Robert J Barry

Unregistered visual impairment: is registration a failing system?

Background/aims: To assess the current level of under-registration of blindness and partial sight among patients attending a large teaching hospital, and to determine any risk factors for under-registration. Methods: Medical records of all patients attending general ophthalmology outpatient clinics over a 3 month period were included in a retrospective analysis of registration rates; questionnaire survey assessing the level of knowledge of registration practices among 35 ophthalmologists working in the West Midlands. Results: 146/2161 (7%) patients were eligible for blind or partial sight registration, or were in possession of a completed BD8 form. Of these 146 patients, 65 (45%) were unregistered with 18 fulfilling the criteria for blind and 47 for partially sight. In addition, 32/81 (40%) registered patients appeared to have been inappropriately registered. Partially sighted patients were more likely to be unregistered than blind patients (OR 2.31, 95% CI 1.15 to 4.63, p = 0187), and patients from ethnic minorities were more than three times more likely to be unregistered than white patients (OR 3.23, 95% CI 1.56 to 6.65, p = 0.0015). A patient with a treatable condition was more likely to be unregistered than a patient with an untreatable condition (OR 4.87, 95% CI 2.10 to 11.33, p = 0.0002). The overall level of knowledge of registration practices among doctors was found to be low and there was no indication of increasing knowledge with increasing experience. Conclusions: There has been little improvement in registration rates of visually impaired patients over the past decade. Ophthalmologists lack the necessary knowledge to cater for visually impaired patients’ needs.

‘It’s like taking poison to kill poison but I have to get better’: A qualitative study of beliefs about medicines in Rheumatoid arthritis and Systemic lupus erythematosus patients of South Asian origin

Objective: To investigate factors that influence beliefs about medicines in patients of South Asian origin with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods: Qualitative methodology was used to explore the health beliefs of South Asian patients and in particular the factors that influenced their beliefs about medicines and disease modifying anti-rheumatic drugs (DMARDs). Thirty two patients with RA and SLE took part in focus group discussions. Patients who chose to participate in focus groups conducted in English were compared with those who chose to participate groups conducted in Punjabi or Urdu. Results: Three main themes emerged to explain patients beliefs about medicines: (1) Beliefs about the necessity of DMARDs; (2) Concerns about DMARDs and other prescribed medicines including: (a) long-term side-effects; (b) the apparent lack of efficacy of some therapies; (c) concerns about changing from one drug to another and the large numbers of different medicines being taken; (3) Contextual factors which informed the patient’s view on the necessity for particular medicines and concerns about them including: (a) beliefs about the causes of disease and the influence of religious beliefs on this; (b) barriers to communication with health care professionals about the medications being prescribed in clinic. In addition, our data revealed that these beliefs about DMARDs had important consequences for patient behaviour, including the use of traditional dietary and other non-pharmacological approaches. There were differences in views expressed between those who chose to speak in English and those who did not. Conclusion: This study has identified themes that explain previous findings of negative beliefs about medicines in patients of South Asian origin. Beliefs about the causes of disease had an important impact on the way some patients viewed medicines for RA and SLE. This will have implications for educational programmes designed to promote patient involvement in disease management.

Patient-reported outcomes in primary Sjögren's syndrome: comparison of the long and short versions of the Profile of Fatigue and Discomfort—Sicca Symptoms Inventory

OBJECTIVES The long-form 64-item Profile of Fatigue and Discomfort--Sicca Symptoms Inventory (PROFAD-SSI) questionnaire was developed as a patient-reported assessment tool for use in primary SS (PSS) and other rheumatic disorders. In this study, we assess whether the (shorter and more practical) 19-item PROFAD-SSI-SF (short form) gives similar results and whether a still briefer version using visual analogue scales (VASs) is feasible. METHODS Questionnaire surveys comprising the long and short versions of the PROFAD-SSI were mailed to 43 patients with PSS and 50 patients with RA, who were asked to complete these contemporaneously as well as repeating the process 1 month later. PSS patients also completed a series of VASs comprising fatigue and sicca domains of the SSI. RESULTS Surveys were returned from 35 PSS patients and 35 RA patients. All domains of the long- and short-form PROFAD-SSI showed strong correlations (Spearman rho between 0.779 and 0.996, P < 0.01). Factor analysis generally confirmed the previously validated domain structure with Cronbachs alpha = 0.99. The PROFAD-SF somatic fatigue domain correlated more strongly with a fatigue VAS than did the mental fatigue domain. The SSI-SF domain scores correlated with equivalent VAS scores. CONCLUSION The long- and short-form PROFAD-SSI questionnaires correlate closely suggesting that the PROFAD-SF is valid as an outcome tool. Preliminary data also suggest that an even briefer form with compression of the domains into single VAS is also feasible.

Pharmacotherapy for uveitis: current management and emerging therapy

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects.

Ten-year experience of pulsed intravenous cyclophosphamide and methylprednisolone protocol (PICM protocol) in severe ocular inflammatory disease

Aims Severe ocular inflammation is a blinding ophthalmological emergency. This study evaluates the efficacy and patient tolerance of a validated regime of pulsed intravenous cyclophosphamide and methylprednisolone (‘PICM protocol’) for these patients. Methods 26 patients with severe inflammatory eye disease (43 eyes: 22 uveitis, 21 scleritis/sclerokeratitis; median age 52 years (IQR 40.25–62.25)) presenting to a regional tertiary referral centre were recruited over a 10-year period (January 2002–December 2011) into the PICM protocol, comprising intravenous cyclophosphamide 15 mg/kg, intravenous methylprednisolone 10 mg/kg, maximum nine pulses over 20 weeks supplemented with low-dose continuous oral prednisolone. Data were captured pretreatment and at 6 and 12 months follow-up. Primary outcome measures were control of inflammation according to standard criteria and reduction in systemic glucocorticoid to ≤10 mg prednisolone/day. Results A median of six pulses (IQR 5–6) were administered over a median of 3 months (IQR 2.25–4). In the scleritis/sclerokeratitis group, 15/21(71%) achieved success or partial success at 6 and 12 months versus 9/22 (41%) for the same time points in the uveitis group (χ2=4.058, p=0.044). Two patients had adverse events requiring treatment withdrawal. Conclusions This PICM protocol is a well-tolerated regimen for managing severe ocular inflammation and appears particularly useful in patients with scleritis/sclerokeratitis.

Birdshot chorioretinopathy: current knowledge and new concepts in pathophysiology, diagnosis, monitoring and treatment

AbstractBirdshot chorioretinopathy (BCR) is a rare form of chronic, bilateral, posterior uveitis with a distinctive clinical phenotype, and a strong association with HLA-A29. It predominantly affects people in middle age. Given its rarity, patients often encounter delays in diagnosis leading to delays in adequate treatment, and thus risking significant visual loss. Recent advances have helped increase our understanding of the underlying autoimmune mechanisms involved in disease pathogenesis, and new diagnostic approaches such as multimodality imaging have improved our ability to both diagnose and monitor disease activity. Whilst traditional immunosuppressants may be effective in BCR, increased understanding of immune pathways is enabling development of newer treatment modalities, offering the potential for targeted modulation of immune mediators. In this review, we will discuss current understanding of BCR and explore recent developments in diagnosis, monitoring and treatment of this disease. Synonyms for BCR: Birdshot chorioretinopathy, Birdshot retinochoroiditis, Birdshot retino-choroidopathy, Vitiliginous choroiditis. Orphanet number: ORPHA179 OMIM: 605808.

Drug discovery in ophthalmology: past success, present challenges, and future opportunities

BackgroundDrug discovery has undergone major transformations in the last century, progressing from the recognition and refinement of natural products with therapeutic benefit, to the systematic screening of molecular libraries on whole organisms or cell lines and more recently to a more target-based approach driven by greater knowledge of the physiological and pathological pathways involved. Despite this evolution increasing challenges within the drug discovery industry are causing escalating rates of failure of development pipelines.DiscussionWe review the challenges facing the drug discovery industry, and discuss what attempts are being made to increase the productivity of drug development, including a refocusing on the study of the basic biology of the disease, and an embracing of the concept of ‘translational research’. We consider what ophthalmic drug discovery can learn from the sector in general and discuss strategies to overcome the present limitations. This includes advances in the understanding of the pathogenesis of disease; improvements in animal models of human disease; improvements in ophthalmic drug delivery and attempts at patient stratification within clinical trials.SummaryAs we look to the future, we argue that investment in ophthalmic drug development must continue to cover the whole translational spectrum (from ‘bench to bedside and back again’) with recognition that both biological discovery and clinical understanding will drive drug discovery, providing safe and effective therapies for ocular disease.

Evidence-based practice in Behçet’s disease: identifying areas of unmet need for 2014

BackgroundBehçet’s Disease (BD) is characterized by a relapsing-remitting course, with symptoms of varying severity across almost all organ systems. There is a diverse array of therapeutic options with no universally accepted treatment regime, and it is thus important that clinical practice is evidence-based. We reviewed all currently available literature describing management of BD, and investigated whether evidence-based practice is possible for all disease manifestations, and assessed the range of therapeutic options tested.MethodsWe conducted an internet search of all literature describing management of BD up to August 2013, including pharmacological and non-pharmacological interventions. We recorded treatment options investigated and disease manifestations reported as primary and secondary study outcomes. Quality of data was assessed according to the Scottish Intercollegiate Guideline Network (SIGN) hierarchy of evidence.ResultsWhilst there is much literature describing treatment of ocular and mucocutaneous disease, there is little to guide management of rheumatoid, cardiovascular and neurological disease. This broadly reflects the prevalence of disease manifestations of BD, but not the severity. Biologic therapies are the most commonly investigated intervention. The proportion of SIGN-1 graded studies is declining, and there are no SIGN-1 graded studies investigating neurological or gastrointestinal manifestations of BD.ConclusionsThis is the first study to investigate trends in published literature for management of BD over time. It identifies neurological, cardiovascular and gastro-intestinal disease as particular areas of unmet need and suggests that overall quality of evidence is declining. Future research should be designed to address these areas of insufficiency to facilitate evidence-based practice in BD.

Association analysis of TGFBR3 gene with Behçet's disease and idiopathic intermediate uveitis in a Caucasian population

Background Transforming growth factor β (TGFβ) is an important immunoregulatory cytokine in regulatory T cell (Treg) and Th17-mediated pathology, including uveitis due to Behçets disease (BD). Of the three isoforms, TGFβ2 is found at highest levels in the aqueous humour of uninflamed eyes. TGFβ signals through a cell-surface receptor comprising three subunits (TGFBR1, 2 and 3). TGFBR3 is considered necessary for TGFβ2 signal transduction, but not for other isoforms. A polymorphism in TGFBR3 (rs1805110) has previously been identified in Han Chinese patients with BD. We investigated the frequency of this polymorphism in a Caucasian population with BD and idiopathic intermediate uveitis (IIU). Methods The single-nucleotide polymorphism (SNP) rs1805110 in TGFBR3 was genotyped in 75 BD patients, 92 IIU disease controls and 85 disease-free controls. The association with both diseases was analysed using Fishers exact test. Results No significant difference in rs1805110 allele or genotype frequency was observed. A low frequency of the T allele was observed (5.88% control, 9.33% BD, 10.33% IIU) with the TT genotype absent in patients with BD and IIU (1.18% control, 0% BD and 0% IIU). Stratification analysis according to clinical features of BD did not associate with the tested SNP. Conclusions RS1805110 is not associated with BD or IIU in Caucasian patients. The T allele frequency is consistent with that presented for Caucasian populations in the HapMap database (p>0.05). Our results differ from the previous analysis in Han Chinese patients (p<0.0001), however, the possibility of having a much smaller effect due to the low minority frequency cannot be excluded.

Anterior lamellar excision and laissez-faire healing for aberrant lashes in ocular cicatricial pemphigoid.

PurposeTo describe the outcomes of a simple technique of anterior lamellar excision (ALE) with laissez-faire healing for management of aberrant lashes in ocular cicatricial pemphigoid (OCP).MethodsProspective interventional case series.ResultsSeven OCP patients underwent grey line split and ALE with laissez-faire healing over a 24-month period in a tertiary referral centre. All patients had undergone previous interventions for the misdirected lashes. Nine procedures were undertaken (three upper and six lower lids). Mean follow-up was for 25.66±12.3 months (range: 9–43 months). Residual lashes were noted in three patients. In two cases, the lashes were isolated and managed successfully by a single electrolysis treatment. One patient needed further ALE for residual remnant of trichiatic cilia at the lateral edge of the lid. All patients were satisfied with their post-operative appearance. None of the patients showed exacerbation of disease or needed additional immunosuppression as a consequence of the lid surgery.ConclusionsAnterior lamellar excision with spontaneous granulation is a simple and effective procedure for management of aberrant lashes. Risk of disease exacerbation was reduced in OCP with minimal conjunctival manipulation and reduced post-operative lash-globe touch.