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.
Background: To investigate the effect of sirolimus (SRL) eye drops on acute alkali-burn-induced corneal neovascularization (CNV) and explore its possible mechanism.
Methods: A total of 57 male Sprague-Dawley rats weighing 160–180 g were randomly divided into four groups including a normal control group (NC group, n=12), an untreated alkali-burned model control group (MC group, n=15), a blank eye drop treatment group (BT group, n=15), and an SRL eye drop treatment group (ST group, n=15). Corneal inflammation and CNV were observed and scored under a slit-lamp microscope 3, 7, and 14 days after alkali exposure. Three rats were randomly sacrificed in each group before modeling and 3, 7, 14 days after modeling, and the corneas of right eyes were harvested for Western blotting to compare the expression levels of VEGFR2 and caspase-3.
Results: Corneal inflammation scoring showed that the corneal edema and conjunctival congestion were severe in the MC, BT, and ST groups 1 day after alkali exposure but were alleviated at day 3. The corneal transparency was significantly higher in the ST group than in the MC and BT groups at days 7 (F=9.77, P<0.05) and 14 (F=5.81, P<0.05). At day 1, the corneal limbal vascular network was markedly filled. SNV was obvious at days 3, 7, and 14. The new blood vessels were shorter and sparser in the ST group than in the MC and BT groups, and the CNV scores showed significant differences among these groups (day 3: F=8.60, P<0.05; day 7: F=11.40, P<0.05; and day 14: F=41.59, P<0.01). Western blotting showed that the expressions of VEGFR2 and caspase-3 were low before modeling and showed no significant difference among the different groups (F=0.52, P>0.05; F=0.98, P>0.05). The corneal expression of VEGFR2 became significantly higher in the MC and BT groups than in the ST group 3, 7, and 14 days after alkali exposure, and there were significant differences in relative gray-scale values among these groups (day 3: F=32.16, P<0.01; day 7: F=85.96, P<0.01; day 14: F=57.68, P<0.01). The increase in the corneal expression of caspase-3 was significantly larger in the ST group than in the MC and BT groups at days 3, 7, and 14, and there were significant differences in relative gray-scale values among groups (day 3: F=32.16, P<0.01; day 7: F=53.02, P<0.01; day 14: F=38.67, P<0.01).
Conclusions: SRL eye drops can alleviate acute alkali-burn-induced corneal inflammation and inhibit alkali-burn-induced CNV in rat models. It can reduce VEGFR2 expression and increase caspase-3 expression in the corneal tissue, which may contribute to the inhibition of alkali-burn-induced CNV.
Abstract: Cataract surgery is one of the most commonly performed surgeries among the elderly today. The volume of cataract surgeries has dramatically increased in the past few decades due to technological advancements leading to decreased morbidity, better overall outcomes, and increased expectation for correction of refractive error and spectacle independence after cataract surgery. The number of cataract surgeries is expected to continue to rise with the increase of the elderly population. Thus, accurate predictions of intraocular lens (IOL) power and the ability to correct for any postoperative refractive errors are critical. Despite the improved ability of cataract surgeons to accurately calculate IOL power, postoperative refractive errors still do occur due to various reasons such as imperfect preoperative measurements, toric-lens misalignment, and existing or surgically-induced astigmatism. The aim of this article is to review the various surgical options, including intraocular and corneal refractive surgical approaches, to correct post-operative refractive errors after cataract surgery.
Abstract: Cavernous hemangioma is the most primary benign orbital tumor in adults, and majority of cases could be easily settled by surgical treatment. However, cavernous hemangioma lodged deep in the orbital apex remained a challenge because the surgery may pose a high risk of injury to the optic nerve and significant visual loss. This presentation would report a case of cavernous hemangioma located in orbital apex who presented superonasal and inferotemporal peripheral vision defect. The patient received fully transnasal endoscopic surgery, and a 2 cm × 1.5 cm tumor was successfully removed from the left orbital apex. The treatment results were satisfactory, with no after-effects and adverse reactions during follow-up. This case highlighted that transnasal endoscopic surgery is a promising technique for cavernous hemangiomas that are located deep in orbital apex. This approach provides direct pathway to tumor with limiting morbidity, maximal surgical field and ample illumination. The procedure represents a safe and less invasive management.
Abstract: Uveitis can cause significant visual morbidity and often affects younger adults of working age. Anterior uveitis, or inflammation limited to the anterior chamber (AC), iris, and/or ciliary body comprises the majority of uveitis cases. Current clinical biomarkers and conventional grading scales for intraocular inflammation are mostly subjective and have only a moderate degree of interobserver reliability, and as such they have significant limitations when used in either clinical practice or research related to uveitis. In recent years, novel imaging techniques and applications have emerged that can supplement exam findings to detect subclinical disease, monitor quantitative biomarkers of disease progression or treatment effect, and provide overall a more nuanced understanding of disease entities. The first part of this review discusses automated algorithms for optical coherence tomography (OCT) image processing and analysis as a means to assess and describe intraocular inflammation with higher resolution than that afforded by conventional AC and vitreous cell ordinal grading scales. The second half of the review focuses on anterior segment OCT and OCT angiography (OCTA) in scleritis and iritis, especially with regards to their ability to directly image and characterize the pathologic structures and vasculature underlying these diseases. Finally, we briefly review experimental animal research with promising but more distant human clinical applications, including in vivo molecular microscopy of inflammatory markers and investigation of gold nanoparticles as a potential contrast agent in OCT imaging. Imaging modalities are discussed in the broader context of trends within the field of uveitis towards greater objectivity and quantifiable outcome measures and biomarkers.
