Topical WIN55212-2 alleviates intraocular hypertension in rats through a CB1 receptor mediated mechanism of action.

INTRODUCTION: Systemically administered cannabinoids can reduce intraocular pressure (IOP), but produce undesirable cardiovascular and central nervous system effects. In a chronic model of ocular hypertension, we examined the efficacy of acute topical administration of WIN55212-2 (WIN) in a novel commercially available vehicle and in combination with timolol. METHODS: IOP was chronically elevated by the surgical ligature of vortex veins in Sprague Dawley rats. IOP was measured by using Goldmann applanation tonometry. IOP, blood pressure (BP), and heart rate (HR) were measured at baseline and 30, 60, 90, and 120 min after the topical administration of WIN 1.0%, 0.25%, 0.06%, or 0.015%, the commercially available vehicle, timolol 0.5%, or a combination of WIN and timolol. SR141716 (CB1 antagonist) or SR144528 (CB2 antagonist) was administered topically 30 min before WIN to determine receptor specificity. To determine ocular and systemic penetration, 3H WIN 55212-2 was administered topically and tissues were collected at 60 and 120 min. Ocular irritation was evaluated by slit-lamp examination (SLE) at baseline and 120 min. RESULTS: WIN significantly decreased IOP in the hypertensive eye, with no BP or HR effects. SR141716 pretreatment significantly inhibited the IOP effects of WIN 1.0% in a dose-dependent manner, while SR 144528 was not as effective. No significant additive effects were observed by combining WIN (0.5% or 1.0%) with timolol 0.5%. WIN was retained in ocular tissue with a t1/2 of 80-100 min. SLE at 120 min revealed no solvent or drug-related toxic effects. CONCLUSIONS: In a chronic ocular hypertensive rat model, topically applied WIN is an effective, nontoxic ocular hypotensive agent with no hemodynamic side-effects. This effect was predominantly CB1 receptor mediated, but some CB2 contribution could not be ruled out.

Oncocytoma of the lacrimal gland: case report and review of the literature.

OBJECTIVE: Oncocytomas of the lacrimal gland are rare tumors. We report the eighth case in the literature. DESIGN: Interventional case report and literature review. INTERVENTION: Complete ophthalmologic and systemic examination followed by excisional biopsy and histopathologic examination. RESULTS: A 40-year-old Hispanic woman was evaluated for a right-sided upper eyelid edema and pain on ocular motility. A month earlier an outside ophthalmologist had performed a conjunctival biopsy that disclosed chronic inflammation. Computed tomography and magnetic resonance imaging of brain and orbit demonstrated a right intraorbital extraconal soft tissue density mass that involved the lacrimal gland, upper eyelid and encroached both the superior oblique and superior rectus muscles. Histopathology showed a benign oncocytoma that replaced most of the lacrimal gland. CONCLUSION: Although rare, oncocytomas should be included in the differential diagnosis of any lacrimal gland tumors.

Beta1-adrenergic receptor polymorphisms and clinical efficacy of betaxolol hydrochloride in normal volunteers.

OBJECTIVE: To evaluate the relationship between polymorphisms in the gene encoding the beta1-adrenergic receptor (beta1-AR) and clinical response to betaxolol hydrochloride 0.25% in a small pilot study of normal volunteers. DESIGN: Prospective nonrandomized comparative trial. PARTICIPANTS: Forty-eight consecutive normal volunteers who met all eligibility requirements for inclusion into this study. METHODS: Baseline intraocular pressure (IOP) was recorded. Subjects began treatment with betaxolol (1 drop both eyes twice daily) and underwent follow-up IOP recordings at 3 and 6 weeks. Peripheral blood was obtained for genetic analysis. MAIN OUTCOME MEASURES: Response to betaxolol was calculated as the change in mean IOP from baseline (averaged between both eyes and averaged between both follow-up visits). The beta1-AR genotype was determined by polymerase chain reaction with restriction fragment length polymorphisms at codons 49 (serine [Ser] or glycine [Gly]) and 389 (arginine [Arg] or Gly). RESULTS: There were 32 Ser49 homozygotes and 16 Gly49 carriers. There were no statistically significant differences between the Ser49 homozygotes and the Gly49 carriers with respect to baseline IOP or response to betaxolol therapy. There were 25 Arg389 homozygotes and 23 Gly389 carriers (22 heterozygotes and 1 Gly389 homozygote). As compared with Gly389 carriers, the Arg389 homozygotes had a higher baseline IOP (15.8 mmHg vs. 13.7 mmHg; P = 0.009) and a greater magnitude of response to betaxolol therapy (-3.4 mmHg vs. -1.5 mmHg; P = 0.0009). The Ser49 homozygote genotype was not independently associated with baseline IOP (P = 0.47) or with a response to betaxolol (P = 0.99). The Arg389 homozygote genotype was independently associated with a higher baseline IOP (P = 0.03) and a greater response to betaxolol (P = 0.03), even after adjusting for baseline IOP. CONCLUSIONS: In this small pilot series, a single nucleotide polymorphism at codon 389 in the beta1-AR seems to correlate with a response to betaxolol therapy in normal, nonglaucomatous volunteers. There was no such correlation at codon 49. The polymorphism at codon 389 may predict short-term response to betaxolol and may serve as a determinant of response to betaxolol and other adrenergic agents in glaucomatous eyes requiring treatment.

Surgical treatment of trauma-induced periodic alternating nystagmus.

PURPOSE: To report a new treatment for acquired periodic alternating nystagmus in which medical therapy with baclofen was not tolerated. DESIGN: Interventional case report and literature review. INTERVENTION: Simultaneous adjustable bilateral retroequatorial horizontal rectus muscle recessions. MAIN OUTCOME MEASURES: Ocular alignment and ocular motility recordings. RESULTS: A 30-year-old man had blurred vision after an emergency left temporal craniotomy for gunshot wounds. Ophthalmologic examination revealed periodic alternating nystagmus that was documented by an infrared electronystagmogram. Baclofen was started but was not tolerated. Bilateral lateral and medial retroequatorial rectus muscle recessions were performed and were successful in the treatment of this patient. CONCLUSION: Simultaneous bilateral retroequatorial horizontal rectus recessions may be an effective treatment for intractable acquired periodic alternating nystagmus.

A sticky situation.

A 19-year-old woman presented with frontal headaches, papilledema, and binocular horizontal double vision due to a left VI nerve palsy. MRV demonstrated sagittal sinus and bilateral transverse sinus thrombosis. The clinical and neuro-radiologic signs resolved after anticoagulation.

Unilateral acquired upper eyelid ptosis and decreasing nystagmus.

PURPOSE: To describe a patient with congenital nystagmus that decreased in one eye after the development of a cavernous sinus meningioma. DESIGN: Interventional case report. METHODS: A 45-year-old man with congenital nystagmus, albinism, and high myopia presented with right upper eyelid ptosis that was corrected surgically on three occasions during a 3-year period. An episode of syncope was followed by diagnostic evaluation that disclosed a cavernous sinus meningioma. He commented that his right eye nystagmus progressively decreased. He was found to have ophthalmoplegia on the right eye due to nerve compression by the meningioma. RESULTS: A magnetic resonance imaging scan disclosed a cavernous sinus meningioma extending into the parachiasmal and clival areas. A biopsy specimen of the lesion demonstrated a meningioma. CONCLUSIONS: Any patient with acquired ptosis should have a complete ophthalmic examination, including evaluation of extraocular motility.