Here are abstracts and summaries of all posters, papers, and sessions related specifically to macular degeneration, as presented at the annual meeting of the American Academy of Ophthalmology in San Francisco on October 23-27, 2009.
The reports are categorized by type of intervention:
Nutraceutical
Surgical
Pharmaceutical
Anatomical
Genetic
Daily Living
For easy scanning of basic information, titles and conclusions are printed in bold face.
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NUTRACEUTICAL
Poster: "Is There a Connection Between Vitamin D Levels And AMD?" (Presenting Author:
Shani Golan)
Background: Recent evidence suggests a correlation between vitamin D, angiogenesis and inflammation, which play a role in AMD Design Retrospective cohort study carried out in Maccabi Health Center (HMO in Israel). Members aged = 60 years, whose vitamin D levels were taken for routine examination since 2000 were evaluated for existence of AMD.
Results: The total study cohort included 1045 AMD patients and 8124 controls. The mean level of vitamin D was 24.1± 9.4 and 24.1 ± 9.5ng/mL in AMD patients and control respectively. The proportion of tests in which vitamin D was<16ng/mL or >74ng/mL were not significantly different in both groups.
Conclusion: Members with AMD had a vitamin D level similar to that of matched controls. The difference between our study and other studies can be biased due to increased sun exposure and high awareness to supplement intake.
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Paper: "Plasma Omega 3 Fatty Acids and Risk for Age-Related Maculopathy: The ALIENOR Study" (Presenting Author:
Jean-Francois Korobelnik MD)
Purpose: To study the association of age-related maculopathy (ARM) with plasma fatty acids.
Methods: 671 subjects of the population-based ALIENOR Study had an eye examination 7 years after plasma fatty acid measurement.
Results: In multivariate analyses, lower risk of geographic atrophy was associated with higher plasma levels of total omega=3 fatty acids (OR=0.53, 95 CI, 0.30% O.94%, P=.03), EPA (OR =0.38, 95% CI, 0.16% 0.89%, P=.03), and EPA+DHA (OR=0.54, 95% CI, 0.30% -.98%, P=.04). Neovascular and early ARM were not significantly associated with plasma fatty acids.
Conclusion: This study shows an association of geographic atrophy with plasma omega-3 status, in accordance with previous studies of dietary intake.
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SURGICAL
Session: "Implantable Miniaturized Telescope" (Presenter: Mark R. Wilkins, MD)
The investigational implantable miniature telescope (by Dr. Isaac Lipshitz) is designed to be a solution for moderate to profound vision loss due to advanced, end-stage forms of AMD that have no current surgical or medical treatment options. Smaller than a pea, the telescope prosthetic device is implanted in one eye in an outpatient surgical procedure. In the implanted eye, the device renders enlarged central vision images over a wide area of the retina to improve central vision, while the non-operated eye provides peripheral vision for mobility and orientation. On March 27, the FDA Ophthalmic Devices Advisory Panel unanimously recommended that the FDA approve, with conditions, the premarket application (PMA) for VisionCare's device for End-Stage AMD. The telescope implant is the first medical device to be recommended by the panel for FDA approval for End-Stage AMD, a leading cause of untreatable blindness in the U.S. The company anticipates FDA approval within the next few months. The device has received CE Mark approval in Europe.
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PHARMACEUTICAL
Paper: "Eighteen-Month Results From an Extension Study of a Phase 2, Dose- and Interval-Ranging Study of VEGF Trap-Eye in Wet AMD" (Presenting Author: David S Boyer MD)
Purpose: To present 18-month results from a wet AMD extension study.
Methods: Of 157 patients randomized into a Phase 2 trial of monthly and quarterly fixed doses of VEGF Trap-Eye, followed by p.r.n. dosing to 12 months, 117 entered an open-label extension study of 2 mg p.r.n. dosing.
Results: Mean change in BSVA was +7.3 letters (P < .0002) at 3 months after fixed dosing and +7.1 letters (P < .0001) at 18 months, with a mean of 3.5 injections over the p.r.n. period. VEGF Trap-Eye was generally well tolerated with no drug-related adverse effects.
Conclusion: Improvements in BCVA were maintained over 18 months, requiring relatively few re-treatments.
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Paper: "Fenretinide for the Treatment of Geographic Atrophy in Patients with AMD: One-Year Interim Analysis" (Presenting Author:
Roger Vogel MD)
Purpose: To present 1-year efficacy and safety results for fenretinide 100 mg and 300 mg vs. placebo in the treatment of geographic atrophy (GA) related to AMD.
Methods: Patients (N=245) received fenretinide 100 mg, 300 mg, or placebo capsules for 2 years. Interim efficacy analyses include GA lesion growth and adverse event rates.
Results: At 18 months, 78% of lesions in the 300 mg group grew less than the median of the placebo. The 100 mg dose appears most protective against growth in small lesions (< 3 DA). Conversion to wet AMD occurred less in the 100 mg (6%) and 300 mg groups (7%) than in placebo (13.4%).
Conclusion: There was a strong trend for efficacy regardless of baseline lesion size in the 300 mg group and for smaller lesions in the 100 mg group; dose-related dark-adaptation delay was as expected.
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Paper: "Safety Outcomes Over 2 Years in the HORIZON Extension Trial of Ranibizumab (Lucentis) in Neovascular AMD" (Presenting Author:
Matthew S Benz MD)
Purpose: To evaluate safety of ranibizumab in patients with neovascular AMD who completed the 2-year MARINA, ANCHOR, or FOCUS trial.
Methods: Patients (N=853) could receive open-label 0.5 mg intravitreal ranibizumab p.r.n. at = 30-day intervals. Safety was assessed at all visits.
Results: For 600 patients who received ranibizumab in prior trials, the most common ocular adverse events (AEs) over 2 years were worsening macular degeneration (35%), retinal hemorrhage (25%), and conjunctival hemorrhage (25%); rates of serious ocular and non-ocular AEs were 6.7% and 26.3%; and rate of arterial thromboembolic events was 7.5%.
Conclusion: Incidence of ocular and non-ocular safety events was low and consistent with prior ranibizumab trials.
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Paper: "A Randomized Pilot Study of AMD With Systemic Immunosuppressive Therapy" (Presenting Author:
Robert B Nussenblatt MD)
Purpose: To compare anti-VEGF therapy plus 1 of 3 systemic immunosuppressive therapies or observation for persistent CNV associated with AMD.
Methods: Randomized pilot study.
Results: Thirteen patients requiring ongoing anti-VEGF therapy were randomized. Monthly rates of anti-VEGF injections were 0.42 and 0.34 for daclisumab and sirolimus, respectively, compared with 0.83 for bother the control group and the infliximab group. Daclizumab and sirolimus rates also decreased compared with prestudy rates. Visual acuities were maintained in all groups.
Conclusion: The observed decreases in re-treatment rates for daclizumab and sirolimus suggest that more definitive clinical trials of immune mediation of AMD are indicated.
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Paper: "Interference of Cell Survival Signals by Targeting α5β1 Integrin (Volociximab) and VEGF in Neovascular AMD: A Phase 1 Study" (Presenting Author:
Baruch D Kuppermann MD PhD)
Purpose: To assess safety of intravitreal volociximab, an ±5≤1 integrin antagonist, combined with ranibizumab for neovascular AMD.
Methods: Phase 1 open-label study. Subjects receive 3 monthly injections of volociximab (0.5, 1.25, or 2.5 mg/eye) in combination with ranibizumab.
Results: Results to date have shown no signs of drug toxicity. Ten subjects received 2 doses of the combination. Mean change in VA was +10.8 letters at Week 9, with a 3-line gain of 40% and mean change in OCT center point of -136 ºm.
Conclusion: Initial results of Phase 1 study of colociximab combined with VEGF inhibition suggest a favorable safety profile.
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Paper: "Targeting Platelet Derived and Vascular Endothelial Growth Factors for Neovascular AMD: Phase 1 Study" (Presenting Author:
Allen C Ho MD)
Purpose: To assess the safety of E10030, an anti-PDGF PEGylated aptamer combined with ranibizumab for neovascular AMD.
Methods: Predominantly or minimally classic neovascular AMD lesions were treated in a dose-escalation scheme with 13 monthly E10030 injections (0.3, 1.5, or 3.0 mg) combined with 13 monthly ranibizumab injections.
Results: No drug-related adverse events were detected. Fifty-nine percent of subjects gained "e 15 letters at Week 12 (n=22), mean letter gain was +14.0, mean change in OCT center point was -157 ºm, and 85% of patients exhibited neovascular regression.
Conclusion: E10030 combined with ranibizumab was well tolerated, with resultant significant neovascular regression.
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Paper: "Phase 1 Results of the Complement C3 Inhibitor POT-4 in AMD" (Presenting Author:
Philip J Rosenfeld MD PhD)
Purpose: To determine the safety of POT-4 in an intravitreal dose-escalation study in advanced wet AMD.
Methods: Seven doses (1 1050 ºg) in 27 eyes were investigated for adverse events and pharmacokinetics with imaging by fundus photography, fluorescein/ICG angiography, and OCT.
Results: No drug-related serious adverse events were reported. Sll POT-4 doses were well tolerated and visual acuity was stable or improved. POT-4 exhibited sustained-release properties with visible gel deposits for at least 4 months and detectable serum levels. Complete resolution of macular edema was seen in 2 high-dose patients.
Conclusion: POT-4 was well tolerated, appeared safe, exhibited sustained-release properties, and appeared to improve chronic macular edema.
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Poster: "Macular Hole After Bevacizumab Intravitreal Injection" (Presenting Author:
Andres Emanuelli MD)
Purpose: To report a case of a macular hole following a intravitreal bevacizumab injection (IVB) in the treatment of a submacular hemorrhage (SMH).
Methods: A 76-year-old woman was diagnosed with SMH secondary to a choroidal neovascular membrane (CNVM) due to AMD. Patient was treated initially with IVB.
Results: The patient developed a sudden decline in vision 1 week after IVB and was subsequently diagnosed with a macular hole. Intravitreal injection with SF6 was done for SMH pneumatic displacement. One week later she developed a retinal detachment and she underwent 23-gauge pars plana vitrectomy with C3F8 injection. The macular hole was closed and the retina attached at the patient's final follow-up visit.
Conclusion: IVB injection used for the treatment of SMH secondary to a CNVM can be associated with a subsequent macular hole.
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Poster: "Comparison of 2 Doses of Primary Intravitreal Bevacizumab for Subfoveal CNV in AMD: Results From a Multicenter Study Group at 24 Months" (Presenting Author:
J Fernando Arevalo MD FACS)
Purpose: To report the 24-month anatomic and functional response after primary intravitreal bevacizumab (IVB, 1.25 mg or 2.5 mg) in patients with subfoveal choroidal neovascularization (CNV) secondary to AMD.
Methods: Retrospective review of 180 consecutive patients (207 eyes).
Results: In the 1.25mg group, baseline BCVA improved from a mean logMAR 1.07 to 0.92 at 24 months (P < .0001). Central macular thickness (CMT) at baseline had a mean of 308.4 ± 127.52 µm, which was reduced to 249.27 ± 89.14 µm (P < .0001). Similar changes were observed in the 2.5mg group.
Conclusion: Primary IVB at doses of 1.25 to 2.5 mg seem to provide stability or improvement in BCVA, and CMT in subfoveal CNV secondary to AMD at 24 months. No differences between doses were seen.
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Poster: "Ranibizumab for Neovascular AMD Using a Treat and Extend Regimen" (Presenting Author:
Avni H Patel MD)
Purpose: To evaluate the “treat and extend” approach of managing neovascular AMD (nAMD) with intravitreal ranibizumab (RAN).
Methods: A retrospective study of nAMD eyes treated with monthly RAN until there was no exudation on OCT. Treatment intervals were extended by 2 weeks unless exudation recurred.
Results: Ninety-two eyes were included. Mean follow-up was 1.5 years. Mean number of injections was 7.9 in 1 year. Mean visual acuity (VA) improved from 20/135 to a final VA of 20/71 (P < .001). Ninety-seven percent of patients lost < 3 lines of VA, and 33% improved ≥ 3 lines of VA.
Conclusion: The “treat and extend” approach for managing nAMD with RAN led to significant visual improvement and outcomes similar to RAN pivotal trials, with fewer injections and visits.
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Poster: "OCT and Fluorescein Angiography Outcomes Through 1 Year for a Phase 2 Study of Intravitreal VEGF Trap-Eye in Neovascular AMD" (Presenting Author:
Peter K Kaiser MD)
Purpose: OCT and fluorescein angiography anatomic outcomes 1 year after repeated VEGF Trap-Eye intravitreal injections.
Methods: Phase 2 trial in AMD patients randomized to VEGF Trap-Eye 0.5 or 2.0 mg monthly or 0.5, 2.0, or 4.0 mg quarterly for 12 weeks, followed by p.r.n. dosing.
Results: After 1 year there was a significant decrease in central retinal/lesion thickness (CR/LT), total macular volume (TMV), and pigment epithelial detachment (PED) thickness. There was modest decrease in total lesion size, and significant reduction in active CNV size.
Conclusion: At 1 year, VEGF Trap-Eye produced significant reductions in CR/LT, TMV, PED thickness, and CNV size.
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Poster: "VEGF Trap-Eye Vision-Specific Quality of Life Through 52 Weeks in Patients With Neovascular AMD in CLEAR-IT 2: A Phase 2 Clinical Trial" (Presenting Author:
Allen C Ho MD)
Purpose: To assess the effects of VEGF Trap-Eye on patient-reported vision-specific quality of life (QoL) using NEI VFQ-25.
Methods: AMD patients were randomized to VEGF Trap-Eye 0.5mg or 2mg monthly or 0.5, 2, or 4mg quarterly for 12 weeks, followed by p.r.n. dosing to Week 52. The NEI VFQ-25 was administered at baseline, week 12, and week 52.
Results: Change from baseline at 52 weeks for all groups combined (n = 145) was +4.5 (total), +5.7 (near), +3.4 (distance), and +5.8 (dependency). Patients in the 2.0mg q4 group (n = 28) had notable changes of +6.8 for near activities and +11.6 for dependency.
Conclusion:Patients treated with VEGF Trap-Eye demonstrated improvements in QoL. Most notable improvements were seen in the 2mg q4 group.
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Session: "Emerging Pharmacotherapies for the Treatment of Posterior Segment Diseases"
Despite numerous scientific efforts, delivery of therapeutic amounts of a drug to the retina remains a challenge. This challenge is compounded if chronic therapy is desired. Ongoing clinical trials with various VEGF inhibitors in AMD and diabetic retinopathy were discussed. Included were "Ranibizumab (Lucentis) in AMD & DDME" (Maria H Berrocal MD), "Bevacizumab (Avastin) in AMD & DDME" (J Fernando Arevalo MD FACS), "VEGF Trap" (Quan Dong Nguyen MD), and "siRNA" (Alexander J Brucker MD). Information about these and other VEGF inhibitors under study may be found at www.mdsupport.org/library/anti-angio.html.
Also discussed were "Drug Delivery/Pharmacokinetics and Safety" (Mauricio Maia MD), and "Combined Therapies in AMD" (Colin A McCannel MD). Information on these and related topics may be found in the MD Support Library at www.mdsupport.org/library.html.
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Poster: "Single Subretinal Dose of Bevacizumab (Avastin) for the Treatment of Choroidal Neovascularization in Patients With AMD" (Presenting Author:
Claudio P Juarez MD)
Purpose: To evaluate the clinical experience of a single subretinal (SR) dose of bevacizumab (Avastin) in patients with subfoveal AMD.
Methods: Four eyes of 4 patients with unilateral subfoveal CNV were recruited. All patients had ≤ 20/400 visual acuity (VA) in the affected eye. Each patient underwent vitrectomy with a single SR injection of bevacizumab (0.25 mg/ml).
Results: SR bevacizumab injections were well tolerated. At 1 year follow-up, VA was stable or improved in 100% of eyes. Considerable decrease of subretinal CNV and central foveal thickness was obtained and maintained during 12 months.
Conclusion: A single dose of SR bevacizumab is safe and effective and significantly improves VA in patients with wet AMD.
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Poster: "Intravitreal Bevacizumab vs. Verteporfin Photodynamic Therapy for the Treatment of Myopic CNV" (Presenting Author:
Leila El Matri MD PhD)
Purpose: To compare verteporfin photodynamic therapy (PDT) with intravitreal bevacizumab (IVB) for management of myopic CNV.
Methods: Prospectively collected data of myopic CNV treated by PDT (n = 40) or IVB (n = 40). Main outcome measures were stability or improvement in BCVA and decrease in central retinal thickness at 3, 6, and 12 months.
Results: Mean BCVA and mean central retinal thickness were significantly better at 3 months (P = .04 and P = .035) and at 6 months (P = .032 and P = .04) in the IVB group but were not significantly different at 12 months.
Conclusion: During 12 months, IVB was superior to PDT in controlling myopic CNV.
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Poster: "Long-term Changes in Electroretinogram After Intravitreal Bevacizumab (Avastin) Treatment of Exudative AMD" (Presenting Author:
Teruyo Kida MD PhD)
Purpose: To evaluate the retinal function after intravitreal bevacizumab (IVB).
Methods: Electroretinograms (ERGs) were recorded from 18 patients with exudative AMD; 9 with IVB and 9 by photodynamic therapy (PDT). The ERGs were recorded before and 3 months and 1 year after each treatment. The amplitudes of the oscillatory potentials (OPs), the B/A-wave ratio, and flicker ERGs were assessed.
Results: There were no significant changes in the ERGs in the PDT group; however, the OPs and flicker amplitudes were significantly decreased 1 year after IVB (P = .0295 and .0042).
Conclusion: The decrease in the ERGs after IVB may be due to changes in the retinal circulation or cone function.
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Paper: "Efficacy of Ranibizumab Alone or in Combination With Verteporfin Photodynamic Therapy Analyzed by Demographic and Baseline Variables in the MONT BLANC Study" (Presenting Author:
Peter Wiedemann MD)
Purpose: To assess in wet AMD patients of the MONT BLANC study the efficacy of combined verteporfin PDT + ranibizumab or ranibizumab alone based on demographic and baseline (BSL) variables.
Methods: For both treatment groups, the change in BCVA from BSL to Month 12 was stratified by demographic and baseline characteristics such as age, gender, visual acuity, central retinal thickness, and lesion type and size.
Results: Efficacy outcomes stratified by demographic and BSL variables will be presented and compared between treatment groups.
Conclusion: Results will help identify demographic or BSL characteristics that may impact treatment outcomes for both verteporfin PDT + ranibizumab or ranibizumab monotherapy.
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ANATOMICAL
Poster: "Foveal Preservation in Geographic Atrophy From AMD" ((Presenting Author:
Janet S Sunness MD)
Purpose: To demonstrate the preservation of the fovea over time in eyes with geographic atrophy (GA) from AMD.
Methods: Prospective natural history study of GA, which included 74 patients with GA and visual acuity of 20/50 and better. Median follow-up time was 4+ years.
Results: Forty-four percent of patients had preservation of the fovea at the last follow-up visit. However, mean visual acuity dropped by 2.7 lines at 2 years, and 5.1 lines at 4 years. There was a profound drop in reading rate over time. The eyes most likely to lose 3 or more lines of VA at 2 years had between 25% and 75% of the central 4 disc areas of the macula involved with GA at baseline; those eyes with < 25% or > 75% were at lower risk for VA loss.
Conclusion: Foveal preservation may be present for a number of years. Certain eyes seem to have stronger preservation of the fovea, despite large areas of surrounding GA.
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GENETIC
Poster: "AMD Genetics: Risk and Protective Haplotypes in CFH, Factor B, and LOC387715 Genes for CNV-AMD" (Presenting Author:
Javier Zarranz-Ventura)
Purpose: To analyze the specific SNP haplotypes of principal genes implicated in CNV-AMD in a cohort of 97 patients and 98 controls.
Methods: Six SNPs within CFH gene, 5 within MCP, 3 within Factor B, 1 of C3, and 1 of LOC387715 were genotyped by allelic discrimination using TaqMan SNP genotyping assays or by automatic DNA sequencing. Haplotype frequencies were estimated by the SNPstats software.
Results: CFH H1 and Factor B B1 haplotypes are associated to a higher risk of CNV-AMD (OR: 2.6, P < .001; 1.9, P=.008), whereas CFH H2, H4a, and Factor B B3 has a protective effect (OR: 0.5, P=02; 0.26, p < .001; 0.33, P=.008). Significant ratios were also observed for Y402H, IV15, A695, and iCFHR1-3.
Conclusion: CFH and Factor B haplotypes are specifically associated with CNV-AMD.
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Paper: "Genome-Wide Association Study Reveals New Loci Associated With Patient Response to Ranibizumab Treatment for Neovascular AMD" (Presenting Author:
Jason S Ehrlich MD)
Purpose: Genetic influence on response to wet AMD therapy is poorly understood.
Methods: We performed a genome-wide association study on 352 patients from Phase 2/3 ranibizumab trials. Single nucleotide polymorphyisms (SMPS were evaluated for association with mean change in visual acuity after 12 months of therapy.
Results: More thaqn 5 SNPs previously unassociated with wet AMD were identified at a P-value of < 1X10-6. The candidate loci were enriched for genes related to wound repair and extracellular matrix remondeling (3 of 5 loci).
Conclusion: These findings suggest that genetic heterogeneity in tissue healing responses can affect visual acuity improvements after wet AMD treatment. Validation of these results with independent data sets is necessary.
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DAILY LIVING
Poster: "Reading With a Macular Ring Scotoma" (Presenting Author:
Janet S Sunness MD)
Purpose: To describe the difficulties encountered by patients with macular ring scotomas when they try to read. These patients have difficulty with reading that far exceeds their reduction in visual acuity.
Methods: Data from a prospective study of 75 patients with macular-sparing scotomas.
Results: Patients with macular ring scotomas may display a sharp peak in reading rate at small character size, with a rapid fall-off as character size increases. For some patients, there is a second peak at large character size, corresponding to a shift to an eccentric retinal site. This second peak may be higher than the first, but it is often difficult to get patients to ignore the foveal input in favor of extrafoveal input.
Conclusion: Patients with macular ring scotomas have a "catch 22" situation when it comes to reading.
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Poster: "Vision-Related Mental Health Changes in Response to Ranibizumab Therapy in MARINA and ANCHOR" (Presenting Author:
Ivan J Suner MD)
Purpose: To examine patient-reported changes over 24 months in vision-related mental health in neovascular AMD patients enrolled in MARINA and ANCHOR.
Methods: The 4 items of the NEI VFQ-25 mental health subscale ask about worrying about eyesight, frustration, control, and embarrassment due to eyesight.
Results: After 24 months, ranibizumab-treated groups were more likely to report improved mental health compared to baseline. For example, for the 0.5mg ranibizumab group, mean improvement (95% CI) in the ‘feeling frustrated’ item 0.72 (0.52, 0.92), compared to only 0.07 (-0.15, 0.30) for the sham group in MARINA.
Conclusion: Patient vision-related perception of mental health items was more likely to improve after ranibizumab in MARINA and ANCHOR.
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