Alastair K.O. Denniston

Bilateral retinal vasculitis in a patient with systemic lupus erythematosus and its remission with rituximab therapy

Severe retinal vasculitis is a rare, but potentially blinding, complication of patients with systemic lupus erythematosus (SLE). We describe here the first reported case of treating severe bilateral SLE-associated retinal vasculitis with the anti-CD20 monoclonal antibody rituximab, a drug which has established its role in rheumatoid arthritis and has shown promise in case series for the treatment of severe SLE that is unresponsive to other therapies. This case suggests that rituximab-induced B-cell depletion may provide an important new therapeutic option for refractory cases of this devastating ocular complication.

Systemic therapies for inflammatory eye disease: Past, Present and Future

In this review we consider the current evidence base for treatments in inflammatory eye disease, and in particular uveitis, from a historical perspective. We consider the challenges that have traditionally hindered progress in inflammatory eye disease including small target populations, heterogeneous disease groups, poorly defined phenotypes, diagnostic inconsistency, subjective outcome measures, specific issues around visual acuity as an outcome measure and low commercial interest. Strategies to address these issues are considered de novo and with reference to recent advances outside of ophthalmology and highlight the promise for ocular inflammation. Progress in these specialties has included the development of thriving clinical-trial cultures, public-private partnerships, pathogenetic- and structure-led drug design, efficient drug development pipelines, and biomarker-defined treatment protocols enabling personalization of medicine. Although there are challenges, these are exciting opportunities as we seek to develop safe and effective treatments for patients with inflammatory eye disease.

Research into Glaucoma And Ethnicity (ReGAE) 8: is there a relationship between social deprivation and acute primary angle closure?

Objectives Social deprivation as measured by the Index of Multiple Deprivation (IMD) and Townsend scores has been shown to be associated with advanced presentation of primary open angle glaucoma. The aim of this study was to investigate the putative association of social deprivation as a risk factor for acute primary angle closure (APAC) in a UK urban population. Methods Case notes of 139 consecutive patients presenting with APAC at the Birmingham and Midland Eye Centre, Birmingham, UK, were examined. Deprivation was scored using the IMD 2004 and Townsend scores. These score were compared with the West Midlands reference population. Results The level of deprivation in patients with APAC was graded according to the IMD quintiles, in which quintile 1 represents the highest level of deprivation and quintile 5 represents the lowest level of deprivation. Of the patients studied, 66.1% (n=90) were from quintiles 1 or 2 (most deprived) whereas 9% (n=12) came from quintile 5 (least deprived), compared with predicted frequencies of 40% and 20%, respectively. Deprivation levels measured by frequency within each IMD quintile were significantly higher in the APAC group compared with the reference population (χ2, p<0.001). Conclusions In this population patients presenting with APAC were more likely to come from areas with a high level of social deprivation.

Evaluation of Objective Vitritis Grading Method Using Optical Coherence Tomography: Influence of Phakic Status and Previous Vitrectomy.

PURPOSEnTo evaluate a proposed method for objective measurement of vitreous inflammation using a spectral-domain optical coherence tomography (SD OCT) device in a large cohort of uveitis eyes, including pseudophakic eyes and vitrectomized eyes.nnnDESIGNnRetrospective, observational cohort study.nnnMETHODSnOne hundred five uveitis eyes (105 patients) with different vitreous haze score grades according to standardized protocols and corresponding SD OCT images (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, California, USA) were included. Clinical data recorded included phakic status, previous vitreoretinal surgery, and anterior chamber (AC) cells and flare. SD OCT images were analyzed using custom software that provided absolute measurements of vitreous (VIT) and retinal pigment epithelium (RPE) signal intensities, which were compared to generate a relative optical density ratio with arbitrary units (VIT/RPE-relative intensity) and compared to VHS.nnnRESULTSnVIT/RPE-relative intensity showed a significant positive correlation with vitreous haze score (r = 0.535, P < .001) that remained significant after adjusting for factors governing media clarity, such as AC cells, AC flare, and phakic status (R(2)-adjusted = 0.424, P < .001). Significant differences were also observed between the different vitreous haze score groups (P < .001). Preliminary observation did not observe differences in VIT/RPE-relative intensity values between phakic and pseudophakic eyes (0.3522 vs 0.3577, P = .48) and between nonvitrectomized and vitrectomized eyes (0.3540 vs 0.3580, P = .52), overall and respectively for each vitreous haze score subgroup.nnnCONCLUSIONSnVIT/RPE-relative intensity values provide objective measurements of vitreous inflammation employing an SD OCT device. Phakic status and previous vitrectomy surgery do not appear to influence these values, although these preliminary findings need validation in future studies.

Social deprivation as a risk factor for late presentation of proliferative diabetic retinopathy

Purpose The aim of this study was to determine whether social deprivation is a risk factor for late presentation of patients with proliferative diabetic retinopathy and whether it affects their access to urgent laser treatment. Methods Using a 2:1 case: control design, 102 patients referred to a UK teaching hospital as part of the UK Diabetic Retinopathy National Screening Programme were identified for the period between 1 June 2010 to 1 June 2013. Social deprivation was scored using the Index of Multiple Deprivation 2010. Additional variables considered included age, duration of disease, ethnicity, and HbA1c at time of referral. Results The cases comprised 34 patients referred with proliferative (grade R3) retinopathy with a control group of 68 patients with lower retinopathy grades; two control patients were excluded due to incomplete data. On univariate analysis, R3 retinopathy was associated with higher social deprivation (P<0.001, Mann–Whitney U-test), and with higher HbA1c (11.5% vs 8.4%; P<0.001, Mann–Whitney U-test). Forward stepwise multivariable analysis showed that the association of R3 retinopathy with deprivation was significant even after adjusting for HbA1c (P=0.016). On univariate analysis South Asian ethnicity was also identified as being a risk factor for presentation with R3 retinopathy, but this was no longer significant when HbA1c was adjusted for in a forward stepwise logistic regression analysis. Conclusion In our cohort social deprivation appears to be associated with late presentation of proliferative diabetic retinopathy. Our study supports the need to target these groups to reduce preventable blindness and to identify strategies which overcome barriers to care.

Development and Validation of Quality-of-Life Questionnaires for Birdshot Chorioretinopathy

Birdshot chorioretinopathy (BCR) is a rare form of chronic posterior uveitis, usually requiring long-term, systemic immunosuppression.1 The severe impact of the disease on acuity, visual field, color discrimination, and electrodiagnostics is well-documented,1 ; 2 but studies on quality of life (QoL) have been limited. Furthermore, existing QoL tools fail to capture the unique and wide range of symptoms associated with BCR and BCR medications.

Long-term biocompatibility and visual outcomes of a hydrophilic acrylic intraocular lens in patients with uveitis

Purpose To report the long‐term visual outcomes and biocompatibility of a single‐piece hydrophilic acrylic intraocular lens (IOL) in patients with uveitis having cataract surgery. Setting Tertiary referral center, Birmingham, United Kingdom. Design Retrospective case review. Methods The review included consecutive uveitis patients in whom phacoemulsification and acrylic IOL implantation was performed by the same surgeon. Outcomes measures are reported as rate/eye‐year and included visual acuity and signs of bioincompatibility. Results The review identified 171 eyes (140 patients; mean age 51 years [range 16 to 85 years]) with uveitis. The mean follow‐up was 3.8 years (range 0.9 to 10.3 years). Signs of uveal bioincompatibility were found in 31 eyes, with visually insignificant deposits on the IOL in 17 eyes. The rate of uveal bioincompatibility was 0.06/eye‐year. Signs of capsule bioincompatibility were found in 107 (63%) of 171 eyes (0.31/eye‐year). Posterior capsule opacification was documented in 102 eyes (0.29/eye‐year); neodymium:YAG laser capsulotomy was required in 31 eyes (0.05/eye‐year). The rate of failure to maintain a 3 logMAR line improvement in corrected distance visual acuity (CDVA) was 0.08/eye‐year; to maintain better than 0.3 logMAR, 0.15/eye‐year; and to maintain either, 0.04/eye‐year. At 1 year, 85% of eyes had a CDVA of better than 0.3 logMAR or maintained a 3 logMAR–line improvement. Eyes with preexisting macular or optic nerve disease had significantly worse visual outcomes. Conclusions The long‐term safety profile of the hydrophilic acrylic IOL was good in uveitis cases, leading to good visual outcomes and a low rate of vision‐impairing uveal and capsule complications. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Chapter 80 – Rheumatic Disease

March 01, 2004 ABSTRACT: The basic screening studies for rheumatic diseases are a complete blood cell count, a determination of the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level, a rheumatoid factor assay, an antinuclear antibody (ANA) test, a measurement of serum uric acid level, and a urinalysis. Test results must be interpreted within a clinical context; for example, a positive ANA assay suggests the possibility of a rheumatic disorder, but it is not specific for any diagnosis. Tests that reveal the nature and extent of target-organ involvement, such as renal function studies in patients with systemic lupus erythematosus, can help guide the selection of therapy. Laboratory results also reflect disease activity; the ESR and CRP level are useful gauges of the activity of most inflammatory rheumatic disorders. Finally, laboratory monitoring can help you minimize the significant toxicity associated with many of the drugs used to manage rheumatic diseases.

Preface to second edition

In preparing a new edition of An Introduction to Copulas, my goals included adding some topics omitted from the first edition while keeping the book at a level appropriate for self-study or for a graduate-level seminar. The major additions in the second edition are sections on: • a copula transformation method; • extreme value copulas; • copulas with certain analytic or functional properties; • tail dependence; and • quasi-copulas. There are also a number of new examples and exercises and new figures, including scatterplots of simulations from many of the families of copulas presented in the text. Typographical errors in the first edition have been corrected, and the references have been updated. Thanks again to Lewis & Clark College for granting me a sabbatical leave in order to prepare this second edition; and to the Department of Mathematics and Statistics at Mount Holyoke College for again inviting me to spend the sabbatical year with them. Finally, I would like to thank readers of the first edition who found numerous typographical errors in the first edition and sent me suggestions for this edition.