Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Optical Coherence Tomography Angiography in Glaucoma.

Optical coherence tomography angiography (OCTA) is a relatively new, noninvasive, dye-free imaging modality that provides a qualitative and quantitative assessment of the vasculature in the retina and optic nerve head. OCTA also enables visualization of the choriocapillaris, but only in areas of parapapillary atrophy. With OCTA, the movement of red blood cells is used as a contrast to delineate blood vessels from static tissues. The features seen with OCTA in eyes with glaucoma are reduction in the superficial vessel density in the peripapillary and macular areas, and complete loss of choriocapillaris in localized regions of parapapillary atrophy (called deep-layer microvascular dropout). These OCTA changes correlate well topographically with the functional changes seen on visual field examination and structural changes seen on optical coherence tomography (OCT) (ie, parapapillary retinal nerve fiber layer changes and inner retinal layer thickness changes at macula). The OCTA measurements also have acceptable test-retest variability and well differentiate glaucomatous from normal eyes. OCTA measurements can be affected by various subject-related, eye-related, and disease-related factors. Vessel density reduction on OCTA reaches a base level (floor) at a more advanced disease stage than the structural changes on OCT and therefore has the potential to monitor progression in eyes with advanced glaucomatous damage. OCTA also adds information about glaucoma patients at risk of faster progression. OCTA, therefore, complements visual field and OCT examinations to diagnose glaucoma, detect progression, and assess risk of progression

Optical Coherence Tomography Angiography in Glaucoma.

Optical coherence tomography angiography (OCTA) is a relatively new, noninvasive, dye-free imaging modality that provides a qualitative and quantitative assessment of the vasculature in the retina and optic nerve head. OCTA also enables visualization of the choriocapillaris, but only in areas of parapapillary atrophy. With OCTA, the movement of red blood cells is used as a contrast to delineate blood vessels from static tissues. The features seen with OCTA in eyes with glaucoma are reduction in the superficial vessel density in the peripapillary and macular areas, and complete loss of choriocapillaris in localized regions of parapapillary atrophy (called deep-layer microvascular dropout). These OCTA changes correlate well topographically with the functional changes seen on visual field examination and structural changes seen on optical coherence tomography (OCT) (ie, parapapillary retinal nerve fiber layer changes and inner retinal layer thickness changes at macula). The OCTA measurements also have acceptable test-retest variability and well differentiate glaucomatous from normal eyes. OCTA measurements can be affected by various subject-related, eye-related, and disease-related factors. Vessel density reduction on OCTA reaches a base level (floor) at a more advanced disease stage than the structural changes on OCT and therefore has the potential to monitor progression in eyes with advanced glaucomatous damage. OCTA also adds information about glaucoma patients at risk of faster progression. OCTA, therefore, complements visual field and OCT examinations to diagnose glaucoma, detect progression, and assess risk of progression

A Sectoral Analysis of Vessel Density Measurements in Perimetrically Intact Regions of Glaucomatous Eyes: An Optical Coherence Tomography Angiography Study

Purpose:To study sectoral vessel density (VD) and structural alterations in the peripapillary and parafoveal hemiretina corresponding to perimetrically intact regions of glaucomatous eyes with hemifield defects and to compare these with healthy eyes using optical coherence tomography.Methods:This cross-sectional study included 37 eyes with open-angle glaucoma having visual fields defects restricted to 1 hemifield and 45 age-matched controls. Peripapillary VD and retinal nerve fiber layer (RNFL) thickness were measured in 8 sectors. Parafoveal VD and ganglion cell complex thickness were measured in the superior and inferior hemispheres of the macula. These parameters were compared between the intact hemiretinae of glaucomatous eyes and corresponding sectors of healthy eyes using the t test.Results:Within the perimetrically intact regions of glaucomatous eyes, the mean VD and RNFL thickness were significantly reduced in inferotemporal, superonasal, and nasal upper peripapillary sectors as compared with healthy eyes (P<0.008). The temporal upper sector had reduced mean VD (60.3% vs. 62.9%, P=0.04) despite similar mean RNFL thickness (P=0.18). The superotemporal sector had decreased mean RNFL thickness (121 vs. 138 mu m, P=0.0001) despite similar VD (P=0.06). At the macula, ganglion cell complex thickness was reduced in the superior and inferior hemispheres, but mean VD was reduced in the superior parafoveal region only.Conclusions:Peripapillary and parafoveal vascular changes precede functional decline. The extent of VD reduction and RNFL thinning varies in different peripapillary sectors and longitudinal studies are required to better understand the temporal relationship of vascular and RNFL loss

Optical Microangiography and Progressive Retinal Nerve Fiber Layer Loss in Primary Open Angle Glaucoma.

PurposeTo evaluate the association between optical microangiography (OMAG) measurements and progressive retinal nerve fiber layer (RNFL) loss in primary open angle glaucoma (POAG).DesignProspective case series.MethodsSixty-four eyes of 40 patients with POAG (108 quadrants) with mild to moderate functional damage were longitudinally studied for at least 2 years and with a minimum of 3 optical coherence tomography examinations. OMAG imaging was performed at the baseline visit. Effect of clinical parameters (age, sex, presence of systemic diseases, central corneal thickness, presence of disc hemorrhage, and mean and fluctuation of intraocular pressure during follow-up), baseline hemifield mean deviation, baseline quadrant optical coherence tomography RNFL and ganglion cell inner plexiform layer thickness), and OMAG (peripapillary and macular perfusion density [PD] and vessel density [VD]) on the rate of RNFL change was evaluated using linear mixed models.ResultsAverage (±SD) mean deviation, RNFL, and ganglion cell inner plexiform layer thickness of the analyzed quadrants at baseline were -5.5 ± 2.9 dB, 96.5 ± 17.9 µm, and 73.8 ± 8.6 µm, respectively. Peripapillary PD and VD in the quadrant were 44.6% ± 5.9% and 17.5 ± 2.2 mm/mm2, respectively. Rate of quadrant RNFL change was -1.8 ± 0.6 µm/y. Multivariate mixed models showed that lower peripapillary PD (coefficient&nbsp;=&nbsp;0.08, P&nbsp;=&nbsp;.01) and lower VD (coefficient&nbsp;=&nbsp;0.21, P&nbsp;=&nbsp;.02) were significantly associated with a faster rate of RNFL loss.ConclusionsLower baseline peripapillary PD and VD measured using OMAG were significantly associated with a faster rate of RNFL loss in POAG. OMAG imaging provides useful information about the risk of glaucoma progression and the rate of disease worsening