Ophthalmology Times welcomes ophthalmic professionals from around the world to Chicago’s McCormick Place. Over the next four days, Ophthalmology Times’ Conference Brief will provide live clinical news coverage from the 2010 joint meeting of the American Academy of Ophthalmology (AAO) and the Middle East Africa Council of Ophthalmology (MEACO).

Enjoy the meeting!

Chicago—Results of the 2010 International Society of Refractive Surgery (ISRS) survey of refractive surgery among U.S. members show a reversal in the previous downward slope in the volume of laser vision correction, according to Richard J. Duffey, MD.

The 2010 survey represents the 14th year of the data collection project that is conducted by Dr. Duffey and David Leaming, MD, and the second year in which the survey was conducted online. Surveys were sent to 1,165 enrolled U.S. ISRS members, opened by 561 of those physicians, and returned by 112 surgeons as of Oct. 1.

Although the proportion of respondents identifying themselves as high-volume LASIK surgeons (defined as performing more than 75 cases per month) has continued to decrease from its peak of 27% in 2001 to 12% in the latest survey, the volume of laser vision correction was up 7% from 2 years ago.

“This is the first time since 2001 that the survey shows an increase in volume,” Dr. Duffey said.

Increases also were seen in the proportion of surgeons and their family members who had laser vision correction. Among 2010 survey respondents, 11% reported having surface ablation and 28% had LASIK. Rates for these procedures in 2009 were just 4% and 18%, respectively.

“This is fascinating because it is a pretty big jump from previous years, and it will be interesting to see the results for this question in next year’s survey,” Dr. Duffey said.

Data on family members showed that almost one-third of the respondents’ spouses as well as at least one child had laser vision correction while almost two-thirds had at least one sibling who had the surgery.

Chicago—Although published studies suggest that surface ablation is safer than LASIK in eyes with thin corneas in terms of the risk of postoperative ectasia, surgeons should not infer that it is always safe to do PRK in these cases, said Marguerite B. McDonald, MD.

“Remember that a special informed consent will not protect you from a lawsuit,” said Dr. McDonald, clinical professor of ophthalmology, NYU Langone Medical Center, New York. “Perform PRK to spare tissue in an otherwise completely normal eye with a thin cornea. If the preoperative corneal thickness is thin, go back and look again at the preoperative topography because the likelihood of a corneal dystrophy is increased in thinner corneas, and don’t operate on [patients with] high myopia with refractive error more than –8 D.”

Although the true incidence of postLASIK ectasia and postPRK ectasia remain unknown, there is evidence that the ectasia risk is greater after LASIK versus PRK. Dr. McDonald noted that in reviewing the world’s literature, ectasia after surface ablation has been reported in only 32 eyes in 13 papers. In a 2008 paper on risk assessment for ectasia after corneal refractive surgery, Randleman et al. reviewed the world’s English literature and found 23 times as many cases of postLASIK ectasia as postPRK ectasia. In the same year, Woodward et al. reported that among eyes with ectasia presenting for treatment to their tertiary referral center, there were 36 times as many LASIK cases compared with PRK.

“These relative differences occurred in spite of the fact that according to market data, surgeons most often reserve surface ablation for eyes with the thinnest corneas,” Dr. McDonald said.

Data from OMIC on refractive surgery-related lawsuits also highlight a difference in ectasia risk between LASIK and surface ablation. In a review of 20 years of insuring for refractive surgery, Menke et al. reported almost 200 LASIK-related malpractice cases versus only 16 surface ablation cases. Even after adjusting for the seven-fold difference between LASIK and surface ablation in case volume in the United States, there remained a two-fold greater chance of being sued for LASIK. Furthermore, ectasia was the primary cause for a LASIK lawsuit whereas it was much further down on the list of causes for PRK litigation.

Chicago—Safety, predictability, and efficacy outcomes from retrospective studies support the use of thin-flap LASIK in eyes with thin corneas, said Jan A. Venter, MD, medical director, Optical Express, London.

Dr. Venter presented the results of one analysis based on data from 81,715 consecutive eyes that underwent LASIK between April 1, 2008 and March 31, 2009 at an Optical Express Center using a femtosecond laser or mechanical microkeratome for flap creation. Outcomes were compared between 2,181 eyes with central corneal thickness <500 μm that had LASIK with a 100-μm femtosecond laser flap and 79,534 eyes with central corneal thickness >500 μm. All eyes had normal preoperative topography.

There was no significant difference between the two groups in preoperative sphere, although there were proportionately fewer patients with high myopia in the thin cornea group. At 3 months after surgery, there were no significant differences between the groups in analyses of uncorrected visual acuity or change in best-corrected visual acuity (BCVA). With follow-up of 18 to 30 months, there were no study group-related differences in complications, although there were two cases of ectasia that both occurred in the thick cornea group.

Results of a second study showed the BCVA outcomes, predictability, efficacy, and complications were comparable in two groups of 2,000 eyes each undergoing wavefront-guided LASIK with a femtosecond laser-created 90-μm flap versus with a 100-μm or thicker flap.

“Thin-flap LASIK offers the refractive surgeon and the patient the rapid visual recovery and comfort of LASIK combined with the biomechanical benefits and tear function of PRK,” Dr. Venter concluded. “In our clinics, we prefer thin-flap LASIK over surface ablation in eyes with corneal thickness less than 500 μm.”

Chicago—Results of a prospective, randomized study show that for the treatment of low-to-moderate myopia, wavefront-guided PRK provides similar efficacy and safety outcomes compared with wavefront-guided LASIK but with a disadvantage of slower visual recovery, said David J. Tanzer, MD.

The study was conducted at the Naval Medical Center, San Diego, to evaluate the efficacy and safety of wavefront-guided PRK, which is not an FDA-approved procedure, and to further validate the safety of wavefront-guided LASIK in a larger warfighter patient population. It enrolled 200 subjects with myopia between –1 and –6 D and up to 2 D of astigmatism. The two treatment groups were well matched at baseline with respect to mean age (~30 years) and mean spherical equivalent (–3 D).

After 12 months, outcomes of the two procedures were comparable for predictability, safety (change from preoperative best spectacle-corrected visual acuity), quality of vision metrics (higher-order aberrations and low-contrast acuity), and subjective appraisal of outcomes, said Dr. Tanzer, program director, U.S. Navy Refractive Surgery Center.

However, there were statistically significant differences favoring the LASIK group for better uncorrected visual acuity through 3 months whether considering the proportion of eyes achieving 20/20 or better or 20/16. Results also were better through 3 months in the LASIK group for significantly better MSE and change in best-corrected visual acuity outcomes.

“Slower visual recovery is the Achilles' heel for wavefront-guided PRK, and especially for an active duty population in the Navy where wavefront-guided LASIK allows faster return to full duty and deployability,” Dr. Tanzer said. “However, based on the results of this study, when indicated, wavefront-guided PRK is a safe and effective procedure.”

Chicago—A few drugs are under investigation to determine their effect on the complement system. Studies already have implicated complement-mediated inflammation in age-related macular degeneration (AMD), according to Philip Rosenfeld, MD, PhD.

“Activation of complement component 3 (C3) causes downstream activation and formation of membrane attack complex,” Dr. Rosenfeld said.

Genetic association studies and histopathologic studies have suggested that inhibiting complement activation seems a reasonable approach to treating nonexudative AMD. Four primary drugs currently are in early-phase clinical trials to test their efficacy against the complement system.

• POT-4/AL-78898A (Potentia/Alcon Research), a cyclic peptide composed of 13 amino acids, binds to C3 and prevents proteolytic activation to C3a and C3b. The phase I single-injection, dose-escalation study has been completed and the drug was found to be safe and well tolerated up to the 1-mg dose. POT-4/AL-78898A inhibits all three major complement pathways of complement activation.

• FCFD4514S (Genentech/Roche), a Fab derived from a monoclonal antibody against complement factor D, is injected intravitreally. The phase I single-injection, dose-escalation study has been completed and the drug was found to be safe and well tolerated up to 10 mg in patients with geographic atrophy. The drug inhibits the alternative pathway of complement activation.

• ARC1905 (Ophthotech), an intravitreally injected aptamer against complement component 5, is being tested in a phase I study of 0.3- and 1-mg doses given at baseline and months 1, 2, 6, and 9. Results are expected in 2011.

• Eculizumab (Alexion Pharmaceuticals), a monoclonal antibody against complement component 5, is being evaluated in an ongoing phase II study that includes patients with geographic atrophy and high-risk drusen.

“Dry AMD is a uniquely human disease,” Dr. Rosenfeld said. “We do not know if complement inhibition will affect disease progression. Many questions still surround the disease, but several drugs are available and the trials are under way.”

Chicago—Accumulation of toxins in the retina resulting from environmental and/or genetic insults causes retinal degeneration. Lawrence Singerman, MD, clinical professor of ophthalmology, Case Western Reserve University School of Medicine, Cleveland, OH, described work being done to reduce vision inhibitors.

ACU-4429 (Acucela) is an oral drug that modulates the isomerase needed to convert transretinol to 11-cis-retinal in the retinal pigment epithelium, slowing the visual cycle in rod receptors and decreasing accumulation of A2E. A phase II randomized, double-masked, placebo-controlled trial (ENVISION) began in January 2010 to study the efficacy and safety of three escalating doses and up to two additional dose levels. Patients receive either the oral drug or placebo for 3 months.

Fenretinide (ReVision Therapeutics), a vitamin A derivative, was tested in a phase II double-masked, placebo-controlled, dose-ranging clinical trial of geographic atrophy. Two doses (100 and 300 mg) of the drug and placebo were given orally to 246 subjects. The drug was associated with decreased retinol binding protein, resulting in lower buildup of retinal toxins. The decrease of retinol binding protein was correlated with the decrease in lesion growth with the 300-mg dose and a decreased incidence of choroidal neovascularization. The drug was well tolerated. Reversible delayed dark adaptation was reported in association with fenretinide.

“This drug was associated with half the risk of progression to wet age-related macular degeneration at 24 months,” Dr. Singerman said. A phase III clinical trial will begin in 2011.

Chicago—Though vascular endothelial growth factor (VEGF) drugs have transformed the treatment of age-related macular degeneration (AMD), only about one-third of patients have been estimated to benefit substantially, according to Jayakrishna Ambati, MD, professor and vice chairman, Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington.

“We need additional superior targets to improve the visual outcomes for substantially more patients,” Dr. Ambati said.

Earlier diagnosis and treatment of choroidal neovascularization (CNV) will improve the visual outcomes, he said.

“Any delay in diagnosis or treatment leads to worse final visual outcomes,” Dr. Ambati added. The goals, therefore, are to identify a specific molecular marker of human CNV, determine whether inhibition of this specific marker results in decreased CNV, and develop an imaging strategy using the newly identified marker to visualize subretinal pigment epithelial CNV.

Considering these goals, Dr. Ambati conducted studies that found that chemokine receptor 3 (CCR3), a cell surface G protein-coupled receptor, and eotaxins, protein ligands for the CCR3 receptor, were found on endothelial cells in submacular surgical specimens from patients with AMD. CCR3 is responsible for eosinophil and mast cell recruitment in asthma and eosinophilic esophagitis.

Dr. Ambati found that when CCR3 or the eotaxins were targeted with neutralizing antibodies, laser injury-induced CNV was inhibited in mice. He explained that this resulted from CCR3 blockade because of direct inhibition of endothelial cell proliferation. CCR3 blockage inhibited CNV even without eosinophils or macrophages. The blockade reduced CNV in mice more effectively than antibodies targeting VEGF-A, and CCR3 antibodies did not have toxic effects on the murine retina as VEGF-A did.

“CCR3 is a molecular signature of CNV and targeting of CCR3 may reduce vision loss due to AMD by earlier detection and therapeutic angioinhibition,” Dr. Ambati said.

Chicago—Compounds are being identified that can stabilize opsins in the retina and prevent deterioration of vision following retinal detachments, said Anne Hanneken, MD.

The rationale for this research is that following retinal detachment, the vision acuity does not return to the preoperative level. This was attributed to photoreceptor damage possibly due to deficiency of the visual chromophore, 11-cis retinal, in the outer segment, said Dr. Hanneken, associate professor of molecular and experimental medicine, The Scripps Research Institute, La Jolla, CA.

Dr. Hanneken explained that the human visual pigments are composed of four related G protein-coupled receptors, the opsins, and a light-sensitive chromophore, 11-cis retinal, which binds to all opsins and stabilizes the visual pigment. Extensive previous research had shown that active opsin is associated with photoreceptor degeneration and that occupancy of the retinal binding site is necessary for survival of the photoreceptor cells.

Using computational modeling and design, Dr. Hanneken and colleagues identified several compounds that bind to the retinal binding pocket of rod and cone opsins and modulate rod and cone activity.

“These findings represent a new approach to stabilizing opsin, controlling signal transduction in the setting of chromophore deficiency, and protecting photoreceptors from degeneration in a variety of retinal degenerations,” she said.

Chicago—In a point-counterpoint debate on whether to discontinue use of anticoagulants before performing oculofacial procedures, two physicians agreed that there is no simple answer. But given that about one-third of adults in the United States take some form of anticoagulation therapy, the risks of bleeding or thromboembolic events must be assessed.

“There are no randomized clinical trials at this point to guide physicians as to which patients should or should not receive anticoagulation therapy in the perioperative period,” said Yoash R. Enzer, MD, FACS, associate professor, Alpert School of Medicine at Brown University, Providence, RI. “Yet, this is clearly an issue that’s important for all of us.”

Lacking evidence, physicians have to do decide how to proceed by performing intelligent risk stratification. This entails examining the indications for anticoagulation, the type of the agent, the type of procedure, its urgency, and the patient’s ability to withstand a severe hemorrhage, Dr. Enzer said.

He also recommended identifying low-, moderate-, and high-risk patients and focusing in particular on the large segment of patients in the moderate category. Although many moderate-risk patients can discontinue use safely, it is in this group that individual evaluation, consultation with the physician who prescribed the anticoagulants, appropriate timing, and provision of informed consent are of even greater importance.

Jonathan J. Dutton, MD, PhD, suggested that the answer to the question of discontinuation was “sometimes yes, sometimes no.” Factors to consider in a particular case are whether the surgery is urgent or elective, the risk of intraoperative bleeding—which is procedure-specific, the potential consequences of any hemorrhagic event, and the risk of a thromboembolic event, which tends to be patient-specific, as well as the possible consequences.

If an oculoplastic surgeon performs 1,000 procedures a year, about 300 patients will be on some form of anticoagulation. At the highest estimated rate of significant bleeding (21%), 60% to 65% will have significant bleeding at the time of surgery, Dr. Dutton said. However, in most cases the bleeding can be controlled easily. Further, assuming that only 10% of patients are on anticoagulation because of a significant medical condition, with a risk of 1.7% of a thromboembolic event, up to one patient per year is at risk of such an event with serious consequences.

“I would submit that even one patient a year is probably too much for most of us,” Dr. Dutton said.

He recommended that if a patient has a high risk of bleeding and a high risk of thromboembolism, the best of course of action may be to delay elective surgery until the patient can more safely discontinue use of the medication. If the surgery is urgent, bridge therapy should be considered, although it, too, carries a risk.

Chicago—Four principles can guide the physician in approaching difficult cases in oculoplastic surgery: analyze and understand, establish surgical goals, base surgery on existing anatomy, and plan and execute every part of the procedure, said John Shore, MD, who is in private practice in Austin, TX.

The central objective of analysis and understanding is to take the time to obtain the surgical or traumatic history and meld it with the patient’s understanding of the problem. The clinician needs to be aware of comorbidities, anatomic constraints, and visual needs and, most importantly, seek a balance between cosmesis and function, Dr. Shore explained.

“Every operation that we do on the eyelid, be it functional or purely cosmetic, has a cosmetic component, and we must keep that in mind,” he said.

When setting goals, both short- and long-term outcomes should be considered. Developing goals forces the physician to analyze the anatomy and identify and list problems. It’s also useful in educating patients and synchronizes the goals of the surgeon and patient. Having a clear set of goals, preferably written, also allows the physician to revisit these plans if the outcome is other than anticipated or the patient is dissatisfied.

Dr. Shore said that many of the complications that have occurred in his cases resulted from failure to evaluate existing anatomy properly. When the anatomy has changed because of trauma or prior surgery, the surgeon has to work with what’s left, not a textbook ideal, to complete the reconstruction.

His fourth suggestion was to perform precise technical execution, which involves more than cutting and sewing. It also includes venue, anesthesia, medical problems, preoperative preparation, postoperative patient care, selection and use of implants, sutures, medications, and other surgical items.

He offered a final pearl from several decades of oculoplastic surgery experience: “Be sure your goals match those of the patient.”

Chicago—Heidelberg Engineering GmbH announced that the FDA has granted clearance for the company’s Spectralis age-adjusted retinal nerve fiber layer thickness normative database.

The normative database provides clinicians with a tool for assessing glaucoma risk from a patient’s initial visit. Combined with unique features including fovea-to-disc alignment software (FoDi) and the posterior pole asymmetry analysis, the normative database increases the power of the platform for glaucoma risk assessment and progression management.

With its active eye tracking (TruTrack) capability, the system offers image detail and measurement precision not previously available, according to the company. In peer-reviewed literature, the system has been shown to offer precise measurement reproducibly, the company said.

“This new technology is an important addition to our glaucoma assessment toolbox,” said Sanjay Asrani, MD, associate professor of ophthalmology, head of the Glaucoma OCT Reading Center, and director of education, Duke University Eye Center, Durham, NC. “The combination of [the platform’s] precision with the new normative data and the asymmetry analysis adds to our ability to detect glaucomatous changes as well as changes over time.”

The normative database, asymmetry analysis, and other new features are a part of the system’s version 5.3 software. Shipment of the new software is expected later this fall.

Chicago—The Pediatric Cataract Initiative (www.PediatricCataract.org) has set a Nov. 15 deadline for receipt of applications for its inaugural single small research grant. A grant of $75,000 will be awarded to a qualified individual, institution, or organization investigating the causes of pediatric cataract and/or improved treatment tools and protocols.

The grant will support innovative research that can be carried out in 12 months with limited resources. It is not geographic dependent, although the research should have a degree of applicability regionally or globally. Applicants may submit more than one proposal provided that each is scientifically distinct.

The newly founded Pediatric Cataract Initiative is a partnership between the Bausch + Lomb Early Vision Institute and Lions Clubs International Foundation to identify, fund, and promote innovative methods of overcoming pediatric cataract for the long-term benefit of children, their families, and their communities.

Attendees of the joint meeting of the American Academy of Ophthalmology and Middle East Africa Council of Ophthalmology can obtain more information at the Bausch + Lomb and Lions Clubs International Foundation booths in McCormick Place. In addition, attendees may go to www.pediatriccataract.org/grant_funding.html to download the complete request for proposals.

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