Volume 6, Number 20
Monday, May 22, 2006



In this issue: (click heading to view article)
Editorial: How Did It Happen?
Keratoconus and Cellular Susceptibility to Stress-Related Challenges
Topography of the Central and Peripheral Cornea
Corneal Thicknesses and Endothelial Morphology in Diabetes
Evaluation of Wall Shear Stress on Retinal Microcirculation
Briefly











Editorial: How Did It Happen?

Recently, a staff member of my practice began to experience symptoms that were potentially cardiac in nature. At first, she discussed these symptoms with my office manager while I was out of town speaking. My manger contacted several internal medicine practices from which we receive referrals in the hope of securing a prompt appointment for the staff member. Not only was our manager unable to do so, but every office informed us that their physician would not consent to see our staff member in the office at all. The reason: the physician was unwilling to accept any liability if anything should happen to the patient while she was in their office.

Mind you, our staff member was not experiencing these symptoms frequently and was by no means physically compromised. She just needed a good generalist to help her sort out symptoms. All the manager was able to receive in the way of advice was to tell her to go to the emergency department of a hospital. Ultimately, I called a cardiologist for whom I’d performed LASIK. He agreed to see our staff member in his office.

Maybe I’m a bit off base, but this strikes me as an example of how seriously broken our medical system is when physicians are afraid to see certain patients in their offices for fear of assuming medical liability. How appropriate would it be if I refused to see a patient who experienced severe eye pain, a mid-dilated pupil, vomiting, and halo effects around lights at night? What is the ED going to do for this patient?

How have we allowed the fear of medical liability to so heavily influence how we practice? What message does this send to patients? I can assure you that patients do not feel sorry for us. Instead, they’re likely assuming that we think only of ourselves and not about their medical needs. It’s vital that we remain unwavering in our efforts to overcome this problem. Physicians deserve the freedom to practice medicine in a caring and compassionate manner rather than having the law watching over their shoulders and assessing every move.
Stephen E. Pascucci, MD
Medical Editor
[email protected]

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Keratoconus and Cellular Susceptibility to Stress-Related Challenges

Investigators at the University of California Irvine Medical Center conducted a study to determine whether keratoconus (KC) corneal fibroblast cultures increase reactive oxygen species (ROS) production and are more susceptible to stress-related challenges.

Nine normal and 10 KC stromal fibroblast cultures were incubated in either neutral- or low-pH conditions, with or without hydrogen peroxide. Researchers measured catalase activities with a fluorescent substrate assay and determined superoxide and ROS/reactive nitrogen species (RNS) productions with an amine-reactive green-dye assay and 2",7"-dichlorodihydrofluorescein diacetate (H2DCFDA) dye assay, respectively. They analyzed cell viability using a dye-exclusion assay and measured caspase 3 activity using a fluorochrome inhibitor of caspase (FLICA) assay. A cationic (green) dye was used to measure the mitochondrial membrane potential (m).

KC fibroblasts increased superoxide and ROS/RNS production (6.2-fold and 1.8-fold, respectively) and catalase activity with higher concentrations of H2O2 compared with normal cultures. After a low-pH stress challenge, KC fibroblasts maintained higher ROS/RNS levels (3.3-fold), showed higher caspase-3 activity (7.5-fold) and decreased m (2.6-fold), and had decreased cell viability (37 percent vs. 20 percent) compared with normal fibroblasts. The authors believe that these properties may play a role in the pathogenesis of KC.

SOURCE: Chwa M, Atilano SR, Reddy V, et al. Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts. Invest Ophthalmol Vis Sci 2006;47(5):1902-10.		 Table of Contents











Topography of the Central and Peripheral Cornea

This Australian study investigated the topography of the central and peripheral cornea in a group of young adult subjects with a range of normal refractive errors.

Researchers acquired corneal topography data for 100 young adult subjects using a method that allows central and peripheral maps to be combined to produce one large, extended corneal topography map. This computer-based method involves matching the common topographical features in the overlapping maps. The investigators analyzed corneal height, axial radius of curvature and axial power data; they also fit the corneal height data with Zernike polynomials.

Conic fitting to the corneal height data revealed the average apical radius (Ro) was 7.77 +/- 0.2-mm and asphericity (Q) was -0.19 +/- 0.1 for a 6-mm corneal diameter. The conic fit parameters both changed significantly for increasing corneal diameters. For a 10-mm corneal diameter, Ro was 7.72 +/- 0.2 mm and Q was -0.36 +/- 0.1. A slight but significant meridional variation was found in Q, with the steepest principal corneal meridian flattening at a slightly greater rate than the flattest meridian. The RMS fit error for the conic section increased markedly for larger corneal diameters. Higher-order polynomial fits were needed to fit the peripheral corneal data adequately. Analysis of the axial power data revealed highly significant changes occurring in the corneal best-fit spherocylinder with increasing distance from the corneal center. The peripheral cornea became significantly flatter and decreased slightly in its toricity. Individual subjects exhibited a range of different patterns of central and peripheral corneal topography. Several of the higher-order corneal surface Zernike coefficients changed significantly with increasing corneal diameter. Based on these results, the investigators concluded that a conic section is a poor estimator of the peripheral cornea.

SOURCE: Read SA, Collins MJ, Carney LG, Franklin RJ. The topography of the central and peripheral cornea. Invest Ophthalmol Vis Sci 2006;47(4):1404-15.		 Table of Contents











Corneal Thicknesses and Endothelial Morphology in Diabetes

In this study, Korean researchers evaluated the differences of corneal thickness and corneal endothelial morphology in diabetes compared with age-matched, healthy control subjects. Additionally, they tested for correlation according to the duration of diabetes.

The researchers performed ultrasound pachymetry and noncontact specular microscopy on 200 patients with diabetes and 100 control subjects. They compared the values for diabetics and normal persons with analysis of covariance to adjust for age. They also examined the correlation between the subject parameters and the duration of diabetes using a partial correlation coefficient that controlled for age.

Results showed that the diabetic subjects had thicker corneas, less cell density and hexagonality and more irregular cell size of the corneal endothelium than did the controls. Central corneal thickness and the coefficient of variation for cell size were significantly higher for diabetes of more than 10 years" duration than for diabetes of less than 10 years" duration. The endothelial cell density and percentage of hexagonal cells were lower for diabetes of more than 10 years" duration than for diabetes of less than 10 years" duration. Central corneal thickness was correlated with duration of diabetes, but corneal endothelial morphology was not.

SOURCE: Lee JS, Oum BS, Choi HY, et al. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye 2006;20(3):315-8.		 Table of Contents











Evaluation of Wall Shear Stress on Retinal Microcirculation

Wall shear stress (WSS) in retinal vessels can be evaluated noninvasively in humans using laser Doppler velocimetry (LDV) and cone-plate viscometry, according to Japanese investigators at Asahikawa Medical College.

In the study, the researchers used LDV to measure retinal vessel diameter and mean centerline blood velocity (V[max, mean]) in the retinal arterioles and venules at first- and second-order branches in 13 subjects. They calculated retinal blood flow (RBF) and wall shear rate (WSR) using these two parameters. They also measured blood viscosity at the calculated shear rate using a cone-plate viscometer. WSS was calculated as the product of the WSR and the blood viscosity.

In the first-order branches, the averaged diameter, V(max, mean), RBF and WSR (mean) were 108 +/- 13 microns, 41 +/- 10 mm/s, 11 +/- 4 microliters/min, and 1539 +/- 383 s(-1) in the arterioles and 147 +/- 13 microns, 23 +/- 3 mm/s, 12 +/- 4 microliters/min, and 632 +/- 73 s(-1) in the venules, respectively. The apparent blood viscosities at the measured shear rates were 3.5 +/- 0.3 centipoise (cP) in the arterioles and 3.8 +/- 0.4 cP in the venules. Therefore, the averaged WSS was 54 +/- 13 dyne/cm(2) in the arterioles and 24 +/- 4 dyne/cm(2) in the venules. The WSS in the second-order arterioles was significantly lower than that in the first-order branches, but the WSS in the first-order venules was similar to that in the second-order venules. The authors of this study believe that their system may be useful for further clinical investigation of the role of shear stress in the pathogenesis of various retinal disorders.

SOURCE: Nagaoka T, Yoshida A. Noninvasive evaluation of wall shear stress on retinal microcirculation in humans. Invest Ophthalmol Vis Sci 2006;47(3):1113-9.		 Table of Contents





BRIEFLY
  • BAUSCH & LOMB PULLS MOISTURELOC SOLUTION WORLDWIDE. Bausch & Lomb has permanently removed ReNu with MoistureLoc MultiPurpose Solution from the market. The product has been linked to an outbreak of Fusarium keratitis, although to date, no evidence has been found of product contamination, tampering, counterfeiting or sterility failure. "Bausch & Lomb"s top priority is the safety of our customers, and we want them to have complete confidence in our products," B&L chief executive Ronald Zarrella said. Federal health authorities recently announced that the number of confirmed cases of Fusarium keratitis is now at 122. Many of the confirmed cases involved contact lens wearers who reported using ReNu with MoistureLoc. The company halted U.S. sales of MoistureLoc on April 13 after the CDC said it was investigating an unusual spike in infections in Americans who said they’d used the product. B&L’s Zarella says that the FDA’s extensive investigation "confirmed our confidence in our other ReNu formulas" and that eyecare practitioners "can continue to recommend ReNu MultiPlus [products] with confidence" to their patients.
  • SURMODICS LICENSES OPHTHALMIC TECHNOLOGY TO BAUSCH & LOMB. SurModics, Inc. has granted Bausch & Lomb an exclusive license to patents relating to the use of Genistein in the treatment and prevention of retinal diseases, including diabetic macular edema. Genistein is a soy isoflavone with strong anti-oxidant and anti-VEGF activity that has been shown to reduce retinal vascular leakage in diabetic animals. Technology relating to the use of Genistein was among the those acquired by SurModics in connection with the acquisition of InnoRx in January 2005. Terms of the agreement were not announced.
  • STUDY PROVIDES A GLIMPSE OF THE "BIRTH" OF A RETINAL CELL. Scientists at the University of Michigan Kellogg Eye Center have observed the period of time during which embryonic retinal cells have been designated to play a particular role but have not yet begun functioning. The discovery provides new information on how the human visual system develops, and it raises the possibility that the production of cell types can be redirected as needed to prevent eye disease. The study focuses on the role of gene regulator Nrl, the earliest marker of rod precursors and proven to be essential in rod development. In a mouse model using an Nrl regulatory DNA sequence, investigators produced a protein that becomes fluorescent when exposed to blue light, allowing them to identify cells destined to be rods before they began functioning as such and to trace their differentiation into full-fledged rod cells. The research team also confirmed that a rod precursor will change course and acquire the identity of a cone in the absence of Nrl, implying the existence of progenitor cells that have the potential to become either type of cell. The study’s primary author, Anand Swaroop, PhD, Harold F. Falls Collegiate Professor of Ophthalmology and Visual Sciences and Professor of Human Genetics at Kellogg, believes that gene profiling of rods and cones in disease models may help researchers identify molecular targets for future drug treatments.

    SOURCE: Akimoto M, Cheng H, Zhu D, et al. Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors. Proc Natl Acad Sci USA 2006;103(10):3890-95.


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