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Joint AAO-SOE meeting highlights collaboration
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NEW ORLEANS – International collaboration among ophthalmologists is essential in confronting the current and emerging challenges to the profession, said speakers at the first joint meeting of the American Academy of Ophthalmology and the European Society of Ophthalmology.
Because physicians make up just 1% of the general U.S. population, and ophthalmologists make up roughly 2% to 3% of physicians, “we need the support of others on both international and local levels,” said Allan D. Jensen, MD, the president of the AAO.
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“In light of various challenges that face us, it seems appropriate to have a joint meeting now because the spirit of success … requires coalitions and alliances,” Dr. Jensen said in his remarks at the opening session of the meeting.
Challenges for ophthalmology include improving education for post-graduates and practicing professionals, as well as addressing the controversy surrounding optometric scope of practice, he said.
Zdenek Gregor, MD, president of the SOE, agreed that cooperation between the American and European societies is imperative to advancing education and research and to battling political pressures. He said he hopes “this meeting will foster closer collaboration between the two societies, which will ultimately lead to improved care.”
In contrast to this emphasis on collaboration within the profession, Dr. Jensen and others repeatedly urged the audience during the 90-minute opening session to be mindful of attempts on the part of optometric groups to expand the scope of procedures they are legally allowed to perform.
The theme recurred several times, culminating in a speech by Gary S. Schwartz, MD, trustee-at-large of the AAO, who explained the genesis of a decision by the AAO to exclude optometrists from this year’s annual meeting.
Dr. Schwartz’s explanation of the rationale was briefly interrupted by a disgruntled audience member who yelled out that the AAO’s decision “goes against the Hippocratic oath.”
Unfazed by the disruption, Dr. Schwartz continued his speech, emphasizing that ophthalmologists should be conscious of actions they might take that could inadvertently “blur the line” between ophthalmology and optometry.
Susan H. Day, MD, president-elect of the AAO, also addressed the hot-button issue, explaining that “knowledge is on our side.” She said that ophthalmologists can “reverse the irresistible tide” by maintaining their ties to the rest of medicine, staying current with education, involving themselves in the medical community and helping to train future ophthalmologists.
Culminating the opening session was the presentation of the Jackson Memorial Lecture by Stuart L. Fine, MD. Dr. Fine offered his perspective on how age-related macular degeneration treatment options have evolved over the past 35 years. He said that the fourth era of treatment begins now, with the advent of anti-vascular endothelial growth factor therapies, as well as photodynamic therapy and a wealth of information on the pathogenesis of the disease.
“During my 35 years in ophthalmology, AMD has moved from the rear balcony to center stage,” he said. Despite “a plethora of trials,” AMD is still the cause of severe and irreversible vision loss and therefore remains one of ophthalmology’s greatest unsolved problems, Dr. Fine said. His hope for the future, he said, is that one highly effective treatment will emerge from the array of options currently on the table.
The joint meeting drew a total of 25,000 people to New Orleans, according to an estimate released here by the AAO. That total number included 11,350 physicians, 3,480 international AAO members and 1,500 members of the Joint Commission on Allied Health Personnel in Ophthalmology. The subspecialty days preceding the meeting were also well-attended, with almost 2,400 people for refractive surgery and more than 1,600 each for glaucoma and retina.
Other news from the meeting follows.
Cataract surgery
Endophthalmitis and anti-infectives
A documented increase during the past decade in the incidence of endophthalmitis after cataract surgery justifies the trend toward use of newly available fluoroquinolones, according to surgeons at a session on cataract controversies.
The speakers said post-cataract endophthalmitis has increased during the same period of time that use of clear corneal sutureless incisions has increased. They discussed the possibility that these two trends are related and focused on possible prevention of endophthalmitis with the newest generation of fluoroquinolones.
Peter J. McDonnell, MD, presented a review of the ophthalmic literature showing an increase in the reported incidence of post-cataract endophthalmitis since 1992, reversing a declining trend over the previous 3 decades. Similarly, he said, a review of Medicare data showed that the incidence of post-cataract endophthalmitis was higher from 1998 to 2001 than in the previous 4 years.
Dr. McDonnell described cadaver eye studies done at the Wilmer Eye Institute showing that fluid on the surface of the cornea can travel through a clear corneal incision and reach the interior of the eye. Observations during cataract surgery also showed that blood from the surface of the cornea can enter the anterior chamber through the wound, he said.
These factors suggest that the unsutured corneal wound can be a route for ingress of bacteria during or after surgery, Dr. McDonnell said.
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I. Howard Fine, MD, said there is no question there has been an increase in the incidence of endophthalmitis during the era of clear corneal surgery, but “not all clear corneal incisions are the same.”
Dr. Fine said meticulous attention to detail in surgery can help to prevent endophthalmitis.
“We have gone at least 8 years and 7,000 cataract surgeries without a case of endophthalmitis, and I do not believe that has been because of good luck,” Dr. Fine said.
He said several factors have contributed to the avoidance of endophthalmitis in his practice. These factors include careful draping, preparation of the surgical field with povidone iodine, attention to incision architecture and surgical technique, careful wound closure including stromal hydration in all the incisions, testing of the wound for leaks, and use of a newer generation fluoroquinolone preoperatively, intraoperatively and postoperatively.
Francis S. Mah, MD, said that, since their introduction in the 1990s, fluoroquinolones have become the standard topical antibiotic for ophthalmologists. Unfortunately, he said, resistance to the second- and third-generation topical fluoroquinolones has emerged, especially among staphylococcal strains.
Dr. Mah said the current generation of fluoroquinolones, which includes gatifloxacin and moxifloxacin, covers resistant isolates and shows improved activity against gram-positive organisms.
For surgical prophylaxis, Dr. Mah recommended the use of povidone iodine and a topical antibiotic.
He noted that ophthalmologists have rapidly moved to use of the latest generation of fluoroquinolones. Only months after the commercial introduction of the two drugs in 2003, the annual survey of practice trends among members of the American Society of Cataract and Refractive Surgery showed that 60% of respondents had already adopted the fourth-generation agents, he said.
Given the broad-spectrum efficacy and good safety profile of the new agents, Dr. Mah said, “there is no place for ciprofloxacin and ofloxacin in ophthalmology.”
Crystalens at 3 years
Even after 3 years in the eye, an accommodative IOL still demonstrated movement upon pharmacological manipulation, according to one study. A separate study of the same lens found good near and distance vision and high patient satisfaction 3 years after implantation.
| Restasis campaign | |
To coincide with Allergan’s first direct-to-consumer advertising campaign for Restasis, actress Janine Turner, a real life chronic dry eye sufferer and Restasis user, made an appearance at the Allergan booth during the American Academy of Ophthalmology meeting. Ms. Turner, who is featured in the advertising campaign, is best known for her roles in Northern Exposure, Strong Medicine and Cliffhanger. |
Steven J. Dell, MD, discussed his study of movement of the eyeonics Crystalens accommodative IOL. He said the degree of movement observed using immersion ultrasound was consistent with the near visual acuity demonstrated by the patients in the study.
Dr. Dell said he had observed that patients with the Crystalens were demonstrating near visual acuity about as good at 3 years postop as they had at 1 year, “and the question we had was, ‘Is the IOL still moving?’”
The study was performed in 10 eyes at least 3 years after Crystalens implantation. All patients had “excellent distance vision,” Dr. Dell said, with a mean uncorrected distance acuity slightly better than 20/20. Their distance-corrected near visual acuity was also good, with a mean of J 2.1, he said.
Immersion ultrasound was performed in each eye under the influence of cyclopentolate and under the influence of pilocarpine to determine the maximum range of movement of the IOL, Dr. Dell said.
He found that the lenses moved anteriorly a mean of 0.84 mm under cyclopentolate compared to their position under pilocarpine.
Taking into account the IOL powers implanted, this movement would correspond to a mean accommodative change of 1.79 D, Dr. Dell said, which he said was consistent with patients’ near visual performance with distance correction in place.
At a separate presentation, George I. Papastergiou, MD, said patients implanted with the Crystalens had excellent distance and near visual acuity without glasses at 36-month follow-up.
“Patients who received Crystalens were very satisfied even 36 months after the operation,” he said.
Dr. Papastergiou and colleagues measured near and distance visual acuity with and without correction, as well as accommodative range, in 84 pseudophakic eyes at least 3 years after the Crystalens was implanted.
All eyes achieved uncorrected distance visual acuity of 20/40 or better, and 93% had uncorrected near acuity of J 3 or better, Dr. Papastergiou said. The pseudoaccommodative amplitude ranged from 0.75 D to 2 D, he added.
Dr. Papastergiou cautioned that the lens should not be implanted in eyes with pupils larger than 6 mm and that the long-term incidence of fibrosis still must be studied.
These results were similar to those attained in the study submitted for Food and Drug Administration approval of the Crystalens, according to Dr. Howard Fine, the discussant of Dr. Papastergiou’s presentation. Dr. Fine, who participated in the FDA study, said one aspect of the Crystalens that has always troubled him is that investigators have never been able to consistently demonstrate the lens’ exact mechanism of action in the eye. Despite this, he said, the data have conclusively shown that “the lens works,” and furthermore it has scored well among patients who were asked pointed questions about their quality of life following surgery.
Capsule staining technique
A new technique for staining the anterior capsule with trypan blue helps to prevent the dispersion of the stain throughout the anterior chamber and into the posterior chamber, according to Robert H. Osher, MD. Dr. Osher described the technique at a session on cataract innovations.
In the technique, the anterior chamber is first filled with viscoelastic, Dr. Osher said. Then a monolayer of saline solution is injected under the viscoelastic just anterior to the lens capsule. The trypan blue can then be injected through a cannula, past the viscoelastic and into the monolayer of saline, to stain the anterior capsule.
Dr. Osher noted that, using this method, the stain is contained in the small monolayer in front of the lens without spreading to other areas of the eye. The viscoelastic keeps the stain away from the corneal endothelium, and the technique also prevents the stain from reaching the vitreous cavity where it might interfere with the red reflex, he said.
He noted that trypan blue is not available commercially in the United States, but it can be prepared by a pharmacy.
IOL update
At the same session, organized and led by Dr. Osher, a panel of leading cataract surgeons discussed a number of innovative IOLs currently in development.
The rapid-fire session, called “Cataract Surgery: Living on the Edge,” included investigators’ and others’ impressions of ultrathin lenses, adjustable IOLs and more technologies on the horizon.
Dr. Osher noted that the ThinOptX Ultra Choice IOL has by now been implanted in “thousands of eyes worldwide.”
The ThinOptX lens is less than 0.5 mm thick at its thickest point and can be rolled to fit through an incision of less than 2 mm. One face of the 5.5-mm optic is divided into concentric zones, stepped in height, with a different curvature on each step so that all light traveling through the lens is focused at the same point on the retina.
The lens is in early stages of U.S. clinical trials, Dr. Osher said, and the company is seeking funding.
An entirely diffractive phakic IOL, the VisionMembrane lens, is now in clinical trials in Mexico, Dr. Osher said. This silicone lens with a 6-mm optic is less than 1 mm thick, he said.
Richard L. Lindstrom, MD, one of the panel members at the session, said diffractive optics “may be the way to go” for phakic IOLs. He said with the limited space for a lens in the anterior chamber, the thin profile that can be achieved with diffractive optics may be an advantage over conventional refractive optics.
The Light Adjustable Lens (LAL) from Calhoun Vision has now begun clinical trials outside the United States, Dr. Osher said. The spherical and astigmatic power of this lens can be adjusted after implantation with a special laser made by Carl Zeiss Meditec.
Dr. Osher said that about 30 of these lenses have been implanted to date. Twenty patients have undergone spherical adjustment of the lens, he said, and 70% of those achieved a plano refraction. There have also been toric adjustments in two patients with good results, he said.
The LALs implanted to date have been made of silicone. Samuel Masket, MD, another panel member, said it is hoped the light-adjustable concept can be carried over to acrylic materials.
Dr. Howard Fine, also on the panel, said the full promise of the technology will be serial adjustment. If the lens can be adjusted over the course of the patient’s life, it can be changed to refine its accuracy or to adapt to different visual needs at different times, he said.
Dr. Osher suggested that the adjustable lens technology may be especially important for refractive lens exchange.
“If we’re going to be tackling young patients who see well and who have to pay a lot of money for a refractive surgical procedure, a 0.5-D error can be significant,” he said.
Dr. Masket spoke about the SmartLens, in development by Medennium. This lens, made from a hydrophilic acrylic material, is inserted into the eye in the shape of a 1-mm-diameter rod, and it expands to fill the capsular bag. Dr. Masket said the lens has been implanted in cadaver eyes through a 2-mm incision and is currently undergoing toxicology and other preclinical studies.
Panel members speculated that the ReStor lens, a diffractive-refractive pseudoaccommodative IOL from Alcon, will be available in the “very near future.” (An Alcon official said in an interview with Ocular Surgery News that U.S. regulatory approval of the ReStor is anticipated in the first quarter of 2005.)
Dr. Lindstrom noted that Alcon had acquired the diffractive multifocal IOL concept used by 3M in the 1980s and “clearly made it significantly better.” He and Dr. Osher, who were both investigators of the 3M lens, said they thought the ReStor shows promise and has performed well in clinical trials to date.
Another Alcon IOL, the Toric AcrySof, is “right behind ReStor in the regulatory process,” according to Stephen S. Lane, MD, another panelist. He said the fact that the Toric and the ReStor are both built on Alcon’s AcrySof design raises the possibility that the two elements can be combined in the future.
The panelists also discussed two IOLs currently available, the Alcon AcrySof HOA and the Bausch & Lomb SofPort AO. The Alcon lens was released earlier this year, and B&L lens was launched here at the AAO meeting.
Both the new lenses have aspheric surfaces on one or both sides, and both seem to have been inspired by the success of the Tecnis IOL from Advanced Medical Optics, the panel members said. The Tecnis was designed with a modified prolate anterior surface to correct for negative asphericity in the human cornea.
The AcrySof HOA has its aspheric surface on the back of the IOL, avoiding the need to make the edge of the lens thicker. The SofPort AO has aspheric optics on both its front and back surfaces so that it induces no spherical aberration.
“The idea that aspheric lenses provide superior vision is not a surprise, based on experience with the Tecnis,” Dr. Masket said.
Dr. Lindstrom said the SofPort AO lens “will be robust to decentration and tilt.”
Cataract blindness worldwide
The worldwide ophthalmic community currently lacks the focus and commitment to effectively combat cataract blindness in underdeveloped countries, but all hope is not lost, according to Bruce E. Spivey, MD, FACS.
“There is a confluence of organizations, people and needs that I believe allows us to think that we can work together in a way that is not so stratified,” Dr. Spivey said. A commonly accepted estimate of cataract incidence is a backlog of roughly 145 million cataracts throughout the world, Dr. Spivey said. In approaching this “overwhelming problem,” he said, one possibility is to focus on operating on all these patients; another option is to focus on the particular population at risk.
“Clearly focusing on the population at risk is the more appropriate option,” Dr. Spivey said. There might not be an immediate response to the challenge posed by the international blindness prevention program Vision 2020, he said, but the groundwork is in place for a successful effort.
”It’s all there. We don’t have to search for suggestions, structures or solutions. As we approach population-based areas, we know pretty much what to do,” he said.
Empiric IOL estimation
A purely refractive algorithm to predict IOL power intraoperatively without the need for axial length and keratometry measurements has been developed, one speaker said. This approach shows promise for bypassing some of the difficulties that have been encountered in predicting IOL power after refractive surgery, said Tsontcho Ianchulev, MD, MPH.
“If we have to go to emmetropic nirvana, how do we get there?” Dr. Ianchulev asked. “Do we need better oil or a new engine?”
The challenge for cataract surgeons in the future will be IOL power prediction in the 1 million or so patients who have undergone LASIK and will eventually need cataract surgery.
In a pilot study, Dr. Ianchulev and colleagues used “spot optical refractive biometry” for modeling in 22 cataract cases and an additional 16 cases for validation. Of the 16 eyes, six were post-LASIK, he said.
The spherical equivalent of the intraoperative aphakic autorefraction correlated linearly with the emmetropic IOL power after adjustment for postoperative outcomes, he said.
“For the eyes that had undergone LASIK, 83% were within 1 D [of emmetropia]; 100% of the normal eyes using the conventional methodology were within 1 D,” he said.
Using conventional methodology, 67% of the LASIK eyes and 100% of the normal eyes were within 1 D of emmetropia, he said.
“The relationship was sustained over an axial length range of 21.43 mm to 25.25 mm and an IOL power implant range of 12 D to 25.5 D,” he said.
Refractive surgery
Refractive surgery survey
LASIK is still the refractive surgical procedure of choice for treating patients with myopia, said Richard J. Duffey, MD. Phakic IOLs are becoming more common as a treatment choice for patients with high myopia, he said, and surgeons are beginning to employ refractive lens exchange more often for those with high hyperopia.
Dr. Duffey presented the “hot off the presses” results of the 2004 refractive surgery survey of members of the International Society of Refractive Surgery of the American Academy of Ophthalmology.
Of the 184 respondents to the survey, 98% said they perform LASIK bilaterally.
“What I found interesting is that 8% of respondents found bilateral phakic IOL implantation acceptable,” Dr. Duffey said.
Scleral expansion is “a fading procedure” for correction of presbyopia, he said.
As in previous years, the Bausch & Lomb Hansatome was the microkeratome of choice for respondents. This year it was followed by the IntraLase FS laser keratome and the Moria M2, Dr. Duffey said.
“The accommodating IOL is showing a 14% growth rate,” he said.
The Visx platform was the most commonly used wavefront system among respondents, Dr. Duffey said. The Visx platform was used at about a two-to-one ratio over others, he said.
The survey also found that “90% of physicians are offering wavefront services” to patients, he said.
Comanagement “has seen a big drop-off” with about half as many respondents saying they use these arrangements this year as in 2002, Dr. Duffey said.
He said the survey showed that LASIK remains the most common procedure for patients with refractive errors between –8 D and +3 D. Surgeons offering wavefront customization are charging about $400 more per procedure than for standard LASIK, he said.
On the down side, he noted, 56% of respondents reported having at least one case of post-LASIK ectasia. On the upside, “LASIK has a 7% [market] penetration rate, yet 29% of [the respondents] have had the procedure,” he said.
Dr. Duffey said full results of the survey are available at www.duffeylaser.com.
Beyond the numbers
Refractive surgeons are “not asking the right questions” to determine if their patients have good functional vision, said Kerry D. Solomon, MD. Surgeons must look beyond the Snellen chart, J score and diopters of accommodation when dealing with patients who are looking for real world vision improvement, he said.
“Truth is not always in the numbers. We need to be looking at functional things that allow us to have a better understanding … of criteria that are important to our patients,” he said.
Dr. Solomon said that patients who have been implanted with Alcon’s AcrySof ReStor lens have experienced vision improvement that meets this challenge. Eighty percent of ReStor patients in the FDA clinical trials of the lens are not using glasses for near, intermediate or distance vision, he said at an Alcon-sponsored symposium during the AAO meeting. There was also high patient satisfaction with tasks such as working at a computer and reading fine newspaper print, he said.
“This information is far more useful than 20/20 or J1 or diopters of accommodation,” Dr. Solomon said.
“As new technologies come along, this issue will affect all our practices. Patients want to know what the side effects are, how well will they be reading and what can they really expect,” he added.
Altitude affects LASIK
Altitude has a linear effect on the laser performance in LASIK, requiring a greater nomogram adjustment at higher elevations, according to a study that looked at data from centers across the United States.
Louis Probst, MD, one of the directors of the laser center chain TLC Vision, presented the study, in which data from 13 centers spanning 2 years were analyzed. To be included in the analysis, each center had to perform more than 1,000 surgeries during that time period, he said. The personalized nomogram adjustments used by each center for correction of myopia between 3 D and 6 D were compared using regression analysis.
All centers had standardized temperature and humidity controls, leaving altitude as the sole variable in atmospheric pressure, Dr. Probst said.
The analysis showed a relationship – “not a tight relationship, but linear” – between altitude and the nomogram reduction factor used in each center, Dr. Probst said.
The reduction factor varied from 0.7% at sea level to 12.7% at 1,000 feet elevation to 34.9% at 3,000 feet, he said.
Taking altitude into account may help surgeons in developing and adjusting their own nomograms for LASIK, Dr. Probst suggested.
Epi-LASIK and patient comfort
A clinical study to measure the level of postoperative patient discomfort after epi-LASIK is set to begin, according to Marguerite B. McDonald, MD.
The trial, employing the Centurion SES Epikeratome from Norwood EyeCare, will enroll 35 patients each at three clinical sites in the United States, Dr. McDonald said during a press briefing arranged by Norwood. Up to 70 eyes per site will undergo the procedure, she said. Enrollment in the trial will begin immediately after the AAO meeting.
The SES Epikeratome has already received FDA 510(k) approval, but “we’re conducting the study to provide physicians with more information about the technology,” Dr. McDonald said. Among the parameters for study are postoperative discomfort, recovery time and the use of wavefront-guided customized ablation with the epi-LASIK procedure.
The inclusion criteria dictate a myopic range of –0.5 D to –8 D with up to –2.5 D of astigmatism, Dr. McDonald said.
“With criteria like that, enrollment should be fairly easy,” she said.
Ioannis Pallikaris, MD, PhD, also at the press briefing, said he has found in previous studies that epi-LASIK creates minimal haze. “We are not killing the epithelium,” he said.
Custom LASEK vs. LASIK
Using the same algorithm with the same wavefront-guided laser system, both laser epithelial keratomileusis and LASIK had similar refractive outcomes, said James McDonald, MD. But a slightly higher percentage of patients achieved 20/20 vision after undergoing LASEK, he said.
Dr. McDonald described a study of 25 eyes with low myopia that underwent wavefront-guided LASIK and 21 eyes that underwent wavefront-guided LASEK. All surgeries were performed using the Bausch & Lomb Zyoptix system.
Eyes that had surgery-specific complications were eliminated from evaluation, he said.
“Both groups had excellent results,” he said. “There were no significant higher-order aberrations induced, but there was a slight trend of overcorrection in the LASEK group.”
In the LASIK group 14 of 17 patients ac.hieved 20/20 or better acuity, compared to 19 of 20 patients in the LASEK group.
Dr. McDonald said physicians should be aware that they may need to adjust their LASIK nomograms when performing wavefront-guided LASEK.
Surface ablation after LASIK
Surface ablation for patients who need re-treatments after initial LASIK surgery is a promising approach, said Raymond Stein, MD, FRCSC. Using PRK or LASEK to enhance LASIK “results in no significant haze and no loss of best corrected visual acuity,” he said.
Patients should be considered for surface ablation after initial LASIK if there were flap complications during the initial surgery or if the residual stromal bed is too thin for re-treatment, Dr. Stein said.
Of 99 eyes re-treated with surface ablation after an unsatisfactory LASIK result, “99% were 20/40 or better with no corneal haze,” Dr. Stein said.
Preoperative conditions associated with an increased risk of corneal haze after surface ablation techniques include the presence of a LASIK flap or RK incisions, a corneal graft, epikeratophakia, high myopia or hyperopia and high astigmatism.
Although it is rare, corneal haze may occur with surface ablation techniques, but it can be reduced with use of mitomycin C use or vitamin C, he said.
Intrastromal ablation is not without potential complications, Dr. Stein said. “Among the possible complications … is a displaced flap, diffuse lamellar keratitis, corneal ulcer, sterile infiltrate, a nonhealing epithelial defect, recurrent corneal erosion, corneal haze or scarring and the possibility of under- or over-correction,” he said.
Retina
Macugen at 2 years
A drug that inhibits vascular endothelial growth factor showed good preservation of vision at 2 years in a study in patients with AMD. Vision preservation was better in patients who were treated for 2 years than in those treated for 1 year, according to data presented by Steven D. Schwartz, MD.
“There was virtually no loss of visual acuity for the Macugen (pegaptanib sodium injection) group in the second year of therapy,” Dr. Schwartz said of the drug’s phase 3 study results.
“[The new data] confirm that treatment with Macugen is effective in patients with neovascular AMD who are at risk of losing their vision,” said David R. Guyer, MD, chief executive officer of Eyetech Pharmaceuticals, in a press release.
“Two-year data on Macugen demonstrate that longer term use may be beneficial for patients suffering from this chronic disease,” Dr. Guyer said.
In a phase 2/3 multicenter trial, 1,186 patients were randomized to receive 0.3 mg, 1 mg, or 3 mg of Macugen or sham injection every 6 weeks for 1 year. At 1 year, 1,053 patients were randomized either to continue treatment for a second year or not.
In patients who received 0.3 mg of Macugen for 2 years, there was a 45% treatment benefit over standard care (P < .05), Dr. Schwartz said.
Dr. Schwartz said Macugen was beneficial in preserving vision and well tolerated after 2 years of treatment.
A new drug application for Macugen has been filed with the FDA. The drug has received priority review status, according to Eyetech officials.
Vision and quality of life
Slight or moderate vision loss from AMD can have a devastating effect on a patient’s quality of life, affecting the ability to read, drive, walk and function normally in everyday life, said Lyas G. Mogk, MD, at a press briefing during AAO.
“We live in a sighted culture,” Dr. Mogk said. “Even a little vision loss to a fully sighted adult can compromise function more globally than any other impairment, increasing the risk of falls and injuries, medication mix-ups, poor nutrition, social isolation and clinical depression.”
According to Dr. Mogk, patients rate vision loss as more traumatic and debilitating than the loss of both legs. “In terms of debilitating disease, vision loss is second only to loss of mental capacity,” Dr. Mogk said.
Clinical depression accompanies vision loss in many patients, Dr. Mogk said, but depression and ability to function can improve with visual rehabilitation.
“Visual rehabilitation keeps patients active. It’s about living with visual loss but maximizing one’s independence,” she said. Occupational therapists can provide visual rehabilitation that helps patients learn how to cope with their lack of vision by manipulating light and contrast levels using the aid of magnifiers and products with large print.
“It’s extremely important to initiate rehabilitation early on in the disease,” Dr. Mogk said. “Early intervention helps patients transition into vision loss more easily and can actually help those patients with vision loss get their life back.”
PDT plus intravitreal triamcinolone
Photodynamic therapy combined with intravitreal triamcinolone may be more effective in treating choroidal neovascularization in AMD than PDT alone, according to a poster presentation.
“Eyes treated with photodynamic therapy (PDT) and intravitreal triamcinolone appear to have lower re-treatment rates compared to PDT alone,” Robert N. Johnson, MD, and colleagues reported. The addition of intravitreal triamcinolone may have promoted and prolonged the antiangiogenic effect in eyes with choroidal neovascularization (CNV) better than PDT alone, the researchers suggested.
In a retrospective review of 43 eyes with CNV that underwent PDT, 23 eyes received intravitreal triamcinolone 1 week after PDT and 20 eyes received PDT alone. After a median follow-up of 270 days, 70.8% of patients who had adjunctive intravitreal triamcinolone therapy did not require re-treatments of PDT. Patients who did not have adjunctive therapy required one additional treatment each.
The researchers said that visual acuity was “enhanced” in the study group: three eyes had improved vision, 19 eyes remained stable and two eyes had visual acuity decreased by more than 2 lines.
“Combination treatment may be an efficacious, relatively safe and less costly way of treating subfoveal CNV secondary to AMD,” the study authors concluded.
A larger, multicenter study is needed to fully determine the benefits of PDT with intravitreal triamcinolone, they said.
Cardiovascular factors, AMD
Two biomarkers of cardiovascular disease, C-reactive protein and homocysteine, have been identified as risk factors for AMD, said Andrew K. Vine, MD.
“C-reactive protein and homocysteine levels are significantly elevated in patients with AMD,” Dr. Vine said. “The obvious question is, will reducing C-reactive protein and homocysteine in patients reduce the incidence of AMD?”
He said the statin drugs have been associated with reducing these biomarkers of cardiovascular disease and may have the potential to reduce C-reactive protein and homocysteine levels. However, statins have produced “mixed outcomes” in previous studies, he said.
In a study described by Dr. Vine, 156 patients with and without AMD were age-matched with similar profiles for cardiovascular disease and vitamin supplementation. Patients with AMD had a mean C-reactive protein level of 3.42 mg/L, compared with 2.30 mg/L in patients without AMD. Similarly, patients with AMD had higher mean homocysteine level, 11.72 µmol/L, compared with 8.88 µmol/L in patients without AMD (P < .0001). Men and patients older than 65 years had a higher incidence of increased homocysteine as well, Dr. Vine said.
Dr. Vine also noted a higher level of atherosclerosis and inflammation in the macula of patients with AMD. These additional risk factors “are likely involved” in disease pathogenesis, he said.
“It is imperative that we conduct further study to understand the poorly understood pathogenesis of this disease,” Dr. Vine said.
Telemedicine for ROP
Remote digital screening was effective in detecting retinopathy of prematurity, resulting in diagnosis of the disease earlier than with traditional methods, according to Antonio Capone Jr., MD.
“Clinically significant ROP was diagnosed 1 to 2 weeks earlier than with indirect ophthalmoscopy,” he said at the retina subspecialty day.
The findings of the PhotoROP Study could benefit the ophthalmic community by providing an effective method of screening quickly for the early stages of ROP, Dr. Capone said. Early detection could help to reduce the risk of malpractice lawsuits regarding ophthalmologists’ diagnosis of ROP, he said.
He described the study, in which 57 premature infants with a birthweight of 440 g to 1675 g were screened for ROP weekly for 5 weeks using digital photography and indirect ophthalmoscopy. The digital images were sent to a central reading center for interpretation.
Ninety-three percent of the images were deemed interpretable. From the digital images, 33% of patients were diagnosed with clinically significant ROP.
Noting the success of the study, Dr. Capone said that a national standardized protocol for telemedicine should be instituted for the diagnosis of ROP.
AMD prevention strategies
Therapies aimed at prevention may be more effective in reducing vision loss from AMD than those aimed at treatment of existing disease, said Paul Sternberg Jr., MD.
“Prevention could prove to be an effective strategy for treating our patients with AMD or those who are at risk for the disease,” Dr. Sternberg told attendees of the retina subspecialty days.
Currently available treatments for AMD are directed toward stabilization of visual loss in existing disease, Dr. Sternberg said. Initiatives directed toward disease delay or prevention may ultimately provide better, more efficient care, he said.
“Research directed towards delay or prevention may not only find that vision may be better preserved, but that [prevention therapy] has the potential to provide socioeconomic advantages,” Dr. Sternberg said.
He noted that studies of heredity and of the use of micronutrient supplements such as the formulation used in the Age-Related Eye Disease Study (AREDS) are important milestones in prevention research, but said “more studies are necessary.”
Future AREDS study
A study set to begin recruiting patients in early 2005 will investigate the potential benefits of lutein, zeaxanthin and omega-3 fatty acids in the prevention of AMD, said Johanna M. Seddon, MD, ScM.
“The trial is similar to the Age-Related Eye Disease Study, which found that a high-dose combination of vitamin C, vitamin E, beta-carotene and zinc significantly lowered patients’ risk of developing severe AMD,” she said during a press event.
Dr. Seddon told Ocular Surgery News that the AREDS researchers will test whether supplements containing the carotenoids lutein and zeaxanthin (found in green leafy vegetables) and omega-3 fatty acids (found in fish) can reduce the risk of developing wet AMD.
“These compounds aid in preventive health, so we are doing a second study to investigate that benefit [in AMD],” Dr. Seddon said. She said trials that focus on prevention of AMD may prove to be important.
“There hasn’t been enough emphasis on prevention,” she said.
The follow-up to the AREDS study, sponsored by the National Eye Institute, will be led by Frederick L. Ferris, MD, lead investigator of AREDS and clinical director at the NEI. Patients will be randomized into three study arms, receiving either a lutein supplement, an omega-3 fatty acid supplement or a lutein and zeaxanthin supplement. Patients will be further randomized either to receive or not to receive the AREDS formulation with their experimental supplement, Dr. Seddon said.
Vein development after neurotomy
The development of retinochoroidal collateral veins on the optic nerve head after radial optic neurotomy was found to be a strong indicator for improved visual acuity after surgery, according to a poster by John O. Mason III, MD, and colleagues with the Central Vein Occlusion Study Group.
Prior to this study, best corrected visual acuity was considered to be the strongest prognostic indicator of improved vision following radial optic neurotomy (RON), the authors said.
Dr. Mason and colleagues conducted a retrospective review of 31 eyes that underwent RON for central retinal vein occlusion.
They found that 68% of eyes developed retinochoroidal collateral veins. An average improvement of 3.8 lines of vision was noted in patients with retinochoroidal collateral vein development, compared with a –0.5 line loss in eyes that did not develop retinochoroidal collateral veins after RON. At 9 months, 52% of eyes with retinochoroidal collateral veins had a BCVA of greater than 20/100, while 19% of eyes with retinochoroidal collateral veins and 70% of eyes without vein development had a BCVA of 20/400 or worse.
Gene therapy, stem cells for AMD
Gene vector therapy and embryonic stem cell transplantation may one day be effective therapies for rehabilitating the retinas of patients with AMD, speakers here suggested. Both therapies are under investigation for promoting survival of photoreceptors and/or retinal pigment epithelium (RPE) cells during choroidal neovascularization (CNV), said two presenters.
“Gene vector therapy was well tolerated, with few adverse reactions, in patients with severe AMD,” said Eric R. Holtz, MD.
He presented outcomes of a compassionate-use study of AdPEDF, a gene product in development by GenVec that contains an adenovector and pigment epithelium-derived factor. In animal studies, AdPEDF was found to inhibit progression of CNV and promote survival of photoreceptors and RPE cells, he said. Further study will be needed to assess the efficacy of the agent in the human population, he said.
Another investigation, presented by Kourous A. Rezaei, MD, found that stem cells implanted into the retinas of primates and rats effectively converted to RPE cells.
“After transplantation into the subretinal space, [the stem cells] promoted the survival of photoreceptors in dystrophic rats,” Dr. Rezaei said. Studies are under way to convert human embryonic stem cells into RPE cells for transplantation for the treatment of AMD, he said.
Glaucoma
5-FU improved surgery
Intraoperative 5-fluorouracil “significantly” improved the long-term survival of glaucoma surgery in a large study in England, said Peng T. Khaw, MD, PhD.
Dr. Khaw presented results of the More Flow Study, conducted at Moorfields Eye Hospital in London, during a free paper session. The study was a randomized, prospective trial of intraoperative 5-FU vs. placebo that included 368 patients. The study set out to determine whether a single 5-minute application of 5-FU extended the survival of glaucoma filtration surgery and reduced postoperative field loss and optic disc progression.
The study found that one application improved the survival of glaucoma surgery up to 80 months.
There were no differences in blebitis, endophthalmitis, visual loss, field or disc progression between the 5-FU group and the placebo group, Dr. Khaw said.
SLT compared to drugs
A randomized trial to compare selective laser trabeculoplasty (SLT) to medical management as initial therapy for open-angle glaucoma has begun enrolling patients, according to Joel S. Schuman, MD.
SLT has previously been shown to be as effective as argon laser trabeculoplasty (ALT) in lowering IOP in patients with open-angle glaucoma, Dr. Schuman said. Logically then, he said, SLT should prove equally effective when compared with medical therapies. The SLT-Med study will be undertaken to confirm that theory.
The SLT-Med clinical study will include 60 eyes, randomized “by patient, not by eye,” he said. Enrollment has begun at 16 sites across the United States and Canada. “It’s an 18 month study with a 1-year follow-up,” he said.
Both eyes of each patient will be treated within 2 weeks of enrollment. Patients undergoing SLT will receive 100 pulses around up to 360° of the trabecular meshwork, Dr. Schuman said. Those randomized to medical therapy will be treated first with prostaglandins, with the addition of beta-blockers and alpha agonists if they are nonresponsive, he said.
Other studies have shown no difference in IOP between ALT and medical therapy with follow-up of 3 years, Dr. Shuman said. “The first 5-year studies are showing similar survival rates,” he added.
The Glaucoma Laser Trial, in which 271 patients with primary open-angle glaucoma were randomized to medical therapy or ALT, “suggested ALT is effective as a first-line treatment in glaucoma management,” Dr. Schuman said. After 7 years, 203 patients who had undergone the laser procedure had lower IOPs than those randomized to medical therapy, Dr. Schuman said.
He said he believes the SLT-Med study will show similar results.
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Pascal dynamic contour tonometry
A new device may overcome some of the limitations of Goldmann applanation tonometry in measuring IOP, according to one clinician.
Leon W. Herndon Jr., MD, said that the new technology, Pascal dynamic contour tonometry, is a “promising” alternative to Goldmann tonometry, which he said is “flawed.” Dr. Herndon said although Goldmann tonometry is the most widely used method of measuring IOP, several factors can affect its accuracy, including variations in corneal thickness and changes in the cornea after refractive surgery.
The Pascal Dynamic Contour Tonometer, from Ziemer Ophthalmic Systems, is a contact tonometer with a tip that fits into a standard Goldmann tonometer stand, Dr. Herndon said. It reads IOP using an electronic pressure sensor placed in the center of the cornea.
Dr. Herndon described a study in 62 patients who underwent unilateral LASIK. IOP was measured with both Goldmann and dynamic contour tonometry pre- and postoperatively. The researchers found that the mean Goldmann tonometry reading decreased by 3 mm Hg postoperatively. There was no significant change in IOP from preop to postop as measured by dynamic contour tonometry, he said.
In another study, IOP was measured using both methods in 118 healthy eyes before and 1 and 4 weeks after LASIK. Dr. Herndon said that from preop to 1 week postop there was a mean drop of 4.9 mm Hg in the Goldmann tonometry reading, and preop to 4 weeks postop the drop was 5.4 mm Hg. There was no significant change in IOP at either follow-up as measured by dynamic contour tonometry, he said.
Fixed combination agents
Available data suggest that three fixed combination drugs currently being investigated for glaucoma treatment hold great promise, according to presenters here.
When approved, these drugs “will ultimately benefit patients and will likely prove to be important adjuncts,” said Eve J. Higginbotham, MD.
Dr. Higginbotham said one of the combination drugs on the horizon is Xalcom, from Pfizer, a fixed combination of timolol 0.5% and latanoprost 0.005%. This drug has been approved in some markets outside the United States under the name Xalacom.
Dr. Higginbotham said two multicenter trials showed a statistical difference in reduction in IOP between patients who received the combination drug and patients who received another combination. In one study, 32 patients were started on timolol twice a day, and 1 month later they were randomized to either the fixed combination of latanoprost and timolol or an unfixed combination of brimonidine twice a day and timolol twice a day for 6 weeks. Starting from a baseline of 20.9 mm Hg, the mean IOP decreased to 17.9 mm Hg in the fixed combination group, and to a mean of 19 mm Hg in the unfixed brimonidine/timolol group.
Another drug in the works is Combigan, from Allergan, a fixed combination of brimonidine and timolol. Dr. Higginbotham said a 1-year study showed that the reduction from baseline IOP was greater in patients receiving the combination than in patients who received either drug individually.
Howard Barneby, MD, presented a study comparing Alcon’s Extravan (travoprost 0.004%, timolol 0.5%) to Travatan (travoprost, Alcon) alone or timolol 0.5% alone.
The fixed combination of travoprost and timolol was found to be safe and well tolerated and to reduce mean IOP more than either of its individual components, he said.
In the trial, patients were randomized to one of three regimens for a 6-month period: 85 patients received the fixed combination in the morning plus vehicle in the evening; 86 patients received the vehicle in the morning and travoprost in the evening; and 92 patients received timolol in both the morning and evening.
The study found that mean IOP reduction following treatment with Extravan was greater than with either travoprost alone (up to 2.2 mm Hg difference) or timolol alone (up to 3 mm Hg difference).
“The advantages of this drug,” Dr. Barneby said, “are that it proves IOP-lowering efficacy, its safety profile is similar to single agents and it is convenient.”
Intravitreal steroids raise IOP
The prevalence of IOP increase after intravitreal steroid injection is greater than has been previously reported, according to Douglas J. Rhee, MD.
Dr. Rhee and colleagues reviewed results in 324 eyes with at least 6-month follow-up after receiving injections of intravitreal Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) to determine the prevalence of clinically significant IOP elevations after injection. Triamcinolone is currently being investigated as a treatment for diabetic macular edema, Dr. Rhee said.
The researchers found that 48% of the eyes developed a “significant” IOP elevation, defined as more than 5 mm Hg, he said. Moreover, 35% of those patients had an IOP increase of more than 10 mm Hg. Among the eyes with elevated IOP, 42% had the initial elevation within 1 month, while 17% were seen at 6 months.
“There were a large number of subjects with repeat injections,” he said.
Laser-shunt procedure
A 35-µm gold shunt that acts as a channel for egress of aqueous fluid after glaucoma laser surgery “puts the doctor in charge of compliance,” according to the device’s developers.
Gabriel Simon, MD, PhD, director of research for Solx, said the shunt is designed to be inserted in a channel created with a Ti:sapphire laser.
The procedure, called gonioscopic laser trabecular ablation (GLTA), uses the Solx DeepLight laser to open a channel in the trabecular meshwork. The laser delivers microsecond pulses in a near-infrared wavelength. The energy is delivered transcorneally using a goniolens.
Doug Adams, president and chief executive officer of Solx, said the DeepLight laser has received the CE Mark in Europe. The company has applied for an investigative device exemption in the United States, and the device will be investigated at 10 U.S. sites. He said the procedure can be performed in 7 to 8 minutes in either a hospital or office setting.
Cornea/external disease
Emollient drops for dry eye
An emollient-based topical tear substitute was “highly effective” in increasing the tear film’s lipid layer and resolving symptoms in patients with dry eye, according to a poster by Jack V. Greiner, DO, PhD, and colleague.
The topical drops, marketed as Soothe by Alimera Sciences, are designed to thicken the tear film’s lipid layer, according to the poster. By thickening the lipid layer, the drops minimize evaporation and the burning, redness and itching that accompany dry eye, the poster authors said.
Following a routine ophthalmologic exam, 100 patients with complaints of dry eye symptoms in both eyes completed an evaluation questionnaire. Tear film breakup time was measured in each patient, and the Schirmer test with anesthesia was performed using standard methods.
The metastable emulsion was instilled into both eyes of each subject. All patients were observed to have increased lipid layer thickness over baseline following instillation, the poster authors said.
“All subjects evidenced an increase in lipid layer thickness, symptoms decreased in 92% of subjects and blurring was present with 2%,” the poster said.