Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Effects of graft detachment on the central corneal thickness after uncomplicated Descemet membrane endothelial keratoplasty.

PURPOSE: To determine if early central corneal thickness (CCT) and best-corrected visual acuity (BCVA) changes indicate graft detachment after uncomplicated Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this analysis of our prospectively collected ADDA registry data ( https://drks.de/search/de/trial/DRKS00027180 ), 45 pseudophakic eyes underwent DMEK surgery at the Department of Ophthalmology, RWTH Aachen University. Anterior segment optical coherence tomography (AS-OCT), the presence of stromal ripples on the posterior corneal surface, and BCVA measurements were assessed prior to, 1 day, 1 week, 1 month, and 6 months after surgery. RESULTS: Eyes were categorized into three groups: no graft detachment (group 1) (20/45; 44.4%), < 1/3 graft detachment (group 2) (14/45; 31.1%), ≥ 1/3 graft detachment followed by rebubbling (group 3) (11/45; 24.4%). Eyes in group 3 had a greater CCT prior to (746.8 ± 95.8 µm vs. 665.0 ± 74.4 µm, P = 0.041), and 1 week (666.8 ± 119.5 µm vs. 556.5 ± 56.8 µm, P = 0.001) after DMEK compared to group 1. By 1 month, CCT in all groups aligned. Comparing prior to and 1 week after DMEK, none of the eyes in group 1 had an increase in CCT, while the CCT increased in 25.0% of eyes in group 2 and 22.2% in group 3. In group 1, 90.0% had a CCT of < 600 µm 1 week after DMEK, compared to only 50.0% in group 2 and 36.4% in group 3. In group 1, 90.0% (18/20) had an improved BCVA 1 week after DMEK, while in groups 2 and 3, 86.7% (12/14) and 18.2% (2/11) improved, respectively. One patient in group 3 showed posterior stromal ripples 1 day and 1 week after DMEK. CONCLUSION: If 1 week after uncomplicated DMEK CCT is < 600 µm and has decreased from before surgery, BCVA has improved, and there are no posterior stromal ripples, a graft detachment ≥ 1/3 and the need for rebubbling are very unlikely. In all other cases, meticulous slit-lamp and OCT inspection of the peripheral graft for detachments should be advised.

Outcomes of 360° suture trabeculotomy after unsuccessful canaloplasty.

BACKGROUND: Canaloplasty is a well-established non-penetrating glaucoma surgery. Unsuccessful outcomes can be enhanced by micro-invasive 360° suture trabeculotomy (360°trabeculotomy), analyzed in this study. METHODS: This retrospective study included twenty eyes of 19 patients, mean age 59.7±17.2 years, with primary open-angle glaucoma (POWG n = 14), pseudoexfoliation glaucoma (PEX n = 3), juvenile glaucoma (n = 2) and aphakic glaucoma (n = 1), who underwent micro-invasive 360° trabeculotomy after unsuccessful (intraocular pressure (IOP) >21 mmHg under maximum glaucoma eye drop therapy (Meds)) canaloplasty. IOPs, Meds, complications and failure rates (IOP >21 mmHg at two consecutive follow-ups) were evaluated. Complete success (no Meds) and qualified success (with Meds) rates for IOP levels ≤21 mmHg and ≤ 18 mmHg at the last follow-up were evaluated. RESULTS: IOPs and Meds were significantly reduced from before to 1 week (10.3±3.1 days) after 360° trabeculotomy (IOP, 28.3±6.0 mmHg to 15.8±4.5 mmHg; p < 0.001; Meds, 3.1 ± 1.2 to 1.0 ± 1.2; p < 0.001). IOPs (p = 0.37) and Meds (p = 0.33) did not decrease further from 1 week until the last follow-up (18.3 ± 8.2 months (IOP, 14.4±3.8 mmHg; Meds, 1.5±1.3)). Complete and qualified success was 25% (5/20) and 70% (14/20) for IOP ≤21 mmHg, as well as 25% (5/20) and 60% (12/20) for IOP ≤18 mmHg. Four eyes had postoperative hyphema, which resolved after a mean period of 4.0 ± 2.2 days. Five failures occurred after a mean of 40.6 ± 51.9 days after 360° trabeculotomy. All failures underwent trabeculectomy. Eyes that needed early (≤3 months post canaloplasty) 360° trabeculotomy showed higher IOPs before (p < 0.001) and lower (p = 0.03) IOPs 2 months post 360° trabeculotomy than eyes with late (>3 months) 360° trabeculotomy surgery. CONCLUSIONS: 360° trabeculotomy is a safe, micro-invasive, simple and successful method to enhance failed canaloplasty.

Vasoconstriction and Impairment of Neurovascular Coupling after Subarachnoid Hemorrhage: a Descriptive Analysis of Retinal Changes.

Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5-14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels-central retinal arteriolar and venular equivalent-was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.