THE LATEST RESEARCH

Intravitreal Bevacizumab for CNV Secondary to AMD
In a retrospective study involving 266 eyes (266 consecutive patients) with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD), intravitreal injection (1.25 mg) of bevacizumab (Avastin) decreased macular thickness and improved visual acuity with no apparent short-term safety problems. Follow-up information was available for 251 (94.4 percent) of the 266 eyes.

The mean central macular thickness decreased to 247 µm at one month and 213 µm at three months from the baseline mean of 340 µm (p<0.001). Mean visual acuity at baseline was 20/184. At one month, (n=244) mean visual acuity was 20/137 (p<0.001). Mean visual acuity at two months (n=222) was 20/122 (p<0.001). Mean visual acuity at three months (n=141) was 20/109 (p<0.001). The proportion of patients whose visual acuity improved (halving of the visual angle) was 30.3 percent, 31.1 percent and 38.3 percent at one, two and three months respectively.

At one month, two patients had mild vitritis, as did one patient at two months. No endophthalmitis, increased intraocular pressure, retinal tears, or retinal detachments occurred. The risk for thromboembolic disorders was not different than previously reported from studies of bevacizumab and AMD.

Source: Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina 2006;26(4):383-390.

Studies Evaluate Repeat and Dose-Escalating Injections of Ranibizumab
Two recently published studies, one with dose escalation, evaluated the safety and effects of repeat intravitreal injections of ranibizumab (Lucentis) in patients with subfoveal CNV secondary to AMD.

In one of the studies (Rosenfeld et al.), which was uncontrolled, randomized, and conducted at two centers, patients with primary or recurrent CNV were treated with five, seven, or nine injections at two- or four-week intervals for 16 weeks and followed through day 140 (four weeks after last injection). Three different escalating doses, ranging from 0.3 mg to 2.0 mg, were administered. The study enrolled 32 patients; 29 received an injection at baseline; and 27 completed the study through day 140 (week 20).

Results were similar across all three treatment groups. Inflammation did not increase with repeat or dose-escalating injections. No significant lesion growth occurred through day 140, and area of leakage decreased. Median and mean visual acuities improved in all three dose groups; three patients lost 15 or more letters. All patients experienced mild ocular adverse events; iridocyclitis (83 percent) and injection-site reactions (72 percent) were the most common. Transient and mild elevations of intraocular pressure were common. No serum anti-ranibizumab antibodies were detected.

In another study (Heier et al.), which was multicenter and controlled, repeat intravitreal injections of ranibizumab were found to be safe and associated with improved visual acuity and decreased leakage from subfoveal predominantly or minimally classic CNV. Sixty-two of the 64 randomized patients completed the two-part, six-month study.

In Part One, patients were randomized to monthly injections for three months (four injections of 0.3 mg or one injection of 0.3 mg followed by three injections of 0.5 mg) or usual care. In Part Two, patients could continue their regimen for three additional months or cross over to the alternative treatment. Eighty percent of patients randomized to 0.3-mg of ranibizumab and 79 percent randomized to 0.5-mg in Part One continued the same treatment in Part Two. Eighty-two percent of patients randomized to usual care in Part One crossed over to ranibizumab treatment in Part Two.

After four injections (day 98), mean visual acuity increased 9.4 +/-13.3 letters in the 0.3-mg group and 9.1 +/-17.2 letters in the 0.5-mg group, while it decreased 5.1 +/-9.6 letters in the usual care group. In Part Two, (day 210), visual acuity increased from baseline 12.8 +/-14.7 and 15.0 +/-14.2 letters in patients who continued with 0.3 and 0.5 mg, respectively. Among patients who were initially randomized to or continued ranibizumab treatment, visual acuity improved 15 letters or more from baseline in 26 percent of patients at day 98 and 45 percent of patients at day 210. Areas of leakage and subretinal fluid decreased.

The most common ranibizumab-related adverse events were reversible inflammation and minor injection-site hemorrhages. Serious adverse events included iridocyclitis (one patient), endophthalmitis (one patient), and central retinal vein occlusion (one patient). The proportion of patients experiencing increased intraocular pressure, which was transient, was 22.6 percent.

Sources: Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N. Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. Ophthalmology 2006;113(4):632. Heier JS, Antoszyk AN, Pavan PR, et al. Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study. Ophthalmology 2006;113(4):642.

Sequenced, Combined Treatment for RAP Shows Promise
Treatment with intravitreal triamcinolone followed in seven to 14 days by indocyanine green angiography-guided photodynamic therapy with verteporfin (Visudyne) reduced or eliminated cystoid edema, achieved rapid regression of neovascularization, and stabilized or improved visual acuity in patients newly diagnosed with retinal angiomatous proliferation (RAP).

The 27 eyes of 26 patients treated with this sequenced combination therapy, termed pharmacology-pause-photodynamic therapy (PPP), were followed for 12 months. Angiographic leakage completely resolved in 89 percent of the eyes. Leakage recurred in eight eyes in three to 11 months and completely resolved after subsequent treatment.

Visual acuity improved in 37 percent of the eyes and remained stable in 52 percent. The mean Snellen equivalent visual acuity at baseline as well as after triamcinolone injection before PDT was 20/150 (range 20/40 to 20/400). At six months, mean visual acuity was 20/100 (range 20/40 to 20/400). After six months, visual acuity improved by three or more lines in five eyes (19 percent), remained stable (+/-2 lines) in 19 eyes (70 percent), and decreased by three or more lines in three eyes (11 percent). After 12 months, mean visual acuity was 20/100 (range 20/50 to 20/400). Visual acuity improved by three or more lines in 10 eyes (37 percent), remained stable (+/-2 lines) in 14 eyes (52 percent), and decreased by three or more lines in three eyes (11 percent).

Source: Freund KB, Klais CM, Eandi CM, et al. Sequenced combined intravitreal triamcinolone and indocyanine green angiography-guided photodynamic therapy for retinal angiomatous proliferation. Arch Ophthalmol 2006;124:487-492.

Direct Injection of tPA and Air-Fluid Exchange for Macular Hemorrhage
Direct injection of tissue plasminogen activator (tPA) and air-fluid exchange (no intraoperative clot lysis period) produced positive results in a case series involving 17 patients with subretinal macular hemorrhages due to AMD.

The patients underwent three-port pars plana vitrectomy to enable direct cannulation of the subretinal space and injection of 48 µg of tPA into the hematoma and partial fluid-air exchange. They spent one hour after the procedure in a face-up supine position and spent the night in an upright position.

Visual acuity stabilized or improved in 88 percent of the patients. The hemorrhage completely cleared in nine patients and partially cleared in eight patients. The hemorrhage recurred in two patients, and one patient underwent a retinal detachment repair. Outcomes were similar for predominantly classic and occult lesions.

Source: Singh RP, Patel C, Sears JE. Management of subretinal macular haemorrhage by direct administration of tissue plasminogen activator. Br J Ophthalmol 2006;90:429-431.

Report Number 1 from PTAMD Trial Published
According to Report Number 1 from the Prophylactic Treatment of Age-Related Macular Degeneration (PTAMD) trial, using a subthreshold 810-nm diode laser to treat an eye with multiple large drusen when neovascularization from AMD has already affected the other eye increases the risk of developing CNV in the treated eye.

The 244 patients in the multicenter, prospective, randomized, controlled trial had a neovascular or advanced AMD lesion in one eye, and the fellow (study) eye had at least five drusen greater than or equal to 63 µm, best-corrected visual acuity of 20/63 or better, and no evidence of neovascularization at baseline. Study eyes were treated with a grid of 48, 125-µm extrafoveal laser spots delivered in a ring outside of the foveola. Patients returned for follow-up at three, six, 12, 18, 24, 30, and 36 months. Retreatments were not permitted.

Throughout the follow-up period, the rate of CNV in study eyes consistently exceeded the rate in observed eyes (15.8 percent vs. 1.4 percent at one year, p=0.05). Study eyes showed a higher rate of visual acuity loss at three and six months, but after six months, no significant differences were observed between groups.

Source: Friberg TR, Musch DC, Lim JI, et al. Prophylactic treatment of age-related macular degeneration Report Number 1: 810-nanometer laser to eyes with drusen. Ophthalmology 2006;113:612.

PDT Plus Triamcinolone for Occult CNV with Two-Year Follow-Up
In a single-center, nonrandomized, prospective, interventional case series, improvement in visual acuity was maintained for the two-year follow-up period in most patients treated with a combination of verteporfin PDT and intravitreal triamcinolone for occult CNV due to AMD.

Forty-one eyes of 41 patients underwent PDT and intravitreal injection of triamcinolone (solution containing 25 mg) 16 hours later. If CNV persisted, the procedure was repeated after three months. Thirty-four eyes (82.9 percent) received re-treatment at three months, but no additional re-treatments were necessary. The mean number of re-treatments was 1.8. Mean visual acuity at baseline and three, six, 12, 18, and 24 months were as follows: 20/133, 20/115, 20/101, 20/84, 20/83, and 20/81.

Eleven of the 41 eyes (26.8 percent) underwent cataract surgery between six and 15 months after the first treatment. Nine patients were treated for a transient steroid-induced increase in intraocular pressure.

Source: Augustin AJ, Schmidt-Erfurth U. Verteporfin and intravitreal triamcinolone acetonide combination therapy for occult choroidal neovascularization in age-related macular degeneration. Am J Ophthalmol 2006;141(4):638.

ACE Inhibitor Shown to Have No Effect on CME
The results of a 40-patient, single-center study indicated that treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril had no effect on inflammatory cystoid macular edema (CME) or visual acuity. In the randomized, double-blind study, the patients, diagnosed with CME, received 10 mg of lisinopril or placebo daily for three months. After a two-month wash-out period, patients crossed over to the opposite study group for three additional months.

Fluorescein angiography showed no effect on CME, visual acuity, papillary leakage, retinal vasculitis or choroidal leakage. A subgroup analysis showed a decrease in both blood pressure and morning urinary albumin excretion.

Source: van Kooij B, Fijnheer R, Joke de Boer J, et al. A randomized, masked, cross-over trial of lisinopril for inflammatory macular edema. Am J Ophthalmol 2006;141:646-651.