Small Study Jumps the Gun on CATT
■ While the retina community eagerly awaits data from the larges cale CATT trial directly comparing Avastin and Lucentis in wet AMD, a group of researchers from the VA Boston Healthcare System has conducted a similar head-to-head studyon a much smaller scale.
In data presented at the recent ARVO meeting, 11 patients receiving Avastin and seven patients receiving Lucentis were evaluated for one year. All patients received three initial monthly doses, followed by an OCT-guided variable dosing regimen. Main outcome measures were visual acuity and foveal thickness at one year.
The average preoperative visual acuity was 31.5 letters in the Avastin group and 32.7 letters in the Lucentis group. At one-year follow-up, meanvision was 43.6 letters in the Avastin group and 39.0 letters in the Lucentis group. Central subfield thickness (CST) improved in both groups. Subjects receiving Avastin had a baseline CST of 288.6 μm, which improved at one year to 235.8 μm. Subjects receiving Lucentis had a baseline CST of 340.8 μm, improving to 203.6 μm. Patients in the Avastin group underwent an average of 8.0 injections, while patients in the Lucentis group underwent a mean of 4.2 injections.
The researchers concluded that one-year outcomes of this head-to-head, randomized, prospective, doublemasked, controlled trial comparing Avastin and Lucentis failed to show a difference in visual outcomes for treatment of wet AMD. However, a significant difference in central foveal thickness was seen, and patients in the Avastin group required more injections over one year.
Some of the same researchers from the VA Boston Healthcare System also conducted a second study presented at ARVO. This study was a retrospective review of 34 wet AMD patients treated with Avastin or Lucentis in an OCT-guided regimen and evaluated over a one-year treatment period. Ten received Avastin while 24 were treated with Lucentis.
Pretreatment groups were matched in terms of visual acuity (logMAR 0.52 Avastin vs. logMAR 0.52 Lucentis), and central macular thickness (269 Avastin vs. 308 Lucentis). There was no statistically significant difference in the number of injections received at one year (5.3 Avastin vs. 5.6 Lucentis) and visual acuity outcomes were also similar (logMAR 0.38 Avastin vs. logMAR 0.40 Lucentis). No subjects in the Avastin group and one subject in the Lucentis group lost more than 15 letters on ETDRS chart.
Fourteen of the 34 patients required four or fewer injections, while 11 required seven or more. There was no statistical difference noted between the two groups when parametric values such as visual acuity, central macular thickness (CMT), lesion size and nonparametric values, such as presence of pigment epithelial detachment, hemorrhage and lesion locations were compared.
The researchers concluded that this case series of 34 patients yieldedsimilar injection numbers and similar visual acuity outcomes at one year. No pretreatment characteristics were identified that predict required injection number. Further studies with larger sample sizes are needed for confirmation of these findings.
Data on PDT/Lucentis Combinations
Fewer retreatments with combo therapies.
■ QLT, Inc. says data from two key studies show that PDT and ranibizumab used in combination can reduce the need for retreatment in wet AMD patients. However, the best vision gains were achieved from ranibizumab monotherapy.
Recently-released 12-month data from QLT's 321-person phase 3b DENALI study show that a combination of PDT and as-needed ranibizu - mab injections can reduce the number of injections needed to maintain vision gains. But at 12 months, average vision gains from monthly ranibizumab injections were superior (8.1 letters) to the combination regimen (5.3 letters with standard-fluence PDT and 4.4 letters for reduced-fluence PDT).
QLT said that most patients in the combination groups had a ranibizumabfree interval of at least three months during the study. The need for retreatment was based on a number of generally accepted retreatment criteria, including changes in central retinal thickness, presence of subretinal fluid, OCT assessment and decrease in visual acuity.
"This study adds support that Visudyne combination therapy can improve visual outcomes and may provide a treatment alternative that has the potential to reduce the treatment burden for patients with wet AMD," said Bob Butchofsky, president and CEO of QLT.
QLT has also released final results from the 24-month phase 2 phase RADICAL study, which compared ranibizumab monotherapy against several PDT/ranibizumab combinations. Though ranibizumab monotherapy produced the best mean vision gains, a "triple-therapy" regimen of half-fluence PDT, ranibizumab and dexamethasone required fewer retreatments (mean of 4.2 vs 8.9 monotherapy retreatments).
"The Visudyne/Lucentis combination therapy significantly decreased the number of retreatment visits required over two years, while patients' vision outcome was maintained within one line with an acceptable safety profile, compared with Lucentis alone," said Henry Hudson, MD, of Tucson, one of the two lead investigators for the study.
"The two-year results from the RADICAL study are consistent with the primary one-year results and demonstrate that combination therapy is a potential treatment option for patients with wet AMD," said Allen C. Ho, MD, a professor of ophthalmology at Philadelphia's Wills Eye Institute, the other lead investigator for the study.
Radiation as a Supplement to Anti-VEGF
Study: potential for fewer injections
■ One of the primary current aims in the treatment of wet AMD is finding ways to reduce the number of intravitreal injections that a patient must undergo. To this end, researchers from King's College Hospital in London and Retinal Consultants of Arizona are conducting a study using macular epiretinal brachytherapy as a safe and effective supplement to anti-VEGF therapy. Their interim findings were reported at the recent ARVO meeting.
Fifty subjects with classic, minimally classic and occult lesions were enrolled. Patients must have had a minimum of three intravitreal anti-VEGF retreatment injections in the six months prior to enrollment, or five injections in 12 months before enrollment. Patients had received a mean of 12 total injections prior to enrollment.
All subjects in the study underwent pars plana vitrectomy and 24 Gy beta irradiation for four to five minutes, using a retractable strontium-90 source in an endoscopic probe (NeoVista, Freemont, CA).
Following this treatment, anti-VEGF injections were resumed if there was a five ETDRS letter loss, >50 μm central retinal thickness increase on OCT, new macular hemorrhage or new activity visible with fundus fluorescein angiography (FFA). Patients were retreated with the same anti-VEGF agent they were receiving prior to enrollment (bevacizumab 1.25 mg or ranibizumab 0.5 mg). Co-primary outcome measures were mean ETDRS visual acuity and mean number of anti-VEGF retreatment injections.
The researchers reported that, to date, 16 patients have reached the six-month milestone. Patients received a mean of two retreatment injections in that period, with 88% maintaining vision and 63% gaining vision. Mean visual gain was 1.2 letters (+3.0 in pseudophakes). There was an encouraging safety profile, with no retinal breaks, detachments or radiation retinopathy.
The researchers say these interim results suggest that epimacular brachytherapy may reduce the number of anti-VEGF retreatments required, while maintaining vision. However, further follow-up is needed. A large multicenter clinical trial is now underway.
The Future of Eye Examinations
■ It is always interesting to look at the capabilities of current technology and project its potential into the future. Alexander C. Walsh, MD, of the Doheny Eye Institute in Los Angeles, caught the attention of many attendees at the recent ARVO meeting with his vision of a single, patientoperated, OCT-based instrument that could screen from home for a broad range of eye diseases and deliver the results directly to an ophthalmologist's office.
"We believe that diagnostic technologies exist today that can decrease the cost, increase the efficiency and improve the quality of ophthalmic care and eye disease screening around the world. A simple, inexpensive, automated, patient-operated binocular device containing bilateral optical coherence tomography imaging systems has the potential to make the ophthalmic examination more objective, consistent, quantitative, documented and efficient," wrote Dr. Walsh in his presentation. "Furthermore, it has the potential to screen for diseases in all eye tissues, not just retinal diseases such as diabetic retinopathy."
Dr. Walsh wrote that Fourier domain OCT images of the entire central axis of the eye, so-called OCT biomicroscopy, may be able to replace many of the functions of a slit-lamp biomicroscope with permanently recorded, quantifiable, high-resolution OCT imaging.
He further contends that a selfadministered OCT-based binocular instrument with internal display screens and buttons for input may be able to perform such quantitative analyses as pupillometry, extraocular motility, measurements of strabismus and many or all of the functions of the following diagnostic tests: visual acuity testing, autorefraction, static perimetry, kinetic perimetry, confrontation visual fields, ocular alignment and motility testing, corneal topography, corneal pachymetry, gonioscopy, color vision assessments, Amsler grid testing, reading speed assessments, contrast sensitivity testing, stereoacuity testing, suppression testing, exophthalmometry, and optical coherence tomography.
Dr. Walsh posits that, given the feasibility of patient-administered testing, "this single OCT-based, binocular instrument may be capable of collecting enough data outside of a clinical setting to support remote, comprehensive, electronic ophthalmic evaluations."
Looking out even further with a global view, Dr. Walsh writes that "an automated version of this device capable of making point-of-care risk assessments and providing immediate results and direction to the patient may also be one method of enabling accessible, affordable eye disease screening even in the world's poorest countries where blindness is more common."
For these reasons, Dr. Walsh believes that self-administered testing using advanced OCT technology has the potential to reduce the cost, increase the efficiency, and improve the quality of ophthalmic care around the world.
He concludes by writing that his somewhat futuristic ideas are primarily intended to stimulate discussion and encourage the development of alternatives to current eye examination technologies.
Anti-VEGF and Reading Speed
■ Hundreds of patients who participated in Genentech's phase 3 trials for macular edema associated with branch and central retinal vein occlusion (BRVO and CRUISE) were also tested to determine if treatment with ranibizumab could have an effect an reading speed.
Using a specially designed reading test, BRAVO patients who received 0.3 mg of ranibizumab monthly for six months showed a mean improvement of 21.9 words per minute from baseline at six months, while patients receiving the 0.5 mg dose of ranibizumab showed a mean improvement of 31.3 words. BRVO patients who had sham injections showed a mean improvement of 15.0 words at six months.
CRUISE patients who received the 0.3 mg dose showed a mean improvement of 23.7 words per minute after six months, which was better than the 0.5 mg cohort, which demonstrated mean improvement of 20.6 words. The sham group improved by 8.1 words per minute.
Researchers, who presented this data at the recent ARVO meeting, concluded that improved reading speed following ranibizumab therapy indicated a direct patient performance metric of reading ability and visual function. RP