Abstract: Retinopathy of prematurity (ROP) is a proliferative disorder of the developing retina in premature and low birth weight infants. Recently, the role of vascular endothelial growth factor (VEGF) in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways. At first, ophthalmologists began to give intravitreal bevacizumab (IVB) or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil. Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP. Questions remain regarding long-term safety, dose, timing, visual outcomes and long-term effects, including systemically.
Abstract: Diabetic retinopathy (DR) is a leading cause of visual loss worldwide. Disease severity is graded from mild non-proliferative DR to proliferative DR. Optical coherence tomography angiography (OCTA) has become widely accepted as a useful noninvasive technique that provides detailed imaging of the ocular vessels. It is also becoming an increasingly essential tool for both qualitative and quantitative assessment of DR, especially with the advent of wider imaging capabilities. Various angiographic features of DR, such as microaneurysms, intraretinal microvascular abnormalities, neovascularization, and nonperfusion have been comprehensively studied and described using OCTA. Different quantitative OCTA metrics have been introduced, such as vessel density, foveal avascular zone (FAZ) area, and area of nonperfusion. Current research has been focusing on the application of quantitative OCTA for the diagnosis of DR and treatment monitoring. The primary purpose of this article is to review the use of OCTA, including its challenges, in the diagnosis and management of DR.
Background: Diabetic macular edema (DME) is a leading cause of severe visual impairments in older and the working-age population. An important target of current therapy is vascular endothelial growth factor (VEGF), which plays a role in the pathogenesis of DME by inducing angiogenesis and increasing vascular permeability. Currently available anti-VEGF agents include off-label use of Bevacizumab, which has been shown to be effective in the treatment of DME. However, many patients with DME do not respond or demonstrate only a partial response to this agent. As of November 2016, the Canadian Health authorities approved Aflibercept as an anti-VEGF agent for treatment of DME, and the patients who are non-responders to Bevacizumab are switched to this non-off label medication. We aimed to investigate the anatomical and functional visual changes associated with response to Aflibercept in a real-life Canadian population of Bevacizumab non-responders.
Methods: A retrospective review of chronic DME patients refractory to bevacizumab treatment who were switched to Aflibercept was done. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), central subfield thickness (CST), average macular thickness, and total macular volume were extracted at the visit prior to switching to Aflibercept (baseline) as well as the first, second and third follow-up visits after switching. Anatomical and functional visual changes were compared using Generalized Estimating Equations and the association between variables was tested using Pearson correlation test with significance set at P<0.05.
Results: Twenty-six eyes with mean age of 63 were included. Average CST at baseline was 421.5±116.1 μm and the number of Bevacizumab injections received prior to switching was 15.3±8.0. No significant changes were observed in terms of BCVA and IOP, from baseline to any of the follow-ups. Switching to Aflibercept significantly improved CST, average macular thickness, and total macular volume. From baseline to the first follow-up visit, CST decreased from 421.5±116.1 to 333.0±91.2 μm (P=0.001) and average macular thickness reduced from 344.6±74.9 to 322.2±60.5 μm (P=0.008). Similarly, total macular volume decreased from 12.4±2.7 to 11.6±2.2 μm3, measured at baseline and the first follow-up (P=0.007). No further improvements were observed from the first follow-up to the subsequent ones. The median CST value at baseline (378 μm) was used to classify the patients into low and high CST groups. We observed that those with higher CST at baseline (>378 μm) showed a trend for improvements in visual acuity (P=0.058). Pearson correlation test confirmed the association between higher CST at baseline and better visual outcomes in response to switching to Aflibercept (P=0.018).
Conclusions: Our data evidenced significant anatomical improvements in macula, which did not translate to immediate functional vision improvements. Bevacizumab non-responders with higher CST might also gain visual acuity and benefit functionally from switching to Aflibercept.
Abstract: Successful management of a case of aggressive posterior retinopathy of prematurity (APROP) poorly responsive to laser therapy with intravitreal bevacizumab (IVB) is discussed. IVB is useful as rescue therapy in such cases, if given within the correct window period post laser therapy.
Abstract: Statins are used widely to treat hypercholesterolemia and atherosclerotic cardiovascular disease. They have inflammatory and immunomodulatory effects potentially useful for managing systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis. Statins also have anti-oxidative and large-vessel endothelial supportive properties that occur independent of their lipid-lowering effects. Additionally, statins can suppress macrophage and microglial activation responsible for initiating inflammatory cytokine release. More than forty percent of adults aged 65 years or older use statins in the United States and Australia, a prevalence that increases with age. The effects of statin usage on ophthalmic practice are probably underrecognized. Cardiovascular disease and age-related macular degeneration (AMD) share common risk factors, consistent with the “vascular model” of AMD pathogenesis that implicates impaired choroidal circulation in Bruch’s membrane lipoprotein accumulation. AMD has a complex multifactorial pathogenesis involving oxidative stress, choroidal vascular dysfunction, dysregulated complement-cascade-mediated inflammation and pro-inflammatory and pro-angiogenic growth factors. Many of these components are hypothetically amenable to the primary (cholesterol lowering) and secondary (anti-inflammatory, anti-oxidative, anti-vasculopathy) effects of statin use. Experimental studies have been promising, epidemiological trails have produced conflicting results and three prospective clinical trials have been inconclusive at demonstrating the value of statin therapy for delaying or preventing AMD. Cumulative evidence to date has failed to prove conclusively that statins are beneficial for preventing or treating AMD.
Abstract: In developed countries, age-related macular degeneration (AMD) is the main cause of visual impairment in the elderly. Though the etiology of AMD is still unclear, it has been well understood that vascular endothelial growth factor (VEGF) is involved in the development of aberrant vasculature that represents the neovascular AMD (nAMD). Hence, VEGF inhibition is a more effective way to control nAMD. Pegaptanib, ranibizumab, and aflibercept are three drugs approved by the US Food and Drug Administration (FDA) to treat nAMD. Bevacizumab (an anti-VEGF medication comparable to ranibizumab) is already widely used off label. Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies. Synthetic designed ankyrin repeat proteins (DARPins) imitate antibodies introduced recently by evolutions in bioengineering technology. These agents are designed to have high specificity and affinity to a specific target, smaller molecular size, and better tissue penetration, making them more stable and longer-acting at less concentration. Abicipar pegol (Allergan, Dublin, Ireland) is a DARPin that interlocks all VEGF-A isoforms. It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab, making it a feasible anti-VEGF agent. This review describes the properties and efficacy of abicipar, the new anti-VEGF agent, in clinical practice, which aims to improve outcomes, safety, and treatment burden of nAMD.
