Background Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis. Main body Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor. Conclusion Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.
Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major cause for functional visual loss in the developed world. Laser photocoagulation has been used for decades in the treatment of DME. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment of DME. Three important anti-VEGF agents whose efficacy has been well established via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept. However, even in the era of anti-VEGF therapies, there are some challenges that retina specialists have to confront in managing patients with DME. These include the need for frequent treatment and an unpredictable response to therapy. There is evidence to suggest that pathways other than the VEGF pathway may be playing a role in the development of DME. Thus, extensive research is focused on development of novel agents that target these pathways. This review focuses on novel therapeutic agents in development, which may be used as a monotherapy or in combination with anti-VEGF agents, for the management of DME in the future.
PurposeTo assess normal vessel flow density (VFD) in macular and peripapillary regions of eyes with no known ocular pathology using optical coherence tomography angiography (OCTA).MethodsAngioVue (Optovue, Fremont, CA, USA) was used to capture OCTA images. A 3 × 3 mm grid and a 4.5 × 4.5 mm grid was used to scan parafoveal and peripapillary regions, respectively. ReVue software was utilized to measure VFD in five sectors within the inner two circles of ETDRS grid in macular region and correlated to retinal thickness of same sectors. At optic disc, VFD was calculated in six sectors based on Garway-Heath map. Area and morphology of foveal avascular zone (FAZ) was correlated with VFD in central 1 mm. The influence of myopia on mean VFD was also assessed.ResultsTwenty-four eyes (mean age: 30 years) were analyzed. Mean VFD in macular sectors was 43.5 (±4.5) and 45.8 (±5.0) % in superficial and deep retinal plexuses, respectively. Mean VFD was significantly higher in deep retinal plexus compared to superficial retinal plexus in all sectors except central 1 mm (p < 0.05). Mean VFD in central 1 mm increases with an increase in central retinal thickness in both superficial and deep retinal plexuses (p < 0.001). Mean parafoveal VFD at level of both superficial and deep retinal plexuses decrease with an increase in spherical equivalent in myopics (p < 0.05). Mean VFD in myopics was found to be significantly lower in parafoveal region of deep retinal plexus (p < 0.05). Mean area of FAZ was 0.33 (±0.15) and 0.47 mm2 (±0.15) in superficial and deep retinal plexuses, respectively. Area of FAZ decreases with an increase in central 1 mm thickness and foveal VFD (p < 0.001).ConclusionsOCTA may be used to measure VFD in macular and peripapillary regions. Vessels in the parafoveal region are more densely packed in the deep retinal plexus leading to higher VFD compared to superficial plexus. Thicker retina in fovea translates into higher foveal VFD due to more compact arrangement of retinal layers and continuity of inner nuclear layer (INL). Myopia is associated with lower VFD in parafoveal region at level of deep retinal plexuses which may explain thinning of INL in myopics.
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