Jules Gonin meeting highlights posterior segment research, clinical practice

Advanced research and practice is developing rapidly worldwide, leading to promising techniques and treatments.

MONTREUX, Switzerland – The 23rd meeting of the Club Jules Gonin, held this year in the surroundings of Lake Geneva, presented an extensive survey of all the main aspects of advanced research carried out by the most prestigious posterior segment surgeons from around the world.

“This is undoubtedly an exciting time for the treatment of vitreoretinal diseases. New diagnostic means, surgical techniques and medications are rapidly developing, and the most recent studies on genetics, artificial implants and cell transplantation are opening a whole new world of future possibilities. This meeting gives us the opportunity for a true and exhaustive update on all the newest developments on a worldwide basis,” said Club president D. Jackson Coleman, MD.

Tumor diagnosis and treatment

The program began with the tumor section, which concentrated on new techniques for diagnosing and stratifying tumors. Because of these developments, Dr. Coleman said, melanomas are no longer classified as single entities but can be divided into more lethal and less lethal, and more targeted care can be provided. This allows for early detection of possible metastases and increasing survival rate.

Dr. Coleman presented a new technique for acoustic spectrum analysis as a noninvasive substitute for biopsy in uveal melanoma. The technique, he said, provides information not evident in conventional gray-scale ultrasonograms regarding tissue microstructure.

Prediction of metastatic disease by bone marrow testing was described by Nils Eide, MD, of Oslo University National Hospital.

“Detectable tumor cells were found in the bone marrow of a high number of patients. In the future, bone marrow testing using an immunomagnetic technique employing a panel of melanoma antibodies may be valuable in predicting metastatic disease,” he said.

The second main aspect dealt with treatment modalities.

“Endoresection is now being applied to large uveal melanomas as an adjunct to traditional irradiation or enucleation, with the double aim of reducing the severe inflammatory reaction following conventional radiotherapy and preserving vision,” Dr. Coleman said.

According to Michael H. Foerster, MD, of Berlin University Eye Clinic, endoresection is a particularly valuable alternative approach in the case of large uveal melanomas located close to the optic nerve. These tumors normally have an unfavorable prognosis with regard to visual preservation and eye retention, due to the high incidence of radiation-induced complications.

Other forms of therapy were also discussed, from proton beam irradiation to iodine-125 plaque brachytherapy treatment for the larger tumors. A modified protocol for ruthenium plaque radiotherapy, which allows for lower radiation doses, was presented by Bertil E. Damato, MD, PhD, of Liverpool University Hospital.

Transpupillary thermotherapy was confirmed as a valuable adjunctive therapy in some cases, particularly in treating recurrences or in reversing visual loss from exudation following radiation therapy. As a primary treatment, however, despite its much lower rate of complications, it should not be considered as an alternative to radiotherapy, due to the high incidence of early recurrences, according to Jean-Daniel Grange, MD, of Lyon University Eye Clinic.

PDT on the move

Results of the main international clinical trials on photodynamic therapy in age-related macular degeneration were thoroughly discussed.

The 3-year results of an extension study of the Verteporfin in Photodynamic Therapy (VIP) trial, presented by Ursula Schmidt-Erfurth, MD, of Lübeck University, demonstrated that visual acuity in patients with subfoveal choroidal neovascularization due to pathologic myopia remained stable over the total follow-up of 36 months following PDT.

Again within the parameters stabilized by the results of the VIP and TAP trials, Gisele Soubrane, MD, PhD, of Creteil University, gave some positive news on the incidence of acute severe vision decrease after PDT in AMD.

“Acute severe vision decrease is an infrequent event, and some spontaneous visual recovery usually occurs. The risk of vision loss without treatment remains, however, greater than the risk of vision loss with treatment in AMD patients,” she said.

Promising new developments of PDT were highlighted in the lecture of Joan W. Miller, MD, of Harvard Medical School, and winner of the Retina Research Foundation award, showing the effects of anti-neovascular medications potentiating the effects of photodynamic treatment.

“Our laboratory has begun exploring improvements to PDT by combining it with other agents, including angiostatic steroids, anti-vascular endothelial growth factor agents and pigment epithelium-derived factor, or by improving selectivity through targeting. We have recently synthesized a targeted verteporfin using a homing peptide to the VEGF receptor VEGFR2, in order to direct the photosynthesizer to the neovascular endothelium,” Dr. Miller said.

Research is also being conducted on the impact of vitamin and mineral supplementation on the prevention and progression of AMD. As demonstrated by the results of the Age-Related Eye Disease Study, presented by another Harvard professor, Johanna M. Seddon, MD, a combination of high-dose antioxidant and zinc supplementation reduces by 25% the risk of progression from intermediate to advanced AMD. The use of these supplements would therefore prevent more than a quarter-million people in the United States from developing advanced AMD.

Macular surgery

“Other areas we covered were vitreoretinal and macular hole surgery,” Dr. Coleman said. “The treatment of macular hole by membrane peeling has been popular for the past 5 to 6 years, and the results are increasingly good. However, new ways of evaluating the characteristics of the macula and the size of macular holes using optical coherence topography and ultrasound have enhanced predictivity of surgical outcomes.”

An overall view of the developments of epiretinal membrane peeling tools and techniques was given by Steve Charles, MD, who was awarded the Hermann Wacker prize. Dr. Charles himself has developed forceps peeling and delamination using fine, curved scissors with a special low-friction coating.

Indocyanine green-assisted peeling of the internal limiting membrane was discussed by numerous presenters. Most studies, like the one presented by Arnd Gandorfer, MD, of Munich University Eye Clinic, seem to follow the direction of discouraging the use of this dye. Though it facilitates membrane peeling in macular surgery, ICG seems to cause retinal damage, regardless of the underlying disease.

Short-term tamponade in macular hole surgery, which would relieve the burden of long-term prone positioning especially in elderly patients, might not be such a distant achievement, according to some surgeons. Michel Gonvers, MD, of Lausanne Jules Gonin Hospital, has obtained encouraging results with a new technique of surgically-induced limited detachment of the posterior retina and gentle manipulation of the macula.

“We still don’t know for sure how these maneuvers work, but in six patients we have obtained the complete closure of the macular hole within 12 hours,” he said.

Functional and anatomic results of macular translocation were also extensively reviewed. Series of cases presented by different surgeons seem to converge on the conclusion that, at present, the procedure can benefit a significant number of selected cases, but surgical complications may still be a problem.

New medical therapy

“The next area, only recently recognized as being as important as the newer surgical techniques, not only for macular holes but for various forms of maculopathy and retinopathy, is the use of new drugs that may be able to suppress inflammation and macular edema, especially in diabetes,” Dr. Coleman said. “There is no question that we are in a transition stage between surgical techniques and newer medications that may be able to prevent and suppress the development of some major degenerative retinal disorders.”

Panagiotis G. Theodossiadis, MD, of Athens University, reported the impressive results of a single intravenous infusion of the anti-tumor necrosis factor (TNF) antibody Infliximab in the treatment of chronic, refractory cystoid macular edema.

“We treated in this way patients who did not respond to prolonged and intensive therapy. Our findings also suggest that TNF plays a central role in the pathogenesis of the disorder,” he said.

In the session dedicated to pediatrics, epidemiological data and long-term follow-ups of preterm infants were presented.

“In a population of 2,390 very-low-birth-weight infants surveyed over a 15-year period, nearly 50% developed retinopathy of prematurity. Less than 20% developed severe ROP stage 3-5. One-half percent of babies became blind with stage 5 ROP in both eyes,” said Volker Seiberth, MD, of Osnabrück Hospital, Germany.

Visual function and educational attainments of very-low-birth-weight young adults with ROP stage 3-5 were evaluated by Fritz H. Koerner, MD, of Bern University. He found that more than 80% have reading vision, and the majority achieved an average educational attainment, in spite of the high incidence of strabismus, amblyopia, myopia and various fundus abnormalities.

Retinal pigment epithelium cell culture and transplantation has great potential, and research on new, more successful methods is ongoing.

“We need new insights to improve the adhesion, survival and function of translocated RPE cells,” said Jan van Meurs, MD, of the Rotterdam Eye Hospital.

Artificial Vision

One session was dedicated to the most recent experiments on artificial vision. Intraocular retinal prostheses to replace lost photoreceptor functions have reached various stages of experimentation in many centers worldwide. One of the problems more frequently discussed was that of providing sufficient electrical stimulation to the implants without mechanically or electrically damaging the retina.

“After we had accomplished the stage of experimental observation in dogs, we performed psychophysical studies in sighted volunteers using pixilated images, and found that epiretinal electrical stimulation over prolonged periods is feasible,” said Mark Humayun, MD, of the University of Southern California. “What is encouraging is the relatively few pixels that are needed to perform various activities of daily living. The usefulness of delivering pattern stimulation via such mechanism is now in the process of being demonstrated in blind patients.”

The Club Jules Gonin The Club Jules Gonin was founded in 1959, in honor of Jules Gonin, professor of ophthalmology in Lausanne, Switzerland. Between 1910 and 1914, he was the first to recognize the importance of retinal breaks and the first to develop a successful surgical procedure for the management of retinal detachment. From 1914 to 1935, he performed retinal detachment surgery on a large number of patients. The value of his method was later confirmed worldwide. It was only due to his unexpected death from cerebral hemorrhage in 1935 that he could not be nominated for the Nobel Prize, according to D. Jackson Coleman, MD, Club president. The Club is international in scope. It is based in Switzerland, where it has its permanent secretariat and organizes biannual meetings for its members. Every third meeting is held in Switzerland. The Club Jules Gonin has reserved membership for those who are actively performing research and are true innovators in the area of vitreochoroidal disorders, Dr. Coleman said. Applicants must be sponsored by two members of the Club to become candidates for membership and be admitted to the upcoming meetings. Over a trial period of 6 years, they will then be required to exhibit a minimum number of publications in peer reviewed journals as first authors, and to present at least two papers during meetings of the Club. Evaluation of eligibility for membership will then be performed by the Executive Committee. The General Assembly of Club members has the final vote on the proposed candidature. Currently, there are 230 members of the Club.

For Your Information:

• D. Jackson Coleman, MD, is professor and chairman of ophthalmology at New York-Presbyterian Hospital/Cornell University. He can be reached at Weill Medical College of Cornell University, Department of Ophthalmology, 520 East 70th Street, New York, NY 10021; (212) 746-5588; fax: (212) 746-8732; e-mail: djcole@med.cornell.edu.
• Nils Eide, MD, can be reached at Rickshospitale, Eye Department, 0027 Oslo, Norway; (47) 2286-7831; fax: (47) 2286-7848.
• Michael H. Foerster, MD, can be reached at Department of Ophthalmology, Universitatsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany; (49) 30-8445-2331; fax: (49) 30-8445-4450: e-mail: michael.foerster@medizin.fu-berlin.de.
• Bertil E. Damato, MD, PhD, is Head of Ocular Oncology Service at the Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, England; (44) 151-706-3973; fax: (44) 151-706-5436: e-mail: Bertil@Damato.co.uk.
• Jean-Daniel Grange, MD, can be reached at Clinique Ophtalmologique Universitaire, Hopital de la Croix-Rousse, 93 Grand Rue, 69004 Lyon, France: (33) 4-207-1716: fax: (33) 4-7207-1708; e-mail: jean-daniel.grange@chu-lyon.fr.
• Ursula M. Schmidt-Erfurth, MD, can be reached at Augenklinik Der Univ., Ratzeburger Allee 160, Lübeck D-23538, Germany; (49) 451-500-2229; fax: (49) 451-500-3085; e-mail: uschmidterfurth@ophtha.mu-Lübeck.de.
• Gisele Soubrane, MD, PhD, can be reached at Hopital Intercommunal de Créteil, University of Creteil, 40 Avenue Verdun, 94010 Creteil, France; (33) 14-517-5221; fax: (33) 14-517-5227; e-mail: gisele.soubrane@chicreteil.fr.
• Joan W. Miller, MD, can be reached at Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, Massachusetts 02114; (617) 573-3915; fax: (617) 573-3678. e-mail: jwmiller@meei.harvard.edu.
• Johanna M. Seddon, MD, can be reached Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, Massachusetts 02114; (617) 573-4010; fax: (617) 573-3570; e-mail: johanna_seddon@meei.harvard.edu.
• Steve Charles, MD, can be reached at the Charles Retina Institute, 6401 Poplar Ave., Suite 190, Memphis, TN 38119; (901) 767-4499; fax: (901) 761-0727; e-mail: scharles@.att.net; Web site: www.charles-retina.com.
• Arnd Gandorfer, MD, can be reached at Department of Ophthalmology, Ludwie Maximilians University, Matildenstrasse 8, 80336 Munich, Germany; (49) 895-160-3800; fax: (49) 895-160-4778.
• Michel Gonvers, MD, can be reached at Hôpital Ophtalmique Jules Gonin, Av. De France 15, CH-1004 Lausanne, Switzerland; (41) 21-626-8111; fax: (41) 21-626-8888; e-mail: mgonvers@worldcom.ch.
• Panagiotis G. Theodossiadis, MD, can be reached at 10 Orfeos Sfr., 14565 Ekali, Athens, Greece; (30) 107-25-7585; fax: (30) 108-13-4684; e-mail: panosthe@otenet.gr.
• Volker Seiberth, MD, can be reached at Marienhospital Osnabrück, Johannisfreiheit 2-4, 49074 Osnabrück, Germany; (49) 541-326-4402; fax: (49) 541-326-4412; e-mail: Dr.Seiberth@t-online.de.
• Fritz H. Koerner, MD, can be reached at Department of Ophthalmology, University of Bern, Inselspital, CH-3010 Bern, Switzerland; (41) 31-632-8501; fax: (41) 31-632-4882; e-mail: fritz.koerner@insel.ch.
• Jan van Meurs, MD, can be reached at the Rotterdam Eye Hospital, Schiedamsevest 180, 3011 BH Rotterdam, Netherlands; (31) 10-202-0878; fax: (31) 10-411-1747; e-mail: janvanmeurs@cs.com.
• Mark S. Humayun, MD, PhD, can be reached at Doheny Retina Institute, 1450 San Pablo St., Los Angeles, CA 90033 (323) 442-6521; fax: (323) 442-6519; e-mail: humayun@hsc.usc.edu.