Ocular Intracameral Pharmacokinetics for a Cocktail of Timolol, Betaxolol, and Atenolol in Rabbits.

The mechanisms of drug clearance from the aqueous humor are poorly defined. In this study, a cocktail approach was used to simultaneously determine the pharmacokinetics of three ß-blocker agents after intracameral (ic) injection into the rabbit eyes. Aqueous humor samples were collected and analyzed using LC-MS/MS to determine drug concentrations. Pharmacokinetic parameters were obtained using a compartmental fitting approach, and the estimated clearance, volume of distribution, and half-life values were the following: atenolol (6.44 µL/min, 687 µL, and 73.87 min), timolol (19.30 µL/min, 937 µL, and 33.64 min), and betaxolol (32.20 µL/min, 1421 µL, and 30.58 min). Increased compound lipophilicity (atenolol < timolol < betaxolol) resulted in higher clearance and volume of distributions in the aqueous humor. Clearance of timolol and betaxolol is about 10 times higher than the aqueous humor outflow, demonstrating the importance of other elimination routes (e.g., uptake to iris and ciliary body and subsequent elimination via blood flow).

In vitro larvicidal activity of ivermectin and povidone-iodine against Oestrus ovis.

PURPOSE: To assess the in vitro larvicidal activity of ivermectin and povidone-iodine (PVP-I) against Oestrus ovis, the most frequent cause of external ophthalmomyiasis. METHODS: L1 O. ovis larvae were collected from the nasal boots of sheep slaughtered in local abattoirs and transferred onto Petri dishes containing mucosal tissue (25 larvae/dish). The larvicidal activity of the following formulations was tested: 1% ivermectin suspension in balanced sterile saline solution (BSSS), 1% ivermectin solution in propylene glycol, propylene glycol, 0.6% PVP-I in hyaluronic acid vehicle (IODIM®), and combination of ivermectin 1% solution and 0.6% PVP-I. One mL of each formulation was added to different Petri dishes containing the larvae. The time needed to kill the larvae was recorded. RESULTS: 893 larvae were tested. The median time needed to kill the larvae was 46, 44, 11, 6, and 10 minutes for Iodim®, ivermectin 1% suspension, propylene glycol, ivermectin 1% solution, and a combination of ivermectin 1% solution with 0.6% PVP-I, respectively. Kaplan-Meyer analysis disclosed that the survival curves were significantly lower in samples treated with ivermectin 1% solution, ivermectin 1% solution + 0.6% PVP-I, and propylene glycol than in samples receiving other treatments or BSSS. CONCLUSION: In this in vitro study, ivermectin 1% solution in propylene glycol, ivermectin 1% solution + 0.6% PVP-I, and propylene glycol alone showed a good, relatively rapid larvicidal activity against O. ovis larvae. Further experimental and clinical studies are necessary to establish whether, or not, these formulations may be considered as potential candidates for the topical treatment for external ophthalmomyiasis caused by O. ovis.

Ocular pharmacokinetics of atenolol, timolol and betaxolol cocktail: Tissue exposures in the rabbit eye.

Quantitative understanding of pharmacokinetics of topically applied ocular drugs requires more research to further understanding and to eventually allow predictive in silico models to be developed. To this end, a topical cocktail of betaxolol, timolol and atenolol was instilled on albino rabbit eyes. Tear fluid, corneal epithelium, corneal stroma with endothelium, bulbar conjunctiva, anterior sclera, iris-ciliary body, lens and vitreous samples were collected and analysed using LC-MS/MS. Iris-ciliary body was also analysed after intracameral cocktail injection. Non-compartmental analysis was utilized to estimate the pharmacokinetics parameters. The most lipophilic drug, betaxolol, presented the highest exposure in all tissues except for tear fluid after topical administration, followed by timolol and atenolol. For all drugs, iris-ciliary body concentrations were higher than that of the aqueous humor. After topical instillation the most hydrophilic drug, atenolol, had 3.7 times higher AUCiris-ciliary body than AUCaqueous humor, whereas the difference was 1.4 and 1.6 times for timolol and betaxolol, respectively. This suggests that the non-corneal route (conjunctival-scleral) was dominating the absorption of atenolol, while the corneal route was more important for timolol and betaxolol. The presented data increase understanding of ocular pharmacokinetics of a cocktail of drugs and provide data that can be used for quantitative modeling and simulation.

Gentle endodiathermy of retinal vessels to mark paravascular posterior retinal breaks in highly myopic eyes.

PURPOSE: To show a new method to highlight posterior paravascular retinal breaks, responsible for posterior retinal detachment in highly myopic eyes, by gentle endodiathermy on the nearby retinal vessel, in areas of patchy chorioretinal atrophy. METHODS: A standard 25-gauge (25-G) 3-port pars plana vitrectomy with internal limiting membrane (ILM) peeling was performed. A gentle endodiathermy was applied on the vessel close to the retinal break until a clear withe spot became visible. This spot was used as a landmark to identify the retinal break after fluid-air exchange. RESULTS: The retina was attached after a single operation and no retinal redetachment was reported. A complete blood flow restoration in the treated vessel was documented with fluorescein angiography after 5 days. CONCLUSIONS: This simple technique may help the vitreoretinal surgeon to identify paravascular retinal breaks after fluid-air exchange. No damage to the retinal vessels undergoing endodiathermy was observed.

Shall we stay, or shall we switch? Continued anti-VEGF therapy versus early switch to dexamethasone implant in refractory diabetic macular edema.

AIMS: To compare functional and anatomical outcomes of continued anti-vascular endothelial growth factor (VEGF) therapy versus dexamethasone (DEX) implant in eyes with refractory diabetic macular edema (DME) after three initial anti-VEGF injections in a real-world setting. METHODS: To be included in this retrospective multicenter, case-control study, eyes were required: (1) to present with early refractory DME, as defined by visual acuity (VA) gain ≤ 5 letters or reduction in central subfield thickness (CST) ≤ 20%, after a loading phase of anti-VEGF therapy (three monthly injections) and (2) to treat further with (a) anti-VEGF therapy or (b) DEX implant. Main outcome measures were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Due to imbalanced baseline characteristics, a matched anti-VEGF group was formed by only keeping eyes with similar baseline characteristics as those in the DEX group. RESULTS: A total of 110 eyes from 105 patients were included (anti-VEGF group: 72 eyes, DEX group: 38 eyes). Mean change in VA at 12 months was - 0.4 ± 10.8 letters (anti-VEGF group), and + 6.1 ± 10.6 letters (DEX group) (P = 0.004). Over the same period, mean change in CST was + 18.3 ± 145.9 µm (anti-VEGF group) and - 92.8 ± 173.6 µm (DEX group) (P < 0.001). Eyes in the DEX group were more likely to gain ≥ 10 letters (OR 3.71, 95% CI 1.19-11.61, P = 0.024) at month 12. CONCLUSIONS: In a real-world setting, eyes with DME considered refractory to anti-VEGF therapy after three monthly injections which were switched to DEX implant and had better visual and anatomical outcomes at 12 months than those that continued treatment with anti-VEGF therapy.

Bromfenac eyedrops in the treatment of diabetic macular edema: a pilot study.

PURPOSE: To evaluate the efficacy and safety of topical bromfenac in patients with newly diagnosed diabetic macular edema (DME). METHODS: In this pilot study including 17 patients with monocular, newly diagnosed DME, diagnosis of DME was established by the detection of retinal thickening at or within 500 µm of the center of the macula on ophthalmoscopic examination, according to the Early Treatment Diabetic Retinopathy Study classification. Central macular thickness (CMT) was determined by optical coherence tomography. Bromfenac sodium hydrate 0.9 mg/mL eyedrops were administered in the affected eye twice daily for 30 days. Primary endpoints were changes in best-corrected visual acuity (BCVA) and CMT at the end of therapy. RESULTS: Topical bromfenac significantly reduced mean CMT, from 465.41 ± 118.47 µm at baseline to 388.88 ± 152.63 µm posttreatment (p = 0.02). There was no significant change in BCVA and differences in mean macular volume fell just short of statistical significance (p = 0.06). Treatment was well-tolerated, and there were no topical or systemic side effects. CONCLUSIONS: Topical bromfenac twice daily may play a role in the reduction of DME. These preliminary results warrant further larger multicenter studies to confirm our findings and establish whether topical bromfenac may be of long-term benefit in the treatment of DME.