Article Date: 1/1/2010

Recent noteworthy studies to stimulate discussion and debate.

Recent noteworthy studies to stimulate discussion and debate.

New life for Visudyne? Though intravitreal anti-VEGF agents have eclipsed it, verteporfin/PDT (Visudyne) is still used in combination regimens for wet AMD. However, the interest in VEGF's role in AMD has complicated factors for verteporfin/PDT because a series of studies demonstrated that the drug actually enhances VEGF expression in choroidal neovascular membranes.

Now, a study in the November 2009 issue of Acta Ophthalmologica indicates that verteporfin may have a protective role against VEGF synthesis. A team of Turkish ophthalmologists studied 42 rabbit eyes, dividing them into three groups: a verteporfin/PDT group; an infusion group receiving verteporfin without PDT; and a control group. One eye of each animal was covered with Visudyne eyeglass and the other was closed with sutures. Animals were exposed to sunlight for 30 minutes at two hours and 48 hours following infusion. At 48 hours, sutures and eyeglass were both removed. Enucleation was performed on half the animals on day 5 and the other half on day 10. Day 5 and day 10 mean VEGF were then measured in all eyes.

While there was no statistically significant difference in VEGF levels between the glass and suture subgroups at day 5, at day 10 VEGF levels were higher in the irradiation/ eyeglass group than in the irradiation/suture group.

The study authors state that their trial constitutes proof that Visudyne eyeglass offers protection against the VEGF increases that verteporfin may cause, but it is only partially protective in eyes that are subjected to PDT. They recommend that physicians performing verteporfin/PDT patch irradiated eyes to avoid excess VEGF expression.

More good news for Avastin. Interim data from the CATT study is expected later this year, but studies continue to appear that suggest that bevacizumab may not pack the systemic wallop that many ophthalmologists feared it would. A group of retinal physicians in South Korea enrolled 135 patients, both with and without high blood pressure, in a six-month study of a single 1.25-mg injection of bevacizumab for a number of retinal vascular diseases. The doctors measured IOP and blood pressure before the injection and then at 30 minutes, one day, one week and three weeks postinjection. They were also followed monthly after the three-week mark. The results of the study can be found in the November/December 2009 issue of Retina.

Not surprisingly, even though all patients with hypertension were taking medication for their conditions, baseline blood pressure was higher in that group. However, the study found no significant increases in either systolic or diastolic blood pressure at any time after the initial injection. The group did find in the nonhyptertensive patients that 30-minute mean systolic measurements were higher than baseline and that one-day mean diastolic values were higher in this group as well. IOP in both groups increased at the 30-minute mark but had fallen below baseline means at day one and day three.

The authors of the study suggest that the 30-minute rise in blood pressure in patients without high blood pressure and subsequent one-day drop may be a result of the so-called white coat syndrome, rather than the result of bevacizumab injection. IOP elevations were expected and related to varying intraocular volumes. Finally, the authors recommend more studies of blood pressure in patients receiving injections of bevacizumab, particularly in those patients receiving repeat injections.

Erythropoietin safe for intravit injection. Erythropoietin was identified in a 2005 article in the New England Journal of Medicine as playing a role in the treatment of diabetic retinopathy. A glycoprotein important to the production of hemoglobin, erythropoietin has been investigated since then in many models of retinal vascular disease.

Now, a German study published in the December 2009 British Journal of Ophthalmology has found that erythropoietin is safe for intravitreal use. Although the study was very small (three patients with posterior vascular occlusions), the authors used a variety of monitoring techniques (ERG, visual acuity, visual fields, blood testing) to track patients receiving injections of erythropoietin over three months.

In concluding that this single injection of 2000 IU is safe, the study authors urge further in vivo experimentation with erythropoietin. As the protein is already being used in a number of human clinical trials, primarily for oncology, the authors are hopeful more research will be undertaken.

OCT vs FA vs the sun. Recent articles in different journals come to different conclusions about the efficacy of OCT in comparison to fluorescein angiography. The first, from the October 2009 Ophthalmology, suggests that OCT is a good noninvasive alternative to FA, after looking at 124 eyes in 63 patients with diabetic retinopathy and finding a high correlation between damage to the foveal avascular zone detected using both technologies.

By contrast, a report in the September/October 2009 European Journal of Ophthalmology reporting on the use of both technologies in patients with wet AMD undergoing PDT came to the opposite conclusion. While OCT demonstrated good sensitivity in detecting active neovascularization in 14 patients studied, its specificity was rated as only moderate. The authors of the EJO study urge that OCT not be used as a substitute for FA; rather, they suggest, it should be used as an adjunct. RP

Retinal Physician, Issue: January 2010