Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration

Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal collection or leakage, new-onset of macular hemorrhage, and depletion of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001). Furthermore, while better control of the foveal thickness was achieved (P < 0.001), vision improvement was similar to that achieved with standard therapy (P > 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent—doxycycline.Â

Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration

Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal collection or leakage, new-onset of macular hemorrhage, and depletion of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001). Furthermore, while better control of the foveal thickness was achieved (P < 0.001), vision improvement was similar to that achieved with standard therapy (P > 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent—doxycycline.

Photopigment Bleaching Phenomenon on Fluorescein Angiography in a Patient with Impending Central Retinal Vein Occlusion

Purpose: To present the second case of photopigment bleaching phenomenon in fluorescein angiography (FA) and the first case of this phenomenon due to impending central retinal vein occlusion (CRVO). Case Report: A 32-year-old healthy female noticed blurred vision in her right eye one day before presentation. Despite the 20/20 visual acuity at presentation, mild increased retinal vascular tortuosity and unilateral photopigment bleaching phenomenon in FA was observed in the right eye. Three weeks later, she developed a complete CRVO with visual acuity reduction to 20/40 that responded well to the intravitreal injection of aflibercept. Conclusion: Impending CRVO can cause unilateral photopigment bleaching phenomenon in FA that may be due to retinal ischemia

Optical Coherence Tomography Angiography Findings in Malignant Hypertensive Retinopathy

Background: To report the findings of fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) in a patient with malignant hypertensive retinopathy. Case Report: A 41year-old male was referred to our clinic with sudden visual loss in both of his eyes after an acute rise of blood pressure (200/150 mmHg). Optic disc swelling, flame shape hemorrhages especially around the optic disc, arterial narrowing, vessel tortuosity, cotton wool spots, hard exudate deposition, and multiple deep orange spots (Elschnig spots) were visible in both eyes. In the OCTA, disruption in the normal tapering patterns of the superficial and deep capillary plexuses was observed. Elschnig spots were observed as hypointense spots in the choriocapillaris slab. Leakage of the optic nerve head was seen in the FA. Conclusion: When compared with the FA, the OCTA can illustrate the ischemic areas and the Elschnig spots with greater detail

Oguchi Disease Associated with Keratoconus

This is a Photo Essay and does not have an abstract. Please download the PDF or view the article in HTML

Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes

Purpose: To evaluate the safety of intravitreal injection of Stivant, a biosimilar to bevacizumab, in rabbits using electrophysiological and histological analysis. Methods: Both eyes of 41 New Zealand albino rabbits were injected with 0.1 mL (2.5 mg) of Stivant. The rabbits were scheduled to be sacrificed 1, 2, 7, 14, and 28 days after injection for histopathological evaluations. Clinical examinations and electroretinography (ERG) were performed at baseline and just before sacrificing the rabbits. Fourteen separate rabbits received a reference drug (Avastin) and were considered as the control group. Furthermore, three other rabbits received the same volume of saline (saline control group). Rabbits of both control groups were sacrificed four weeks after injection. ERG was performed 1, 2, 7, 14, and 28 days after injections. Results: No significant difference was observed in a- and b-wave amplitudes and latency after intravitreal Stivant injection between baseline and different time points. Moreover, there was no statistically significant difference in wave amplitudes and latency between the Stivant and control groups. The histology of rabbit eyes of the Stivant and control groups after intravitreal injections was not distinguishable. Conclusion: The biosimilar Stivant, up to a dose of 2.5 mg, did not appear to be toxic to the retina in albino rabbits. These results suggest that this drug could be a safe and inexpensive alternative to intravitreal bevacizumab. The efficacy of these injections was not investigated in this study and needs to be evaluated in future studies

Intraocular Injection of Stivant® (A Biosimilar to Bevacizumab): A Case Series

Purpose: To report the results of intravitreal injection of a bevacizumab biosimilar called Stivant®. Methods: This prospective interventional case series was conducted on eyes with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), and diabetic macular edema (DME). Stivant® was injected in three consecutive months and changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at baseline and monthly up to one month after the third injection. Results: Three hundred and eighty-five eyes with DME (234 eyes, 61%), nAMD (87 eyes, 22%), and macular edema secondary to RVO (64 eyes, 17%) were enrolled. The mean ± standard deviation age of the patients was 61.7 ± 7.20 years. The mean BCVA and CMT changed from 0.63 ± 0.3 to 0.51 ± 0.3 LogMAR (P = 0.12 ) and from 420.4 ± 47.3μm at baseline to 316.7 ± 50.6 μm (P < 0.001) in the DME group; from 0.79 ± 0.3 to 0.68 ± 0.3 LogMAR (P = 0.19) and from 376.1 ± 31.7 μm to 303 ± 31.3 μm (P = 0.019) in the nAMD group; and from 0.81 ± 0.4 to 0.63 ± 0.4 LogMAR (P = 0.05) and from 424.21 ± 18 μm to 303.4 ± 18.8 μm (P < 0.001) in the RVO group, respectively. Conclusion: Our limited experience showed that the intravitreal injection of Stivant® was well tolerated. Although the results of this case series showed relative improvement in CMT one month after the last injection of Stivant®, BCVA improvement was statistically significant only in the RVO group. This would be essential to design a randomized clinical trial to evaluate the non-inferiority of Stivant® in comparison to bevacizumab

Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks

The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease