advances make for a memorable meeting.
JACQUELINE ZUMMO, MEDICAL EDITOR
MACULA 2006, a combined meeting of the Atlantic
Coast Retina Club and the tri-annual New York conference on vitreous-retina and
macular diseases, brought together an elite group of researchers and clinicians
to present their most recent findings and observations on understanding and attacking
A heightened sense of excitement surrounded the meeting as
recent advances on a number of fronts have created promising new possibilities for
treating a wide range of macular diseases.
Overall, MACULA 2006 provided a better understanding of current
critical issues relating to macular abnormalities and their treatments. The meeting
covered imaging and technology, medical and surgical treatment of retina diseases,
and new initiatives to approach both the wet and dry forms of age-related macular
Highlights of the meeting were the presentation of impressive
new study data from the phase 3 ANCHOR study of ranibizumab (Lucentis, Genentech)
for wet AMD, as well as studies that focused on the off-label use of bevacizumab
(Avastin, Genentech) for the treatment of wet AMD (for full details of the ANCHOR
study please turn to page 19).
The meeting, held at the Uris Auditorium, Weill Medical College,
Cornell University, New York, NY, was led by an organizational committee representing
the medical school ophthalmologic departments in the greater New York City area,
a regionally based and sponsored academic program.
This article focuses on a few presentations given at MACULA 2006.
IMAGING AND TECHNOLOGY
Richard Rosen, MD, of the New York Eye & Ear Infirmary, addressed
optical coherence tomography ophthalmoscope (OCT/SLO) in detail. His presentation
discussed OCT/SLO being recently commercialized by OTI (Toronto, Ontario,) to provide
superior imaging and quantitative studies of the retina.
This technology also utilizes coronal scanning (C scans).
Another key discussion point was how OCT/SLO provides pixel-to-pixel registration
between simultaneous matching pairs of OCT and SLO images, as well as high-resolution
cross-sections (B scans). By scanning parallel to the retinal surface, OCT/SLO produces
enhanced views of the vitreoretinal and RPE-choroidal interfaces, and topographic
thickness maps, which use vascular patterns to accurately register serial studies.
Dr. Rosen also discussed how ultra-high resolution imaging at standard speeds using
broadband illumination is also a feature of this technology.
MEDICAL RETINAL DISEASES
With an increase in retinal diseases being seen by many retina
specialists, it comes as no surprise that this year's MACULA had a major focus on
central serous chorioretinopathy (CSC), AMD, and diabetic retinopathy.
Lawrence Yannuzzi, MD, of the Vitreous, Retina, Macula Consultants
of New York, presented on a standard of care for CSC. His presentation highlighted
that for more than a century, ophthalmologists have been aware of CSC as a distinct
clinical entity. A myriad of clinical manifestations and defining fluorescein angiographic
changes have traditionally described the entity. For persistent macular detachment
with visual decline and eccentric focal retinal pigment epithelium (RPE) leaks,
photocoagulation has been used to treat patients with CSC in the past. However,
in recent years other diagnostic and therapeutic modalities have been used in the
management of these patients. Dr. Yannuzzi's presentation also reviewed new developments
in the diagnosis and treatment of CSC, utilizing the following modalities: OCT,
indocyanine green (ICG) angiography, and fundus autofluorescence.
Guy Barile, MD, from the Columbia University College of Physicians
& Surgeons, discussed a neurovascular therapeutic target for the prevention
and treatment of diabetic complications in the retina. The "RAGE" axis comprises
the formation of advanced glycation endproducts (AGEs) and their interaction with
a cellular receptor (Receptor for AGEs or RAGE). Chronic hyperglycemia accelerates
the development of AGEs, irreversible chemical adducts of proteins, lipids, and
nucleic acids. In the vitreous cavity of diabetic eyes, AGE formation results in
collagen cross-linking, facilitating diabetic "vitreoschisis" or "vitreopathy."
In early diabetic retinopathy, the RAGE axis is amplified within the neural retina
and is accentuated along the vitreoretinal interface, with AGEs present in the internal
limiting membrane (ILM) where they have contact with the footplates of RAGE-expressing
Müller cells. This anatomically close apposition suggests that a possible physiologic
benefit of diabetic vitrectomy is the removal of AGE ligands from the posterior
vitreous cortex and ILM, down regulating the proinflammatory RAGE axis in adjacent
Müller cells. In a murine model of early diabetic retinopathy, antagonism of
the RAGE axis reduces neurovascular perturbations, validating this pathway as a
therapeutic target for intervention in diabetic retinopathy.
Lee Jampol, MD, of Feinberg School of Medicine, Northwestern
University, focused on an epidemiologic study of white dot syndromes and "the black
Dr. Jampol presented a case of reactive lymphoid hyperplasia involving
the retina and choroid (leopard spots), both orbits, the lids, the pancreas, kidneys,
and many lymph nodes including the mediastinum. The diagnosis of this systemic pseudolympohoma
was discussed. Possibilities included Castleman's disease, an unusual prelymphoma
disease that is often seen in HIV-positive patients (this patient was not). Another
possibility was atypical sarcoid.
Dr. Jampol's presentation also involved 4 cases of a new disease,
which is now tentatively being called white geographic maculopathy. The patients
have serpiginous bilateral macular lesions but initially have good vision (unless
there is choroidal neovascularization [CNV]). The white changes last months or years.
The hypofluoresent changes on the FA and ICG last many months or years, and CNV
is very common.
Michael J. Cooney, MD, MBA, from the Manhattan Eye, Ear &
Throat Hospital, discussed emerging concepts in nutritional supplementation for
diabetic retinopathy. He presented that Diabetes mellitus has become a worldwide
scourge and a medical pandemic. He also asserted that preventive strategy for diabetic
retinopathy could have significant public health impacts by decreasing the incidence
of vision loss and decreasing the costs to society.
The AREDS study provided the proof of principle that nutritional
supplementation can positively impact retinal disease progression and slow vision
loss. He also discussed Genistein, an isoflavone derived from soybeans, as having
a multiple biological mechanisms of action, a wide therapeutic index, and has been
studied in many disease states. Genistein inhibits tyrosine kinase and aldose reductase
pathways, both of which are pathophysiological pathways that have been implicated
in diabetic retinopathy. Genistein has been studied in several animal models of
retinal ischemia and diabetic retinopathy and can significantly inhibit the upregulation
of tyrosine kinase pathways found in these animals. Gensitein also protected against
retinal morphologic changes associated with these disease states in animals. He
concluded by adding that a clinical development program for genistein as a nutritional
supplement for diabetic retinopathy is underway.
Donald J. D'Amico, MD, of Harvard Medical School, discussed his
perspectives on evolutionary and revolutionary trends in vitreoretinal surgery over
the past 25 years. He considers evolutionary trends to be those that extend naturally
from previous instrumentation and techniques, and described the following as evolutionary
trends in vitreoretinal techniques and instrumentation: 1) the use of fine forceps,
as opposed to membrane pics, for membrane peeling; 2) small-guage vitrectomy; 3)
temporary keratoprosthesis; 4) endoscopy; 5) the progression from lens removal to
retention to IOL implantation at the time of vitrectomy; 6) ICG and other tissue
stains for tissue visualization; and 7) the shift from buckling to vitrectomy for
Revolutionary trends are those that could not have been easily
foreseen 25 years ago, and arise almost disruptively. He included as revolutionary
trends: 1) retinotomy/retinectomy for retinal reattachment, drainage; 2) perfluorchemical
techniques; 3) wide-angle and noncontact viewing; 4) permanent keratoprosthesis
for ocular rehabilitation; 5) adjuvant pharmaceuticals at vitrectomy; and 6) the
shift from either scleral buckling or vitrectomy to pneumatic retinopexy for primary
He considers the endolaser and tamponades to be the most substantial
advances in that period, and although they are currently without demonstrated clinical
success, he believes retinal vascular surgery (CRVO, BRVO) techniques have been
revolutionary in their attempt. He suggested that trends for the future will be
1) increasing attention to combined IOL and vitreoretinal surgery; 2) research to
find alternatives to eye-filling tamponades for retinal break closure; 3) continued
advancement in permanent keratoprosthesis, and most importantly; 4) extraordinary
refinement in adjuvant pharmaceuticals at the time of vitreoretinal surgery.
Carl Regillo, MD, from Wills Eye Hospital, discussed how 25-g
pars plana vitrectomy (PPV) offers several potential advantages over the traditional
20-g approach, including sutureless sclerotomy sites, shorter operating time, reduced
surgical trauma, improved patient comfort after surgery, and faster postoperative
The Wills Experience consisted of 70 eyes of 70 patients having
25-g PPV for a variety of indications. Both the entire study population and the
individual subgroups had a statistically significant visual improvement at final
follow-up compared with the baseline preoperative acuity. There were no intraoperative
or postoperative complications that affected the final visual outcome in any eye.
Two eyes (2.8%) had intraoperative retinal breaks detected and treated without further
sequelae. Four eyes (6%) had postoperative hypotony (IOP <6 mm Hg) the day after
surgery, but all cases resolved within 1 week and no choroidal detachments or other
problems occurred. One eye (1.4%) had a postoperative limited retinal detachment.
Overall, rates of intraoperative and postoperative problems were very low and comparable
to previously published studies on 25-g surgery. Furthermore, significant complications
such as retinal tear and detachment appeared no greater than what has been reported
for 20-g vitrectomy surgery.
Richard Spaide, MD, of Vitreous, Retina, Macula Consultants of
New York, presented his experience with 23-g vitrectomy. He described the rationale
for minuturization in vitrectomy surgery, including obviating the need for sutures,
reducing postoperative recovery times, sparing of the conjunctiva with reduction
in scarring, and decreasing operating room times. Like 25-g systems, 23-g systems
provide a sutureless, transconjunctival approach to vitrectomy. Twenty-three-g systems
provide several additional possible advantages, including tunnelled sclerotomies
to avoid postoperative hypotony, stiffer instrumentation, larger bore cutters with
greater suction forces to create a posterior vitreous detachment, and brighter light
pipes. With more than 1 year's experience with the system, no safety issues were
Avastin: The Miami Experience
Andrew Moshfeghi, MD, of Bascom Palmer Eye Institute, discussed
his use of bevacizumab in Miami.
He described how in May of 2005 the Bascom Palmer group first
started using off-label intravitreal bevacizumab (Avastin) as salvage therapy for
patients with advanced and refractory neovascular AMD. Dr. Moshfeghi noted the similarity
between bevacizumab and ranibizumab (Lucentis), and the availability of bevacizumab
(FDA-approved for metastatic colorectal cancer), as strong rationales for intravitreal
use of bevacizumab.
Dr Moshfeghi said his experience with intravitreal bevacizumab
has been clinically indistinguishable from the open-label experience with intravitreal
ranibizumab. He estimates that at least 500 patients have been treated at the Bascom
Palmer Eye Institute with intravitreal Avastin since May 2005, and it has been found
to be a well-tolerated treatment with no serious ocular or systemic complications
reported. Until Lucentis is granted FDA approval, bevacizumab is nicely filling
the AMD treatment-gap, primarily as salvage therapy, he noted.
At MACULA 2006, Genentech announced positive 1-year results from
its second pivotal phase-3 study of the investigational drug Lucentis in patients
with wet AMD. Data from the ANCHOR study comparing ranibizumab to verteporfin (Visudyne,
Novartis) photodynamic therapy (PDT) showed a difference in mean change in visual
acuity of 18 letters for patients treated with 0.3 mg of ranibizumab and 21 letters
for patients treated with 0.5 mg of ranibizumab from study entry compared to those
treated with PDT at 12 months. Overall, the data show that ranibizumab maintained
or improved vision in approximately 95% of patients at 1 year.
In an off-site interview with Lawrence Singerman, MD, of Retina
Associates of Cleveland and Carl Regillo, MD, of Wills Eye Hospital, pegaptanib
sodium was presented as the foundation therapy for wet AMD. Recent data suggest
that pegaptanib sodium (Macugen, OSI (Eyetech)/Pfizer) used as early treatment may
result in optimal vision outcomes. In clinical practice, it appears that the clinical
value of pegaptanib sodium is greater than that demonstrated in the original pivotal
trials, as the original trials included more difficult cases that may have had previous
treatment with PDT. Additionally, because there are potential safety issues with
the use of nonapproved anti-VEGF therapies, pegaptanib sodium should be a strong
consideration for treatment based on demonstrated 2-year safety data. Because pegaptanib
sodium is the only approved anti-VEGF therapy for wet AMD, reimbursement for pegaptanib
sodium will likely not be a challenge for the retinal clinician.
Retinal Physician, Issue: March 2006