EyeNet Magazine

News in Review
A Look at Today's Ideas and Trends
News in Review is edited by Brian A. Francis, MD, with assistance this month from Sharon Fekrat, MD.

Cardio Drug May Protect Diabetic Eye

Although laser treatment can slow or prevent further vision loss from diabetic retinopathy, it is frequently associated with visual field reduction and other ocular side effects. This adds urgency to the need for managing associated risk factors, such as hyperglycemia, high blood pressure or microalbuminuria. However, neither management of glycemia nor blood pressure has successfully prevented progression in the past.

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study examined whether long-term lipid-lowering therapy could reduce macrovascular and microvascular outcomes in type 2 diabetes, lessening progression of retinopathy and the need for laser treatment. This multinational five-year trial randomly assigned 9,795 patients with type 2 diabetes mellitus, ages 50 to 75, into two groups—those receiving fenofibrate 200 mg/day (n=4,895) or matching placebo (n=4,900).1

In the FIELD study, participants with greater clinical microvascular disease and those with poorer glycemic or blood pressure control required laser treatment more often than those with good control. Although the need for first laser treatment was significantly lower (P = 0.0002) in the fenofibrate group (3.4 percent) than in the placebo group (4.9 percent), there was no clear correlation between lipid concentrations and development of retinopathy requiring laser. The reduction in need for treatment was mainly associated with a lower prevalence of macular edema.

After four months of fenofibrate treatment, total cholesterol was reduced by 14 percent, LDL by 12 percent and triglycerides by 29 percent. HDL increased by 5 percent, but effects on individual lipid parameters were reduced over the course of the study. In addition, lipid concentrations at baseline did not appear to increase the likelihood of developing retinopathy requiring laser treatment.

In a substudy of 1,012 patients at 22 centers, the researchers assessed the cumulative incidence of diabetic retinopathy and its component lesions by using standardized retinal photography graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. The primary endpoint of two-step progression of retinopathy after at least two years did not differ significantly between the groups overall. Nor did it differ in a subset of patients without preexisting retinopathy. However, of those with preexisting retinopathy, significantly fewer participants on fenofibrate (3.1 percent) had a two-step progression than did those on placebo (14.6 percent).

These are impressive results, especially considering that the placebo group was already receiving a pretty good standard of care, said Karl G. Csaky, MD, PhD, director of Ophthalmic Clinical Trials Unit at the Duke Clinical Research Institute in Durham, N.C.

The study results presented other surprises, said Dr. Csaky, namely that the lipid-lowering strategy worked only for those who had developed retinopathy. “There really was no preventive benefit for someone without existing retinopathy.” The disconnect between serum lipid levels and progression of retinopathy was also surprising, he said. “This suggests that there is something about the lipid cascade and these agents that we don’t yet understand.”

This study brings attention to the issue of aggressive lipid lowering in patients with established diabetic retinopathy, said Dr. Csaky. “For my cardiology friends, I think we may be entering a world where the standard targets for lipids are continuing to be lower and lower,” he said. “We as ophthalmologists perhaps should be in on that discussion about how aggressively our patients need to be treated.”

—Annie Stuart

1 Keech, A. C. et al. Lancet 2007;370:1687–1697.


Retina Report 

Intravitreal Injections May Change Ocular Structure

Given the effectiveness of intravitreal pharmacotherapy to treat choroidal neovascularization and other diseases of the retina, it is not surprising that this treatment approach has become increasingly popular, with frequent, repeated injections commonly performed. Yet are these multiple intravitreal injections affecting the ocular structure?

A report by Ingrid E. Zimmer-Galler, MD, and colleagues out of the Wilmer Eye Institute1 indicates that structural changes such as increased temporal scleral reflectivity can, in fact, occur after multiple injections. “While we haven’t found any of these changes to be clinically significant,” Dr. Zimmer-Galler said, “it is important to know that we are changing the eye structurally, especially in light of the fact that most retina practices across the country are doing multiple intravitreal injections on a daily basis.”

In this prospective, nonrandomized study, Dr. Zimmer-Galler, associate professor of ophthalmology at Johns Hopkins, and colleagues used conventional and high-resolution ultrasound to examine 16 patients with neovascular age-related macular degeneration and choroidal neovascularization and a history of five or more intravitreal injections in one eye; they used the noninjected fellow eye as a control.

In these patients, a total of 112 intravitreal injections were delivered: 22 pegaptanib, 47 bevacizumab, 41 ranibizumab and two triamcinolone. The patients underwent an average of seven injections (with a range of five to 14 injections).

Results showed that 31 percent (five of 16) of the injected eyes but only 6 percent (one of 16) of the fellow noninjected eyes revealed focal increased temporal scleral reflectivity on ultrasound examination. The eyes with this finding underwent an average of nine intravitreal injections. In addition, 31 percent (five of 16) and 12 percent (two of 16) of fellow eyes were noted to have pars plana cysts, which were thought to be unrelated to intravitreal injections and are known to occur increasingly with age.

“The injections were made in the same quadrant, and with our limited data we do not have enough information to recommend that the injection site be changed to different quadrants with multiple injections,” she explained. “Thus, we don’t recommend changing practice patterns at the moment.”

Dr. Zimmer-Galler said this research will continue. “Our goal is to recruit a total of 50 patients. We also plan to study at least 50 patients with macular degeneration who have never had an intravitreal injection but are beginning a course of therapy with intravitreal injections. We plan to look at the ocular structure before and after multiple injections in these patients to determine if changes occur over time.”

—Lori Baker Schena


For more on intravitreal injections, see “Community Eye M.D.s Tackle the Intravitreal Injection”.

1 Presentation on Tuesday, Dec. 4, during the December 2007 annual meeting of the American Society of Retina Specialists, Indian Wells, Calif.


In the Pipeline 

Tear Testing in the Clinic

The increasing realization that dry eye consists of much more than inadequate lubrication has led to a new device that a San Diego company hopes will enable ophthalmologists to measure tear osmolarity easily in the office.

Although the company, OcuSense, does not initially intend to pursue a specific diagnostic label indication for dry eye, tear osmolarity is well-documented in the literature as an objective and quantitative measurement for the identification and management of patients suffering from dry eye disease.

OcuSense’s TearLab system is a “lab on a chip” that requires a tear sample of only 40 nl and just a few seconds to determine the concentration of dissolved salts in the tears. In dry eye, excess evaporation of water from the tear film, or insufficient tear production, raises the micromolar levels of these solutes in tears. This activates molecular inflammatory pathways, producing the surface inflammation characteristic of dry eye.

The idea that osmotic stress is involved in surface damage in dry eye patients was first proposed in 1941, but hyperosmolarity of the tears was not demonstrated until more recently. Those studies led to the development of hypotonic artificial tears, which have had limited acceptance because patients complain that they sting. In addition, they correct the osmotic balance only for the short time in which they remain on the ocular surface.

Currently available methods for detecting hyperosmolarity are impractical for routine clinical use because they require larger volumes of tears than are usually available in dry eye patients. Also, they are complex to perform and subject to evaporative corruption of the sample during handling or dilutional effect from stimulation reflex tearing during tear collection. Alternatively the tear samples, or the patient, would need to go to a reference lab for the testing. These problems have limited tear osmolarity to research settings.

A survey of the 1978 to 2005 medical literature1 calculated the mean osmolarity of normal tears at 302.2 milliosmoles (mOsM) per liter (SD 9.7), compared with 326.9 mOsM (SD 22.1) in dry eyes. OcuSense is planning a 600-patient study to develop more precise reference numbers for tear osmolarity at the four different stages of dry eye.

The company plans to introduce TearLab to the European market in mid-2008 and in the United States in late 2008 or in early 2009.

—Linda Roach


1 Tomlinson, A. et al. Invest Ophthalmol Vis Sci 2006;47:4309–4315.


Glaucoma Update 

Obese Kids Risk High IOP

It has been established that obesity in children can bring on a variety of health problems. The latest on the list may be an increase in IOP. The results of a Turkish study1 reveal that “in addition to its indirect effect on IOP via blood pressure change, obesity is also an independent risk factor for increased IOP.” This was the first published study that examined this relationship in children.

Forty-nine boys and 23 girls, ages 11 to 17 years, with a body mass index (BMI) in the 95th percentile or greater were compared with 72 age- and sex-matched controls. In addition to finding that the mean IOP between the obese children and controls was significantly different, the researchers found both diurnal variation of IOP and Hertel values were higher among the obese children: 18 percent had a diagnosis of bilateral exophthalmos. Systolic blood pressure and diastolic blood pressure were also significantly higher.

“While these are interesting findings, we do not know how this affects the risk for the development of glaucoma later in life,” said Michael X. Repka, MD, professor of ophthalmology and pediatrics at Johns Hopkins University.

The investigators point out that IOP is usually only slightly increased in obese children. As a result, the signs and symptoms of elevated IOP are often lacking and, therefore, repeated IOP measurements may be necessary for these children. However, said Dr. Repka, “we do not routinely measure intraocular pressure in obese children, which highlights the need for additional studies to fully characterize this issue. The results of this study should remind clinicians who are managing overweight children and teenagers about the risk of increased pressure associated with weight, as well as increased systolic and diastolic blood pressures. If you treat an obese child with increased IOP, remind the parents that the child’s blood pressure needs to be checked periodically.”

—Leslie Burling-Phillips


1 Akinci, A. et al. J Glaucoma 2007;16:627–630.


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