Volume 5, Number 27
Monday, July 11, 2005



In this issue: (click heading to view article)
Effects of Cholesterol-Lowering Statins on the Aqueous Humor Outflow Pathway
Visual Outcome in 10-Year-Old Preterm and Full-Term Children
Conjunctival and Corneal Calcification Associated with Vascular Calcification in Dialysis Patients
Briefly











Effects of Cholesterol-Lowering Statins on the Aqueous Humor Outflow Pathway

Cholesterol-lowering statins exert an ocular hypotensive response in an organ-culture perfusion model, indicating the potential for this class of drugs in glaucoma therapy, according to investigators at Duke University School of Medicine, Durham, NC.

Researchers treated primary cell cultures of porcine trabecular meshwork (PTM) and ciliary body (PCB) either with lovastatin or compactin in an effort to determine the effects of statins on cell shape, actin cytoskeletal organization and cell-extracellular matrix interactions (focal adhesions) using immunofluorescence staining. Using Western blot analysis, they evaluated changes in myosin light-chain (MLC) phosphorylation and changes in Rho GTPase content of membrane fractions from lovastatin-treated PTM cells. They employed a constant-flow, organ-culture perfusion system to measure the effects of statins on aqueous humor outflow facility in the anterior segments of porcine eyes.

PTM and PCB cells treated with lovastatin or compactin exhibited dramatic changes in cell shape and cytoskeletal organization within 24 hours. The changes consisted of cell rounding, actin depolymerization and decreased focal adhesions. These effects were reversible on supplementation with geranylgeranyl pyrophosphate. Lovastatin and compactin both decreased MLC phosphorylation in PTM and PCB cells. PTM cells treated with lovastatin exhibited marked decreases in membrane-bound Rho GTPase. In addition, perfusion of organ-cultured porcine eye anterior segments with 100 microns lovastatin for 96 hours caused a significant increase (110 percent) in aqueous humor outflow facility in a reversible manner, compared with control eyes.

The authors believe their results demonstrate that lovastatin and compactin induce changes in cell shape and actin cytoskeletal organization and decrease MLC phosphorylation in PTM and PCB cells, all of which are events that are likely to lead to cellular and tissue relaxation. These effects appear to be mediated by inhibition of isoprenylation of the small GTP-binding proteins such as Rho GTPase. The finding that they exert an ocular hypotensive response may indicate that they may be useful in glaucoma therapy.

SOURCE: Song J, Deng P-F, Stinnett SS, et al. Effects of cholesterol-lowering statins on the aqueous humor outflow pathway. Invest Ophthalmol Vis Sci 2005;46(7):2424-32.		 Table of Contents











Visual Outcome in 10-Year-Old Preterm and Full-Term Children

Investigators in Sweden reported on the visual outcome in prematurely born and full-term children at age 10 and evaluated the effects of prematurity per se, retinopathy of prematurity (ROP) and cryotreatment on visual acuity.

The study included 216 prematurely born children and 217 children born at full-term from the same geographical area and study period. Researchers assessed best-corrected distance and near visual acuities using linear letter logarithm of the minimum angle of resolution charts. They also investigated crowding.

Results showed that, although the prematurely born children had an overall good visual outcome, they had reduced distance and near visual acuities compared with full-term children, even when children with ROP and neurologic disorders were excluded. Children who had been treated with cryotherapy had the highest risk of a reduced visual acuity. Two percent of the prematurely born children were visually impaired (less than 20/60).

SOURCE: Larsson EK, Rydberg AC, Holmstrom GE. A population-based study on the visual outcome in 10-year-old preterm and full-term children. Arch Ophthalmol 2005;123(6):825-32.		 Table of Contents











Conjunctival and Corneal Calcification Associated with Vascular Calcification in Dialysis Patients

Conjunctival and corneal calcification (CCC) is a well-known and easily detectable extraskeletal calcification, but its association with vascular calcification has not been investigated. The aim of this study by the Department of Nephrology, Istanbul University, Turkey, was to investigate the relationship of CCC with vascular calcification and bone metabolism parameters in kidney dialysis patients.

Researchers evaluated 63 patients (30 men, 33 women; mean age, 43.5 +/- 13.4 years) who were on dialysis therapy for more than six months. Forty-four patients were on peritoneal dialysis and 19 patients were on hemodialysis therapy. Using a slit lamp microscope, the same observer evaluated the presence of CCC in these patients and in 52 age- and sex-matched healthy controls and recorded a total CCC score for each individual. Researchers collected biochemical data from patient files and measured bone mineral density (BMD) of the lumbar spine and femoral neck. They assessed the presence of vascular calcification using X-ray exams of the pelvis and hands.

Mean CCC score in patients was significantly higher than that of controls (6.2 +/- 5.1 vs. 1.3 +/- 1.8). CCC score correlated significantly with duration of renal replacement therapy, serum phosphorus level, and calcium x phosphorus product. However, investigators found no significant correlation with calcium, parathyroid hormone, alkaline phosphatase, albumin or C-reactive protein level or BMD. The frequency of vascular calcification was significantly greater in patients with a high CCC score (CCC score of 10 or greater) compared with a low CCC score (3 or lower; 56.3 percent vs. 5.6 percent). The authors concluded that CCC score evaluation is an easy, fast and noninvasive method that may be used as an additional tool to assess the status of extraskeletal calcification in dialysis patients.

SOURCE: Seyahi N, Altiparmak MR, Kahveci A, et al. Association of conjunctival and corneal calcification with vascular calcification in dialysis patients. Am J Kidney Dis 2005;45(3):550-6.		 Table of Contents





BRIEFLY
  • VEGF TRAP PROGRAM OFFERS POTENTIAL TREATMENT FOR AMD. Regeneron Pharmaceuticals, Inc., has launched a clinical program evaluating its proprietary VEGF Trap technology for treating eye diseases. The Phase I clinical trial is a dose-escalating study being conducted in patients with wet AMD; it is designed to assess the safety and tolerability of VEGF Trap in wet AMD patients. Evidence suggests that there are many growth factors and cytokines whose blockade could offer substantial clinical benefit. But because cytokines use complex receptor systems that involve at least two distinct receptor components to bind the cytokine tightly, decoy receptors incorporating a single receptor component are not as effective. Based on insights into the basic mechanisms of receptor action, Regeneron researchers developed a method to create high affinity blockers for these cytokines. These "Traps" are composed of fusions between two distinct receptor components and a portion of an antibody molecule called the "Fc region," resulting in the generation of blockers with affinity that is markedly greater than what is offered by single component reagents. Patients in the initial part of the Phase I trial will receive a single dose of the VEGF Trap delivered by intravitreal injection and will be evaluated for three months to measure the durability of effects and provide guidance for dosing regimens for use in future trials. For more information, go to www.regeneron.com.
  • NIDEK EARNS CE MARK FOR CUSTOMIZED ASPHERIC LASER TREATMENT AND SOFTWARE. NIDEK Co., Ltd., has received CE Mark approval for its proprietary Optical Path Difference Customized Aspheric Treatment (OPDCAT) algorithm and software for the NIDEK EC-5000 Excimer Laser System. The approval clears the way for NIDEK to market OPDCAT throughout the EU market for the correction of myopia and myopia with astigmatism with aberrations of the entire optical system. OPDCAT uses a proprietary ablation algorithm based on topography and wavefront data generated by the NIDEK OPD-Scan. With a combination of slit scan and multi-point ablation, OPDCAT is intended to correct refractive errors and optical aberrations of the entire eye, resulting in shorter visual recovery period and better post-operative visual acuity. In the clinical data submitted to gain CE mark approval, 97 percent of patients had an uncorrected visual acuity of 20/20 or better and 86 percent gained at least one line of best-corrected visual acuity after treatment. Eighty-six percent of patients were within 0.50D of the targeted refractive correction. Average contrast sensitivity was maintained three months post-operatively, indicating the potential of excellent quality of vision after the procedure.
  • ALCON AWARDS $1 MILLION GRANT FOR BLINDNESS PREVENTION. Alcon, Inc., recently awarded ORBIS International a $1 million grant (USD) spanning a period of two years for use in programs to prevent and cure blindness in the developing world. The company will launch the first of many activities funded through the grant as the Official Sponsor of the K.K. Prefecture Flying Eye Hospital Program, from July 2 to 15, when ORBIS’ Flying Eye Hospital, a specially outfitted DC-10 aircraft equipped with an operating room and teaching facility and carrying a multinational medical team, will travel to China"s rural southwestern Kizilsu Kirgiz Autonomous Prefecture (K.K. Prefecture) near the Kyrgyzstan border. While there, the medical team will conduct an intensive training program for nearly 100 local doctors, nurses and other essential eye care personnel. For more information, go to www.orbis.org.
  • PFIZER REVIEW: VIAGRA DOESN"T CAUSE BLINDNESS. Pfizer, Inc., said that a company review concluded that Viagra doesn"t increase patients" risk of blindness, but that it is still working with federal regulators to update the drug"s label to reflect rare reports of vision loss. The FDA announced in June that it had 38 reports of blindness among users of Viagra, caused by non-arteritic anterior ischemic optic neuropathy (NAION). But Pfizer says that its review of all post-marketing ocular event reports concluded that there is no evidence of increased risk of blindness among patients taking the erectile dysfunction drug. The FDA has concluded that no causal relationship between Viagra and NAION has been established, but the company agreed to include information on the Viagra label that these reports exist, in order to inform physicians and patients. Pfizer said it is the company"s understanding that the FDA has asked that similar information be included in the labels of all oral erectile dysfunction medicines. The FDA has also reported instances of NAION among those taking Cialis (Eli Lilly and ICOS Corp.) and Levitra (marketed by Bayer AG, GlaxoSmithKline PLC and Schering-Plough Corp.). A spokesman for Bayer AG has said that the company was working with the FDA to investigate the claims.


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