A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy.

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1alpha and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1alpha. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.

Horizons in therapy for corneal angiogenesis.

Corneal neovascularization can lead to a devastating disease process that involves the breakdown of the limbal barrier and the formation of blood vessels in the cornea, leading to severe visual impairment. This review discusses the delicate balance between antiangiogenic and angiogenic factors that govern the antiangiogenic privilege of the cornea. Current treatment methods, clinical trials, and future prospects in the management of corneal neovascularization also are discussed.

CT and orbital ultrasound findings in a case of Castleman disease.

A 53-year-old man with a 2-month history of left periorbital swelling was found to have a large solid intraconal mass on CT scan. Orbital ultrasound showed that the lesion had a cavernous pattern of internal reflectivity. Histopathology revealed hyaline-vascular type Castleman disease (CD). This article represents the first reported orbital ultrasound findings in CD. The findings of CT scan and ultrasound may be useful in the preoperative evaluation of orbital hyaline-vascular type CD.

Two-year follow-up of the Artisan/Verisyse iris-supported phakic intraocular lens for the correction of high myopia.

PURPOSE: To evaluate the implantation of Artisan/Verisyse phakic intraocular lenses (pIOLs) (Advanced Medical Optics) as an effective and safe method for the correction of high myopia. SETTING: Department of Ophthalmology, John A. Moran Eye Center, University of Utah Medical Center, Salt Lake City, Utah, USA. METHODS: This retrospective outcomes trial examined the implantation of Artisan/Verisyse pIOLs in 85 highly myopic eyes (mean spherical equivalent -12.2 diopters). Patients were followed for 2 years and examined postoperatively at 1,6,12, and 24 months. Data collected included best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), corneal endothelial cell density, and adverse events. RESULTS: Six months postoperatively, 5 (7%) eyes lost 1 line of the BSCVA; no eye lost 2 or more lines. The UCVA was better than 20/40 in 83% of eyes and better than 20/25 in 32%. Endothelial cell density decreased by 3.3% and 6.5% over the 1-year and 2-year intervals, respectively. Glare and halos, the most common complications of surgery, were reported by 6% of patients at 1 month and by 3% at 2 years. CONCLUSION: Implantation of the Verisyse/Artisan pIOL yielded accurate refractive results with acceptable safety in highly myopic eyes.

An anterior chamber toxicity study evaluating Besivance, AzaSite, and Ciprofloxacin.

PURPOSE: We determined whether Besivance (Bausch & Lomb), AzaSite (Inspire Pharmaceuticals, Inc; both with DuraSite bioadhesive [InSite Vision, Inc]) and ciprofloxacin are toxic inside the anterior chamber. DESIGN: Randomized, masked, placebo-controlled animal study. METHODS: Twenty New Zealand white rabbits (40 eyes) were randomized to 1 of 4 study groups: Besivance, AzaSite, ciprofloxacin, and balanced salt solution. Each eye was injected with 0.1 mL of the study medication. Clinical slit-lamp examinations were conducted at 24 and 48 hours after injection. All rabbits then were killed and all eyes were enucleated. We randomized eyes to either corneal vital staining or histopathologic examination. The main outcome measures were clinical and pathologic signs of toxicity. RESULTS: The 2 DuraSite-based study groups (Besivance and AzaSite) showed clinically and pathologically significant differences when compared with the ciprofloxacin and balanced salt solution groups. Besivance and AzaSite eyes exhibited significantly similar and severe clinical damage, including severe corneal edema. Ciprofloxacin and balanced salt solution eyes appeared very similar and had only mild conjunctival injection and limbal vascularity. Vital staining and histopathologic evaluation revealed glaucomatous and toxic damage in eyes given DuraSite-based medications, whereas non-DuraSite groups showed minimal changes. CONCLUSIONS: DuraSite blocks the trabecular meshwork and may be additionally toxic when introduced as a large bolus. Until the safety of these medications is established with further studies using smaller injected volumes, we recommend placement of a suture over a clear corneal wound if DuraSite-based medications are used.

Comparison of wound strength with and without a hydrogel liquid ocular bandage in human cadaver eyes.

PURPOSE: To determine whether a hydrogel liquid ocular bandage improves wound strength. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Laboratory investigation. METHODS: The wound strength of 2.8 mm clear corneal incisions and 23-gauge scleral incisions was tested in cadaver eyes by raising the intraocular pressure (IOP) until leakage occurred. The pressure at the first sign of incision leakage with the liquid bandage and without the liquid bandage was determined. RESULTS: Four corneal incisions and 4 scleral incisions were made in 5 cadaver eyes. The mean pressure at the first sign of corneal incision leakage was 59.5 mm Hg ± 21.0 (SD) without the liquid bandage and 198.1 ± 57.6 mm Hg with the liquid bandage (P<.0001). The mean pressure at the first sign of scleral incision leakage was 47.9 ± 21.4 mm Hg and 209.0 ± 42.9 mm Hg, respectively (P<.0001). Eight corneal incisions and 8 scleral incisions did not leak at the maximum pressure of 246 mm Hg. With both incision types, the difference in leakage with a liquid bandage in place and with no liquid bandage was statistically significant (P = .002). CONCLUSION: With application of a hydrogel liquid ocular bandage, incisions withstood significantly higher IOP before leakage occurred than when no liquid bandage was used.