Article Date: 5/1/2010

JOURNAL CLUB

JOURNAL CLUB

Recent noteworthy studies to stimulate discussion and debate

Shorter laser duration, shorter recovery. Laser panretinal photocoagulation remains the standard of care for diabetic retinopathy, and among the newest innovations in that field is a 100-msec higher-fluence laser. However, some studies have suggested that these lasers may lack long-term therapeutic effects. Pascal PRP with Nd:YAG laser, which produces 20-msec burns, was compared head to head with 100-msec laser in a trial conducted by physicians in Manchester, United Kingdom.

The study authors, who published their data in the April 2010 issue of Archives of Ophthalmology, tested both types of lasers on 24 eyes with proliferative diabetic retinopathy. All patients were treatment-naïve. The authors report that 20-msec laser and 100-msec laser produced burns that appeared the same on initial examination with optical coherence tomography and fundus autofluorescence. However, after the four-week mark, 20-msec burns had decreased in size by 35%, while the 100-msec burns had remained the same.

The authors believe that the progressive reduction in the size of the Pascal 20-msec burns indicates a healing response localized to the junction of the inner and outer segments of the photoreceptors and apical retinal pigment epithelium. They suggest that retinal physicians may want to consider titration of laser fluence to achieve threshold burns and healing responses in the outer retina.

Lucentis for PCV. Seeking to determine whether ranibizumab is an effective treatment for polypoidal choroidal vasculopathy, scientists from Hawaii and Taiwan collaborated on a small trial, dubbed the PEARL trial, of 12 patients, reporting their findings in the March 2010 issue of the British Journal of Ophthalmology.

Patients were treated with monthly injections of 0.5 mg ranibizumab, and data were collected at the six-month point. Study subjects were also examined with OCT at six months and with fluorescein angiography and indocyanine green angiography at one, three and six months.

Five of eight patients who had subretinal fluid at baseline experienced a reduction, and four of five patients with baseline macular edema experienced improvement. On the downside, however, only four of the full cohort of patients experienced a decrease in polypoidal complexes amounting to regression. As the PEARL trial continues to recruit, more results are expected in the coming months and years.

Looking forward. A pair of articles in the May 2010 issue of Current Opinions in Ophthalmology look at the present and future of retinal disease and its treatment. In the first article, Gary Brown, MD, and Melissa M. Brown, MD, of Philadelphia's Wills Eye Institute and Scheie Eye Institute, respectively, issue a call to US physicians — both ophthalmologists and general practitioners — to improve the quality of life of Americans with age-related macular degeneration.

The Drs. Brown reports that ophthalmologists routinely underestimate the quality-of-life decline associated with AMD by as much as 750%, with the tendency to underestimate more as visual acuity improves, while other physicians have so little knowledge about how AMD affects quality of life that they equate it carpal tunnel syndrome and kidney stones. Thus, the problem has two prongs within the medical community.

The authors recommend that ophthalmologists be better able to rate quality of life by taking into account comorbid conditions such as psychiatric depression, and that general practitioners and other specialists be educated by ophthalmologists of the true impact of AMD.

In the second Current Opinions article, also from Wills, Julia A. Haller, MD, and Allen Chiang, MD, report on innovations in treating vitreoretinal disease expected over the next 10 years. They cover pharmacologic vitreolysis, nanotechnology genetic therapies (including stem cells) and the development of artificial viewing systems. These technologies hold promise in treating any number of vitreoretinal disorders, from AMD to inherited retinal dystrophies. With pharmacologic vitreolysis agents already in clinical trials, we may see the results sooner rather than later.

Combination Avastin fails. With growing concerns over the costs of repeated intravitreal injections, combination therapies to extend the benefits of anti-VEGF agents are under investigation. Unfortunately, a recent trial comparing bevacizumab combined with verteporfin photodynamic therapy to bevacizumab alone did not find any greater benefit to combination therapy in terms of visual outcomes or number of injections required.

The study, the results of which appear in the April 2010 issue of Retina, compared 139 eyes treated with bevacizumab to 236 eyes given combination therapy. At follow-up, mean improvement in visual acuity was 5.05 letters in the monotherapy arm and 4.8 letters in the combination arm. Visual stabilization occurred in 74.1% of monotherapy patients vs 80.1% of combination therapy patients. Furthermore, mean number of injections was 3.32 in the monotherapy cohort and 3.14 in the combination cohort. None of these results bore statistical significance, however, the researchers noted.

The one positive finding was that complications from intravitreal injections were low, numbering only two in each treatment arm, or 0.3%.

AMD and COPD. Is there a relationship between chronic obstructive pulmonary diseases such as emphysema and early AMD? This has been suggested because of the putative role of inflammation and decreased oxygenation in both diseases. Scientists considered the relationship and reported findings in the April 2010 issue of Archives of Ophthalmology.

This trial, which looked at patients enrolled in a prospective study called MESA (Multi-Ethnic study of Atherosclerosis), had 6,814 participants ages 45 to 85 from six states. Patients were subjected to spirometry to measure lung function, fundus photography to grade for early states of AMD, and CT scanning to detect emphysema.

While the rate of early AMD in the patients studied was 3.7%, the study authors did not find any cross-sectional association between lung function and emphysema on CT scan. The authors hypothesize that this lack of relationship may actually reflect the relatively low rate of cigarette smoking (12% currently smoking vs 35% ex-smokers and 53% who never smoked) in the cohort and the finding that, among those patients who were smokers, there was a statistical association between lung density and early AMD.

Wired patients. According to a letter in the March 2010 issue of the British Journal of Ophthalmology, ophthalmology patients in the United Kingdom are using the Internet at high rates. Four ophthalmologists from Hereford and Wolverhampton report that, based on questionnaires returned from 397 adult patients and 98 parents of pediatric patients, 57% had home Internet access.

Among their findings were that Internet uses over the age of 65 — so-called silver surfers — actually spend more time online than any other age group. Furthermore, 83% of individuals surveys indicated that they would like their ophthalmologists to provide healthcare information that they can access on the Web. The percentage of patients wanting to research their conditions on their own was actually higher than the percentage who owned computers at home, indicating that perhaps they would seek out access to computers if they were provided with education.

The authors further posit that providing information to patients with Internet access could reduce the anxiety felt by many. However, the authors do not report whether the information found online could be a detriment to the treatment goals of physicians.

Off-label bevacizumab not justified. Genentech will perhaps be happy to learn that, in a study published in the May 2010 issue of Current Opinions in Ophthalmology, a group of German retinal physicians are concluding that off-label use of bevacizumab for treating wet AMD is not borne out by the available data.

These results come from a systemic literature review of 3,628 published articles, which were reduced finally to 41 articles dealing with nine clinical trials and 25 case series in which patients with AMD were treated with either ranibizumab or bevacizumab. The total number of patients examined was 2,519.

The authors determined that bevacizumab was relatively more efficacious in recovering visual acuity over PDT, comparable to combination therapy of ranibizumab and PDT. However, they note, because this finding was based on only one trial that was comparable to the ranibizumab data, the ability to generalize from the result is limited. Furthermore, long-term data on visual improvement are limited, they found.

Perhaps most relevant to Genentech's concerns: although the published literature reports a lower level of adverse events with intravitreal injections of bevacizumab than with ranibizumab, the reporting is often inadequate due to both the aforementioned short follow-up times and the unsystematic evaluation of side effects.

Not surprisingly, the authors of this study point to the forthcoming CATT study for authoritative information on comparisons of bevacizumab and ranibizumab, although those data are several months away.

1-800-RETINA. In May 2007 the German Retina Hotline was launched, providing information to patients for 2.5 hours three times a week. Now the 18-month data from the hotline are available, and appear in the April 2010 Retina.

In total, 1,384 calls were received by the hotline, averaging 7.6 calls per day that the hotline was operating. Average call length was 8.5 minutes. The largest cohort of patients who phoned the hotline consisted of female patients with AMD (63%). After callers asking questions about AMD, those seeking information or assistance with retinitis pigmentosa constituted the second-largest group.

Most of the callers reported being grateful for the existence of the hotline, although many also complained that limitations in clinical settings contributed to their decisions to phone in. Furthermore, three patients called in presenting symptoms of psychiatric disorders. These callers were referred to psychiatric care.

The authors of this study conclude that instituting services such as the German Retina Hotline can be a beneficial adjunct for patients who want or need more information. However, they note, it need not be staffed by ophthalmologists, as the information provided often did not require a consult with a retinal physician. RP



Retinal Physician, Issue: May 2010