Guidance for Anti-VEGF Intravitreal Injections During the COVID-19 Pandemic

The World Health Organization designated the outbreak of the novel coronavirus, COVID-19, as a pandemic on March 11, 2020, after its rapid spread to countries throughout the  world.1 There is a strong need to support the ophthalmic community to help guide decision- making during these unprecedented times, where infection control is of utmost concern and  disruption   to   regular   clinical   practice is highly likely. This is  particularly  important for patients with retinal diseases who are receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents.Older age (>65 years), living in a care facility  or nursing home, and having an underlying health condition are key risk factors for developing severe illness following infection with COVID-19,  and  are  also  common among patients with retinal disease. Health conditions  including  chronic   lung   disease  or moderate-to-severe asthma, serious cardiovascular conditions, diabetes, being immunocompromised, severe obesity, liver disease, and chronic kidney disease requiring dialysis are considered particularly high risk, especially when they are not well-controlled.Several organizations have produced general guidance for ophthalmologists on managing patients during the pandemic. The Vision Academy Steering Committee convened in March 2020 to review these relevant guidelines and  documents,  discuss  key  challenges,  and  develop  recommendations  specifically  for managing patients receiving intravitreal injections of anti-VEGF agents during the COVID-19 pandemic. Recommendations were systematically refined before being voted on by the Steering Committee for consensus

Graefe’s Archives for Clinical and Experimental Ophthalmology: the past and the future

published_or_final_versio

Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator

Background Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. The polymorphism rs10490924 in the ARMS2 gene is highly associated with AMD and linked to an indel mutation (del443ins54), the latter inducing mRNA instability. At present, the function of the ARMS2 protein, the exact cellular sources in the retina and the biological consequences of the rs10490924 polymorphism are unclear. Methods Recombinant ARMS2 was expressed in Pichia pastoris, and protein functions were studied regarding cell surface binding and complement activation in human serum using fluoresence-activated cell sorting (FACS) as well as laser scanning microscopy (LSM). Biolayer interferometry defined protein interactions. Furthermore, endogenous ARMS2 gene expression was studied in human blood derived monocytes and in human induced pluripotent stem cell- derived microglia (iPSdM) by PCR and LSM. The ARMS2 protein was localized in human genotyped retinal sections and in purified monocytes derived from AMD patients without the ARMS2 risk variant by LSM. ARMS2 expression in monocytes under oxidative stress was determined by Western blot analysis. Results Here, we demonstrate for the first time that ARMS2 functions as surface complement regulator. Recombinant ARMS2 binds to human apoptotic and necrotic cells and initiates complement activation by recruiting the complement activator properdin. ARMS2-properdin complexes augment C3b surface opsonization for phagocytosis. We also demonstrate for the first time expression of ARMS2 in human monocytes especially under oxidative stress and in microglia cells of the human retina. The ARMS2 protein is absent in monocytes and also in microglia cells, derived from patients homozygous for the ARMS2 AMD risk variant (rs10490924). Conclusions ARMS2 is likely involved in complement- mediated clearance of cellular debris. As AMD patients present with accumulated proteins and lipids on Bruch’s membrane, ARMS2 protein deficiency due to the genetic risk variant might be involved in drusen formation

Exploring the precision of femtosecond laser-assisted descemetorhexis in Descemet membrane endothelial keratoplasty

Objective Descemet membrane endothelial keratoplasty (DMEK) remains a challenging technique. We compare the precision of femtosecond laser-assisted DMEK to manual DMEK. Methods and Analysis A manual descemetorhexis (DR) of 8 mm diameter was compared with a femtosecond laser-assisted DR of the same diameter (femto-DR) in 22 pseudophakic patients requiring DMEK. We used OCT images with a centred xy-diagram to measure the postoperative precision of the DR and the amount of endothelial denuded area. Endothelial cell loss (ECL) and best corrected visual acuity were measured 3 months after surgery. Results In the manual group, the median error of the DR was 7% (range 3%-16%) in the x-diameter and 8% (range 2%-17%) in the y-diameter. In the femto group, the median error in the respective x and y-diameters was 1% (range 0.4%-3%) and 1% (range 0.006%-2.5%), smaller than in the manual group (p=0.001). Endothelial denuded areas were larger in the manual group (11.6 mm(2), range 7.6-18 mm(2)) than in the femto group (2.5 mm(2), range 1.25.9 mm(2)) (p<0.001). The ECL was 21% (range 5%-78%) in the manual DR and 17% (range 6%-38%) in the femto-DR group (p=0.351). The median visual acuity increased from 0.4 logMAR (range 0.6-0.4 logMAR) in both groups to 0.1 logMAR (range 0.4-0 logMAR) in the manual group and to 0.1 logMAR (range 0.3-0 logMAR) in the femto group (p=0.461). Three rebubblings were required in the manual group, whereas the femto group required only one. Conclusion The higher precision of the femto-DR bears the potential to improve DMEK surgery

Impact of Adjuvant Ocular Interventions on the Quality of Life of Patients with Uveal Melanoma after Proton Beam Therapy

Introduction: Proton beam therapy is an established primary treatment for patients with nonmetastasized uveal melanoma. Adjuvant local interventions, like intravitreal injections or surgery, were shown to improve long-term eye preservation; however, their impact on the patient's quality of life (QOL) remains unknown. Methods: In a post-radiotherapeutic follow-up, we prospectively collected data on QOL, visual acuity, and interventional adjuvant procedures. QOL was measured with QOL-C30 questionnaire and quality of life questionnaire OPT30 at baseline, and at 3 and 12 months after proton therapy. Patients were grouped by the type of adjuvant treatment. The impact on QOL was analyzed by comparing changes in the mean score values and visual acuity for different interventional subgroups, with generalized linear mixed models and Wilcoxon signed-rank tests. Results: We received 108 (100%) and 95 (88.0%) questionnaires at 3 and 12 months post-therapy, respectively. Adjuvant interventions included observation (n = 61, 56.5%), intravitreal injections (n = 17, 15.7%), and an intraocular surgical procedure (n = 30, 27.8%). In the latter group, several QOL items significantly declined after the 3-month adjuvant interval, but they partially recovered at the 12-month follow-up. In all adjuvant-intervention groups, global QOL scores returned to baseline levels at 12 months. Conclusion: Posttreatment adjuvant interventions had no long-lasting effects on QOL in patients with uveal melanoma

España y la República Romana

Peer reviewe

Effects of TNFα receptor TNF-Rp55- or TNF-Rp75- deficiency on corneal neovascularization and lymphangiogenesis in the mouse

Tumor necrosis factor (TNF)α is an inflammatory cytokine likely to be involved in the process of corneal inflammation and neovascularization. In the present study we evaluate the role of the two receptors, TNF-receptor (TNF-R)p55 and TNF-Rp75, in the mouse model of suture-induced corneal neovascularization and lymphangiogenesis. Corneal neovascularization and lymphangiogenesis were induced by three 11–0 intrastromal corneal sutures in wild-type (WT) C57BL/6J mice and TNF-Rp55-deficient (TNF-Rp55d) and TNF-Rp75-deficient (TNF-Rp75d) mice. The mRNA expression of VEGF-A, VEGF-C, Lyve-1 and TNFα and its receptors was quantified by qPCR. The area covered with blood- or lymphatic vessels, respectively, was analyzed by immunohistochemistry of corneal flatmounts. Expression and localization of TNFα and its receptors was assessed by immunohistochemistry of sagittal sections and Western Blot. Both receptors are expressed in the murine cornea and are not differentially regulated by the genetic alteration. Both TNF-Rp55d and TNF-Rp75d mice showed a decrease in vascularized area compared to wild-type mice 14 days after suture treatment. After 21 days there were no differences detectable between the groups. The number of VEGF-A-expressing macrophages did not differ when comparing WT to TNF-Rp55d and TNF-Rp75d. The mRNA expression of lymphangiogenic markers VEGF-C or LYVE-1 does not increase after suture in all 3 groups and lymphangiogenesis showed a delayed effect only for TNF-Rp75d. TNFα mRNA and protein expression increased after suture treatment but showed no difference between the three groups. In the suture-induced mouse model, TNFα and its ligands TNF-Rp55 and TNF-Rp75 do not play a significant role in the pathogenesis of neovascularisation and lymphangiogenesis