Lee M. Jampol, MD   

Introduction

In the retinal disease summary I wrote for Medscape's coverage of the American Academy of Ophthalmology (AAO) meeting in 2005,^[1] I discussed the increasing off-label intravitreal use of the anti-vascular endothelial growth factor (VEGF) drug bevacizumab in the retinal community. With some evidence of efficacy, and while awaiting approval from the US Food and Drug Administration (FDA) for the related intravitreal compound ranibizumab, many retinal specialists began to use bevacizumab for the treatment of age-related macular degeneration (AMD), as well as other diseases with abnormal blood vessel growth or leakage in the eye, including diabetic retinopathy and vein occlusions. Six months after the AAO, in the June 2006 issue of EyeNet,^[2] the magazine produced by the AAO, I related how off-label use of bevacizumab exploded following the meeting. Even since the June 2006 US FDA approval of ranibizumab, the use of bevacizumab has continued. As expected, the 2006 AAO retinal meeting continued the discussion of pharmacologic therapy for AMD. Prior to the meeting, the October 5 issue of The New England Journal of Medicine featured 2 articles^[3,4] describing the 2-year results of the use of ranibizumab for treatment of neovascular AMD. These articles clearly showed that ranibizumab has much greater efficacy than previous treatments (ie, photodynamic therapy [PDT] with verteporfin, pegaptanib, PDT plus intravitreal triamcinolone).

Retina Subspecialty Day at the AAO meeting featured a section devoted to the latest in AMD anti-VEGF therapy, including the debate of off-label bevacizumab vs FDA-approved ranibizumab as well as other options. Joan Miller^[5] reviewed the results of the MARINA study of ranibizumab, one of the 2 articles published in The New England Journal. Other speakers reviewed therapy of neovascular AMD with the use of bevacizumab,^[6] PDT plus steroid given intravitreally,^[7] and PDT in combination with anti-VEGF agents.^[8] Some physicians are using triple therapy, including an anti-VEGF agent, intravitreal corticosteroids, and PDT. Other new anti-VEGF treatments, including RNA interference^[9] and the uses of VEGF trap,^[10] were also discussed.

Ranibizumab vs Bevacizumab

Joan Miller, MD,^[5] reviewed the results of MARINA,^[3] one of the trials that led to the June 2006 FDA approval of ranibizumab. This 2-year, randomized, double-masked, controlled study included 716 patients with occult with no classic or minimally classic choroidal neovascularization (CNV) who were randomized to receive monthly injections of 0.3 mg ranibizumab, 0.5 mg ranibizumab, or sham injection. At 12 months and again at 24 months, ranibizumab was shown to stabilize vision (it prevented 15 letters of visual loss) in approximately 95% of patients. Moreover, about 30% to 40% of patients showed an improvement in vision (15 letters gained). Safety assessments showed that ranibizumab was well tolerated.

Jeffrey Heier, MD,^[11] reviewed the results of the ANCHOR trial, which was also integral to the approval of ranibizumab. In this randomized, controlled, phase 3 trial, PDT with verteporfin was compared with ranibizumab at 0.3-mg and 0.5-mg doses. A total of 423 patients with predominantly classic CNV were assessed. At month 12, the results for the patients receiving ranibizumab were similar to the results of the MARINA trial: Approximately 95% of ranibizumab patients had lost less than 15 letters, and 36% to 40% of patients had 15 or more letters of visual gain. In contrast, only 64% of patients receiving PDT with verteporfin lost less than 15 letters and just 6% gained 15 or more.

The main questions at the present time are:

• Use ranibizumab or bevacizumab?
  
  
• How frequently?
  
  
• For how long do the shots have to be given?

In the studies submitted for FDA approval, ranibizumab was given monthly for up to 2 years. Ursula Schmidt-Erfurth, MD,^[12] reviewed in detail what we know about frequency and duration of injections. Results of the PIER trial,^[13] which tried less frequent dosing by administering monthly ranibizumab for the first 3 months followed by quarterly dosing, were not as good as the monthly dosing results. Nevertheless, she emphasized that reductions in treatment frequency will be required to successfully introduce ranibizumab therapy into clinical practice. One of the promising strategies for reducing treatment frequency is to use diagnostic imaging tools to identify structural changes that might require more or less frequent follow-up. At this time, most retinal specialists are giving 3 or 4 monthly shots of bevacizumab or ranibizumab and then following the patients with ocular coherence tomography (OCT) to detect early recurrence, which is then retreated.

Dr. Phil Rosenfeld^[6] described his experience with intravitreal bevacizumab, as well as an American Society of Retinal Specialists (ASRS) poll of 227 doctors. Bevacizumab is approved by the US FDA for the treatment of colorectal cancer, and its systemic use has raised concern regarding adverse effects such as hypertension and bleeding complications. The experiences of Rosenfeld and others in mainly retrospective studies have been that intravitreal bevacizumab is well tolerated in the eye and has few, if any, systemic effects. In general, it appears that visual acuity improves and neovascular lesions stop growing and leaking shortly after its use. OCT imaging is also used to monitor patients. Dose response curves have not been worked out as yet, but a 1.25-mg dose is being used widely.

Despite the approval of ranibizumab, bevacizumab is still being used widely in the United States and elsewhere in the world for therapy of neovascular AMD and other retinal diseases. This is largely because of its lower price. Although bevacizumab is not FDA-approved for AMD, it is approved for reimbursement by Medicare in 48 of the 50 states. Also, because the dose for injection in the eye is so much smaller than the systemic dose, the cost of bevacizumab is in the range of $25 to $75 per dose, compared with approximately $2000 per dose for ranibizumab. Results of the ASRS poll revealed that 76% of retinal specialists would use bevacizumab or bevacizumab plus PDT if a patient had Medicare coverage with no secondary insurance, as opposed to 21% who would use ranibizumab or ranibizumab plus PDT. In patients with Medicare plus secondary insurance coverage, 55% of doctors would use bevacizumab or bevacizumab plus PDT, compared with 40% who would use ranibizumab or ranibizumab plus PDT. These data are surprising in terms of the number of US doctors preferentially using bevacizumab.

At this point, it is apparent that a large, randomized prospective trial is needed to determine the safety and efficacy of bevacizumab. Fortunately, a randomized trial comparing intravitreal bevacizumab with intravitreal ranibizumab for neovascular AMD, funded by the National Eye Institute, is scheduled to begin in 2007.

Other Treatment Approaches to AMD

The success of the anti-VEGF agents has led to a number of potential new treatment strategies. The use of combination therapy with the existing PDT with verteporfin has been proposed as having the potential to synergistically enhance results and perhaps decrease the need for injections. In addition, other types of antiangiogenic drugs, which inhibit VEGF in different ways, are under development. A number of these approaches were reviewed during Retina Subspecialty Day.

Dr. Evangelos Gragoudas^[8] presented data showing that the combination of the anti-VEGF agent pegaptanib and PDT with verteporfin was not better than the use of pegaptanib alone. Because pegaptanib alone is clearly inferior to the other available anti-VEGF agents, these results will not alter current therapy. It is unclear whether the addition of PDT with verteporfin would add to the efficacy of ranibizumab or bevacizumab or allow less frequent injections.

Other combination therapies, such as PDT with verteporfin and intravitreal triamcinolone, have been tried with mixed results. Although triamcinolone improved the efficacy of PDT with verteporfin, it also led to increases in steroid-induced glaucoma and cataract. With past results in mind, Albert Augustin, MD,^[7] designed a study examining the use of triple therapy: PDT with verteporfin; bevacizumab; and the steroid dexamethasone. In the 28-week study of 59 eyes of 59 patients, all of whom received triple therapy, visual acuity was improved in most patients. Only 1 cycle of treatment was required, supplemented occasionally by intravitreal injections of bevacizumab. Such an approach would require more extensive study, but it offers the possibility of lower cost and less frequent treatment.

RNA interference is a new treatment approach for CNV that seeks to inhibit production of VEGF. John Thompson, MD,^[9] presented the results of a phase 2 study of bevasiranib, a small interfering (si)RNA, for 110 patients with subfoveal CNV with predominantly classic or minimally classic lesions secondary to exudative AMD. Results of the study were not impressive, but it appeared safe and phase 3 clinical trials are expected. Other siRNA drugs are also in preliminary study phases. VEGF that is already in the eye may not be affected by siRNA and may result in progression of the disease for some time. Combination of these drugs with a dose of ranibizumab or bevacizumab may improve outcomes.

Peter Kaiser, MD,^[10] reviewed a number of other antiangiogenic approaches, including the VEGF trap, tyrosine kinase inhibitors, and squalamine. The VEGF trap is a soluble protein that acts as a decoy VEGF receptor. It appears to bind VEGF-A with higher affinity than pegaptanib, bevacizumab, or ranibizumab, and, due to its small size, penetrate all retinal layers. However, early results have been mixed, with some improvements in retinal thickness but also increases in hypertension. A phase 2 randomized study is currently recruiting patients. Tyrosine kinase inhibitors, which target all VEGF receptors and pathways, have been under study. One potential agent, which, similar to bevacizumab, has had preliminary success in oncology studies, is vatalanib. Preliminary studies are under way. Squalamine is an antiangiogenic agent that inhibits VEGF as well as other growth factors. It is given intravenously and thus allows patients to avoid ocular injections. Results from a phase 1/2 trial of single-agent squalamine showed promise, as did results from a phase 2 trial of combination PDT with verteporfin and squalamine. A phase 3 clinical trial of squalamine is currently enrolling patients.

Conclusion: The Current Status of Neovascular AMD Treatment

At this time, anti-VEGF therapy with ranibizumab or bevacizumab is clearly better than other modalities, including pegaptanib and PDT with verteporfin. The use of PDT with verteporfin plus intravitreal triamcinolone does increase the efficacy of PDT, but it is complicated by the development of steroid-induced glaucoma and secondary cataract. Whether ranibizumab or bevacizumab proves to be significantly better than the other in the long term will await a comparison trial, but at present, the price disparity is shifting physicians toward bevacizumab. Indeed, the recent ASRS survey indicated that perhaps 50% of physicians or more are presently preferentially using bevacizumab for neovascular AMD.

References

1. Jampol LJ. Debate over the use of anti-VEGF therapy in retinal disease. Medscape Ophthalmology. Available at: http://www.medscape.com/viewarticle/518884 Accessed November 27, 2006.
2. Jampol LJ. When off-label is on target. EyeNet Magazine. June 2006.
3. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
4. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.
5. Miller J. Results of the MARINA study (ranibizumab) for minimally classic or occult neovascularization. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
6. Rosenfeld PJ. Intravitreal bevacizumab (Avastin). Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
7. Augustin AJ, Offermann I. Photodynamic therapy and steroids: initial combination therapy leading to the study of triple therapy with verteporfin PDT, bevacizumab, and dexamethasone. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
8. Gragoudas ES. Verteporfin (Visudyne) and pegaptanib (Macugen). Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
9. Thompson JT. RNA interference. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
10. Kaiser PK. Other treatments for neovascular AMD: VEGF trap, squalamine, and tyrosine kinase inhibitors. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
11. Heier JS. The ANCHOR study: ranibizumab and photodynamic therapy. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
12. Schmidt-Erfurth U. How often is re-treatment with Lucentis needed? Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
13. Brown DM. Lucentis: PIER data. Program and abstracts of the Retinal Physician 2006 Symposium; May 31-June 3, 2006; Atlantis, Paradise Island, Bahamas.

Paul Latkany, MD   

　

　

Introduction

During the last few years, the retinal research field has undergone a dramatic change in terms of therapies that have resulted in substantial benefits for patients suffering from retinal disease. Specifically, anti-vascular endothelial growth factor (VEGF) therapies and optical coherence tomography (OCT) imaging have resulted in some of the central changes to retinal disease understanding and management. This new level of interest was reflected at Retina Subspecialty Day at the 2006 Joint Meeting of the American Academy of Ophthalmology (AAO) and Asia Pacific Academy of Ophthalmology (APAO), where the 3154 registrants represented over a 30% increase in attendance from the previous year and required an overflow room. This review highlights some of the advances discussed in the non-age-related macular degeneration portions of the 2-day event, including diagnostic imaging and genetic testing advances, pediatric retinopathy, and uveitis.

Advances in Diagnostic Imaging and Genetic Testing

There is a major paradigm change taking place in the field of ocular oncology. It is estimated that 17% of all white persons will have some type of uveal melanocytic tumor, and 0.5% of patients in the United States, or 80,000-100,000 people, will be at risk for metastasis. Tumors that do metastasize are thought to do so very early in tumor formation -- most likely by the time the ocular tumor is identified. Metastatic disease is not easily treated once it has spread to the liver. J. William Harbour, MD,^[1] Washington University, St. Louis, Missouri, argued that because the population at risk for uveal melanoma metastasis is not accurately identified by current clinical methods, molecular testing should be considered as a means to identify high-risk patients. Dr. Harbour used the analogy of glucose monitoring to explain the goal of molecular testing: to identify changes early and thereby initiate preemptive treatment.

Molecular testing involves classifying tumors as Class I or Class II uveal melanoma. Class I tumors almost never metastasize, while Class II tumors usually do. With as few as 10 genes RNA-profiled (obtained from fine-needle aspirate of tumors), ocular melanoma can be divided into Class I or Class II uveal melanoma. Relying on monosomy 3 (the loss of 1 copy of chromosome 3) may not be as accurate because it occurs later in tumor progression and does not appear as uniformly distributed throughout the tumor as results that can be obtained by RNA profiling. For example, Class I tumors usually lack monosomy 3. Because the gene profile characteristics likely occur earlier in tumor formation, Class I and Class II profiling appear more predictive than monosomy 3. In a related poster session during the general meeting, Paul Finger, MD,^[2] presented data on a noninvasive means to detect biomarkers to determine risk for metastasis through positron emission tomography (PET)/computed tomography (CT). He showed that a standardized uptake value > 4 on PET/CT corresponded with a markedly increased mortality risk.

Yale Fisher, MD,^[3] and Richard Rosen, MD,^[4] brought the audience up to date on the importance of optical coherence tomography (OCT). Both speakers discussed OCT's c plane (or en face) imaging capability, which allows an image similar to that seen in a normal fundus camera. However, both speakers highlighted the threshold of a new era in OCT imaging with the transformation of technology from the current "time-domain" OCT to the "spectral domain" OCT. Spectral OCT will allow much quicker image capture because it doesn't require the internal mirror movement that is necessary in current "time-domain" systems. It appears that spectral OCT can result in as many as 40,000 A-scans per second. The major benefit of spectral OCT is that it permits point-to-point registration and can give accurate volumetric analysis. Several companies are likely to make spectral-OCT technology commercially available over the next year.

There has been a maturing of gene testing and profiling according to Edward Stone, MD.^[5] He detailed plans for his lab to develop nonprofit tests for each of the 120 retinal disease genes that have been discovered. Their goals for characteristics of all gene tests are:

• to have a standardized test result report structure;
  
  
• to cost less than $500;
  
  
• to have a greater than 50% chance of being clinically meaningful; and
  
  
• to have results within 8 weeks.

At present, his lab can identify a mutation result in 50% of the 3000 people in the United States with Leber's congenital amaurosis (LCA) and is looking to identify all LCA patients.

Pediatric Retina

The Age-Related Eye Disease Study (AREDS)^[6] established the value of antioxidant consumption in the treatment of AMD. Lois Smith, MD, PhD,^[7] presented compelling preclinical data regarding the potential of the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to be used in the treatment of retinopathy of prematurity (ROP). These substances are found in the retina and are obtained primarily from oily fish in our diet. Lower mortality rates have been correlated with higher intakes of fatty acids. Through animal models, it appears that omega-3 fatty acids correspond with a strong reduction of neovascularization in a ROP model, apparently through a reduction of several factors, including tumor necrosis factor (TNF). Clinical studies involving supplementation in ROP and diabetic retinopathy are being planned.

In other approaches to ROP treatment, Michael Trese, MD,^[8] encouraged caution regarding the use of anti-VEGF therapy outside of a well-designed clinical trial. In a small series with pegaptanib in ROP, there was no difference in retinal detachment outcome. However, a trial involving bevacizumab, which has met with greater success in AMD treatment, is planned.

Pediatric uveitis is a rare disease, with estimates suggesting that 20,000 children in the United States are affected. Janet Davis, MD,^[9] reviewed some of the complications that have been connected with this disorder. In one series, 28% of children with pars planitis had a vitreous hemorrhage. In Bascom Palmer Eye Institute's series of 148 pediatric patients with uveitis accrued over 5 years, 112 had noninfectious uveitis. Cataract occurred in about half of patients after 5 years, and cystoid macular edema occurred in 35% of patients. Dr. Davis cautioned against intraocular lens implantation in children with uveitis. She also recommended delaying surgical intervention for cataract until adulthood if it occurs outside of the amblyopic risk group and is unilateral. The best treatment for cataract and cystoid macular edema is avoidance. She advised referral to a uveitis-trained specialist early in the disease process because systemic immunomodulatory therapy can help prevent the need for surgical intervention. Pars planitis has peripheral membranes; ultrasound biomicroscopy can help select vitrectomy entry sites to avoid peripheral membranes in select cases.

Logistic Retinal Office Discussion

Kirk Packo, MD,^[10] led a panel of 5 experts discussing "nightmares in the office and how to avoid them." The first scenario was anaphylaxis secondary to fluorescein angiogram; the panel suggested having an unexpired EpiPen (Dey LP; Napa, California) available. If that wasn't feasible, they stated that at the very least, all offices should know how to get emergency personnel promptly. Previous severe hives usually preclude the use of future fluorescein angiograms. Some panelists used subconjunctival lidocaine while others used a topical soaked xylocaine preparation alone for intravitreal injections. General office logistic solutions included recommendations to have an embezzlement insurance policy in place and to have an active billing compliance protocol.

Vein Occlusions

Carmen Puliafito, MD,^[11] discussed the use of the anti-VEGF agent bevacizumab in vein occlusion and highlighted the need to do repeat injections in most patients (67% in his study). With about 6 months of follow-up, his retrospective nonrandomized study showed improvement in all forms of nonischemic retinal vein occlusion. However, ischemic retinal vein occlusion does not appear to respond well to bevacizumab and also appears to prolong the time of the classic "90-day glaucoma" from neovascularization. His group planned to supplement bevacizumab with triamcinolone in cases that don't respond to initial bevacizumab.

Uveitis

Russell van Gelder, MD,^[12] discussed polymerase chain reaction (PCR), a short tandem amplification of multiple pathogens which, from mixed primers and subsequent hybridization, can distinguish between pathogens to identify the etiology of posterior uveitis. He cautioned against false negatives because of inherent inhibitors within the vitreous and aqueous humor. Intraocular antibody to rubella was present in all samples and positive PCR occurred in 5 of 28 aqueous humor samples in Fuch's heterochromic iritis. PCR and local antibody production were also used to identify active CMV infection in unilateral chronic uveitis associated with high intraocular pressure.

Doug Jabs, MD,^[13] discussed the Multicenter Uveitis Steroid Treatment Trial (MUST), a National Eye Institute-sponsored, multicenter, randomized trial designed to compare systemic immunosuppression with fluocinolone acetonide implant therapy for posterior and intermediate uveitis. The fluocinolone implant, while showing benefit in its initial trial, had not been directly compared with standard, systemic therapy; MUST is the first trial to do so. Questions that the investigators hope to answer include a comparison between the 2 approaches of visual outcomes, efficacy, rates of ocular and systemic side effects, and quality of life.

Vitreoretinal Surgical Trends

A panel looked at recent trends in vitreoretinal surgery.^[14] The recent development of 25-gauge surgery vitreoretinal port size is being supplemented by an intermediate port size. Several companies have released a variety of 23-gauge vitrectomy systems. The other topic under discussion looked at anti-VEGF therapy prior to diabetic vitrectomies. Its use usually results in less intraoperative bleeding from proliferative diabetic retinopathy (and less of a need to increase intraoperative intraocular pressure). Panelists warned that because of contraction forces from neovascular retraction from the therapy, intervention should usually be planned about 1 week post-intravitreal injection.

References

1. Harbour JW. Molecular predictive testing using gene expression profiling of fine needle biopsy. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
2. Finger PT, Chin K, Iacob CE. Positron emission tomography/computed radiographic tomography (PET/CT) imaging of choroidal melanoma: pathology and ultrasound correlations. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Poster 199.
3. Fisher YL, Loud K, Koizumi H, Orlock D. Clinical status: spectral OCT. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
4. Rosen RB. High resolution OCT. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
5. Stone EM. Nonprofit genetic testing of inherited eye disease. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
6. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417-1436.
7. Smith LEH, Connor K, Sangiovanni JP, Chew E. Animal model of retinal neovascularization and DHA therapy. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
8. Trese MT. Anti-VEGF treatment for pediatric retinal diseases. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
9. Davis JL. Pediatric uveitis. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
10. Packo KH. Nightmares in the office and how to solve them. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
11. Puliafito C. Intravitreal bevacizumab. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
12. Van Gelder RN. Advances in polymerase chain reaction diagnostics for ocular disease. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
13. Jabs DA. Multicenter uveitis steroid treatment trial. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.
14. Lewis H. Vitreoretinal surgery: videotape case presentation and discussion. Program and abstracts of the 2006 Joint Meeting of the American Academy of Ophthalmology and Asia Pacific Academy of Ophthalmology; November 11-14, 2006; Las Vegas, Nevada. Retina Subspecialty Day.