Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

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.

Pathology of 219 human cadaver eyes with 1-piece or 3-piece hydrophobic acrylic intraocular lenses: capsular bag opacification and sites of square-edged barrier breach.

PURPOSE: To assess capsular bag opacification and sites of initial posterior capsule opacification (PCO) in human cadaver eyes with square-edged 1-piece or 3-piece hydrophobic acrylic intraocular lenses (IOLs). SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Eyes were immersed in 10% formalin after enucleation and had anterior segment scanning with very-high-frequency ultrasound (Artemis). After the eyes were sectioned at the equator, gross examination of the anterior segment was performed from the posterior aspect to assess capsular bag opacification, anterior capsule coverage of the IOL edge, and IOL fixation. Selected eyes had histopathologic examination. RESULTS: One hundred nineteen eyes with 1-piece IOLs and 100 with 3-piece IOLs were included in the analyses of capsular bag opacification. There was no difference in central (P=.29) or peripheral (P=.76) PCO. In 63 of 84 eyes with a 1-piece IOL and peripheral PCO, the optic-haptic junction was the site of initiation. In eyes with a 3-piece IOL, initial peripheral PCO was observed at nearly the same rate whether there was full 360-degree anterior capsulorhexis overlap of the optic or no overlap (P=.13). In the latter, the site of PCO initiation was in areas lacking capsulorhexis coverage in 46% of eyes. CONCLUSIONS: There was no difference in central or peripheral PCO between 1-piece and 3-piece hydrophobic acrylic IOLs. With 1-piece IOLs, PCO tended to start at the optic-haptic junctions. With 3-piece IOLs, full anterior capsule coverage did not produce a statistically significant benefit with respect to PCO prevention.

Pathology of 157 human cadaver eyes with round-edged or modern square-edged silicone intraocular lenses: analyses of capsule bag opacification.

PURPOSE: To assess the degree of capsular bag opacification in human cadaver eyes with silicone intraocular lenses (IOLs), specifically comparing the differences between round-edged IOLs and modern square-edged IOLs. SETTING: John A. Moran Eye Center, University of Utah, USA. DESIGN: Experimental study. METHODS: The eyes were immersed in 10% formalin on enucleation. They had anterior segment scanning with a very-high-frequency ultrasound (Artemis). After the eyes were sectioned at the equator, gross examination of the anterior segment was performed from the posterior aspect to assess the degree of capsular bag opacification, coverage of the IOL edge by the anterior capsule, and IOL fixation. Selected eyes also had histopathologic examination. RESULTS: Eighty-seven eyes with a 3-piece round-edged IOL, 43 with a 3-piece square-edged IOL, 26 with a 1-piece plate IOL, and 1 with an accommodating IOL design were included in the analyses of capsular bag opacification. Comparison between 3-piece round-edged IOLs and square-edged IOLs showed statistically significant differences in central posterior capsule opacification (PCO) (P=.0001687) and peripheral PCO (P<.0001). In eyes with square-edged IOLs, PCO had a tendency to start in areas without capsulorhexis coverage of the optic. Twenty-one of 26 eyes with a silicone plate IOL had a neodymium:YAG posterior capsulotomy for dense PCO. CONCLUSIONS: This first study using pseudophakic human cadaver eyes that includes a significant number of modern 3-piece silicone IOLs with square optic edges confirmed the role of this design in the prevention of PCO. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Long-term pathological follow-up of 2-loop iridocapsular intraocular lens.

We analyzed an enucleated postmortem eye from an 86-year-old donor who had a 2-loop iridocapsular intraocular lens (IOL) that had been implanted at least 30 years earlier. High-frequency ultrasound showed a relatively well-centered iris-supported optic in front of the pupil. Gross and light microscopic analyses of the eye and the IOL showed loop fixation outside the capsular bag remnants, a thickened cornea, mild attenuation of the corneal endothelium, multiple areas of iris trauma secondary to haptic abrasion, fragments of iris tissue attached to the haptics, as well as pigment dispersion within the eye with pigmented epithelial cells attached to the IOL haptics. Histopathological examination of the posterior segment was unremarkable.

Mechanized model to assess capsulorhexis resistance to tearing.

PURPOSE: To evaluate a model of mechanically measuring resistance to tearing of a continuous curvilinear capsulorhexis (CCC) using the entire capsular bag of fresh human cadaver eyes isolated from the eyes after complete evacuation. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: After the cornea and iris were removed, a 5.0 to 5.5 mm anterior CCC was created. The nucleus was hydroexpressed and the capsular bag evacuated by irrigation/aspiration. A pair of metal shoetree-shaped fixtures, designed based on human lens geometric dimensions, were implanted separately in the capsular bag and assembled together with a screw nut. After complete zonulectomy, the fixture-capsular bag assembly was removed from the eye and loaded onto a mechanical tester. The fixtures were separated at a velocity of 7.0 mm/min in 0.15 µm intervals to stretch the CCC to its rupture point. Rupture load (N) and extension were measured and graphed. RESULTS: Testing of 23 donor eyes a mean of 69.04 hours ± 22.72 (SD) after death showed the following mean values: CCC diameter, 5.3 ± 0.12 mm; load, 0.39 ± 0.16 N; extension at CCC tearing, 5.85 ± 1.17 mm. There was a moderately strong negative correlation between donor age and load (P = .0018). CONCLUSIONS: Previous mechanized methods of assessing CCC strength used excised anterior capsules or partially phacoemulsified crystalline lenses, yielding lower tension strength values. This force-displacement method may facilitate assessment of small differences between anterior capsulotomy techniques.

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.

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.

Mediators of ocular angiogenesis.

Angiogenesis is the formation of new blood vessels from pre-existing vasculature. Pathologic angiogenesis in the eye can lead to severe visual impairment. In our review, we discuss the roles of both pro-angiogenic and anti-angiogenic molecular players in corneal angiogenesis, proliferative diabetic retinopathy, exudative macular degeneration and retinopathy of prematurity, highlighting novel targets that have emerged over the past decade.

The effects of COX-1 and COX-2 inhibitors on prostaglandin synthesis and the formation of heterotopic bone in a rat model.

INTRODUCTION: Traumatic heterotopic ossification (HO) is a common clinical condition associated with various orthopedic procedures that involve injury to soft tissues near bone. In this study, we tested the hypothesis that the prophylactic effects of NSAID's in the treatment of HO are mediated via inhibition of the COX-2 enzyme. Here we describe a rat model that simulates HO in the human that was used to test the above hypothesis. MATERIALS AND METHODS: Heterotopic ossification was surgically induced in the quadriceps by injury to the muscle and femoral periosteum and transplantation of donor bone marrow cells containing osteoprogenitors into the site of injury. HO was imaged and quantified by micro-CT scanning of femurs removed from sacrificed animals at 6 weeks post-injury, three-dimensional computer reconstructions of the scanned bones and computer-assisted morphometric analysis. Prostaglandin E(2) (PGE(2)) synthesis was quantified using an enzyme immunoassay system. The effects of a nonselective COX inhibitor or specific inhibitors of COX-1 or COX-2 following oral administration on the content of ectopic bone and PGE(2) were also measured. RESULTS: Micro-CT and histological analyses demonstrated that all of the femurs in operated limbs developed HO in the vastus lateralis muscle belly of the quadriceps close to the anterior femur. Only the COX-1,2 nonselective and COX-2 inhibitors significantly decreased HO formation (by about one-third in each case; P < 0.05). PGE(2) synthesis at the site of injury was increased 50- and 100-fold (to 25 ng/g tissue) within 1 and 7 days, respectively, post-injury with the levels declining to near baseline within 2 weeks of surgery. Both the COX-1,2 nonselective and COX-2 inhibitors significantly decreased PGE(2) levels to 25% of control HO levels within 24 h of the first administration, even at low dosages. The COX-1 inhibitor only produced the same effect after 1 week of administration. CONCLUSION: These findings suggest that although inhibitors of COX-2 or COX-1 reduced PGE(2) synthesis, only the COX-2 enzyme plays a role in the mechanism of traumatic HO.