Volume 10, Number 38
Monday, September 27, 2010

In this issue: (click heading to view article)
From the Editor: McDonald's in Rome

Isometric Exercise and Choroidal Blood Flow in Patients with AMD

Symptomatic Dry Eye and Its Influence on Vision-Related Daily Activities
Relationship of AMD with Polymorphisms in VEGF and its Receptor
Evaluating Stereoscopic Color Fundus Photographs and Fluorescein Angiograms Using Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study System
Briefly


From the Editor: McDonald's in Rome

Recently, my wife and I had the distinct pleasure to travel to Italy to experience la dolce vita. While walking about Rome, I was impressed at how many McDonald's restaurants there are in a city where drop-dead good food exists. With all due respect to the McDonald's food corporation, I could not connect the dots, but let me assure you every McDonald's we passed was busy.

I was equally impressed and concerned at what we observed walking around various cities. The world is a bit overweight. It depresses me. I am concerned that the way the world eats is changing. Processed foods seem to play a greater role in our diets. That is not good. As a physician, I recognize the potential harm to one's health as well as the potential financial burden to society and governments if this is allowed to continue. My wife drags me to the gym three days a week for an encounter with our trainer and we cycle two days a week. It is hard work and it takes dedication, but frankly, I have never felt better. Why is an ophthalmologist concerned about this? It is because I am first and foremost a physician and I am concerned about everyone"s health and welfare. Enough said . . .

Stephen Pascucci, MD, FACS


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Isometric Exercise and Choroidal Blood Flow in Patients with AMD

To investigate choroidal vascular regulation in age-related macular degeneration (AMD), the regulatory responses induced by isometric exercise in control subjects and patients with AMD were compared. The study results suggest that the response of the choroidal circulation to this type of isometric exercise resulting in a moderate increase in blood pressure does not seem to be affected by AMD.

Included in this study were 17 eyes of 17 patients with dry AMD in the study eye and 19 eyes of 19 controls. Both groups were well matched for age, race and sex. Brachial artery blood pressure determinations and laser Doppler flowmetry (Oculix) measurements of relative foveolar choroidal blood velocity, volume and flow were obtained in the study eye of each subject during 30 x of baseline, and then during 3 min of isometric exercise consisting of squeezing a handgrip in each hand. It was reported that similar measurements were then also obtained during the 2 min following the cessation of exercise and using non-paired, two-tailed t test, changes in circulatory parameters during exercise and following the end of exercise were compared between AMD patients and control subjects. Additionally, the slop for the relationship between circulatory changes and perfusion pressure changes was calculated and compared between patients with AMD and controls using linear regression analysis. Analysis of data was performed in a masked fashion.

No statistically significant differences between the changes in choroidal blood velocity, volume and flow were observed in control subjects and patients with AMD during the isometric exercise phase and after exercise.

SOURCE: Metelitsina TI, Grunwald JE, DuPont JC, Ying GS. Effect of isometric exercise on choroidal blood flow in patients with age-related macular degeneration. Br J Ophthalmol 2010;Sept 13 [Epub ahead of print].

http://www.revophth.com/email/0910AAOmtgs216_RP.html






Symptomatic Dry Eye and Its Influence on Vision-Related Daily Activities

The authors of this population-based survey of eye diseases sought to examine the impact of symptomatic dry eye on vision-related daily activities in 3,280 (78.7% response rate) Malay persons aged 40 years, who were randomly selected from designated areas in southwestern Singapore.

They administered to participants a standardized dry eye questionnaire consisting of six questions on symptoms and a questionnaire on vision-related daily activities; they also conducted a comprehensive systemic and ocular examination of participants. The authors defined symptomatic dry eye as one or more self-reported symptoms that were frequently present (ranked as often or all the time) and used logistic regression method to examine the relationship of symptomatic dry eye with difficulty in performing daily activities.

They reported that in adults without visual impairment, symptomatic dry eye after adjusting for age, gender and presenting visual acuity was significantly associated with difficulty in vision-related activities such as navigating stairs (odds ratio [OR]=1.96, 95% confidence interval [CI]: 1.28–3.00), recognizing friends (OR=1.99, 95% CI: 1.45–2.73), reading road signs (OR=1.87, 95% CI: 1.36–2.57), reading newspaper (OR=1.50, 95% CI: 1.11–2.04), watching television (OR=1.90, 95% CI: 1.26–2.87), cooking (OR=1.94, 95% CI: 1.02–3.71) and driving at night (OR=2.06, 95% CI: 1.32–3.21).

To conclude, the authors associated symptomatic dry eye with difficulty in performing vision-dependent tasks, independent of visual acuity and other factors. These findings have public health significance and suggest that the visual dysfunction in dry eye should be further characterized.


SOURCE: Tong L, Waduthantri S, Wong TY, et al. Impact of symptomatic dry eye on vision-related daily activities: The Singapore Malay Eye Study. Eye 2010;24(9):1486–1491.

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Relationship of AMD with Polymorphisms in VEGF and its Receptor

Italian investigators sought to analyze the association between age-related macular degeneration (AMD) and polymorphisms in vascular endothelial growth factor (VEGF) and VEGF receptor KDR gene polymorphisms in this case-control study. They note that previous investigated the possible association between VEGF-A gene polymorphisms and AMD, with contrasting data, but that no study examined the possible role of VEGF receptor KDR gene polymorphisms.

The study investigators enrolled 226 AMD cases and 148 controls from an ophthlamology hospital center and employed genotyping for 16 polymorphic markers (single nucleotide polymorphisms [SNPs] in VEGF-A and KDR genes. Main outcome measures were distribution of genotypes in AMD cases and controls.

Two polymorphisms (rs833069 in intron 2 of the VEGF-A gene, rs2071559 in the promoter of the KDR gene) were significantly associated with risk of AMD, according to the investigators. In particular, for VEGF-A rs833069 the AMD risk was increased >5-fold for G homozygotes compared with homozygous carriage of the A allele, they found. For KDR rs2071559, the AMD risk was increased >3-fold for T homozygotes compared with homozygous carriage of the C allele. The investigators determined that carriers of risk alleles for both markers have a >6-fold increased risk of AMD with respect to carriers of non-risk alleles.

They report that their study expands previous data on the association of AMD with VEGF-A gene variations and identifies for the first time an association with variations in the KDR gene. Because the SNP-604T-bearing KDR promoter has higher transcription activity, their findings further support the role of the VEGF pathway in the pathophysiology of AMD. The investigators conclude that it is possible that applications of haplotype/genotype analysis in these genes will play a role in risk assessment and pharmacogenomic approaches to AMD diagnosis and management.

SOURCE: Galan A, Ferlin A, Caretti L, et al. Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor. Ophthalmol 2010;117(9):1769–1774.















Evaluating Stereoscopic Color Fundus Photographs and Fluorescein Angiograms Using Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study System

In this paper, researchers sought to describe the procedures and reproducibility for grading stereoscopic color fundus photographs and fluorescein angiograms of participants in the SCORE Study and found that such grading procedures are reproducible and can be used for multicenter longitudinal studies of RVO. They also found that a systematic temporal drift occurred in evaluating area of retinal thickening.

Standardized stereoscopic fundus photographs and fluorescein angiograms taken at 84 clinical centers were evaluated by graders at a central reading center, the researchers noted. Type of retinal vein occlusion (RVO), area of retinal thickening and area of retinal hemorrhage are evaluated from fundus photographs; area of fluorescein leakage and area of capillary nonperfusion are measured on fluorescein angiography. The researchers reported that temporal reproducibility consisted of annual regrading of a randomly selected dedicated subset of fundus photographs (60 subjects) and fluorescein angiograms (40 subjects) for three successive years. Contemporaneous reproducibility involved monthly regarding of a 5% random selection of recently evaluated fundus photographs (n=73).

According to the study researchers, the intergrader agreement for RVO type and presence of retinal thickening was greater than 90% in the three annual regrades. They also observed that the intraclass correlation (ICC) for area of retinal thickening in the 3 years ranged from 0.39 to 0.64 and for area of retinal hemorrhage, 0.87 to 0.96. Furthermore, the ICC for area of fluorescein leakage ranged from 0.66 to 0.75 and for capillary nonperfusion, 0.94 to 0.97. The contemporaneous reproducibility results were similar to those of temporal reproducibility for all variables except area of retinal thickening (ICC, 0.84).

SOURCE: Blodi BA, Domalpally A, Scott IU, et al. Standard care vs corticosteroid for retinal vein occlusion (SCORE) study system for evaluation of stereoscopic color fundus photographs and fluorescein angiograms. Arch Ophthalmol 2010;128(9):1140–1145.


  • TOBRADEX ST SUSPENSION NOW AVAILABLE IN THE U.S. Alcon has launched its new combination anti-inflammatory/anti-infective product, TobraDex ST (tobramycin/dexamethasone ophthalmic suspension) 0.3/0.05% in the United States. The suspension, indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or risk for infection risks, was formulated to enhance bioavailability to targeted tissues. Furthermore, according to the company, TobraDex ST is formulated with low viscosity in the bottle, allowing for easier dispensing. Find out more by clicking here.
  • SCIENTISTS AT ST. JUDE CHILDREN'S RESEARCH HOSPITAL SHARE FINDINGS RELATED TO RETINAL DEVELOPMENT. A new press release from St. Jude Children's Research Hospital reads that new research led by investigators at the hospital adds to evidence that in the developing brain and visual system, the Six3 gene safeguards the future retina by keeping the region where the eye is forming free of a signaling protein capable of disrupting the process. The study investigators showed that when Six3 was switched off at a key point in mouse embryonic development, the retina did not form. The investigators further strengthened this association when they found that the retinal pigment epithelium was largely unaffected by the gene's absence. They also directly linked the lack of a retina to the abnormal expansion of Wnt8b (of the Wnt family of signaling proteins) expression into a region where the forebrain normally develops and are now working to understand the pathway activated when Six3 blocks Wnt8b.
  • OPTOVUE'S NORMATIVE DATABASE NOW FDA CLEARED. Optovue, Inc. has received 510(k) clearance on its Normative Database (“NDB”) for the RTVue OCT device, which comprises more than 600 eyes for the pending U.S. release. According to the company, it is the largest FDA-cleared NDB for an OCT device. Optovue plans on releasing the RTVue application update containing the newly cleared NDB for customers in the next few weeks. For more information, click here.
  • BAUSCH + LOMB ACQUISITION OF MIOCHOL-E ASSETS AND INTELLECTUAL PROPERTY COMPLETE, LRI MARKER RELEASED IN U.S. In a recent news release, Bausch + Lomb has announced that it has concluded its worldwide acquisition of the assets and intellectual property for Miochol-E from Affiliates of Novartis AG. (Miochol-E is an injectable miotic pharmaceutical used during ocular surgery to constrict the pupil.) Under the terms of the agreement, Novartis will provide Bausch + Lomb with assistance in the transfer of Miochol-E manufacturing. No further details on purchase terms have been disclosed by either company.

    Bausch + Lomb Storz Ophthalmic Instruments also had a recent announcement: that its E2427 Whitman Double-Ended LRI Marker for LRI procedures is now available in the United States. The double-ended LRI marker, designed using chord lengths for treatment parameters as opposed to degrees, has two astigmatic dials, which cover a wide range of dioptric treatments with one end marked for 3 mm, 5 mm and 7 mm lengths and the other marked for 4 mm, 6 mm and 8 mm lengths. According to the company, both ends include corresponding raised marks on the underside of the dial and, in addition to use in the LRI procedure, the central mark to note axis makes the instrument ideal for marking toric lens implants. Learn more, or view a video of the instrument in surgery by visiting www.storzeye.com.
  • 2010 LASKER AWARD HONORS FERRARA FOR WORK WITH VEGF. Since 1945, the Lasker Awards Program has recognized the contributions of scientists, physicians and public servants who have made major advances in the understanding, diagnosis, treatment, cure and prevention of human disease. The winner of the 2010 Lasker–DeBakey Clinical Medical Research Award is Napoleone Ferrara, for the discovery of vascular endothelial growth factor (VEGF) as a major mediator of angiogenesis and the development of an effective anti-VEGF therapy for wet age-related macular degeneration (AMD). Ferrara's work has uncovered the lynchpin for one of the body's most important physiological processes and unlocked a novel approach for combating a serious eye disorder. In 1994, when Ferrara turned his work toward retinal disease, he and Lloyd Paul Aiello analyzed fluid from the eyes of patients with retinal disorders that stemmed from different underlying causes. They found that VEGF appearance correlated with conditions that involve formation of new blood vessels, but not with other illnesses. Working with colleagues in 2000, Ferrara began wet AMD clinical trials with an anti-VEGF antibody. To learn more about Ferrara's work, click here.

    Other 2010 winners include Douglas Coleman and Jeffrey Friedman (Albert Lasker Basic Medical Research Award) for the discovery of leptin, a hormone that regulates appetite and body weight; and David Weatherall (Lasker–Koshland Special Achievement Award in Medical Science) for 50 years of international statesmanship in biomedical science, exemplified by discoveries concerning genetic diseases of the blood and for leadership in improving clinical care for thousands of children with thalassemia throughout the developing world.


 

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