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1.  Birdshot uveitis: current and emerging treatment options 
Birdshot chorioretinopathy is a relatively uncommon subtype of idiopathic posterior uveitis with distinct clinical characteristics and a strong genetic association with the Human Leukocyte Antigen (HLA)-A29 allele. The diagnosis remains clinical and is based on the presence of typical clinical features, including multiple, distinctive, hypopigmented choroidal lesions throughout the fundus. The long-term visual prognosis of this disorder, however, remains guarded – central visual acuity can be preserved until late in the disease and it is not uncommon for patients to receive inadequate immunosuppressive treatment, leading to a poor long-term outcome in which peripheral retinal damage eventually leads to visual deterioration. Birdshot chorioretinopathy has proven a particularly attractive area of study within the field of uveitis, as it is a relatively easily defined disease with an associated human leukocyte antigen haplotype. Despite this, however, the immune mechanisms involved in its pathogenesis remain unclear, and some patients continue to lose retinal function despite therapy with corticosteroids and conventional immunosuppressive agents. Laboratory research continues to investigate the underlying mechanisms of disease, and clinical research is now being driven to improve the phenotyping and monitoring of this condition as, in the era of so-called personalized medicine, it is becoming increasingly important to identify patients at risk of visual loss early so that they can be treated more aggressively with targeted therapies such as the newer biological agents. This approach requires the formation of collaborative groups, as the relative rarity of the condition makes it difficult for one center to accumulate enough patients for worthwhile studies. Nevertheless, results obtained with newer therapies, such as biological agents directed against particular cytokines or cell-surface receptors, demonstrate ever improving control of the inflammation in refractory cases, providing hope that the outlook for visual function in this condition can only improve.
PMCID: PMC3872035  PMID: 24379650
birdshot chorioretinopathy; HLA-A29; retinal vasculitis; Th17 cells; monoclonal antibodies; interleukin antagonists
2.  Local therapies for inflammatory eye disease in translation: past, present and future 
BMC Ophthalmology  2013;13:39.
Despite their side-effects and the advent of systemic immunosuppressives and biologics, the use of corticosteroids remains in the management of patients with uveitis, particularly when inflammation is associated with systemic disease or when bilateral ocular disease is present. The use of topical corticosteroids as local therapy for anterior uveitis is well-established, but periocular injections of corticosteroid can also be used to control mild or moderate intraocular inflammation. More recently, intraocular corticosteroids such as triamcinolone and steroid-loaded vitreal inserts and implants have been found to be effective, including in refractory cases. Additional benefits are noted when ocular inflammation is unilateral or asymmetric, when local therapy may preclude the need to increase the systemic medication.
Implants in particular have gained prominence with evidence of efficacy including both dexamethasone and fluocinolone loaded devices. However, an appealing avenue of research lies in the development of non-corticosteroid drugs in order to avoid the side-effects that limit the appeal of injected corticosteroids. Several existing drugs are being assessed, including anti-VEGF compounds such as ranibizumab and bevacizumab, anti-tumour necrosis factor alpha antibodies such as infliximab, as well as older cytotoxic medications such as methotrexate and cyclosporine, with varying degrees of success. Intravitreal sirolimus is currently undergoing phase 3 trials in uveitis and other inflammatory pathways have also been proposed as suitable therapeutic targets. Furthermore, the advent of biotechnology is seeing advances in generation of new therapeutic molecules such as high affinity binding peptides or modified high affinity or bivalent single chain Fab fragments, offering higher specificity and possibility of topical delivery.
PMCID: PMC3750406  PMID: 23914773
3.  Histopathological features predictive of a clinical diagnosis of ophthalmic granulomatosis with polyangiitis (GPA) 
The limited form of Granulomatosis with Polyangiitis (GPA), formerly known as Wegener’s Granulomatosis (WG) primarily involves the head and neck region, including the orbit, but is often a diagnostic challenge, particularly as it commonly lacks positive anti-neutrophil cytoplasm antibody (ANCA) titres or classical features on diagnostic orbital biopsies. The purpose of this study was to relate biopsy findings with clinical outcome and to determine which histopathological features are predictive of a clinical diagnosis of GPA.
Retrospective case series of 234 patients identified from the database of the UCL Institute of Ophthalmology Department of Eye Pathology as having had orbital biopsies of orbital inflammatory disorders performed between 1988 and 2009. Clinical records were obtained for the patients and analysed to see whether patients had GPA or not, according to a standard set of diagnostic criteria (excluding any histopathological findings). Biopsy features were then correlated with the clinical diagnosis in univariate and multivariate analyses to determine factors predictive of GPA.
Of the 234 patients, 36 were diagnosed with GPA and 198 with other orbital pathologies. The majority of biopsies were from orbital masses (47%). Histology showed a range of acute and chronic inflammatory pictures in all biopsies, but the presence of neutrophils (P<0.001), vasculitis (P<0.001), necrosis (P<0.001), eosinophils (P<0.02) and macrophages (P=0.05) were significantly associated with a later clinical diagnosis of GPA. In a multivariate analysis, only tissue neutrophils (OR=3.6, P=0.01) and vasculitis (OR=2.6, P=0.02) were independently associated with GPA, in contrast to previous reports associating eosinophils and necrosis with the diagnosis.
Neutrophil, eosinophil and macrophage infiltration of orbital tissues, together with vasculitis and necrosis, are all associated with a clinical diagnosis of GPA, but only neutrophil infiltration and vasculitis are independently associated with this diagnosis. These features may assist in the establishing the diagnosis of limited GPA among patients with early orbital disease, particularly in the absence of positive serum ANCA titres.
PMCID: PMC3438764  PMID: 22977665
Granulomatosis with polyangiitis; histopathology; eosinophils; nuclear dust
4.  Valacyclovir in the treatment of acute retinal necrosis 
BMC Ophthalmology  2012;12:48.
To report the outcome of oral valacyclovir as the sole antiviral therapy for patients with acute retinal necrosis (ARN).
This study reports a retrospective, interventional case series of nine consecutive patients with ten eyes with newly diagnosed ARN treated with oral valacyclovir as the sole antiviral agent. Eight patients received oral valacyclovir 2 g tid (Valtrex, GlaxoSmithKline) and one patient with impaired renal function received oral 1 g tid. The main outcome measures were response to treatment, time to initial response to treatment, time to complete resolution of retinitis, best corrected visual acuity (BCVA) at final follow-up, retinal detachment and development of recurrent or second eye disease.
Retinitis resolved in ten of ten (100%) affected eyes. The median time to initial detectable response was seven days and the median time to complete resolution was 21 days. A final BCVA of 20/40 or better was achieved in 6/10 (60%) of eyes. 3/10 eyes (30%) developed a retinal detachment. No patients developed either disease reactivation or second eye involvement over the course of the study (mean follow up 31 weeks, range 7 to 104 weeks).
Treatment with oral valacyclovir as the sole antiviral therapy resulted in complete resolution of retinitis. Final BCVA and retinal detachment rate were comparable with previously reported outcomes for intravenous acyclovir.
PMCID: PMC3487766  PMID: 22947428
Acute retinal necrosis; Herpetic retinitis; Acyclovir; Valacyclovir
5.  Topical Prostaglandin Analogues and Conjunctival Inflammation in Uveitic Glaucoma 
A pilot study to determine whether topical prostaglandin analogues alter the expression of conjunctival inflammatory markers in patients with uveitic glaucoma.
Prospective, single-masked case series of 20 patients with uveitis and secondary raised intraocular pressure. Participants were divided into four groups of five patients dependent on their use of topical medication: (1) prostaglandin analogues only, (2) corticosteroids only, (3) both prostaglandin analogues and corticosteroids, (4) no topical medication. Conjunctival cells were harvested by impression cytology and were examined for inflammatory markers (CD3, CD54, HLA-DR, CCR4, CCR5) by flow cytometry. A tear fluid sample was also examined for inflammatory cytokines (IL-12p70, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IFN-gamma, IL-1beta, IFN-alpha, IFN-beta) by multiplex bead arrays.
All groups demonstrated increased markers of conjunctival inflammation. There was no significant difference in levels of any inflammatory markers between the four groups, suggesting that the use of topical prostaglandin analogues does not increase conjunctival levels of inflammation beyond those already seen in uveitis.
The use of topical prostaglandins does not appear to induce conjunctival inflammation over that which is already present in patients with uveitic glaucoma. This supports the use of topical prostaglandin analogues in patients with uveitic glaucoma, indicating that their use is unlikely to adversely affect subsequent glaucoma filtration surgery through the induction of chronic conjunctival inflammation.
PMCID: PMC3428634  PMID: 22934125
Uveitic glaucoma; prostaglandin analogues; conjunctival inflammation; trabeculectomy.
6.  Clinical and Molecular Features Associated with Cystic Visceral Lesions in Von Hippel-Lindau Disease 
Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ.
This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic.
Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas.
VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients.
PMCID: PMC3447160  PMID: 23002415
von Hippel-Lindau; retinal capillary haemangioma; epididymal cyst; renal cyst; gene deletion.

Results 1-6 (6)