Glaucoma is the leading cause of irreversible blindness, affecting 111 million people by 2040 worldwide. Intraocular pressure (IOP) is the only controllable risk factor for the disease and current treatment options seek to reduce IOP via daily taking eye drops. However, shortcomings of eye drops, such as poor bioavailability and unsatisfied therapeutic effects, may lead to inadequate patient compliance. In this study, an effective brimonidine (BRI)-loaded silicone rubber (SR) implant coated with polydimethylsiloxane (BRI@SR@PDMS) is designed and fully investigated for IOP reduction treatment. The in vitro BRI release from BRI@SR@PDMS implant reveals a more sustainable trend lasting over 1 month, with a gradually declined immediate drug concentration. The carrier materials show no cytotoxicity on human corneal epithelial cells and mice corneal epithelial cells in vitro. After administrated into rabbit's conjunctival sac, the BRI@SR@PDMS implant releases BRI in a sustained fashion and effectively reduces IOP for 18 days with great biosafety. In contrast, BRI eye drops only maintain IOP-lowering effect for 6 h. Therefore, as a substitute of eye drops, the BRI@SR@PDMS implant can be applied as a promising non-invasive platform to achieve long-term IOP-lowering in patients suffering from ocular hypertension or glaucoma.

The success of oral propranolol for treatment of infantile hemangiomas (IHs) has led practitioners to use topical β-blockers. In preterm infants, clinicians frequently turn to topical timolol, with the presumption that topical application will result in less systemic absorption. We used Holter monitoring to assess for drug-induced bradycardia in high-risk infants.

We retrospectively reviewed the charts of 22 at-risk infants who received a Holter monitor to assess for association between timolol administration and development of significant bradycardia.

Four infants had episodic bradycardia detected by Holter monitoring. Two of these infants were full term; weighed more than 3,000 g; and had rare, brief, asymptomatic episodes unrelated to the timing of the timolol application. The other two infants had symptomatic bradycardia while on timolol and were the only two babies that weighed less than 2,500 g at initiation of therapy. Both were young (postmenstrual age [PMA] 34 and 37 wks) at initiation and had a timolol dose above the average exposure for the cohort.

In this cohort of at-risk infants, topical timolol appeared to provide safe treatment for IHs in full-term infants receiving a dose of less than 0.2 mg/kg/day, but infants with a PMA of less than 44 weeks and weight at treatment initiation of less than 2,500 g may be at risk of adverse events, including bradycardia, hypotension, apnea, and hypothermia. We recommend close monitoring of temperature, blood pressure, and heart rate in premature and low-birthweight infants with IHs at initiation of and during therapy with topical timolol.

Determine the safe dose of intravitreal propranolol (IVP), and evaluate its inhibitory effect on laser-induced choroidal neovascularization (CNV).

To determine the IVP safe dose, 32 rabbits were divided into 4 groups. Three of these groups received IVP (15 μL) corresponding to 15 μg (group B), 30 μg (group C), and 60 μg (group D). The control group (A) received 15 μL saline. Safety was assessed by ocular examination, electroretinography (ERG), routine histopathologic evaluation, immunohistochemistry for glial fibrillary acidic protein (GFAP), and real-time qPCR for GFAP, VEGF, thrombospondin 1 (TSP1), and pigment epithelium-derived factor (PEDF). A similar experiment was performed in 24 mice by using a 100-fold lower amount of propranolol (0.15, 0.3, and 0.6 μg in 2 μL) based on vitreous volume. For assessment of the angioinhibitory effects of IVP, CNV was induced in 42 mice via laser burns. Mice were divided into two groups: group 1 received the safe dose of IVP (0.3 μg in 2 μL) and group 2 received saline. Neovascularization area was quantified by intercellular adhesion molecule (ICAM)-2 immunostaining of choroidal-scleral flat mounts by using ImageJ software.

According to clinical, ERG, and histopathologic findings, 30 μg IVP was chosen as the safe dose in rabbit eyes, comparable to 0.3 μg IVP in mouse eyes. As compared to the control eyes, the development of CNV was attenuated (4.8-fold) in mice receiving 0.3 μg IVP.

Intravitreal propranolol injection up to the final dose of 30 μg in rabbits and 0.3 μg in mice was safe, and was effective in attenuation of CNV in mice.