Reversal of Pharmacologically Induced Mydriasis with Phentolamine Ophthalmic Solution.

PURPOSE: Evaluate safety and efficacy of 0.75% phentolamine ophthalmic solution (POS), an alpha-1 antagonist, in reversal of pharmacologically induced mydriasis. DESIGN: Two Phase 3, multicenter, placebo-controlled, randomized, double-masked clinical trials in healthy subjects. SUBJECTS: 553 healthy 12 to 80 year old subjects were randomized 1:1 (MIRA-2) and 2:1 (MIRA-3) to receive either POS or placebo eye drops OU. METHODS: Subjects received POS or placebo administered 1 hour after mydriasis, induced by instillation of either 2.5% phenylephrine, 1% tropicamide, or Paremyd (1% hydroxyamphetamine / 0.25% tropicamide). MAIN OUTCOME MEASURES: Primary endpoint was percent of subjects returning to ≤0.2 mm greater than baseline pupil diameter in study eye at 90 minutes after POS administration. Safety measures included treatment-emergent adverse events (TEAEs) and tolerability measures, including conjunctival hyperemia. RESULTS: In MIRA-2, 185 subjects were randomized to treatment with placebo (94) or POS (91). In MIRA-3, 368 subjects were randomized to treatment with placebo (124) or POS (244). A statistically significant greater percentage of subjects treated with POS had study eyes that showed reversal of mydriasis at 90 minutes (primary endpoint) compared with the placebo treatment (48.9% vs 6.6% for MIRA-2; p<0.0001 and 58% VS 6% for MIRA-3; p<0.0001) and as early as 60 minutes (24.5% vs 5.5% for MIRA-2; p<0.0003 and 42% VS 2% for MIRA-3; p<0.0001). Between 28 to 34% of placebo-treated subjects had not returned to baseline PD at 24 hours following pharmacological dilation compared to 8 to 11% treated with POS (p<0.0001). CONCLUSION: POS treatment had a rapid onset in reducing PD within 60- to 90-minutes, with a statistically significant time savings of 3 to 4 hours to return to baseline PD compared to placebo. One or 2 drops of POS rapidly reversed mydriasis in all subjects regardless of mydriatic agent or iris color. More subjects receiving POS reported a perceived benefit in the resolution of visual symptoms caused by pharmacologically induced mydriasis compared to placebo, with statistically significant differences noted as early as 1 hour. The safety profile was favorable, with the most common adverse effects being mild transient conjunctival hyperemia (11.2%), instillation site discomfort (10.9%), and dysgeusia (3.6%).

A randomized phase 2 clinical trial of phentolamine mesylate eye drops in patients with severe night vision disturbances.

PURPOSE: Dim light vision disturbances (DLD) comprise a wide range of symptoms affecting the quality of vision at low illumination including glare, halos, and starbursts. This exploratory study investigated 1.0% phentolamine mesylate ophthalmic solution (PMOS) as a treatment to improve vision and image quality for patients with DLD. METHODS: In this placebo-controlled, randomized, double-masked clinical trial, 24 adult patients with severe DLD were randomized in a 2:1 ratio to receive either one dose of PMOS or placebo. Subjects were eligible if they reported experiencing severe night vision difficulty that was not eliminated by distance spectacle correction and scored ≥0.3 log units below the normal range of contrast sensitivity assessed under mesopic conditions with glare at ≥2 spatial frequencies. Key efficacy outcomes were change from baseline in pupil diameter, contrast sensitivity, and visual acuity. Safety measures including intraocular pressure, conjunctival hyperemia, and systemic effects were also assessed. RESULTS: Eight subjects were randomized to placebo (63% female; mean age 47 years) and 16 were randomized to PMOS (75% female; mean age 42 years). Mean (SD) pupil diameter of PMOS-treated subjects decreased significantly - 1.3 mm (0 to - 2.8 mm) with p < 0.0001. Mean contrast sensitivity with glare in PMOS-treated subjects improved significantly post-treatment at spatial frequencies 3, 6, 12, and 18 cycles per degree (p ≤ 0.03). PMOS also demonstrated improvements in the numbers of letters read for mesopic and photopic, high- and low-contrast visual acuity (LCVA). Importantly, a statistically greater proportion of PMOS-treated eyes registered mesopic LCVA 5 letter (69% vs. 31%, p = 0.029) and 10 letter (34% vs. 6%, p = 0.04) improvement, with a trend at 15 letters (19% vs. 0%, p = 0.16). PMOS was well tolerated with the only reported side effect being a mild increase in conjunctival hyperemia. CONCLUSION: PMOS was well tolerated and effectively reduced pupil size with improvements in contrast sensitivity and visual acuity in adults with severe DLD. Future Phase 3 studies should be conducted to further evaluate its potential to treat DLD. TRIAL REGISTRATION: The trial registration number is NCT04004507 (02/07/2019). Retrospectively registered.

Treatment of ruptured intracranial aneurysms with the Woven EndoBridge device: a systematic review.

The Woven EndoBridge (WEB) device is a barrel-shaped nitinol mesh deployed within the aneurysmal sac. The absence of metallic mesh in the aneurysm's parent vessel lumen obviates the need for potent antiplatelet therapy, making this device appealing for acutely ruptured aneurysms not amenable to clipping or coiling. To assess the literature regarding WEB treatment of these aneurysms, we performed a comprehensive systematic search of PubMed, MEDLINE, and EMBASE databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Keywords were combined with Boolean operators to increase search sensitivity and specificity ('woven endobridge device' AND 'ruptured'). Nine studies comprising 377 acutely ruptured aneurysms were included. Overall, 82.7% were wide-necked, 85.9% were located in the anterior circulation, and 26.9% of patients presented with poor subarachnoid hemorrhage grade. Intraprocedure and postprocedure complications occurred in 8.4% (95% CI 3.6% to 13.3%) and 1% (95% CI 0% to 2%), respectively. The post-treatment rebleeding rate was 0%. Rates of adequate occlusion (complete occlusion to neck remnant) and retreatment at last follow-up were 84.8% (95% CI 73% to 96.6%) and 4.5% (95% CI 2.2% to 6.8%), respectively. The favorable outcome rate (modified Rankin Scale score 0-2) was 62.2% (95% CI 53% to 71.4%); mortality was 13.6% (95% CI 9.7% to 17.6%). WEB treatment of acutely ruptured aneurysms results in high adequate occlusion rates, low perioperative complication rates, no rebleeding, and low recurrence requiring retreatment. This device is promising for acutely ruptured aneurysms not amenable to clipping or coiling, considering the lower need for antiplatelet regimens during the procedure or follow-up.

Continuous Antibiotic Administration Using IRRAflow® Catheter for Treatment of Intracranial Abscess.

Intracranial abscesses are rare lesions with an incidence of approximately 4 per 1 million people. The optimal surgical management of these lesions is still unclear. We present the case of a patient who was discovered to have an intracranial abscess after presenting with right-sided weakness. He was treated via a combination of open craniotomy and continuous antibiotic irrigation using an IRRAflow® catheter (IRRAS, Stockholm, Sweden). Use of the IRRAflow® in this fashion has not yet been described in the literature. This novel approach appears to be safe and resulted in continued decrease in the abscess burden following surgical drainage.

Spontaneous resolution of nontraumatic bilateral Barrow Type D indirect carotid-cavernous fistulas: A case report.

A Caucasian man in his 60s with a history of Cognard Type IIB dural arteriovenous fistula presented to the emergency room with right eye proptosis, chemosis, hyperemia, epiphora, diplopia, and blurred vision. Magnetic resonance imaging and magnetic resonance angiography revealed spontaneous, bilateral Barrow Type D carotid-cavernous fistulas (CCFs) that were later confirmed through cerebral angiography. The patient had no history of head or ocular trauma. Given the acute nature of presentation and worsening diplopia, the patient was scheduled for transvenous embolization. However, during the preprocedure angiogram, spontaneous resolution of the bilateral CCFs was observed. Complete resolution of all symptoms was noticed during follow-up. Given the rare nature of bilateral, indirect CCFs, our case stands out as the only reported instance whereby resolution of bilateral, indirect CCFs occurred spontaneously without any intervention.