Volume 1, Number 9
January 2006



Contents:
WELCOME
THE LATEST RESEARCH
NOTEWORTHY: GENENTECH FILES WITH FDA FOR APPROVAL OF RANIBIZUMAB; NEI TO STUDY ANECORTAVE ACETATE PLUS INTRAVITREAL BEVACIZUMAB; 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 information to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

In this edition:
The latest research
Noteworthy, items of interest

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THE LATEST RESEARCH

Two Studies Focus on RAP Lesions
Two studies of retinal angiomatous proliferation (RAP) lesions in age-related macular degeneration were recently published in the peer-reviewed literature.

One was a retrospective review of 81 consecutive patients with 104 RAP lesions treated from Jan. 1, 2000 through Jan. 31, 2003. Lesions were categorized from early to late stage: stage 1, intraretinal neovascularization; stage 2, subretinal neovascularization; and stage 3, choroidal neovascularization. Forty-two lesions were stage 1; 42 were stage 2; and 20 were stage 3. Five treatments were applied: direct laser photocoagulation of the vascular lesion; laser photocoagulation of the feeder retinal arteriole; scatter "gridlike" laser photocoagulation; photodynamic therapy; and transpupillary thermotherapy. Based on the main outcome measures of complete obliteration of the lesion and final visual acuity, early detection and subsequent direct laser photocoagulation were associated with the best anatomical and functional outcomes. Once the vascular complex is well-established, the researchers wrote, anatomical closure is rarely achieved.

In a second study, researchers retrospectively reviewed a consecutive series of 126 patients newly diagnosed with exudative AMD. They diagnosed RAP when a connection between the retinal vasculature and the neovascular complex was recognized on angiography. Of the 126 patients, 17 (13.5 percent) had RAP. Compared with the other forms of AMD, the eyes with RAP had more hemorrhages (88.2 vs. 59.6 percent), hard exudates (82.4 vs. 26.6 percent), pigment epithelium detachments (64.7 vs. 23.8 percent), and hot spots on indocyanine green angiography (70.6 vs. 22.1 percent). Also in the RAP group, hemorrhages were more frequently superficial, multiple and within the edge of the lesion, and bilateral AMD was more common. Based on the results, the researchers concluded that RAP represents a common lesion in patients with neovascular AMD who were referred to a tertiary care clinic. In addition, they wrote that attention to hemorrhages, hard exudates, pigment epithelium detachment or a hot spot on indocyanine green angiography can assist in correct diagnosis.

Source: Bottoni F, Massacesi A, Cigada M, et al. Treatment of retinal angiomatous proliferation in age-related macular degeneration. Arch Ophthalmol 2005;123:1644-1650. Donati MC, Carifi C, Virgili C, Menchini U. Retinal angiomatous proliferation: association with clinical and angiographic features. Ophthalmologica 2006;220:31-36.

Study Points to Amino Acid as AMD Biomarker
In a cross-sectional, case-control study of 547 people with AMD and 387 controls, an elevated level of the amino acid homocysteine was associated with an increased risk of developing AMD. Controlling for age and other factors, researchers at the Massachusetts Eye and Ear Infirmary in Boston and the Devers Eye Institute in Portland, Ore., measured fasting plasma homocysteine levels and found that median values were higher among people with advanced stages of AMD compared to people without AMD (p=.01). They also found levels considered high in the clinical setting to be associated with a higher risk of AMD (p=.023). Homocysteine is a known biomarker for cardiovascular disease.

Source: Seddon JM, Gensler G, Klein ML, Milton RC. Evaluation of plasma homocysteine and risk of age-related macular degeneration. Am J Ophthalmol 2006;141(1):201-203

Triamcinolone and PDT for Occult CNV
After treatment with intravitreal triamcinolone and photodynamic therapy with verteporfin (Visudyne, Novartis Ophthalmics), leakage on fluorescein angiography and retinal thickness were significantly reduced in 11 eyes of 10 consecutive patients with occult with no classic choroidal neovascularization secondary to AMD. In the prospective, interventional case series, patients received a single injection (25 mg) of triamcinolone followed one month later by PDT. At one month after PDT, BCVA improved by at least three ETDRS lines in 45.5 percent of eyes. The percentages of eyes with a gain of at least three lines at three, six and 12 months were 63.6 percent, 63.6 percent, and 36.3 percent. The percentages of eyes with a gain of at least two lines at one, three, six and 12 months were 54.5 percent, 81.8 percent, 91 percent and 73 percent.

Eighteen percent of eyes lost three or more lines of BCVA at 12 months. One eye developed intraocular hypertension by three months, and one eye developed a dense cataract by the last follow-up visit. No endophthalmitis, retinal detachments or vitreous hemorrhages occurred.

Source: Massimo N, Davidina G, Silvio L, et al. Occult with no classic choroidal neovascularization secondary to age-related macular degeneration treated by intravitreal triamcinolone and photodynamic therapy with verteporfin. Retina 2006;26:58-64.

Evaluation of PDT with Altered Treatment Parameters
Bolus drug administration and a reduced light dose improved the selectivity of verteporfin PDT in a study involving 19 patients with AMD and predominantly classic CNV. The patients were treated with 6 mg/cm2 of verteporfin at a fluence of either 25 or 50 J/cm2 and evaluated for three months. Choroidal hypoperfusion was minimal in eyes treated at the 25 J/cm2 fluence. Most patients treated with 50 J/cm2 showed significant choriocapillary nonperfusion at week one, which lasted as long as three months. Angiography showed that a transient PDT-induced increase in leakage area at day one was more extensive in the 50-J/cm2 group. Complete CNV closure was achieved in all patients at day one.

Source: Michels S, Hansmann F, Geitzenauer W, Schmidt-Erfurth U. Influence of treatment parameters on selectivity of verteporfin therapy. Invest Ophthalmol Vis Sci 2006;47:371-376.

Vitrectomy for Macular Edema with and without ILM Peeling
A prospective, comparative, nonrandomized study of pars plana vitrectomy (PPV) with and without peeling of the internal limiting membrane (ILM) for diffuse clinically significant macular edema showed no significant differences in outcome parameters between the two groups of patients. Eight of the 18 patients underwent PPV with removal of the posterior hyaloid only, and 10 patients underwent PPV and ILM peeling. The patients, who had previously undergone laser photocoagulation, were followed for 12 months with best-corrected visual acuity measurements, fundus fluorescein angiography, optical coherence tomography and perifoveal cone function testing. When treatment included ILM peeling, foveal thickness and macular volume improved at 12 months, but ETDRS vision and perifoveal cone function did not improve significantly.

Source: Patel JI, Hykin PG, Schadt M, et al. Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema. Retina 2006;26:5-13.

Study Finds No Link Between Sun Exposure and AMD
A study using a multiple logistic regression model found no significant association between AMD and sun exposure, iris color, change in iris color or hair color. Results did suggest an association between sunburn-prone skin and geographic atrophy, but the association was only of borderline significance. The model compared 446 patients with end-stage AMD with 283 spouse controls. AMD was defined as choroidal neovascularization or geographic atrophy. Researchers used questionnaires to collect information on sun exposure, places of residence, iris color, subjective assessment of iris color change, hair color at age 20 and skin sensitivity. They also graded iris color clinically using standard photographs. The model took into account all other key variables, including age, sex and smoking status.

Source: Khan JC, Shahid H, Thurlby DA, et al. Age related macular degeneration and sun exposure, iris colour, and skin sensitivity to sunlight. Br J Ophthalmol 2006;90:29-32.

IOP after Pegaptanib Injection
A retrospective review of 79 charts of patients who underwent 122 consecutive injections of pegaptanib sodium [Macugen, (OSI) Eyetech] for wet AMD indicated that post-injection intraocular pressure is not a cause for concern. Mean IOP at baseline was 15.73 +/-3.41 mmHg (range, of 9 to 27 mmHg). Mean IOP post-injection was 24.47 +/-6.29 mmHg (range, 8 to 36 mmHg). Mean change in IOP from baseline to approximately 30 minutes after injection was 8.74 +/-7.23 mmHg. By the time of the five- to seven-day follow-up visit, IOP had normalized. Based on this limited series, the authors of the paper concluded that post-injection monitoring of IOP may not be necessary.

Source: Hariprasad SM, Shah GK, Blinder KJ. Short-term intraocular pressure trends following intravitreal pegaptanib (Macugen) injection. Am J Ophthalmol 2006;141(1):200-201.


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NOTEWORTHY: GENENTECH FILES WITH FDA FOR APPROVAL OF RANIBIZUMAB; NEI TO STUDY ANECORTAVE ACETATE PLUS INTRAVITREAL BEVACIZUMAB; AND MORE ITEMS OF INTEREST

Genentech Files with FDA for Approval of Ranibizumab
In December, Genentech, Inc. submitted a Biologics License Application (BLA) to the Food and Drug Administration for approval of ranibizumab (Lucentis) to treat wet AMD. As part of the submission, the company requested the Priority Review designation, which, if granted, would give the FDA six months to take action on the application. The filing is based on the one-year clinical data from the pivotal Phase III trials ANCHOR and MARINA, as well as one-year data from the Phase I/II FOCUS trial.

Genentech released the top-line ANCHOR data this month. In the first year of the two-year study, patients treated with ranibizumab gained an average of 8.5 letters in the 0.3-mg dose group and 11 letters in the 0.5-mg dose group compared with patients treated with PDT, who lost an average of 9.5 letters. In addition, 94 percent of patients (132/140) treated with 0.3 mg of ranibizumab and 96 percent (134/139) treated with 0.5 mg lost fewer than 15 letters (primary efficacy endpoint) from baseline compared with 64 percent (92/143) of those treated with PDT. Nearly 36 percent of patients (50/140) treated with 0.3 mg of ranibizumab and 40 percent (56/139) treated with 0.5 mg improved vision by 15 letters or more compared with approximately 6 percent of patients (8/143) treated with PDT. Thirty-one percent of patients (44/140) treated with 0.3 mg of ranibizumab and nearly 39 percent (54/140) treated with 0.5 mg achieved visual acuity of 20/40 or better at 12 months compared with approximately 3 percent (4/143) of those treated with PDT.

Common ocular adverse side effects that occurred more frequently in the ranibizumab patients than in the control group were mild to moderate and included conjunctival hemorrhage, increased intraocular pressure, eye pain and vitreous floaters. Serious ocular adverse events that occurred more frequently in the ranibizumab-treated patients were uncommon and included endophthalmitis and intraocular inflammation (each reported in less than 1 percent of patients per group). Among non-ocular serious adverse events, the frequency of cerebral vascular events was less than 1 percent of patients per group. The frequency of myocardial infarctions was higher in patients treated with 0.5 mg of ranibizumab (2.1 percent) than in the other two arms (0.7 percent).

Source: Genentech Inc., January 2005.

NEI to Study Anecortave Acetate Plus Intravitreal Bevacizumab
Alcon Inc. will provide 15 mg anecortave acetate suspension (Retaane) for a National Eye Institute study investigating the long-term safety and potential efficacy of anecortave acetate in patients with all forms of wet AMD who are undergoing intravitreal therapy with the cancer drug bevacizumab (Avastin, Genentech Inc). In addition, Alcon announced that the Australian Therapeutic Goods Administration has approved anecortave acetate suspension for the treatment of subfoveal CNV due to wet AMD where a classic component exists.

Source: Alcon Inc., December 2005.

Clinical Testing of Artificial Vision System Set to Begin
Clinical testing of the 50-electrode Learning Retinal Implant System from Switzerland-based Intelligent Medical Implants is scheduled to begin this month in Germany. The artificial vision system has been implanted successfully in two patients so far. In a previous multisite European clinical study performed with a single electrode, independent researchers reported that 19 of 20 totally blind patients were able to see a small point of light after receiving the implant. The initial target market for the system is patients with retinitis pigmentosa. The company expects that the implant system will allow patients to move independently in an unknown environment by giving them the ability to "see" objects by identifying their size, shape, position and movements.
A high-speed digital signal processor, which is part of the Learning Retinal Implant System provides "intelligent information" to the implant by using tuneable software. The system is said to have learning capability because the tuning is based partly on patient feedback and input about perception.

Source: Intelligent Medical Implants AG, January 2006.

Company Informs Physicians about Postmarketing DME Reports
Last month, GlaxoSmithKline sent letters to health-care providers alerting them to a very small number of postmarketing reports of new onset and worsening diabetic macular edema in patients receiving the company’s diabetes drugs containing rosiglitazone (Avandia, Avandamet). In most cases, concurrent peripheral edema was also reported. In some cases, the macular edema resolved or improved following discontinuation of therapy. In one case, macular edema resolved after dose reduction.

Source: GlaxoSmithKline, December 2005.

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