Birdshot chorioretinopathy.

PURPOSE OF REVIEW: Birdshot chorioretinopathy remains incompletely understood, but new insights into its pathogenesis have been reported recently, and treatment and monitoring options have also expanded. Central visual acuity may remain good until the late stages of the disease, but loss of visual field and peripheral retinal function is common. RECENT FINDINGS: The underlying pathogenesis of the disease has long been believed to be T-cell driven, but examination of the IL-17 pathway has now further refined the potential underlying mechanism. New imaging techniques, including extended depth imaging of the choroid with optical coherence tomography, have demonstrated promise in detecting disease activity earlier, enabling targeted treatment to be given. Treatment options have expanded with the advent of the biological agents, and these may yet improve outcomes, particularly in refractory patients. SUMMARY: Laboratory research continues to investigate the underlying mechanisms of disease, but our understanding remains frustratingly incomplete for a disease with such a clear HLA association. Clinical research is increasingly being driven to improve the phenotyping of affected patients so that those at risk of visual loss can be identified early and treated more aggressively with individually targeted therapies such as the newer biological agents, but how successful this approach will ultimately prove to be remains to be seen.

Intraocular methotrexate can induce extended remission in some patients in noninfectious uveitis.

PURPOSE: To assess the outcomes of the intravitreal administration of methotrexate in uveitis. METHODS: Multicenter, retrospective interventional case series of patients with noninfectious uveitis. Thirty-eight eyes of 30 patients were enrolled, including a total of 54 intravitreal injections of methotrexate at a dose of 400 µg in 0.1 mL. The primary outcome measure was visual acuity. Secondary outcome measures included control of intraocular inflammation and cystoid macular edema, time to relapse, development of adverse events, and levels of systemic corticosteroid and immunosuppressive therapy. RESULTS: Methotrexate proved effective in controlling intraocular inflammation and improving vision in 30 of 38 eyes (79%). The side effect profile was good, with no reported serious ocular adverse events and only one patient having an intraocular pressure of >21 mmHg. Of the 30 eyes that responded to treatment, 8 relapsed, but 22 (73%) entered an extended period of remission, with the Kaplan-Meier estimate of median time to relapse for the whole group being 17 months. The eight eyes that relapsed were reinjected and all responded to treatment. One eye relapsed at 3 months, but 7 eyes again entered extended remission. Of the 14 patients on systemic therapy at the start of the study, 8 (57%) were able to significantly reduce this following intravitreal methotrexate injection. CONCLUSION: In patients with uveitis and uveitic cystoid macular edema, intravitreal MTX can effectively improve visual acuity and reduce cystoid macular edema and, in some patients, allows the reduction of immunosuppressive therapy. Some patients relapse at 3 to 4 months, but a large proportion (73%) enter an extended period of remission of up to 18 months. This larger study extends the results obtained from previous smaller studies suggesting the viability of intravitreal methotrexate as a treatment option in uveitis.

The Use of Sustained Release Intravitreal Steroid Implants in Non-Infectious Uveitis Affecting the Posterior Segment of the Eye.

The treatment of non-infectious uveitis affecting the posterior segment of the eye has been revolutionized by the development of sustained-release corticosteroid implants over the past decade. Their use is now supported by healthcare systems that have licensed and commissioned them on the basis of the high-quality randomised controlled trials that formed part of their development and which have informed clinicians as to their benefits and risks. In particular, they have provided an alternative mode of treatment for patients who do not wish to be systemically immunosuppressed, or in whom such immunosuppression is less desirable, such as those with unilateral disease or those with concurrent illnesses such as diabetes mellitus, renal disease or osteoporosis that are negatively impacted by systemic corticosteroids or other immunosuppressive agents. In this article, we review the evidence for the use of the major licensed corticosteroid implants and assess the advantages and disadvantages of each.

Positive response to intravitreal ranibizumab in the treatment of choroidal neovascularization secondary to punctate inner choroidopathy.

PURPOSE: The purpose of the study was to report the use of ranibizumab in choroidal neovascularization secondary to punctate inner choroidopathy. METHODS: This was a retrospective case series. Clinical notes of 10 patients with choroidal neovascularization secondary to punctate inner choroidopathy were reviewed (mean age, 40.7 years, age range, 25-58 years). RESULTS: Previous therapies included photodynamic therapy, posterior sub-Tenon's triamcinolone, oral prednisolone, and intravitreal triamcinolone. Ten eyes in 10 patients underwent a mean of 1.9 ± 1.3 (± standard deviation) injections of antivascular endothelial growth factor (range, 1-5). All 10 patients had a follow-up review of at least 6 months (median, 12.5 ± 9.2 standard deviation; range, 6-34 months). Nine eyes either maintained or improved vision by at least 1 line on the logarithmic of the minimal angle of resolution calculated equivalent chart at least 6 months after the start of treatment with antivascular endothelial growth factor therapy. No ocular or systemic complications were observed. CONCLUSION: The role of ranibizumab in choroidal neovascularization in association with punctate inner choroidopathy has been shown to be beneficial in this small group in whom improvement or stabilization of vision was observed in 9 of 10 eyes. Recurrent choroidal neovascularization can occur in these patients, and additional injections of ranibizumab appear to be safe and efficacious.

Intravitreal dexamethasone implant Ozurdex in the treatment of diabetic macular edema in patients not previously treated with any intravitreal drug: a prospective 12-month follow-up study.

Objective: To evaluate the mid-long-term efficacy and safety of the dexamethasone intravitreal (DEX) implant (Ozurdex1) in naïve patients with diabetic macular edema (DME).Methods: Prospective and single-center study conducted on consecutive patients with a diagnosis of DME, who received a DEX implant and were followed up for at least 12 months. The main outcomes measurements were the mean change in best corrected visual acuity (BCVA) and in foveal thickness (FT) as compared to the baseline values.Results: Of the 84 screened patients 50 were included in the study. The BCVA significantly improved from 52.4 (20.4) letters at baseline to 62.6 (15.6), 61.2 (18.4), 61.6 (18.6), 60.6 (19.0), and 60.6 (18.8) at 2, 4, 6, 12 months and end of follow-up period, respectively (repeated measures ANOVA and the Greenhouse-Geisser correction; p = .0008). At the end of the follow-up period, a gain of BCVA of ≥5, ≥10, and ≥15 letters were observed in 26 (52.0%), 18 (36.0%), and 16 (32.0%) patients, respectively. The mean FT was significantly reduced from 446.0 (139.9) µm at baseline to 327.2 (103.6) at the end of follow-up (repeated measures ANOVA and the Greenhouse-Geisser correction; p = .0008). During the study follow-up, the patients receive a mean of 3.4 (2.9-3.9) implants. Of the 32 phakic eyes at baseline, 17 (53.1%) either developed new lens opacity or progression of an existing opacity.Conclusion: In eyes with DME not previously treated with intravitreal drugs, DEX implants provide meaningful functional and anatomical benefits, and these results are sustained mid-long-term.

Intraoperative use of intravitreal triamcinolone in uveitic eyes having cataract surgery: pilot study.

PURPOSE: To report the outcomes of cataract extraction with intraoperative intravitreal triamcinolone (IVTA) in eyes with a history of posterior uveitis. SETTING: Moorfields Eye Hospital Uveitis Service, London, United Kingdom. METHODS: Nineteen eyes of 17 patients with posterior uveitis thought to require systemic corticosteroid prophylaxis for cataract surgery were included. The use of systemic corticosteroids at the time of surgery would have been problematic in 7 of the patients, who had a history of systemic hypertension. Three of the 7 patients were also diabetic. All patients were not happy about using oral corticosteroids. RESULTS: Median visual acuity 1 day after surgery was 20/40 (range 20/20 to counting fingers). At final follow-up (mean 25.2 months; range 7 to 41 months), 17 eyes (89.5%) eyes achieved visual acuity of 20/40 or better; 2 eyes failed to achieve a final visual acuity of 20/40 or better, 1 as a result of optic atrophy and the other as a result of macular edema. No patient lost acuity and no eye developed macular edema within 4 months of surgery. Intraocular pressure elevation occurred after surgery in 3 eyes; all were controlled by topical medication that was discontinued after 3 months. One patient developed severe intraocular inflammation after surgery that resolved with intensive topical corticosteroid therapy within 1 week. CONCLUSIONS: Cataract extraction by phacoemulsification with concurrent IVTA appears a useful treatment option. Targeted delivery of corticosteroid is achieved without the risks of systemic corticosteroid prophylaxis. The incidence of postoperative macular edema was markedly reduced. Levels of visual acuity after cataract surgery, similar to those in eyes without uveitis, were achieved in eyes with posterior uveitis.

TNF-857T, a genetic risk marker for acute anterior uveitis.

PURPOSE: To determine the association between 17 single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha, lymphotoxin-alpha, and the TNF-receptors genes (TNF, LTA, and TNFRSF1A and -B) and idiopathic acute anterior uveitis (IAU) and to investigate their association with HLA-B27 and/or the development of visually significant complications. METHODS: Ninety-eight white patients in the United Kingdom were identified (by SL) from the uveitis clinics of Moorfields Eye Hospital (London, UK). Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by PCR amplification. RESULTS: There was a significant increase in the frequency of the TNF-857T allele in patients with IAU when compared with control subjects (15.3% vs. 7.3%, P = 0.0006). The frequency of haplotype 4, containing the T allele at nucleotide position -857, was also significantly increased in patients with IAU compared with control subjects (15.4% vs. 7.1%, P = 0.0003, OR 2.4, 95% confidence interval 1.4-4.0). In subgroup analysis, there were significant differences in the frequencies of the uncommon TNFRSF1A-201T and TNFRSF1A-1135T alleles between HLA-B27(+) patients with inflammation-related complications and those without complications (80.0% vs. 33.6%, P = 0.006; 80.0% vs. 36.6%, P = 0.01, respectively). CONCLUSIONS: A significant difference in the frequency of TNF-857T allele was found in patients with IAU. There was a trend toward the development of inflammation-related complications in HLA-B27(+) patients with IAU who were carriers of TNFRSF1A-201T or TNFRSF1A-1135T alleles. Genetic variations in these proinflammatory mediators and their receptors appear to influence the susceptibility and severity of the inflammatory response within the eyes of patients during the development of IAU.

The development of complications in patients with chronic anterior uveitis.

PURPOSE: This study aimed to identify the factors determining the ocular complications and visual outcome in patients with chronic anterior uveitis. DESIGN: Retrospective, noncomparative case study. METHODS: Ninety-one eyes of 68 patients with anterior uveitis that lasted longer than 3 months were assessed. Patients were divided into idiopathic and nonidiopathic chronic anterior uveitis and Fuchs' heterochromic uveitis. Visual acuity and complications such as posterior synechiae, cataract formation, raised intraocular pressure (IOP), and posterior segment complications (i.e., cystoid macular edema and optic nerve involvement) were evaluated. Poor visual outcome measured by life-table analysis was considered when logMAR (log of the reciprocal of Snellen visual acuity) visual acuity was 0.3 or worse. RESULTS: No statistically significant differences in the visual outcome were found between the three groups of patients with chronic anterior uveitis. Posterior synechiae formation was, as expected, significantly increased in patients with chronic anterior uveitis compared with those with Fuchs' heterochromic uveitis. There was a trend for patients with nonidiopathic chronic anterior uveitis to have an increased risk of cystoid macular edema compared with those with idiopathic disease. There were no significant differences in visual outcome between any of the groups with time. CONCLUSIONS: The visual prognosis for patients with chronic anterior uveitis is generally good. Posterior segment complications appear to be more likely to occur if there is an underlying associated disease. However, the presence of complications does not seem to affect the visual outcome in patients with chronic anterior uveitis.

The eye in systemic vasculitis.

The term 'vasculitis' includes a wide range of disorders characterised by inflammation of the wall of blood vessels, sometimes with necrosis, leading to ischaemia of the affected organ. The exact pathogenesis of most of these vasculitides is not fully understood and although the presence of circulating auto-antibodies seems to be a common feature among them, each vasculitis has its unique pathogenesis and a predilection for vessels of a defined size. Systemic vasculitis may be associated with ocular complications which include scleritis, keratitis, uveitis and optic neuropathy. These can precede the symptoms/signs of the systemic disease and therefore their recognition may lead to detection of the underlying disorder. The eye may also be affected by the treatment required to control the systemic disease.

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.

Dexamethasone implants in retinal vein occlusion: 12-month clinical effectiveness using repeat injections as-needed.

OBJECTIVE: To report the 12-month outcomes of the dexamethasone intravitreal implant in retinal vein occlusion (RVO), using an as-needed repeat injection protocol. DESIGN: Retrospective consecutive case series of 51 eyes of 49 patients with macular oedema as a result of RVO that received an intravitreal dexamethasone implant and were followed up for at least 12 months. RESULTS: 70% of patients responded to dexamethasone implant injection with an improvement in visual acuity (VA) and macular oedema within 3 months of injection, but only 30% of eyes gained ≥15 letters. The mean change in VA letter score at 12 months compared with baseline for branch RVO (BRVO) and central RVO (CRVO) was 5.7±2.3 and 11.5±11.0 EDTRS letters, respectively. 56% of patients relapsed, with the median time to relapse being 17 weeks for patients with branch RVO and 18 weeks for patients with CRVO. Repeat injections achieved similar VA gains, but the duration of effect of repeat dexamethasone implants was much shorter at 10 weeks. 14 eyes (27%) developed a significant rise in intraocular pressure, and three of these required treatment with oral acetazolamide. Four eyes with CRVO developed neovascular glaucoma during the study. CONCLUSIONS: The intravitreal dexamethasone implant does not last the 6 months implied by the retreatment protocol in the GENEVA trial, and improved results can be achieved with an as-needed retreatment protocol, particularly in CRVO. However, visual outcomes remain similar to those previously seen with triamcinolone in the SCORE study and neovascular complications remain a feature of CRVO.

Behçet disease: visual prognosis and factors influencing the development of visual loss.

PURPOSE: To assess the visual prognosis of patients with ocular Behçet disease and to determine factors predictive of visual loss and severe visual loss. DESIGN: Retrospective case series. METHODS: One hundred seventy-five eyes of 107 patients diagnosed with ocular Behçet disease were included. The main outcome measures were visual loss (best-corrected visual acuity, worse than 20/40) and severe visual loss (best-corrected visual acuity, 20/200 or worse). RESULTS: The mean duration of follow-up was 6.5 years. Presenting visual acuity was worse than 20/40 in 50% of eyes and 20/200 or worse in 21% of eyes; approximately one third of this was reversible with treatment. The most common cause of irreversible severe visual loss was ischemic maculopathy. At 10 years, there was a 39% risk of visual loss and a 24% risk of severe visual loss, the latter figure being reduced to 13% if patients with irreversible visual loss at presentation were excluded. After controlling for potentially confounding variables, male sex, unilateral disease, and left eye involvement all were statistically significant risk factors for severe visual loss at 5 and 10 years. Patients who were treated with biologic agents were less likely to have severe visual loss in either eye at both 5 and 10 years. CONCLUSIONS: Many patients with ocular Behçet disease still have irreversible visual loss at presentation. However, the visual prognosis is otherwise improved, with a 10-year risk of severe visual loss of 13% in this cohort. The use of biologic agents is associated with a lower risk of severe visual loss at 5 and 10 years.

Ocular features in neurosarcoidosis.

BACKGROUND/AIMS: To determine the type of ocular involvement in patients with neurosarcoidosis, and evaluate whether the type of eye involvement may help in the diagnosis of neurosarcoidosis. METHODS: Retrospective, case history study. We reviewed the medical records of 46 patients who attended the sarcoidosis clinics at the Royal Brompton and Moorfields Eye Hospital over a 4-year period with a diagnosis of definite and probable neurosarcoidosis supported by laboratory investigations and exclusion of other causes for the neurological symptoms. RESULTS: Cranial nerve involvement was the most common neurological manifestation in this series. Among the 27 patients with cranial neuropathy, lower motor neurone facial palsy was the most frequently seen in 19 patients (70.4%). Diplopia was seen in four patients (14.9%). In three patients, this was because of common oculomotor nerve paresis. Uveitis was the most common intraocular manifestation in patients with neurosarcoidosis. The majority of these patients (9, 64.3%) suffered from anterior uveitis, but in 35.7% of them the inflammatory process involved the posterior segment. CONCLUSIONS: We found a higher incidence of ocular manifestations, including intraocular inflammation in neurosarcoidosis compared to that in systemic sarcoidosis elsewhere. The most common ocular complication seen in our series was anterior uveitis; however there were no associated clinical features of the uveitis in these series that could contribute to the differential diagnosis between neurosarcoidosis and other autoimmune disorders with neuro-ophthalmic features such as multiple sclerosis. Patients with neurological symptoms and associated intraocular inflammation should have a routine work-up for sarcoidosis. Investigations should include MRI scan of the brain and orbits and lumbar puncture in selected cases. Tissue biopsy should be attempted when clinically accessible lesions are available i.e., conjunctiva or lacrimal gland.

Chemokine gene polymorphisms in idiopathic anterior uveitis.

OBJECTIVES: The aim of this study was to determine whether there are any associations between single nucleotide polymorphisms of the chemokine genes IL-8, MCP-1, their corresponding receptors CXCR1 and CCR2 and disease outcome in patients with acute idiopathic anterior uveitis. METHODS: 60 Caucasian patients with idiopathic acute recurrent anterior uveitis together with 120 healthy Caucasian control subjects were tested for the presence of 16 bi-allelic polymorphisms and HLA-B27 using polymerase chain reaction in association with sequence-specific primers with mismatches at the 3' end. The genetic data was then compared between patients and controls, and within the patient group itself for association with clinical disease outcome. RESULTS: As expected, the frequency of HLA-B27 was significantly higher in the patient group than the control group (63.33% versus 15.83%; Pearson's P<0.0001, Fisher's P<0.0001). In addition, the frequency of the T allele of MCP-1 63555 was found to be significantly higher in the control group when compared to the patient group (P=0.0160). CONCLUSION: This study describes an association between acute anterior uveitis and MCP-1 63555 polymorphisms where the T allele may be a protective marker against the disease.

Cytokine gene polymorphisms involved in chronicity and complications of anterior uveitis.

The aim of this study was to identify key cytokine polymorphisms associated with disease susceptibility, clinical phenotype, and outcome in patients with chronic anterior uveitis (CAU) as compared to those with recurrent self-limiting anterior uveitis (RAU). One hundred fifty seven British Caucasian patients with anterior uveitis were identified and divided into those where the inflammatory process lasted less than 3 months (RAU=118) and those where the inflammation persisted longer than 3 months (CAU=39). Patients with CAU were further sub-divided into idiopathic CAU, CAU associated with systemic disease, CAU with and without complications (posterior synechiae, posterior subcapsular lens opacity, raised intraocular pressure, cystoid macular oedema, and poor response to treatment). Sixty-six healthy controls were ethnically matched. TaqMan PCR amplification was used to genotype five single nucleotide polymorphisms in cytokine genes; IL-1RN+2018, IL-6-174, IL-10-1082, TNF-238, TNF-308 and these were correlated with clinical phenotype.

Clinical outcome of chronic immunosuppression in patients with non-infectious uveitis.

AIM: To determine the visual outcome and corticosteroid dose requirement in patients with non-infectious uveitis affecting the posterior segment treated with corticosteroids and additional second-line immunosuppression. METHOD: A retrospective, non-comparative case series was carried out. Seventy-two patients (141 eyes) with uncontrolled non-infectious uveitis on systemic prednisolone were treated with at least one second-line immunosuppressive agent in addition to systemic prednisolone and followed for at least 3 months. Visual acuity (VA), clinical disease activity, corticosteroid-sparing effect, disease relapses requiring corticosteroid dose increase,and side-effects from second-line agents were evaluated. RESULTS: At the end of the follow-up period (mean: 55.5 months),70 eyes (49.6%) had VA of 6/9 or better. There was a reduction in the mean maintenance dose of prednisolone required before the introduction of the second-line agent (19 mg/day +/- 2 SE)when compared to the mean maintenance dose of prednisolone at the end of the data collection (9 mg/day +/- 1 SE; P <0.001). There was also a significant reduction in the number of disease relapses requiring an increase in prednisolone dose after starting the second-line agents as compared to the year before (P <0.02). CONCLUSION: In patients with uveitis affecting the posterior segment, the addition of all second-line immunosuppressive therapy was effective in allowing reduction of the dose of systemic prednisolone to 10 mg/day or less, in controlling intraocular inflammation, reducing the number of relapses and in maintaining vision. Because of their side-effects, immunosuppressive treatment should be individualized and monitored closely but its addition is beneficial in the short and longer term.