Scientific Meeting Highlights
Bascom Palmer Eye Institute kicked off its golden anniversary year by hosting a global scientific meeting February 2 - 4 in Miami. Nearly 650 ophthalmologists from around the world attended, including 300 Bascom Palmer alumni. With 180 distinguished presenters, subjects discussed ranged from research breakthroughs in cataract surgery and gene therapy, to goals of new clinical trials regarding the treatment of glaucoma and optic nerve diseases.
“The tremendous volume of information presented at the Scientific Meeting created a unique collaborative platform, which many of the world’s ophthalmologists can now use to explore new ways of approaching patient care and vision research,” said Eduardo C. Alfonso, M.D., chairman of Bascom Palmer Eye Institute, “From advanced medical and surgical treatment options to new trends in refractive surgery and oculoplastics, didactical presentations and interactive panel discussions covered the gamut of both remarkable achievements and exciting possibilities within the ever-changing field of ophthalmology.”
Meeting highlights include:
Corneal Crosslinking Benefits Patients With Keratoconus »
“Corneal collagen crosslinking has been offered extensively in Europe and other countries, but it's not FDA-approved in America. The treatment combines the vitamin riboflavin and UVA light at a very low dose, which is not harmful to the patient or to the other parts of the eye. That combination crosslinks and hardens the cornea. The objective is to identify patients with early-stage disease and offer them crosslinking to slow down or prevent further progression. Ultimately, we hope that crosslinking will eliminate the need for corneal transplants for these patients, but we still need more prospective and longer studies to know how long the effect lasts,” said Leejee H. Suh, M.D., assistant professor of clinical ophthalmology at Bascom Palmer Eye Institute.
New Drugs for Strabismus May Replace Incisional Surgery »
"This may seem like a provocative statement, that injectable drugs will become the principal intervention for primary forms of strabismus within our generation, but I think certainly this is within our grasp," said Stephen P. Christiansen, M.D., chairman of the department of ophthalmology at Boston University School of Medicine.
He noted the improved understanding of indications for Botox, one potential treatment for strabismus, and said he is encouraged by the expanding array of candidate drugs for modulating extraocular muscle strength - and that these drugs preserve normal biomechanical constructs. Long-term success rates for incisional surgery are poor, and reoperation rates are as high as 67%, he noted. Newer immunotoxin agents are under investigation to extend duration of treatment beyond that of botulinum toxin and rese.
Hemoglobin A1c, BP With Eye Exam for Diabetic Retinopathy »
The Diabetic Retinopathy Clinical Research (DRCR) Network is a network of community- and academic-based ophthalmologists that has been conducting clinical research related to diabetic retinopathy, macular edema, and associated conditions since 2002. David J. Browning, M.D., Ph.D., from Charlotte Eye, Ear, Nose and Throat Associates PA, in North Carolina, presented the latest information about DRCR studies. “Protocol M is a clinical trial to determine whether the ophthalmologist's interaction with the patient can favorably influence systemic risk factors,” said Dr. Browning.
“In this study, diabetic patients with or without retinopathy are prospectively enrolled in 1 of 2 arms — a standard therapy arm, in which the patient receives his typical visit with the ophthalmologist, and a test arm, in which the patient has an in-office hemoglobin A1c test and blood pressure measurement with immediate feedback and personalized education about the risks implied by their data on progression of retinopathy. The outcome of this study is a mean change in A1c at 12 months. Also, DRCR Network studies provide high-level evidence (generally level 1) that can guide clinical care of diabetic retinopathy. This is rare. The majority of studies published are level 2 or 3 studies — good for hypothesis generation, but not for drawing conclusions about care. Protocol S (Prompt Panretinal Photocoagulation [PRP] vs Intravitreal Ranibizumab With Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy) is important because it may provide a nondestructive treatment for proliferative diabetic retinopathy.”
Informed Consent Process for Cataract Surgery Has Become More Complex »
The advent of premium IOLs has complicated the informed consent process, presenting new challenges for surgeons in recommending the appropriate lens for a given patient, stated Charles M. Zacks, M.D., of Maine Eye Center. Dr. Zacks refreshed colleagues on the ethical guidelines of cataract surgery in light of expanding IOL choices and emphasized that surgeons should adhere to their role as medical practitioners and not accept inducements for referrals or kickbacks. According to Dr. Zacks, management should include careful preoperative assessment, patient education and informed consent with absence of bias. He stressed the significance of distinguishing between side effects and potential complications when explaining IOL options, advocating that advertisement remains fair and not economically motivated. "If you are practicing with these lenses or in a cataract practice in general, you should clearly understand the delegation of services and co-management, because this is very likely to come up in the next year. Appropriate fee arrangements, in particular, should be tracked," Dr. Zacks said.
Medical therapies may be preferred for treatment of ocular surface tumors »
Medical therapy may be a favored alternative to surgery for squamous neoplasia tumors, and new imaging technologies could aid treatment. "Excision with cryotherapy is successful but can leave residual disease. Mitomycin, fluorouracil [and] interferon are useful alternatives in the treatment of disease, and imaging techniques can help us treat this subtle lesion," said Carol L. Karp, M.D., professor of ophthalmology at Bascom Palmer Eye Institute.
Of available therapies, which include topical mitomycin and 5-fluorouracil 1%, Dr. Karp prefers interferon alpha-2b. Treatment may be delivered via topical drops or subconjunctival injection, and if a patient has no compliance or insurance barriers, Dr. Karp favors drops. This method is gentle, well-tolerated and causes no pain; however, it requires daily application, is associated with slow resolution (usually 3 to 4 months), demands compounding and costs roughly $225 a month, she said. If compliance or cost issues arise, Dr. Karp performs weekly injections. Interferon delivered subconjunctivally ensures compliance and typically results in rapid resolution after two to five injections. Conversely, flu-like symptoms may occur. Additionally, Dr. Karp uses ultrahigh-resolution optical coherence tomography to image tumors before, during and after treatment. "[Ultrahigh-resolution OCT] has really changed the way I practice ocular surface oncology. I can diagnose subtle lesions and also see when the tumor is gone," Dr. Karp said.
Early Results for Laser-assisted Dacryocystorhinostomy May Be Disappointing »
Despite recent U.S. Food and Drug Administration approval, diode laser for dacryocystorhinostomy may not meet expectations. "When it comes to technology in lacrimal surgery, I think we need to look at the results and not just get caught up in the technology and the marketing," said Michael T. Yen, M.D., associate professor of ophthalmology at Cullen Eye Institute.
Dacryocystorhinostomy (DCR) and conjunctivodacryocystorhinostomy (CDCR) for nasolacrimal duct obstructions were initially performed through external incision, but laser assistance is now entering the treatment paradigm. Of 26 surgeries performed by Dr. Yen and colleagues between August 2010 and June 2011 with an average follow-up of 151 days, complete resolution of epiphora occurred in approximately 26% of patients, and roughly 64% of patients felt that their epiphora was significantly better but still experienced some tearing. Re-operation rate was approximately 27%. "I don't think that the laser DCR is really ready for prime time yet. It is a great concept, but the results just really are not there to justify its use," Dr. Yen said.
He believes that the high failure rate may be attributed to excessive postoperative fibrosis or laser scatter. "I think laser DCR, CDCR shows promise, but success does not approach that of non-laser techniques. Maybe there are things we can do to refine this procedure, like using improved shielding with the probe, using mitomycin C, etc.," Dr. Yen said. "I think laser assistance may be desired in a very select patient group, but at this stage, for most patients, I would not recommend the procedure."
Piggyback Monofocal and Multifocal IOLs May Safely Correct High Myopia »
Placing a monofocal IOL and a piggybacked multifocal IOL in the capsular bag may safely restore distance and near vision in patients with exceptionally high myopia. "This is a safe enough procedure to correct high myopia and presbyopia in cases when the power of the multifocal IOL needed is not available," said Elena Barraquer, M.D., medical director of the Barraquer Ophthalmology Center in Barcelona.
The retrospective study included seven eyes of five patients (three men and two women), with a range of myopia between -16 D and -32 D. Patients had topographic astigmatism between 0.6 D and 2.8 D and averaged 54.4 years of age. Clear lens or cataract extraction was performed followed by placement of a monofocal IOL with negative power in the capsular bag and a multifocal IOL of 0 D also in the capsular bag. Notably, after approximately 2 years of follow-up, no cases of posterior capsular opacification have been observed. "Patients are very happy with the results, and if you have very high myopes, I think they will be happy, too," Dr. Barraquer said.
Endothelial and Lamellar Keratoplasty May Have Lower Risk of Graft Rejection Than PK »
The prevalence of immunologic allograft rejection may be higher with penetrating keratoplasty than with endothelial keratoplasty and deep anterior lamellar keratoplasty, a long-term study showed. In a seven-year comparative analysis reviewing charts of 1,647 patients who underwent corneal transplant between 2004 and 2010 by two surgeons at Toronto Western Hospital, the overall rejection rate was 7.6%.
"Rejection remains a leading cause of graft failure, and the prevalence of rejection is higher with penetrating than with endothelial or deep anterior lamellar keratoplasty," said Allan R. Slomovic, M.D., F.R.C.S.C., Clinical Director of the Cornea/External Disease Service at the Toronto Western Hospital.
"Over 90% of patients were symptomatic of their rejection episode. We know that early detection and management of rejection may improve graft survival." Incidence of rejection for PK was 9.4%, while incidences for EK and DALK were each 3.5%. "Glaucoma was one of the most common comorbid conditions, identified as a significant risk factor for failure [following rejection in PK and EK]. ... Glaucoma patients require closer monitoring post-keratoplasty," Dr. Slomovic said.
He also noted that a large proportion of patients were not on steroids at the time of rejection. "If there are no contraindications, penetrating and endothelial keratoplasty patients may benefit from a long-term daily dose of topical corticosteroids," he said. The study was limited by inability to control for preoperative diagnosis, corticosteroid regimens after transplantation and management of rejection episodes.
Individualized Treatment May Be Key in Managing Ocular Inflammation
After Cataract Surgery »
Individualized management of ocular inflammation following cataract surgery suggested.
"I think it is important that whichever drug you choose, the dosage, frequency, should all be based on ocular inflammation and patient risk factors," said David A. Goldman, M.D., assistant professor of clinical ophthalmology at the Bascom Palmer Eye Institute. "It is really important to get inflammation under control as quick as possible."
Dr. Goldman advised anti-inflammatory treatment for all patients, noting that steroids and NSAIDs are used most commonly. This approach may reduce the risk of cystoid macular edema, decrease postoperative pain and control inflammation early on, he said. When using topical corticosteroids, surgeons should consider that compliance decreases with increased number of drops and dosing frequency and that susceptibility to adverse effects varies by individual. Dr. Goldman also said that acute cases, particularly those with anterior chamber involvement, require aggressive management.
"More studies are needed to really confirm the best protocols for routine cataract surgery and evaluate different dosing regimens, including a more rapid tapering schedule, and looking at the potential for CME prevention and treatment," he added. Additionally, Dr. Goldman suggested pressure monitoring for those who are prescribed anti-inflammatory medications for more than a week and tapering steroid use rather than stopping it abruptly.
CABERNET Study Does Not Meet Primary Endpoint at Two Years »
Visual acuity results for epimacular brachytherapy to treat wet age-related macular degeneration did not meet a study's primary endpoint at two years.
The phase 3, multicenter, prospective, randomized CABERNET (CNV secondary to AMD treated with beta radiation epiretinal therapy) study included a treatment arm of 302 patients receiving strontium-90 epimacular brachytherapy (NeoVista) and two mandatory Lucentis (ranibizumab, Genentech) injections, followed by as-needed injections. The control arm consisted of 155 patients receiving ranibizumab on a modified PIER protocol with 10 mandatory injections. "The bottom line... is that the CABERNET study did not achieve its endpoint with a 10% non-inferiority margin," said Pravin U. Dugel, M.D., with Retinal Consultants of Arizona.
The treatment group required roughly six injections and demonstrated a mean 2.5 letter loss over 24 months, while the control group required approximately 11 injections and achieved a mean 4.4 letter gain. The difference in adverse events for the two groups was not significant. Ten patients had suspected radiation-based retinopathy. "The CABERNET study did demonstrate an acceptable safety profile for epimacular brachytherapy at the 2-year mark, and it did find a subgroup of patients that tended to respond well with this device," Dr. Dugel said.
Whether this subgroup of patients can be reliably and consistently identified in clinical practice is not yet known, he added. "At the end of the day, I think it is important to keep this study in its proper perspective. It was started in 2006 when there were few treatment alternatives. In retrospect, the CABERNET study should not have included treatment-naïve patients. ... The CABERNET study should have [also] placed a lot more importance on probe placement," Dr. Dugel said. "More studies are needed to really confirm the best protocols for routine cataract surgery and evaluate different dosing regimens, including a more rapid tapering schedule, and looking at the potential for CME prevention and treatment," he added.
Study Shows Low Rate of Endophthalmitis After Anti-VEGF injections »
A large-scale, single-center analysis demonstrated a low rate of endophthalmitis associated with anti-VEGF treatment. "In our own study and our review of the literature, we observed a very low rate of endophthalmitis, less than 1 percent. Patients tend to present very quickly after the injections, a contrary distinction from that seen with cataract surgery," Andrew A. Moshfeghi, M.D., M.B.A., assistant professor of ophthalmology at Bascom Palmer Eye Institute.
The study evaluated data for 75,018 anti-VEGF injections performed between January 1, 2005, and December 31, 2010. There were 13 clinically suspected cases of endophthalmitis, eight of which were culture-positive. Five of the culture-positive cases were caused by Streptococcus species, the most common bacteria isolated, and were associated with poorer visual outcomes.
Notably, there was no significant difference in rate of infection for Lucentis (ranibizumab, Genentech) and Avastin (bevacizumab, Genentech). Affected patients tended to present within the first 3 days of injection. "Talking, as I said, should be minimized, but the use of face masks is still controversial and is not standard. Antibiotic prophylaxis, however, does appear to be unnecessary and may actually increase the risk of resistant organisms," Dr. Moshfeghi said.
Variations in National Health Care Regulations Pose Challenge for European Union »
Aside from a centralized approval process for biotechnology drugs and uniform drug labels, widespread variation exists among nations in the European Union regarding patient access to health care.
In an update on anti-VEGF therapy in Europe, Stephan Michels, M.D., M.B.A., with the Department of Ophthalmology at the University Hospital in Zurich said that approval of Lucentis (ranibizumab, Genentech) for diabetic macular edema and macular edema secondary to retinal vein occlusion may not be coupled with a smooth transition to clinical usage. "The point is actually getting the approval and then also getting the reimbursement in Europe, and that is the problem. ... There is no European Union-wide decision on reimbursement. Each country decides individually. ... From [experience with age-related macular degeneration], we know that this can be a quite lengthy process," he said.
Moreover, national reimbursement agreements have led to variations in pricing, and many European health care systems enforce drug labels rather than the best evidence. For instance, the European Medicines Agency label for ranibizumab indicates how to treat patients, but Dr. Michels believes that treatment should be resumed upon lost visual acuity. The label contradicts many national ophthalmology societies, which also suggest management according to disease progression or anatomic surrogates. Approval of Eylea (aflibercept, Regeneron) for neovascular AMD is anticipated to occur during the second half of 2012, but again, there may be a lengthy transition to patient access, Dr. Michels noted. "I think the success will be very much dependent on the label ... the time to national reimbursement, which will likely be very lengthy, the pricing ... and the evolution of the reimbursement [of injection procedure], which is also a key issue in Europe," he said.
Surgery May Not Be Advisable for Patients with Brown's Syndrome »
Long-term follow-up of patients with Brown's syndrome suggested a conservative, nonsurgical approach. Roberto Warman, M.D., with Miami Children’s Hospital, presented data on the largest reported series of patients with bilateral Brown's syndrome. The retrospective review included data on five girls and four boys with a diagnosis age ranging from 3 years to 6 years. Patients were seen at Miami Children's Hospital between 1987 and 2011, and follow-up averaged 7.5 years.
"Most patients with bilateral Brown's syndrome are idiopathic, start early in childhood and remain very stable. There can be sequential presentation and spontaneous resolution, as has been described in unilateral cases," Dr. Warman said. Notably, most patients developed good stereopsis with minimal, if any, compensatory head positioning, and mild amblyopia developed only in those with horizontal strabismus and no stereopsis. "Whenever possible, avoid surgery in unilateral cases until after amblyopic age, not only to avoid amblyopia postop but to see if [the patient] develop a sequential one in the other eye," Dr. Warman said.
Data From Genome-wide Association Studies Suggest Multiple Polymorphisms Associated with Steroid Response »
Varying polymorphisms have been shown to be associated with steroid response.
"Two separate studies have identified multiple polymorphisms with highly statistically significant associations with the change in intraocular pressure following injection of triamcinolone," said Stephen G. Schwartz, M.D., M.B.A., associate professor of clinical ophthalmology at Bascom Palmer Eye Institute.
According to Dr. Schwartz, the genetic basis for steroid responders has been postulated for decades, and approaches have included investigation of candidate genes and pathway analysis, as well as research conducted in genome-wide association studies (GWAS). The GWAS pilot study screened 440,000 polymorphisms and found 48 single nucleotide polymorphisms within 41 separate genes that correlated with steroid response. Interestingly, 24 of these genes are expressed in the retina.
"We know that it is probably not a single gene defect or a single gene polymorphism that determines the steroid response. This [data] would imply that it is a combination of perhaps multiple polymorphisms in multiple genes that contributes to this particular phenotype," Dr. Schwartz said. Notably, the GWAS validation study determined different leading polymorphisms associated with steroid response. "The problem is, [this study's] top 10 polymorphisms and the top 10 within the original pilot study are not the same 10 polymorphisms. This may be due to a variety of reasons. We are trying to reconcile this as we speak," Dr. Schwartz said.