Purpose: To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Methods: Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%). The NK1R antagonist L-703,606 was topically applied to the eye at the same time of induction or 20 min after induction, and phosphate buffered saline (PBS) treatment served as the control. Superior bulbar conjunctival images were taken every 30 s for the first 2 min, followed by every 4 min for 8 min, and then every 10 min until 1 h. The severity of ocular redness was evaluated on the images using ImageJ-based ocular redness index (ORI) calculations. Results: The ORI scores were significantly increased after the application of 0.5%, 1%, 2%, or 5% dapiparzole at each time point evaluated, with the most severe redness induced by the 5% dapiprazole that led to a maximal mean increase in ORI score of 14 at 20 min post-induction and thus used for subsequent evaluation of therapeutic efficacy of NK1R antagonism. Topical L-703,606, when applied at the same time as dapiprazole induction, significantly suppressed the increase of ORI scores at all time points (∼40% decrease). Furthermore, when applied at 20 min after dapiprazole induction, L-703,606 rapidly and effectively suppressed the increase of ORI scores at 30, 40, 50, and 60 min (∼30% decrease). Conclusions: Topical blockade of NK1R effectively prevents and alleviates nonallergic ocular redness in a novel animal model.

OBJECTIVE: Carotid cavernous fistulas (CCFs) represent uncommon and anomalous communications between the carotid artery and the cavernous sinus.
METHODS: Case report RESULTS: We present the clinical details and successful management of a previously healthy 44-year-old patient who presented with one-month worsening headache, bilateral abducens palsy and conjunctival injection. Imaging modalities including magnetic resonance imaging (MRI) with contrast and digital subtraction angiography (DSA) facilitated the diagnosis of CCF. The patient underwent endovascular coiling of the CCF, leading to neurological recovery and symptom remission.
CONCLUSIONS: This case highlights the importance of promptly CCF diagnosis in patients with multiple cranial nerve palsies and conjunctival hyperemia. Moreover, it emphasizes the efficacy of endovascular coiling in achieving symptom remission.

A clinical trial evaluated ocular hypotensive efficacy and safety of netarsudil 0.02% once daily (QD) relative to ripasudil 0.4% twice daily (BID).
This was a single-masked, randomized, phase 3, superiority study. Japanese patients were randomized to either the netarsudil 0.02% group or the ripasudil 0.4% group in a 1:1 ratio and treated for 4 weeks. The primary efficacy variable was mean diurnal intraocular pressure (IOP) (average of diurnal time points at 09:00, 11:00, and 16:00) at Week 4.
A total of 245 patients were included in the primary analysis. At Week 4, least squares (LS) mean of diurnal IOP adjusted for baseline was 15.96 and 17.71 mmHg in the netarsudil 0.02% and ripasudil 0.4% groups, respectively, demonstrating the superiority of netarsudil 0.02% QD over ripasudil 0.4% BID by a margin of - 1.74 mmHg (p < 0.0001). Mean reduction from baseline in mean diurnal IOP at Week 4 was 4.65 and 2.98 mmHg, respectively. Adverse events (AEs) occurred less frequently in netarsudil 0.02% than in ripasudil 0.4%, with the incidence of ocular AEs being 59.8% and 66.7%, respectively. The most frequently reported AE was conjunctival hyperemia in both groups, with an incidence of 54.9% and 62.6%, respectively. No serious eye-related AEs were reported.
Netarsudil ophthalmic solution 0.02% dosed QD (p.m.) was well tolerated and more effective in reducing IOP than ripasudil ophthalmic solution 0.4% dosed BID. Netarsudil 0.02% QD may become an important option for the treatment of Japanese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT).
ClinicalTrials.gov identifier, NCT04620135.

Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α2-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine.
This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics.
Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC.
RBFC significantly reduced IOP compared with each agent alone. A combination of each agent\'s pharmacologic profile was observed in that of RBFC.
Japan Registry of Clinical Trials; Registration No. jRCT2080225220.

BACKGROUND: Cranial autonomic dysregulation is a common symptom of patients suffering from cluster headache or migraine. The peripheral vascular dysfunction may increase the risk for ischemic or hemorrhagic strokes, myocardial infarction, retinal vasculopathy, cardiovascular mortality, and peripheral artery diseases. Furthermore, it may also manifest with ocular symptoms, e.g., increased lacrimation, conjunctival injection, and facial swelling.
METHODS: We here report a case of a patient with migraine and ocular signs of a vascular dysregulation that have led to persisting changes of conjunctival vessels and to a corneal arcus.
CONCLUSIONS: Autonomic vascular dysregulation may not only cause headaches but also persisting changes of ocular tissues, e.g., conjunctival vessel alterations and a corneal arcus.

In this study, clinical, parasitological and histopathological findings of thirteen kelp gulls (Larus dominicanus) found infected with eyeflukes in Brazil are presented. Parasites detected in the ventral conjunctival fornix were identified as Philophthalmus lachrymosus [mean intensity of infection: 16 (5-36) worms/bird]. Eleven birds (85%) presented signs of systemic disease, such as emaciation, dehydration and depressed consciousness. Conjunctival hyperemia was observed in 22 eyes (85%). Keratitis, corneal ulcers, corneal abscess and chemosis were also detected in some eyes (4-8%). Histopathologic lesions, likely due to the parasite attachment to the conjunctiva, were found in the eyes of one infected bird that died from unrelated causes. Philophthalmosis by P. lachrymosus is here reported as a clinically relevant eye disease in kelp gulls.

UNASSIGNED: Studies comparing the two different formulations of bimatoprost, 0.03% and 0.01%, have shown similar efficacy, but a better adverse effect profile for bimatoprost 0.01% in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). This study assesses the efficacy and tolerability of switching from bimatoprost 0.01% to 0.03% in a patient population with broader spectrum of diagnoses in a real-world clinical setting.
UNASSIGNED: Single-centre retrospective observational switch study.
UNASSIGNED: Selected patients were on initial topical therapy with bimatoprost 0.01% prior to switching to bimatoprost 0.03%. Intraocular pressure (IOP) was collected from their pre-switch visit, 6- and 12-week after switch. Paired two-sample t-test was performed to compare IOP at different time points versus baseline. Worsening of hyperemia and other adverse events after the switch were identified. Subgroup analysis was performed for POAG and OHT, secondary open-angle glaucoma (SOAG, including pseudoexfoliative and pigmentary glaucoma), normal tension glaucoma (NTG), and angle closure glaucoma (ACG).
UNASSIGNED: The study population consisted of 248 eyes (143 patients). There was a significant mean IOP reduction of 1.0 ± 3.7 mmHg (p < 0.001, n = 248) from baseline to week-6 and 1.6 ± 4.0 mmHg (p < 0.001, n = 142) from baseline to week-12 after switch. The IOP reduction was statistically significant in patients with POAG and OHT (6-week: 1.0 ± 3.8 mmHg, n = 76; 12-week: 1.5 ± 4.1 mmHg, n = 49), ACG (6-week: 1.5 ± 4.1 mmHg, n = 72; 12-week: 2.3 ± 4.5 mmHg, n = 46), and NTG (6-week: 0.83 ± 2.5 mmHg, n = 42; 12-week: 1.12 ± 2.1 mmHg, n = 25). Patients with SOAG did not show statistically significant reduction in IOP at 6- or 12-week after switch. Forty-two (29%) of 143 patients experienced adverse events, with the most common being hyperemia (16%).
UNASSIGNED: Significant reduction in IOP could be seen after switching from bimatoprost 0.01% to bimatoprost 0.03% in various types of glaucoma except SOAG. Intolerance after switch may be experienced, though not in the majority of cases.

UNASSIGNED: Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining.
UNASSIGNED: One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured.
UNASSIGNED:  Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049).
UNASSIGNED: Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants.

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