Review of Ophthalmology's Retina Online

Volume 3, Number 2

February 2007

Contents:

		WELCOME

		THE LATEST PUBLISHED RESEARCH

		NOTEWORTHY: COMPANY SENDS LETTER REGARDING RANIBIZUMAB SAFETY ANALYSIS; TWO-YEAR RESULTS FROM ANCHOR TRIAL PRESENTED; AND MORE ITEMS OF INTEREST

WELCOME

Welcome to Review of Ophthalmology’s Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

In this edition:

	The latest published research
	Noteworthy, items of interest

THE LATEST PUBLISHED RESEARCH

Bevacizumab for CNV in Pathological Myopia
Two recently published studies indicate that intravitreal bevacizumab (Avastin) may be a safe and effective treatment for choroidal neovascularization (CNV) due to pathological myopia.

One of the studies retrospectively reviewed cases of 11 eyes of nine patients treated with bevacizumab (1.25 mg) for primary or recurrent subfoveal CNV secondary to myopia between August 2005 and January 2006 at the New England Eye Center in Boston. (Also see accompanying images.) Five of the eyes had previously received photodynamic therapy (PDT). Before treatment with bevacizumab, six eyes had visual acuity between 20/50 and 20/100, and five eyes had acuity of 20/200 or worse. During the study period, eight eyes received one injection and three eyes received two injections. Mean follow-up was 153 days. After treatment, visual acuity improved by a mean of 3.5 lines. Eight eyes had 20/50 or better acuity at the last follow-up visit. Central foveal thickness improved an average of 103 µm.


Figure A	Figure B


Figure C	Figure D

This 44-year-old 11D myope presented with a 10-day history of decreasing vision. Visual acuity measured 20/60. Fluorescein angiography revealed a classic CNV (A), and OCT showed mild intraretinal fluid (B). Three months after a single treatment with intravitreal bevacizumab, visual acuity improved to 20/50. Fluorescein angiography revealed no active leakage with a staining of a small central portion of the lesion (C). Based on OCT, the intraretinal fluid resolved and a subfoveal scar was present (D). No further injections have been performed, and 16 months following the initial treatment visual acuity remains 20/50. (Images courtesy of Adam Rogers, MD)

In a second study, a nonrandomized, interventional case series, eight eyes of eight patients were treated with bevacizumab (1 mg). Minimum follow-up was three months. Mean best-corrected visual acuity (BCVA) improved from 0.26 at baseline to 0.51 at the last visit. In six eyes BCVA improved by two or more lines, and in two eyes it remained the same. In seven eyes CNV leakage decreased based on fluorescein angiography. No major complications or drug-related side effects were observed during either study.

Source: Yamamoto I, Rogers AH, Reichel E, et al. Intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation secondary to pathological myopia. Br J Ophthalmol 2007;91:157-160. Sakaguchi H, Ikuno Y, Gomi F, et al. Intravitreal injection of bevacizumab for choroidal neovascularisation associated with pathological myopia. Br J Ophthalmol 2007;91:161-165.

MARINA Trial Subgroup Analyses
According to retrospective analysis of subgroups in the Phase III MARINA trial of ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD), the treatment was associated with a mean increase in visual acuity and was superior to sham in all groups. Univariate or multivariate analyses were applied to subgroups based on gender, age, baseline acuity, baseline CNV lesion size, CNV lesion type, duration of neovascular AMD and change in acuity from baseline to 24 months. Outcomes evaluated were proportion of patients losing fewer than 15 letters from baseline, proportion gaining 15 or more letters, and mean change in acuity from baseline.

Increasing age, larger lesion size at baseline, and higher baseline acuity were associated with greater loss of acuity in the sham group or less gain of acuity in the treatment groups. The net benefit of treatment compared with sham was greater in patients who had higher baseline acuity. The most important predictors of vision outcomes were baseline acuity, CNV lesion size and age.

In the MARINA trial, 716 patients with minimally classic or occult with no classic CNV were randomized to receive either 0.3 mg or 0.5 mg ranibizumab or sham injections.

Sources: Boyer DS, Antoszyk AN, Awh CC, et al. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114:246-252.

15-Year Cumulative Incidence of AMD
Grading of stereoscopic fundus photographs from 3,917 participants in the Beaver Dam Eye Study placed the 15-year cumulative incidence of early and late AMD at 14.3 percent and 3.1 percent respectively. Early AMD was defined as soft indistinct drusen or pigmentary abnormalities and any type of drusen. Late AMD was defined as exudative disease or geographic atrophy.

The participants were 43 to 86 years old at their baseline examinations from 1988 through 1990, and follow-up information was collected from 1993 through 1995, 1998 through 2000, and/or 2003 through 2005. Eyes with soft indistinct drusen or pigmentary abnormalities at baseline were more likely to develop late AMD than eyes without these characteristics.

Source: Klein R, Klein BEK, Knudtson MD, et al. Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmology 2007;114:253-262.

Higher Doses of Triamcinolone for Diabetic Macular Edema
According to the results of a study involving 63 eyes of 63 patients, higher doses of intravitreal triamcinolone acetonide may have more prolonged benefits than lower doses for treating clinically significant diabetic macular edema (CSDME). The patients, who had CSDME and central foveal thickness of 250 µm, were randomized to receive either 4 mg, 6 mg or 8 mg of triamcinolone and were followed for six months.

After treatment, improvement in BCVA and foveal thickness occurred in all groups, but mean BCVA improvement was significantly higher in the 8-mg group at six months (9.9 letters compared with 3.1 letters in the 4-mg group). Also at six months, the mean standardized change in macular thickness was 28.7 percent for the 4-mg dose, 42.3 percent for the 6-mg dose, and 60.5 percent for the 8-mg dose. Intraocular pressure increased by more than 21 mmHg in 39 percent of the 4-mg group, 30 percent of the 6-mg group, and 55 percent of the 8-mg group.

Source: Lam DSC, Chan CKM, Mohamed S, et al. A prospective randomised trial of different doses of intravitreal triamcinolone for diabetic macular oedema. Br J Ophthalmol 2007;91:199-203.

NOTEWORTHY: COMPANY SENDS LETTER REGARDING RANIBIZUMAB SAFETY ANALYSIS; TWO-YEAR RESULTS FROM ANCHOR TRIAL PRESENTED; AND MORE ITEMS OF INTEREST

Company Sends Letter Regarding Ranibizumab Safety Analysis
Genentech issued a letter to health-care providers to inform them of the results of a planned interim safety analysis from the SAILOR study of ranibizumab for neovascular AMD. The letter states that the analysis showed a higher incidence of stroke in the 0.5-mg dose group compared with the 0.3-mg dose group (1.2 percent vs. 0.3 percent, p=0.02). The analysis was performed on data from patients in Cohort 1, who had an average follow-up time of 230 days.

Patients with a history of prior stroke appeared to be at higher risk for a subsequent event. The differences between the doses were not statistically significant for myocardial infarction or vascular death. SAILOR is monitoring the safety of the two doses of ranibizumab (Cohort 1) and has been providing access to the 0.5-mg dose for patients (Cohort 2) since before the drug’s approval in 2006. The overall safety of intravitreal injections of ranibizumab appears to be consistent with the safety experience from Phase III studies as described in the prescribing information.

Physicians with questions regarding the use of ranibizumab can call (800) 821-8590. Any serious adverse events believed to be associated with ranibizumab should be reported by calling (888) 835-2555. Alternatively, this information may be reported to MedWatch at (800) 332-1088 or accessdata.fda.gov/scripts/medwatch.

Source: Genentech, January 2007.

Two-Year Results from ANCHOR Trial Presented
Two-year results from the Phase III ANCHOR study of ranibizumab for the treatment of neovascular AMD showed that the treatment’s benefits compared with PDT were maintained from month 12 to month 24. Patients were randomized 1:1:1 to receive 0.3-mg or 0.5-mg intravitreal injections of ranibizumab once per month or PDT every three months for two years. A total of 343 of 423 patients completed two years of the study (76.9 percent of the PDT group, 83.6 percent of the 0.3-mg group, and 82.9 percent of the 0.5-mg group).

Overall, the safety and efficacy results were consistent with the one-year ANCHOR and two-year MARINA trial data. At two years in ANCHOR, the percentages of patients who lost fewer than 15 letters of visual acuity were 90 percent in the 0.3-mg ranibizumab group, 89.9 percent in the 0.5-mg ranibizumab group, and 65.7 percent in the PDT group. Visual acuity improved by at least 15 letters in 34.3 percent of the 0.3-mg group, 41 percent of the 0.5-mg group, and 6.3 percent of PDT group. Mean change in visual acuity from baseline was +8.1 letters in the 0.3-mg group, +10.7 letters in the 0.5-mg group, and -9.8 letters in the PDT group. This represents a 20.5-letter difference between patients treated with 0.5 mg of ranibizumab and patients treated with PDT.

Source: Genentech, January 2007.

Retisert Assigned J-Code and Payment Rate
The Centers for Medicare & Medicaid Services assigned a product-specific J-Code to the fluocinolone acetonide intravitreal implant (Retisert), which is indicated for the treatment of chronic noninfectious posterior segment uveitis. The new code, J7311, replaces the Medicare hospital outpatient code, C9225. The Medicare payment rate for J7311 is $19,345. The code and payment rate are effective as of January 1, 2007.

Source: Bausch & Lomb, January 2007.

FDA Clears Phase III RHEO Trial
OccuLogix received Investigational Device Exemption clearance from the U.S. Food and Drug Administration to begin a Phase III study of its RHEO procedure for the treatment of the dry form of AMD. RHEO-AMD, a prospective, randomized, double-masked, sham-controlled trial, will take place at up to 25 sites. Each patient will receive either eight RHEO treatments or eight sham procedures over 10 weeks. The study’s primary endpoint is mean change in BCVA from baseline to 12 months. The RHEO procedure is a specific type of apheresis in which the patient's blood is drawn outside the body and certain compounds are removed before it is returned to the body.

Source: OccuLogix, January 2007.

Investigational Uveitis Therapy Receives Orphan Designation
The U.S. Food and Drug Administration granted orphan drug status to LX211, an investigational, next-generation calcineurin inhibitor intended for the treatment of noninfectious posterior, intermediate and panuveitis. Like other molecules of this class, LX211 reversibly inhibits immunocompetent lymphocytes, particularly T-lymphocytes, and inhibits lymphokine production and release.

Lux Biosciences Inc. plans to begin enrolling patients in pivotal clinical trials for LX211 during this quarter. The trials will evaluate an oral formulation of the compound, which the company says has safety advantages over the prototypical calcineurin inhibitor cyclosporine A.

Source: Lux Biosciences, January 2007.

This promotional message was sent to you directly by Jobson Professional Publications as part of its continuing mission to keep the eyecare profession informed. If you do not want to receive this type of information in the future, simply reply to this message with the words "Unsubscribe Mailings" in the subject header. Jobson Professional Publications never releases its e-mail list.