A Meta-Analysis of Studies Evaluating Visual and Anatomical Outcomes in Patients with Treatment Resistant Neovascular Age-Related Macular Degeneration following Switching to Treatment with Aflibercept

With the introduction of aflibercept, eyes with neovascular age-related macular degeneration (AMD) not responding well to injections of ranibizumab or bevacizumab can be switched to treatment with aflibercept. We carried out a meta-analysis to analyze all available evidence of visual and anatomical outcomes of eyes with resistant neovascular AMD switched to aflibercept at six months. Data from seven retrospective and prospective studies looking at change in best corrected visual acuity (BCVA) and central retinal thickness (CRT) were included. Weighted mean difference (WMD) and 95% CI were estimated using the standardized mean change method. The overall results of the meta-analysis showed a small but statistically significant improvement in BCVA six months following treatment switch to aflibercept (WMD 0.142, 95% CI 0.006 to 0.28; = 0.04), and the effect was more significant in data gathered from prospective studies (WMD 0.407, 95% CI 0.023 to 0.791, = 0.038). There was a significant improvement in CRT following treatment switch to aflibercept (WMD −0.36, 95% CI −0.485 to −0.235; < 0.0001). Our meta-analysis indicates that following treatment switch to aflibercept patients may have a significant improvement in CRT with stabilization or even some improvement in their visual acuity

Risk factors for the development of macular edema in children with uveitis

AimTo determine the risk factors for macular edema (ME) in children with uveitis.MethodsA retrospective study was conducted of 150 pediatric patients (264 eyes) with uveitis attending 2 tertiary medical centers. Data were collected from the medical files on demographics, type of uveitis, etiology, clinical findings, treatment, and time to development of ME. Risk factors for the development of ME were identified.ResultsME developed in 63 eyes (23.9%) over a mean period of 15.3 ± 2.95 months from diagnosis of uveitis, at a rate of 0.08 eyes per eye-year. On univariate analysis, risk factors for the development of ME were the non-anterior location of the inflammation (p=0.002), band keratopathy (p <0.0001), posterior synechiae (p=0.003), cataract (p=0.002), and vision impairment at presentation (p <0.0001). On multivariate analysis, non-anterior uveitis, which includes intermediate, pan, and posterior-uveitis, and vision impairment retained significance as independent risk factors of ME.ConclusionWithin the pediatric population with uveitis, non-anterior location is associated with the highest risk of ME, followed by the presence of complications, such as band keratopathy and posterior synechiae. These findings indicate a need for close follow-up in children with uveitis for early detection of ME

Difference in glaucoma progression between the first and second eye after consecutive bilateral glaucoma surgery in patients with bilateral uveitic glaucoma

PURPOSE: To determine whether the second eyes (SE) of patients with bilateral uveitic glaucoma undergoing filtration surgery have more glaucomatous progression in terms of visual acuity, visual field (VF) and optic nerve changes compared to the first eyes (FE). METHODS: This retrospective study analysed data of 60 eyes from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma surgery in both eyes on separate occasions. Humphrey VF progression was assessed using the Progressor software. RESULTS: The pre-operative IOP between the FE (43.1 ± 7.7 mmHg) and SE (40 ± 8.7 mmHg) was not statistically significant (p = 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post-operatively, but the mean IOP at the final visit in the FE (12.3 ± 3.9 mmHg) and SE (14.5 ± 7 mmHg) was not statistically different (p = 0.2). There was no significant change in mean logMAR readings pre and post-operatively (0.45 ± 0.6 vs 0.37 ± 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR > 0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %) progressed at a median of five locations (range 1-11 points) with a mean local slope reduction of 1.74 ± 0.45 dB/year (range -2.39 to -1.26), whereas only one FE progressed. However, there was no significant difference between mean global rate of progression between the FE (-0.9 ± 1.6 dB/year) and SE (-0.76 ± 2.1 dB/year, p = 0.17) in the Humphrey VF. CONCLUSION: In eyes with bilateral uveitic glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and glaucomatous disc progression compared to FEs at the final visit

Role of Autofluorescence in Inflammatory/Infective Diseases of the Retina and Choroid

Fundus autofluorescence (FAF) has recently emerged as a novel noninvasive imaging technique that uses the fluorescent properties of innate fluorophores accumulated in the retinal pigment epithelium (RPE) to assess the health and viability of the RPE/photoreceptor complex. Recent case reports suggest FAF as a promising tool for monitoring eyes with posterior uveitis helping to predict final visual outcome. In this paper we review the published literature on FAF in these disorders, specifically patterns in infectious and noninfectious uveitis, and illustrate some of these with short case histories

Can simvastatin reduce the need for immunomodulatory drugs to treat uveitis? A prospective, randomized, placebo-controlled trial

Objective: To assess the efficacy of simvastatin 80mg/day versus placebo in patients with non-infectious non-anterior uveitis receiving prednisolone ≥10mg/day./ Design: Randomized, double-masked, controlled trial./ Subjects: Adult patients with non-infectious non-anterior uveitis on oral prednisolone dose of ≥10 mg/day./ Methods: Patients were randomly assigned at a 1:1 ratio to receive either simvastatin 80mg/day or placebo. 32 patients were enrolled (16 in each arm) all of whom completed the primary endpoint and 21 reached the two-year visit (secondary end points)./ Main outcome measures: The primary endpoint was mean reduction in the daily prednisolone dose at 12 months follow-up. Secondary end points were mean reduction in prednisolone dose at 24 months, percent of patients with a reduction in second-line immunomodulatory agents, time to disease relapse and adverse events./ Results: Our results show that simvastatin 80mg/day did not have a significant corticosteroid-sparing effect at 12 months (estimate: 3.62, 95% CI: -8.15 to 15.38; p=0.54). There was no significant difference between the groups with regards to prednisolone dose or change in dose at 12 and 24 months. There was no difference between the two groups in percent of patients with reduction in second-line agent by 24 months. Among patients who achieved disease quiescence the median time to first relapse was longer for those receiving simvastatin (8.7 months, 95% CI 3.2-14.19) than placebo (3.2 months, 95% CI 0.17-6.23), though this was not statistically significant. There was no significant difference in adverse events or serious adverse events between the two groups./ Conclusions: Simvastatin 80mg/day did not have an effect on the dose reduction of corticosteroids nor conventional immunomodulatory drugs at one and two years. The results suggest that it may extend the time to disease relapse among those that achieve disease quiescence./ Systemic corticosteroids represent the mainstay treatment for patients with uveitis, particularly those with systemic involvement or bilateral disease. While treatment is very effective in controlling the intra-ocular inflammation, long-term systemic side effects limit their use, so that ophthalmologists continually aim to reduce the dose to ≤10mg/d.1 To achieve this, other immunomodulatory agents can be added to enhance and maintain inflammatory control. While they are effective in the majority of cases,2, 3, 4, 5 they are not without their own risks of complications and can affect hepatic, renal and gastrointestinal function, as well as increase the risk for opportunistic infections./ Statins are routinely prescribed to reduce serum cholesterol levels and improve clinical outcomes in patients with cardiovascular diseases. They are considered an effective treatment with a low risk of systemic side effects, primarily myalgia and rhabdomyolysis. Studies have shown that they also have pleiotropic immunomodulatory effects, both in vitro and in vivo.6 In animal models of uveoretinitis statins reduced the clinical and histological scores of inflammation and inhibited T lymphocyte recruitment into the retina.7 Two large observational population-based studies also showed a protective effect of statins against the development of uveitis.8 9 Clinical studies in multiple sclerosis patients showed a positive effect from simvastatin on brain atrophy, suggesting these drugs cross the blood-brain barrier and can play a role in controlling disease activity.10 In rheumatoid arthritis, statins led to improvement in disease activity scores and reduced the numbers of tender and swollen joints.11 A study on the effect of statins among patients with sarcoidosis, demonstrated an increased time to disease flare among patients with mild-moderate disease.12 Given the relatively safe side effect profile of statins, they would be a suitable treatment option for patients with uveitis, as well as reducing serum cholesterol levels and improving the cardiovascular outcomes in patients on long-term corticosteroid therapy./ The aim of this study was to prospectively examine in a randomized double masked clinical trial the additional anti-inflammatory effect and safety of simvastatin in patients with uveitis and to determine if their addition could reduce the amount of corticosteroid or number/ dose of additional immunomodulatory agents required to keep the uveitis controlled

'Statins in retinal disease'

Statins are known for their blood cholesterol-lowering effect and are widely used in patients with cardiovascular and metabolic diseases. Research over the past three decades shows that statins have diverse effects on different pathophysiological pathways involved in angiogenesis, inflammation, apoptosis, and anti-oxidation, leading to new therapeutic options. Recently, statins have attracted considerable attention for their immunomodulatory effect. Since immune reactivity has been implicated in a number of retinal diseases, such as uveitis, age-related macular degeneration (AMD) and diabetic retinopathy, there is now a growing body of evidence supporting the beneficial effects of statins in these retinopathies. This review evaluates the relationship between statins and the pathophysiological basis of these diseases, focusing on their potential role in treatment. A PubMed database search and literature review was conducted. Among AMD patients, there is inconsistent evidence regarding protection against development of early AMD or delaying disease progression; though they have been found to reduce the risk of developing choroidal neovascular membranes (CNV). In patients with retinal vein occlusion, there was no evidence to support a therapeutic benefit or a protective role with statins. In patients with diabetic retinopathy, statins demonstrate a reduction in disease progression and improved resolution of diabetic macular oedema (DMO). Among patients with uveitis, statins have a protective effect by reducing the likelihood of uveitis development

Ischemic Retinal Vasculitis and Its Management

Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behçet’s disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behçet’s disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied

Ischemic Retinal Vasculitis and Its Management

Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behçet’s disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behçet’s disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied

Examining the Choroid in Ocular Inflammation: A Focus on Enhanced Depth Imaging

The choroid is the vascular layer that supplies the outer retina and is involved in the pathogenesis of several ocular conditions including choroidal tumors, age related macular degeneration, central serous chorioretinopathy, diabetic retinopathy, and uveitis. Nevertheless, difficulties in the visualization of the choroid have limited our understanding of its exact role in ocular pathology. Enhanced depth imaging optical coherent topography (EDI-OCT) is a novel, noninvasive technique that is used to evaluate choroidal thickness and morphology in these diseases. The technique provides detailed objective in vivo visualization of the choroid and can be used to characterize posterior segment inflammatory disorders, monitor disease activity, and evaluate efficacy of treatment. In this review we summarize the current application of this technique in ocular inflammatory disorders and highlight its utility as an additional tool in monitoring choroidal involvement in ocular inflammation