JOURNAL CLUB

RECENT NOTEWORTHY STUDIES TO STIMULATE DISCUSSION AND DEBATE

■ Chinese AMD study. Scientists collaborating among China, Singapore, and Australia recently completed one of the largest studies of cardiovascular risk factors and early age-related macular degeneration. Their study confirmed earlier findings connecting smoking and cardiovascular disease and AMD.

More than 6,500 people at least 30 years old had their cardiovascular risk factors assessed, as well as serum lipid measurements, plasma glucose, and urinalysis. After acquiring fundus photographs of the subjects, the authors performed regression analysis to identify correlations.

Two hundred of the subjects were found to have early AMD, and age, hypertension, heart disease, and smoking were correlated with an increased risk of developing AMD, as well as soft drusen. In addition, smoking was associated with hypopigmentation, while age and cardiovascular disease were associated with large drusen.

The study adds to the growing body of evidence indicating clear links between smoking and cardiovascular disease and AMD.

Yang K, Wang F-H, Liang Y-B, et al. Associations between cardiovascular risk factors and early age-related macular degeneration in a rural Chinese adult population. Retina. 2014;34:1539-1553.

■ Combination anti-VEGF and navigated laser. In a pilot study examining combined use of bevacizumab (Avastin, Genentech, South San Francisco, CA) and navigated laser photocoagulation, retinal physicians from five countries found that a decreased number of injections was necessary for DME.

The charts and imaging results of 23 patients with DME were retrospectively reviewed. All of the enrolled eyes received intravitreal injections of bevacizumab, followed by navigated laser once central retinal thickness was <440 µm.

The vision gain from bevacizumab alone was 10.4 ETDRS letters, with a central retinal thickness reduction of 146 µm. At 12 months following laser, the vision gain decreased but nonsignificantly, while the reduction in central retinal thickness improved to 125 µm.

Moreover, while patients required an average of 4.4 injections during the first year following the first bevacizumab injection, for the year following navigated laser treatment, this number decreased to 1.3 injections, with 57% requiring no further injections at all.

While the study was limited by its retrospective nature, the authors believe that navigated laser could play a major role in stabilizing the vision gains achieved with anti-VEGF drugs.

Barteselli G, Kozak I, El-Eman S, Chhablani J, Cortes MA, Freeman WR. 12-month results of the standardised combination therapy for diabetic macular oedema: intravitreal bevacizumab and navigated retinal photocoagulation. Br J Ophthalmol. 2014;98:1036-1041.

■ OCT for retinal vascular assessment. In an attempt to determine whether spectral-domain OCT could be used to measure retinal vessel diameters, doctors in Berlin undertook a retrospective review of all patients with OCT scans in their medical files that were centered on the optic nerve head.

Scans from 13 eyes of 12 patients were included in the study, of which 194 retinal vessels >40 µm were examined. The mean vessel width was 107.9±36.1 µm, the mean vertical contour diameter was 119.6±29.9 µm, and the mean horizontal contour diameter was 124.1±13.1 µm.

Vertical contour diameter did not differ from vessel width; horizontal contour diameter was not significantly different from width for arteries, but it was very strongly correlated with the width of veins.

The authors see potential for SD-OCT in the assessment of patients with retinal vascular diseases, although significantly more data are needed.

Ouyang Y, Shao Q, Scharf D, Joussen AM, Heussen FM. Retinal vessel diameter measurements by spectral domain optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2014 Aug 17. [Epub ahead of print]

■ Duration of VEGF blockade. Aflibercept (Eylea, Regeneron, Tarrytown, NY) is undoubtedly effective in blocking VEGF intraocularly, but for how long does its suppression last?

To answer that question, scientists in Cologne, Germany, examined the eyes of 27 patients receiving PRN aflibercept for AMD. The authors obtained a total of 132 aqueous humor specimens from the included eyes before aflibercept injection, and the levels of VEGF-A were assessed by multiplex bead analysis.

Before the first aflibercept injection, the mean VEGF-A level was 90.6±37.1 pg/mL, which was suppressed to unmeasurable levels in all 27 patients. The level remained suppressed for >71±18 days, with only one patients experiencing suppression of less than 56 days.

The authors believe that their study could support a recommendation to administer aflibercept every eight weeks, rather than the six-week interval currently recommended on its label.

Fauser S, Schwabecker V, Muether PS. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol. 2014;158:532-536.

■ PPV with and without retinotomy. To compare the outcomes of pars plana vitrectomy with and without retinotomy, surgeons in Tel Aviv conducted a four-year retrospective survey and examined primary and final anatomic success and BCVA.

Ninety-eight of 102 patients were included in the study, with 43 in the retinotomy group vs 59 in the nonretinotomy group. At a mean follow-up of 18 months, primary anatomical success was achieved in 76.7% and 67.8% of the retinotomy and nonretinotomy groups, respectively, with the final success rates increasing to 100% and 93.2%; however, the differences were not statistically significant. Final BCVA was 1.5 logMAR with retinotomy and 1.38 logMAR without, indicating similar efficacy.

Because the outcome were so similar regardless of whether the eye received retinotomy or not, the authors recommend that the matter be left to the discretion of the individual surgeon.

Frenkel T, Moisseiev E, Neudorfer M, Loewenstein A, Barak A. Comparison of retinal detachment surgery outcome among patients undergoing pars plana vitrectomy with and without relaxing retinotomy. Graefes Arch Clin Exp Ophthalmol. 2014 Aug 21. [Epub ahead of print]

■ Gene found in retinal degeneration cases. Mutations in the AIPL1 gene have been implicated in Leber congenital amaurosis and autosomal-dominant cone-rod dystrophy. With an autosomal-recessive retinal degeneration diagnosed in two consanguineous families in Pakistan, a diverse team of scientists collaborated to determine the genotype and found this gene implicated.

Genomic DNA from blood samples were submitted to genomic analysis and sequencing for the detection of candidate genes. In addition, members of both families underwent ophthalmic examinations. Ultimately, a novel mutation in the AIPL1 gene was identified in members of both families.

Although the case examined was comparatively small, the study not only has implications for populations of South Asian descent, but it also identifies the relationship of mutations in an already-known gene with a previous unknown phenotypic presentation.

Li D, Jin C, Jiao X, et al. AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration. Mol Vis. 2014;20:1-14.

■ Treat and extend in Australia. A team of retinal physicians in Victoria, Australia, is the latest group to add to the growing body of data indicating that treat-and-extend administration of ranibizumab (Lucentis, Genentech) or bevacizumab offers equivalent outcomes to monthly dosing with fewer injections.

In a prospective cohort study, the authors gave three monthly loading doses of either drug to 120 patients with AMD. After reversal of choroidal neovascularization, the interval between subsequent doses was increased by two weeks to a maximum of 12 weeks, while if CNV recurred, the interval was shortened by two weeks.

Visual acuity improved by an average of 9.5±10.9 ETDRS letters at 12 months and by 8.0±12.9 letters at 24 months. Moreover, the mean number of injections decreased from 8.6±1.1 during the first year to 5.6±2.0 during the second.

The chief strength of the Australian study is that it is the first to report two-year prospective data on a treat-and-extent protocol. While it was limited by its lack of a control arm, the study does increase the weight of the evidence supporting such a protocol.

Abedi F, Wickremasinghe S, Islam AFM, Inglis KM, Guymer RH. Anti-VEGF treatment in neovascular age-related macular degeneration. A treat-and-extend protocol over 2 year. Retina. 2014;34:1531-1538.

■ More from Down Under. In Sydney, Australia, researchers conducted a literature review to determine how well investigators in randomized, controlled trials are reporting negative side effects. To determine this, they applied the recommendations of the Consolidated Standards of Reporting Trials (CONSORT) statement.

Choosing as a topic the use of intravitreal injections for diabetic macular edema, the authors found 36 studies enrolling more than 7,000 eyes. Of the 10 recommendations made in the CONSORT statement, the median number met by the 36 studies was six. Ninety-seven percent of the articles described how harm-related information was collected, while only 31% addressed adverse events with definitions of each, and 36% described patient withdrawals due to harm. The mean percentage of discussion sections devoted to discussing adverse events was 25.8%.

The authors conclude that reporting of adverse events in DME trials is inadequate, despite recent attempts to standardize them. They suggest that the relative complexity of the CONSORT statement may be the issue, and they indicate that better itemization of the statement could help. RP

O’Day R, Walton R, Blennerhasset R, Gillies MC, Barthelmes D. Reporting of harms by randomised controlled trials in ophthalmology. Br J Ophthalmol. 2014;98:1003-1008.