Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF Loci

PURPOSE The white-dot syndromes are a heterogenous group of chorioretinal disorders that have many common clinical features. Whether these disorders represent distinct clinical entities or different manifestations of the same disease warrants further interrogation. Two white-dot syndromes were investigated, with closely overlapping phenotypes--multifocal choroiditis with panuveitis (MFCPU) and punctate inner choroidopathy (PIC)--for differences in clinical course and genotype frequency at IL10 and TNF loci, known to be associated with noninfectious uveitis. METHODS Twelve polymorphisms were genotyped, spanning the TNFA and IL10 genomic regions, in 61 patients with MFCPU or PIC and 92 population controls from the United Kingdom and Republic of Ireland. RESULTS There were clear differences in clinical course between patients with MFCPU and PIC which had prognostic significance. However, both patient groups demonstrated similar associations with the IL10 haplotype, IL10htSNP2(-2849)AX/htSNP5(+434)TC and negative associations with the TNF haplotype, LTA+252A/TNFhtSNP1(-308)G/TNFhtSNP2(-238)G/TNFhtSNP3(+488)A/TNFd3. CONCLUSIONS Despite clear differences in clinical course and outcome, MFCPU and PIC may still represent two manifestations of the same disease, given their similar genetic associations with IL10 and TNF loci, which are known to be associated with noninfectious uveitis and autoimmunity, in general. Definitive proof will necessitate genomewide sequence analysis. However, the data also support the notion that epigenetic factors have a strong effect on clinical phenotype.

Grading of pars planitis by ultrasound biomicroscopy--echographic and clinical study.

OBJECTIVE To determine the value of high frequency ultrasound biomicroscopy (UBM) in the assessment of pars planitis, and in particular to correlate UBM findings and ophthalmoscopy findings. METHODS All patients with pars planitis were identified from the uveitis database of the Department of Ophthalmology, University of Aberdeen. Fifteen consecutive patients (age 14-52 years) underwent complete ophthalmological examination. UBM was performed at a sound frequency of 50 MHz on 17 eyes of 10 patients to determine the extent of disease. UBM findings were evaluated by two investigators in a blinded fashion and graded from 0 to 3 according to the following grading criteria: 0=no cells, 1=mild cells, 2=marked cells, 3=organization of cells. Opthalmoscopy findings were also graded using the same criteria. UBM and ophthalmoscopy findings were independently graded and compared. RESULTS We found a good inter-observer correlation for the UBM grading of pars planitis (rho=0.86). There was no significant difference in the grading of pars planitis by indirect ophthalmoscopy as compared to grading by UBM (P>0.05). CONCLUSION UBM appears to be a valuable and reliable diagnostic technique for the evaluation of patients with pars planitis and may be useful especially in patients with media opacities to diagnose and/or monitor efficacy of treatment.

Serial Spectral Domain Ocular Coherence Tomography Measurement of Outer Nuclear Layer Thickness in Rhegmatogenous Retinal Detachment Repair

Abstract Introduction: The outer nuclear layer (ONL) contains mostly photoreceptor bodies and reduced post-operative ONL thickness (ONLT) is associated with poor visual outcome in rhegmatogenous retinal detachment (RRD). Methods: Spectral domain ocular coherence tomography was recorded before and 6 weeks following RRD repair in 27 consecutive patients. Results: The repair consisted of combined 20-guage pars plana vitrectomy (PPV) and encirclement in 66.7% of cases, 22.2% underwent PPV alone and 11.1% scleral buckle alone. The mean (± standard deviation) ONLT was reduced in detached retinae (94.1 ± 31.1 microns) compared to the unaffected eye (119.5 ± 26.8 microns). Postoperatively the ONLT increased to 103.3 (± 32.8) microns. ONLT at presentation in the affected eye is significantly and positively correlated with the final ONLT in the affected eye (Pearson’s correlation: r = 0.80, p = 0.029). Conclusion: The finding that ONLT is reduced in detached retinae carries implications for visual prognosis.

Importance of fundoscopy in refractive surgery

PURPOSE: To examine the incidence, treatment, and outcomes of retinal lesions before and after refractive laser surgery. SETTING: Private refractive surgery practice. METHODS: A retrospective review was conducted of patients attending the laser clinic over a 3‐year period. Examined were the incidence, type, management, and outcomes of the posterior segment abnormalities encountered. RESULTS: Fifty two (1.1%) of 4800 patients had posterior segment pathology requiring intervention. Forty‐five cases (0.86%) were detected preoperatively and had a mean refraction of −4.5 diopters (D) ± 3.0 (SD). Seven cases (0.14%) were detected postoperatively at a mean follow‐up of 19 ± 18.3 months; none had preoperative pathology. The mean refraction in this group was −4.4 ± 2.3 D. Ninety‐five percent had myopic prescriptions. All maintained best corrected visual acuity postoperatively. The incidence of retinal detachment was 0.03% per year in the myopic candidates; however, no cases occurred after the refractive procedure. CONCLUSION: Dilated fundus examination is an integral part of optimum clinical care in refractive patients, and shared preoperative assessment by a retinal specialist is advisable in those with predisposing retinal pathology.