JOURNAL CLUB

RECENT NOTEWORTHY STUDIES TO STIMULATE DISCUSSION AND DEBATE

■ Anti-VEGF in DME. In a systematic review of the use of VEGF inhibitors in DME, two retinal physicians report, in the February 2012 issue of the British Journal of Ophthalmology, that these drugs are more effective in the long term than other treatments. The European authors, collaborating between Austria and Croatia, compared improvement in visual acuity and quality of life, plus side effects in studies taken from a literature search conducted in several databases.

Analyzing a total of 11 articles, the authors found that, on average, 25% of the patients treated with VEGF inhibitors had better VA results than patients being treated with laser photocoagulation. However, there were insufficient data to determine whether VEGF inhibitors could claim long-term efficacy, nor could the authors definitively determine whether these drugs are safe in patients with DME.

Nevertheless, the authors did find significant evidence that ranibizumab is effective in the treatment of DME. They are circumspect in recommending off-label use of the drug, but they do cite recent head-to-head comparison studies of anti-VEGF agents to provide evidence for ranibizumab’s overall safety.

■ Nepafenac for postop macular edema. Postoperative macular edema following vitreoretinal surgery remains a problem for many patients. Topical nonsteroidal anti-inflammatory drugs and corticosteroids are typically used to treat this condition. Nepafenac has been used for several years to treat postop inflammation following cataract surgery. In a study published in the February 2012 issue of Retina, a team of doctors from India report their results from testing this NSAID in post–vitreoretinal surgery macular edema.

One hundred twenty eyes of 120 patients who underwent vitreoretinal surgery were randomized to receive either nepafenac or placebo. The eyes were evaluated on the day following surgery and then at two-week intervals to eight weeks to determine retinal thickness and BCVA.

The inflammation scores of the patients receiving nepafenac were significantly better on the day following surgery than the scores of the patients receiving placebo. However, there were no statistically significant differences in central macular subfield thickness between the study groups, nor was there a significant difference in BCVA at one month.

The authors conclude that nepafenac is safe and effective in reducing postoperative pain and inflammation in patients undergoing vitreoretinal surgery, but its effects on reducing postop macular edema and improving visual acuity are no better than the standard post-vitrectomy regimen that is commonly administered.

While studies have confirmed nepafenac’s usefulness in post–cataract surgery macular edema, it has not demonstrated such efficacy following vitreoretinal procedures.

■ Microperimetry in RVO. Visual acuity following treatment for retinal vein occlusion (Figure 1) cannot be correlated with objective measurements, so the search for measurements that will correlate with VA continues. A team of German ophthalmologists undertook a study to determine whether microperimetry would fit that bill. They report their findings in the February 2012 issue of Graefe’s Archive of Clinical and Experimental Ophthalmology.

Figure 1. Central retinal vein occlusion with macular edema in the left eye of a patient with hypertension. COURTESY OF JOHN A . WELLS, III, MD

In a prospective case series of 13 patients, the authors tested microperimetry, as well as visual acuity, reading ability and central retinal thickness as measured on optical coherence tomography. All of the patients were treated with intravitreal bevacizumab, combined with panretinal laser in cases for peripheral ischemia. If macular edema persisted, the patients could be treated with triamcinolone acetonide as well. The patients were grouped based on whether their RVO was a central or branch RVO.

In both groups combined, micro-perimetry detected statistically significant changes at six-month follow-up, while none of the other measurements did. When the groups were evaluated separately, the only significant change seen in the branch RVO group was microperimetry sector, from 6.02 decibels to 9 decibels on average (P =.025). There were no significant changes in the central RVO group.

The study authors are guarded in their conclusions, but they do suggest that microperimetry could be a useful adjunct in the follow-up for branch RVO in the future. Further studies are required.

■ New triple therapy data. As the quest for an effective treatment for refractory DME continues, triple therapy has emerged as a common approach. Retina recently published online the results of a study conducted in Hong Kong, applying triple therapy consisting of high-dose sub-Tenon’s triamcinolone (70 mg), 1.25 mg intravitreal Avastin and laser photocoagulation.

Twenty-nine eyes of 29 patients were followed for one year while receiving triple therapy. Their central foveal thickness, BCVA and adverse events were recorded, and these results were compared with an historical control group that consisted of 18 eyes of 18 patients who had been treated with focal/grid laser.

The triple therapy group experienced a statistically significant reduction in central foveal thickness at the one-year mark, from 441 µm to 298 µm. However, there was no significant change in BCVA at that time point, although a subgroup analysis of seven eyes with the worst baseline BCVA from the triple therapy group revealed a significant improvement in BCVA between one and nine months. Furthermore, the greatest gain in BCVA was seen at six months, when there was a mean gain of 9.5 ETDRS letters. The most common adverse events were increased IOP (31.0%), partial ptosis (17.2%) and cataracts (8.7%).

The authors conclude that triple therapy could be effective in reducing central foveal thickness and improving BCVA in patients with refractory DME and baseline BCVA worse than 20/200. However, they concede that more studies, involving a greater number of patients, are required.

■ Pediatric diabetic retinopathy. Retinal physicians are most accustomed to treating diabetic retinopathy (Figure 2) in elderly and/or overweight adult patients. How does the treatment differ when the patient is a child? Ophthalmologists in the United Kingdom and in New York collaborated on a review of the scholarship on pediatric treatment of diabetic retinopathy, publishing their work in the March 2012 issue of the British Journal of Ophthalmology.

Figure 2. In more advanced cases of diabetic retinopathy, there are many microaneurysms and hemorrhages.

Regarding the epidemiology of DR in children, the authors report that in the nearly two decades since the Diabetes Control and Complications Trial was launched, the prevalence of this condition has decreased. There is also greater understanding of the risk factors for pediatric DR, such as poor glycemic control, elevated blood pressure and other factors, as well as genetic factors, including enzymes involved in glucose and lipid metabolism.

Regarding the condition’s etiology, pathophysiology and clinical manifestations, much of the review is nonspecific, but the section on diagnosis is particularly valuable. The authors recommend yearly screening in pediatric patients with diabetes, and they note that mydriatic fundus photography is particularly useful for these screenings, which should begin two to five years after the diagnosis of diabetes.

Finally, regarding treatment, the authors note the relatively long natural history of DR as the principal factor in treatment for DR in children usually not being required before puberty. In addition, few children will develop DR severe enough to require treatment, although laser is recommended if treatment is warranted.

■ Injection masking. The February 2012 issue of Archives of Ophthalmology features a brief study of the efficacy of masking patients in clinical trials to the drug (or sham) with which they are being injected intravitreally. The participants were given Lucentis, Avastin, triamcinolone or a sham injection. Of the 423 participants, correct group assignment was identified by 9.9% of placebo recipients vs between 88% and 90% for patients receiving anti-VEGF agents and 44.0% for patients treated with intravitreal triamcinolone. If the patient had two study eyes, s/he had a 24.1% likelihood of identifying him-/herself as a placebo recipient. The authors recommend following procedures to the letter with placebo groups to increase the efficacy of masking. For intravitreal injections, this would consist, in part, of pressing the syringe hub against the conjunctiva to simulate an actual injection. RP