Menu 18 Updates for October 2010 – March 2011

I have been negligent in updating the menus for my online Journal. So, here is the update for the past six months.

This update contains a number of new writeups, including the first use of gene therapy in treating retinitis pigmentosa; an overview of what happened at the Second Ophthalmic Innovation Symposium (held last year just prior to the AAO Meeting), a couple of interviews conducted by my colleague in China during lat year’s APAO Meeting in Beijing, and an excellent writeup about how femtosecond lasers are being used in ophthalmology.

I have also included several updates on subjects I have been closely following, including the controversy between the use of Avastin or Lucentis in treating AMD; an AMD update; a CATT Study update; five updates on the use of stem cells in ophthalmology; and updates on the latest news from Iluvien and NeoVista.

Here are synopses and links for the recent postings:

Avastin/Lucentis Updates:
Avastin/Lucentis Update 42: One-Year Results of Controlled Comparison Study Published (Oct. 4, 2010)

Last October (2009), I came across the six-month results of one of the first blinded, double-masked comparison studies run between Avastin and Lucentis, sort of a mini-CATT Study. This study was done by researchers at the Boston University School of Medicine in cooperation with the VA Boston, and was published in the American Journal of Ophthalmology. I published their news release describing the study and the six-month results as Avastin/Lucentis Update 29.

This weekend, the same group announced the one-year results of this study, this time published in Eye, a peer-reviewed publication of The Royal College of Ophthalmologists in the UK.

Avastin/Lucentis Update 43: Secret Rebates Offered for Lucentis (Nov. 4, 2010)

First, Genentech refused to provide Lucentis for the CATT Study, being run by NEI/NIH to compare Avastin to Lucentis for AMD (Avastin/Lucentis Update 12); then they threatened to stop supplying Avastin to compounding pharmacies so that ophthalmologists could continue to obtain the drug for their patients (Avastin/Lucentis Update 18); then they decided to provide Lucentis free of charge for the study looking at the use of panretinal laser treatment plus anti-VEGF (Lucentis) in the treatment of diabetic macular edema – at the exclusion of Avastin, in that “pay to play” study (Avastin/ Lucentis Update 37); and now, the company is offering secret rebates to selected large users of Lucentis – obviously to blunt the potential expected to be offered by Avastin when the CATT Study results are released next Spring.

Here, as written by Andrew Pollack online yesterday and published in today’s NYTimes, is the latest story in the ongoing Avastin vs. Lucentis Controversy:


Avastin/Lucentis Update 44: United Kingdom Closer to Allowing Avastin for AMD (Dec. 8, 2010)

While the U.S. comes closer to showing the equivalency of Avastin to Lucentis for treating the wet form of age-related macular degeneration, when the CATT (Comparisons of Age-Related Macular Degeneration Treatments Trials) Study results become public, hopefully, some time this Spring, the UK’s health services are still fighting over whether or not they should study the two drugs to determine if Avastin would be appropriate for the Brits to use in their National Health Service.


Avastin/Lucentis Update 45: Avastin Drug Treatment for ROP Better than Laser (Feb. 26, 2011)

A new study, published earlier this month in the New England Journal of Medicine, describes the use of intravitreal Avastin to treat Retinopathy of Prematurity (ROP) in premature infants.

This study was widely covered by the press, but I would like to reproduce just a few of the presentations to provide you with the information necessary to best understand the results of this study.


AMD Update:

AMD Update 13: Retinal Procedures on the Rise (Oct. 13, 2010)

A new study, just published in the October issue of Archives of Ophthalmology and reported by Ophthalmology Web, MedPage Today, and Medscape Medical News,  shows that among those in the Medicare population (age 65 plus), treatments for retinal conditions nearly doubled between 1997 and 2007 – and this trend is expected to continue with the aging of the population and seniors living longer.


CATT Study Update:
CATT Study Update 12: Status of WorldWide Studies (Jan. 6, 2011)

With the anticipated arrival of the one-year results of the CATT Study this Spring, I thought it would be appropriate to update where the other worldwide studies stand.

During the Retina Subspecialty Day sessions, held prior to the recent 2010 AAO Meeting in Chicago, Daniel Martin, MD provided an update on the various comparative studies underway around the world between Avastin and Lucentis. Here are Dr. Martin’s comments, as reported by the Market Scope team in the November issue of Ophthalmic Market Perspectives.


Stem Cells in Ophthalmology Updates:
Stem Cells in Ophthalmology Update 2: ACT Gets Go-Ahead to Treat Stargardt’s (Nov. 23, 2010)

As I noted in my September report on the Use of Stem Cells in Ophthalmology, it was anticipated that either the program at The London Project to Cure Blindness or Advanced Cell Technology’s program to treat Stargardt’s disease would be the first to get the go-ahead to begin approved human trials. I have not heard any news out of London, but earlier this week ACT received notification from the FDA that it was cleared to begin its human trials with human embryonic stem cells.


Stem Cells in Ophthalmology Update 3: ACT Files IND to Treat Dry AMD (Nov. 30, 2010)

Furthering its lead in stem cell research in ophthalmology, Advanced Cell Technology Inc., announced today that it  had filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration, to initiate a Phase I/II multicenter study for the  treatment of dry Age-Related Macular Degeneration (dry AMD) using human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells.


Stem Cells in Ophthalmology Update 4: ACT Receives Receives FDA Approval to Use hESCs to Treat Dry AMD (Jan. 3, 2011)

Advanced Cell Technology Inc., announced today that it  had received approval from the FDA to commence its clinical trial using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) to treat the dry form of age-related macular degeneration. ACT is now permitted to initiate a Phase I/II multicenter clinical trial to treat patients with dry AMD, the most common form of macular degeneration in the world. There are currently no approved treatments available for this prevalent disease of an aging global population. Dry AMD, representing a substantial global market opportunity and afflicts between 10-15 million Americans, and a further 10 million Europeans.

Stem Cells in Ophthalmology Update 5: Gene Defects Common in Induced Stem Cells (Mar. 5, 2011)

As the senior editor, John Gever, of MedPage Today reported, following the publication of three studies about induced pluripotent stem cells in the March 3rd, issue of Nature, “The road to regenerative medicine based on induced pluripotent stem cells (iPSCs) may have developed a giant pothole, with new studies showing that the cells are prone to several types of genetic defects.”

The three studies showed that the reprogramming process and subsequent culture of pluripotent stem cells in vitro can induce genetic and epigenetic abnormalities in these cells. The authors of the studies and the editorialist said that the results raise concerns over the implications of such aberrations for future applications of pluripotent stem cells.


Stem Cells in Ophthalmology Update 6: Stemedica Paper Accepted for Presentation at ARVO (Mar. 19, 2011)

I recently received an update from my contact at Stemedica and would like to share the information with you.

A safety study on the use of  stem cells in the eye, in a clinical study underway at the Fyodorov Federal Institution of Eye Microsurgery in Moscow, to treat diabetic retinopathy and diabetic optical neuropathy with stem cells derived from bone marrow, has been accepted for presentation as a poster at the upcoming ARVO Annual Meeting in Fort Lauderdale at the beginning of May. An abstract is shown below.


Iluvien Update:

Iluvien Update: FDA Marketing Approval Delayed (Jan. 5, 2011)

Last July, I wrote a comprehensive report about Iluvien and the status and promise of other sustained release drug delivery systems (Iluvien and the Future of Ophthalmic Drug Delivery Systems). At that time, Alimera Sciences, the company developing Iluvien (under license from pSivida) had filed a new drug application (NDA) to treat diabetic macula edema (DME). The company obtained priority review status for the NDA at the end of August, raising the expectation that an approvable letter might be obtained by the end of 2010.

However, instead of an approvable letter, Alimera Sciences received a “complete response letter” (CRL) from the FDA, communicating to the company that its NDA application “cannot be approved in its present form”.


NeoVista Update:

NeoVista Epi-Retinal Strontium 90 Treatment for AMD: Update 4 (Jan. 20, 2011)

NeoVista just released an update, discussing the first commercial utilization of its Epimacular Brachytherapy device in Germany. The Epi-Rad device, now renamed as the VIDION ANV (Anti Neo Vascular Therapy System) has been commercialized in Europe since November 2009. The first patients treated were in Pisa, Italy, quickly followed by patients treated in London, UK, also in November of 2009, and now in Hamburg, Germany this month.


And, here are the new writeups:
The Use of Gene Therapy in Treating Retinitis Pigmentosa and Dry AMD by Retrosense (Nov. 6, 2010)

A short while ago, I received a message from someone I did not know, who said that he enjoyed the writeups on my online Journal and was wondering if I might be interested in writing about the use of gene therapy as an approach to vision restoration. Since I knew absolutely nothing about gene therapy, the writer got my attention.

After several discussions with Sean Ainsworth, the founder of RetroSense, and much online research, I think I have learned a little about what gene therapy is about, and its application in ophthalmology, especially in the possible restoration of vision in those who suffer from retinitis pigmentosa (RP). Thanks to Sean for whetting my appetite -- here is what I have learned.

The Second Ophthalmic Innovation Summit (Dec. 10, 2010)

Last October, the Second Ophthalmic Innovation Summit (OIS) was held just prior to the 2010 AAO Meeting in Chicago. As was the case last year, my old friend, Larry Haimovitch,an ophthalmic industry veteran, who attended the meeting and wrote about it for the sponsor’s website, Healthcare Syndicate has given me permission to reproduce his writeup in this space.

An Interview with Dr Ronald Krueger (Feb. 17, 2011)

With the permission of Lei Zang, the Managing Editor of Ophthalmology World Report, here is her interview with noted refractive surgeon Dr. Ronald Krueger of the Cleveland Clinic. As noted below, Dr. Krueger was recently in China to perform a corneal transplant on a Mongolian patient and while there, attended the APAO Meeting held last fall in Beijing, where Ms. Zang had the opportunity to interview him.


An Interview with Professor John Marshall (Feb. 17, 2011)   

During the APAO (Asia Pacific Academy of Ophthalmology) Meeting held in Beijing in September, 2010, Lei Zang, the Managing Editor of Ophthalmology World Report,  interviewed Professor John Marshall of St. Thomas Hospital in London and the principal behind the Ellex 2RT (retinal regeneration) program for Ellex Laser, and also an investigator (and inventor?) of the Avedro microwave corneal crosslinking program.

In this interview, Prof. Marshall discussed both his work on 2RT and on microwave crosslinking as well as several other topics that will be of interest to ophthalmic researchers.

              
A Comparison of Commercially Available Femtosecond Lasers for Refractive Surgery (Mar. 17, 2011)

Over the past several years, I have either written or posted other peoples accounts of the use of femtosecond lasers in ophthalmology. Starting with the history of their development in October 2008 (Intrastromal Ablation: A Technology Whose Time Has Come?); an article on the use of the femtosecond laser to treat presbyopia by Dr. Rupal Shah in June 2009  (Another Approach to Intrastromal Ablation); a writeup on the use of femtosecond lasers for performing cataract surgery by Larry Haimovitch, again in June 2009 (Femtosecond Lasers Proposed for Use  in Cataract Surgery); and finally, Dr. Joseph Colin’s writeup about femtosecond laser cataract removal as a second revolution, and my addition about the possibility of using the femtosecond laser to “bleach” the natural lens to delay the onset of needing to remove catatacts, inAugust 2010 (Femtosecond Laser Cataract Removal: The Second Revolution? And, What is Laser Photolysis?).

Earlier this month, I came across an article written by Drs. Ronald Krueger and Glauco Reggiani-Mello, of the Cleveland Clinic, that does an excellent job of summarizing the latest developments in the use of femtosecond lasers in refractive surgery and other applications in ophthalmology. Since the article was written in a professional journal – Expert Review of Ophthalmology, with limited access, I asked the authors for permission to reproduce a significant part of their writeup, along with a link to the original for those that wish to read it in its entirety. Permission was granted, and here is my version of what was presented, along with most of their illustrations and their two tables.

Retina 2007 Subspecialty Meeting Presentations – Day One

I have received brief writeups from both Ophthalmology Times and Ocular Surgery News covering the first day of the Retina 2007 Subspecialty Day presentations. Here are some of the highlights, along with links to the various stories.

First, some updates of on-going studies:

PRONTO (OSN, OT)

The 2-year results of the PrONTO Study, an exploratory open-label trial, indicated that intravitreal injection of ranibizumab (Lucentis, Genentech) produces rapid improvements in visual acuity and findings on optical coherence tomography (OCT) in patients treated for neovascular age-related macular degeneration, said Philip Rosenfeld, MD, PhD professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami.

Forty patients underwent three consecutive monthly injections with 0.5-mg intravitreal ranibizumab during the first year and three patients withdrew during year 2. From months 3 to 24, OCT images were obtained monthly and fluorescein angiography images every 3 months with the goal of determining if OCT-guided regimens could be used over 2 years to maintain visual acuity improvements and OCT outcomes achieved after the three consecutive monthly doses of the drug.

"By day 1 after treatment, we saw about a 50-μm decrease in the central retinal thickness, a 190-μm decrease by 3 months, a 178-μm decrease by 12 months, and a 215-μm decrease by 24 [months]," Dr. Rosenfeld reported.

Patients each received an average of 10 injections during the study period. There was an increase in visual acuity (6 letters) by 14 days after the first treatment that continued to 3 months (11 letters). At 24 months, the mean improvement in visual acuity from baseline was 10.7 letters.

"The PrONTO Study showed that visual acuity and OCT changes appeared to be rapid after intravitreal ranibizumab," he concluded. "The OCT changes always preceded the visual acuity changes, whether for better or worse. OCT-guided treatment appears to preserve the benefits seen after three monthly doses of ranibizumab. A larger prospective study is necessary."

ANCHOR (OSN, OT)

Visual acuity endpoints in the ANCHOR Study showed that ranibizumab (Lucentis, Genentech) surpassed photodynamic therapy (PDT) with verteporfin, (Visudyne, Novartis Ophthalmics/QLT) for treating predominantly classic choroidal neovascularization lesions in age-related macular degeneration, reported Jeffrey Heier, MD, assistant professor ophthalmology, Tufts University School of Medicine, and clinical instructor in ophthalmology, Harvard Medical School, Boston.

"Ranibizumab was found to be a remarkably consistent therapy," said Dr. Heier, Analysis of subgroups in the 2-year ANCHOR Study indicated that the treatment effects of ranibizumab were consistent with all of the primary findings of the drug. Regarding age, the visual acuity results were consistent across all age groups, with the patients treated with PDT more likely to lose three or more lines of visual acuity.

"A gain of about three lines or more of vision was very likely in most age groups treated with ranibizumab," he said. "This finding was slightly less robust in the oldest patients."

Regarding baseline vision, the patients with better vision who were treated with PDT were more likely to lose three lines of vision, according to Dr. Heier. Patients treated with ranibizumab had very consistent results; the only patients who did not gain three lines or more were those with the highest baseline vision, he said.

Compared to PDT, ranibizumab showed a better gain in vision and a threefold greater decline in leakage. The overall treatment benefits were seen across all age groups and lesion sizes, he said.

The ANCHOR study was a multicenter, double-masked, controlled phase 3 study that randomly assigned 423 patients to either verteporfin PDT plus monthly sham or sham verteporfin PDT plus monthly intravitreal ranibizumab, dosed at either 0.3 mg or 0.5 mg.

"Ranibizumab remains a consistent and highly effective treatment," Dr. Heier concluded.


AVASTIN vs. LUCENTIS

Cost disparity between anti-VEGF agents raises economic, moral issues

The substantial difference in cost between ranibizumab, which has U.S. regulatory approval, and off-label bevacizumab presents an economic and moral dilemma for ophthalmologists, according to George A. Williams, MD.

"The retina world changed for better and forever" when bevacizumab (Avastin, Genentech) was introduced as a treatment for AMD [age-related macular degeneration]. He described its impact as "the bevacizumab tsunami, which continues today."

To conduct his economic analysis of the two drugs, Dr. Williams started with the assumption that ranibizumab and bevacizumab are equally effective and are used at the same frequencies. On a microeconomic level, he looked at the cost of each medication both to the physician and to the patient. On a macroeconomic level, he evaluated the cost of each drug to Medicare.

For the physician, bevacizumab costs $45 and ranibizumab costs $2,030.92 per injection; for the patient, Medicare co-pays are $9 and $406, respectively. Referring to delayed reimbursements, Dr. Williams called this the "no pay co-pay."

Dr. Williams estimated that ranibizumab is 44 times more expensive than bevacizumab, on a macroeconomic scale. The disparity raises the question of efficacy vs. cost effectiveness. If put to "the mother test" — referring to which drug surgeons would choose to administer to their mothers — bevacizumab might fail, even though it is cheaper.

He said the upcoming CATT study, the much-anticipated head-to-head comparison of the two drugs funded by the U.S. National Institutes of Health and the National Eye Institute, will hopefully shed more light on the efficacy and safety of both drugs.


Bevacizumab's impact felt despite lack of clinical data

Citing the downturn in sales of verteporfin and pegaptanib, David F. Williams, MD explained how bevacizumab has greatly impacted age-related macular degeneration treatment, despite the fact that is has not gained U.S. approval for treating the disease and the lack of clinical trial data to support its use.

"In 2005 and early 2006, mostly anecdotal reports existed regarding the efficacy of intravitreal bevacizumab (Avastin, Genentech) for neovascular AMD. However, the favorable short-term clinical efficacy was so apparent that use of intravitreal bevacizumab spread rapidly among the retina community,".

While there are no data that show the dominance of bevacizumab use to treat neovascular AMD, indirect evidence can be found in sales trends for other primary treatments that were in use in 2005 when bevacizumab first emerged.

"The cost differential between off-label bevacizumab and the other pharmacological treatments for neovascular AMD was striking," he said. From the time bevacizumab efficacy data were introduced by Philip J. Rosenfeld, MD, PhD, until the last quarter of 2006, pegaptanib sales fell 26% while verteporfin sales fell 63%. In addition, the approval of ranibizumab in July 2006 pushed verteporfin sales down 82% while pegaptanib sales fell 92%.

"The unprecedented growth of off-label bevacizumab as a primary therapy for AMD occurred in the setting of anecdotal reports, reports of non-randomized, non-controlled, small clinical series, and individual personal clinical experience," Dr. Williams said. "It has persisted in the setting of the availability of a highly efficacious, but expensive, [U.S. Food and Drug Administration-approved] product."

Dr. Williams pointed to four reasons for this growth: the value of evidence-based medicine, the value of mass clinical experience, pricing of FDA-approved drugs and the power of physician choice.


NEW TREATMENTS FOR AMD

VEGF Trap promising for neovascular AMD

VEGF Trap (Regeneron Pharmaceuticals) has been seen in two studies (CLEAR-IT AMD 1 and CLEAR-IT AMD 2) to be safe, bioefficacious, and tolerated in the eyes of patients with neovascular age-related macular degeneration. The 2- and 4-mg doses demonstrated more bioactivity than lower doses evaluated, according to Quan Dong Nguyen, MD.

The CLEAR-IT AMD 1 study evaluated six doses of VEGF Trap (0.05, 0.15, 0.5, 1, 2, or 4 mg) with each patient receiving one intravitreal injection of one dose and then followed for 6 weeks, reported Dr. Nguyen, assistant professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

Twenty-eight patients then received one intravitreal injection of either 0.15 or 4 mg and were followed for 8 weeks. Investigators found that the injections in both parts of the study were well tolerated and no ocular inflammation developed. The retinal thickness decreased in the second part of the study, and the treatment duration was longer with administration of the higher dose, he said.

In the CLEAR-IT AMD 2 study, the patients were randomized into five groups and the following VEGF Trap doses were evaluated: 0.5 mg every 4 weeks, 2 mg every 4 weeks, 0.5 mg every 12 weeks, 2 mg every 12 weeks, and 4 mg every 12 weeks.

Analysis of 159 patients indicated that "overall there was a reduction in the central retinal thickness across all time points for 8, 12, and 16 weeks," Dr. Nguyen said. There was also a gain in visual acuity at all time points.

When the investigators evaluated the subgroups for efficacy, administration of 0.5 mg every 4 weeks and 2 mg every 4 weeks resulted in the greatest gains in visual acuity and the greatest reductions in the central retinal thickness at 12 weeks after treatment. Improvement continued at the 16-week evaluation. At week 12, there was no evidence of any ocular or systemic complications.

Dr. Nguyen concluded that VEGF may play a role in the armamentarium of therapy for choroidal neovascularization. He also noted that these results aided the design of the phase III trial in which 0.5 mg for 4 weeks, 2 mg for 4 weeks, 2 mg for 8 weeks, and 0.5 mg of ranibizumab (Lucentis, Genentech) for 4 weeks will be evaluated.

Topical therapy for CNV on the horizon

Topical therapy to treat posterior segment disease is possible despite the limitations of the blood-retinal barrier. The effective route of drug penetrance of topical therapy is either by the transcorneal route or by the transscleral/conjunctival route, said Baruch Kuppermann, MD, PhD, chief of the Retina Service, Department of Ophthalmology, University of California, Irvine.

A few such drugs are currently under development, and the hope is that they will eliminate the complications associated with intravitreal injections of drugs, he said.

• 801 kinase inhibitor (TargeGen) has activity against vascular endothelial growth factor (VEGF) receptor/PDGF receptor/Src family kinases and stops leakage, angiogenesis, and inflammation. In animal studies, the drug has been shown to have high concentrations in the anterior segment, lower effective concentrations in the posterior segment, very low concentrations in the aqueous and vitreous, and extremely low concentrations in the plasma.

• ATG2 (mecamylamine) (CoMentis) is a powerful nonselective nAChR antagonist that has reduced angiogenesis in animal models and inhibits VEGF synthesis/release and responses. Topical mecamylamine was seen to penetrate the retina-choroid in mice, probably by the transscleral-conjunctival route.

• OC-10X (Ocucure) is a nontoxic vascular targeting agent with selective tubulin inhibition. The agent is lipid soluble and crosses the human cornea; it achieves therapeutic concentrations at the retina-choroid. In rats, the drug, when given once every hour for 4 hours, achieved a corneal level of 100%, a lens/vitreous level of 11%, and a retina-choroid-sclera level of 83%.

• OT-551 (Othera) catalytic antioxidant has multiple modes of action, i.e., antioxidant, antiangiogenic, and anti-inflammatory. The agent penetrates the cornea and sclera and reaches the retina. It also suppresses photo-oxidative damage in the retinal pigment epithelium and photoreceptors. A phase II study is ongoing for geographic atrophy, neovascular age-related macular degeneration, and cataract.

• Pazopanib (Glaxo-Smith-Kline) has completed a phase I trial with 38 healthy volunteers. This compound has been in development to treat solid tumors, according to Dr. Kuppermann.

"Historically, we have never contemplated the use of topical therapy for posterior segment disease because of poor ocular penetrance," he said. "The small molecule drugs are being developed to meet this challenge. They have shown good posterior segment penetrance, safety, and efficacy."

New developments in posterior segment drug delivery

New extended delivery methods are under development and in the future should facilitate more effective administration of numerous types of ocular agents, said William F. Mieler, MD, professor and chairman, department of ophthalmology and visual science, University of Chicago.

Dr. Mieler said that new methods are needed to lessen the side effects and invasiveness of current methods as well as to reduce systemic side effects.

Listing delivery methods with potential to address these concerns, Dr. Mieler noted that several types of solid implants are on the market already, such as a fluocinolone acetonide intravitreal implant (Retisert, Bausch & Lomb) and a ganciculovir intravitreal implant (Vitrasert, Bausch & Lomb). A subretinal implant system (I-vation, SurModics) has been tested in rabbits and appears to be capable of long-term sustained delivery.

Microspheres of biodegradable polymers are also being explored and could be a means of reducing toxicity during drug delivery, Dr. Mieler said. Studies are under way of delivering pegaptanib sodium (Macugen, OSI/Eyetech/Pfizer), and the feasibility of delivering other products by this route is also being investigated.

Thermoresponsive gels are another promising delivery method; one such product is currently on the market, although not for ophthalmic use, Dr. Mieler said.

At the University of Chicago and the Illinois Institute of Technology, investigators are studying thermoresponsive hydrogels and have developed one product that becomes a gel at body temperature in less than 1 minute. They hope to design a product that can be placed in a 27- to 30-gauge needle and delivered either intravitreally or in the juxtascleral space. The investigators are studying the delivery of bevacizumab (Avastin, Genentech) by this method.

Surgical-based delivery techniques include microcannulation of the suprachoroidal space. In addition, SurModics has developed a subretinal cannula (RetinaJect). A 25-gauge needle is used to transconjunctivally enter the vitreous; a 39-gauge cannula is then advanced to create the retinotomy.

Encapsulated cell technology (Neurotech SA) is also being tested as a novel means of drug delivery and has been shown to be safe and effective in early studies.


Finally, Ocular Surgery News interviewed Dr. Judah Folkman, who will give the keynote address during the opening session of the AAO meeting on November 11th.

Folkman: Angiogenesis research rooted in ophthalmology
By Matt Hasson, OSN Staff

The concept of anti-angiogenic agents, which has revolutionized cancer research, has led to the development of various ophthalmic therapies, according to a prominent medical researcher.

Angiogenic molecules include vascular endothelial growth factor, a protein contributing to age-related macular degeneration, diabetic retinopathy and other ocular diseases.

“The whole beginning of angiogenesis research for cancer started with ophthalmology,” Judah Folkman, MD, of Harvard Medical School and Children’s Hospital Boston, told Ocular Surgery News. “We always had ophthalmology in mind.”

Revolutionary findings

In a 1971 New England Journal of Medicine article, Dr. Folkman hypothesized that tumor growth depends on angiogenesis, or the growth of new blood vessels. His theory was criticized throughout the biomedical community, but early discoveries soon silenced the detractors.

Early angiogenesis experiments were performed in rabbit eyes, whose corneas were ideal for detecting new blood vessels, Dr. Folkman said.

“In order to prove that a tumor could make a protein that could diffuse from the tumor and stimulate new capillaries, the only way we could show that was in the eye,” he said.

The experiments demonstrated that proteins from the tumor triggered the growth of blood vessels. Before those experiments, the idea of such proteins existing was considered far-fetched, he said.

Dr. Folkman and fellow researchers later used tiny polymer implants that released angiogenic proteins into a rabbit cornea. After the implants were removed and diffusion of angiogenic proteins was halted, the corneal blood vessels gradually disappeared, he said.

New applications and drugs

In ophthalmology, angiogenesis research has reached new heights with the development of new drugs such as Lucentis (ranibizumab, Genentech), Dr. Folkman said.

“The demonstration of what Lucentis can do has brought many researchers and companies into the field, and they’re working now on other angiogenesis inhibitors including eye drops that may treat AMD,” he said. “Diabetic retinopathy is also beginning to be treated with Lucentis in clinical trials.”

PRIVATE CLIENT STUDIES – Arthur D Little 1972 1994 and Spectrum Consulting 1994 2001

In addition to the hundreds of articles and columns written over my 30-plus years of consulting, I led over 100 client-sponsored studies, covering a variety of topics. Here are the titles of most of the reports I either wrote or led the effort in producing. Some of the titles have been partly redacted to prevent identification of the client.

Note that nearly all of the studies until 1985 involved contact lenses, at which time I began consulting in medical lasers.

(Bolded studies can be found online.)

1972
● Worldwide Review of Soft Contact Lenses Made of Hydron (B&L Soflens), August 1972

1974
● Technological Developments in Ophthalmic Lens Materials and Processes, February 1974

1976
● The Contact Lens Business--An Emerging Opportunity, June 1976
● Investigation of the Coating Buildup Problem on Soft Contact Lenses, November 1976
● The Soft Contact Lens Business--Profile of an Opportunity, December 1976

1978
● Technical Assessment of a Soft Contact Lens Automated Machining Center, April 1978

1979
● The Contact Lens Solutions Business: An Opportunity for -- --, January 1979
● An Evaluation of Wesley-Jessen's Contact Lens Technology, August 1979
● Identification of a Soft Contact Lens Licensing Partner for -- --, November 1979
● Current and Future Developments in the Contact Lens Industry, December 1979
● An Evaluation of Titmus Eurocon's Contact Lens Technology, December 1979

1980
● A Technology Forecast: Vision Devices 1980-2000, January 1980
● The Development of an Improved Eyeglass Frame Material and Manufacturing Process, March 1980

1981
● Projections of the Markets for Hard Gas Permeable Contact Lenses, January 1981
● The Technical Evaluation of Frontier Contact Lenses Inc., January 1981
● An Overview of the U.S. Contact Lens Business, January 1981
● The Development of Novel Low Cost Disinfection Systems for Soft Contact Lenses, February 1981
● A Worldwide Review of Hard Gas Permeable Contact Lenses, February 1981
● Technical Evaluation of a New Contact Lens Manufacturing Process, February 1981
● An Analysis of the Contact Lens Business of -- --, March 1981
● A Worldwide Overview of the Ophthalmic Industry for the Scottish Development Authority, June 1981
● A Comparison of Low, Medium, and High Water Content Contact Lens Systems, July 1981

1982
● Technical Evaluation of an IOL Research and Manufacturing Operation, January 1982
● The Offering of a Contact Lens Company to Prospective Buyers, Winter 1982
● The Offering of a Retail Optical Business (Inventory, Lab Equipment and Fully-Equipped Dispensing Offices) to Prospective Buyers, Spring 1982
● The Development of a Low Cost Chemical Disinfection System for Soft Contact Lenses, February 1982
● An Overview of Diagnostic and Surgical Ophthalmic Equipment, July 1982
● Current Developments in Hard Gas Permeable Contact Lenses, December 1982

1983
● Assessment of a New Contact Lens Manufacturing Technology, January 1983
● Evaluation of a Soft Lens Cleaning Device, February 1983
● Technological Developments in the U.S. Contact Lens Industry, April 1983
● Near Term Trends in the U.S. Contact Lens Industry, June 1983
● Technological Assessment of -- --, October 1983
● Packaging of a Peroxide Neutralization System, November 1983
● Analysis of R&D and Regulatory Capabilities of Major U.S. Contact Lens Companies, December 1983

1984
● Background Papers on Soft Contact Lenses and Care Products, January 1984
● A Background Report on the Contact Lens Industry in the U.S., January 1984
● The Establishment of a Transfer Price for Contact Lens Blanks, January 1984
● Development of a Tensile Testing Method for Contact Lens Materials, January 1984
● An Overview of Trends and Developments in Eyeglasses and Contact Lenses, March 1984
● The Offering of a Contact Lens Laboratory and Fitting Clinic, April 1984
● The Establishment of a Transfer Price for Intraocular Lenses, April 1984
● The Outlook for the Ophthalmic Products Industry, May 1984
● An Assessment of Competitive Soft Lens Tinting Technologies, June 1984
● Current Trends in the U.S. Contact Lens Industry, September 1984
● Survey of Practitioner Attitudes Toward Cosmetic Extended Wear, November 1984

1985
● Comparison of Estimated Soft Lens Manufacturing Costs, February 1985
● An Update of Near Term Trends in the U.S. Contact Lens Industry, May 1985
● Contact Lens Manufacturing Techniques, August 1985
● The Offering of a New Soft Bifocal Contact Lens for Licensing, September 1985
● Entry Strategy to the U.S. Contact Lens Market, October 1985
● Update of the U.S. Ophthalmic Industry, November 1985
● Technology Assessment of the Green YAG Laser, November 1985

1986
● The Outlook for Refractive Surgery: The Impact of the LRK Technique, March 1986
● The Valuation of an IOL and a Surgical Instrument Companies, June 1986
● The Valuation of an Ophthalmic Products Company, November 1986
● A Brief Study of the CL Market in Japan, November 1986
● The Valuation of an Ophthalmic Instrument Company, December 1986

1987
● Ophthalmology Technical Alert Service, 1987
● An Overview of the Presbyopic Market Place: The Prospects for a New Viable Bifocal Contact Lens Design, February 1987
● A Detailed Survey of the CL Market in Japan, February 1987
● The Outlook for Viscoelastic Substances in Ophthalmology, May 1987
● An International Overview of Contact Lenses, June 1987
● The Nature and Evolution of the Soft Contact Lens Industry in the United States, August 1987 (B&L vs. the IRS)

1988
● The Current and Theoretical Production Capacity of the U.S. Contact Lens Industry, April 1988
● Evaluation of CooperVision, June 1988
● Medical Laser Overview, August, 1988
● Technical and Market Analysis of -- --, July 1988
● Ophthalmic Market Overview, September 1988
● Technology Overview: Ultrasound Catheter Market, December 1988

1989
● Ophthalmic Surgical Equipment Overview, March 1989
● U.S. Market for Soft Contact Lens Lubricant/Rewetting Drops, March 1989
● Contact Lens and Care Product Market Overview, May 1989
● Update: The Outlook for Laser Refractive Surgery, August 1989

1990
● Development of a Manufacturing Plan for Medical Lasers: Product Selection, January 1990
● Technology Overview: Phoenix Laser Systems, March 1990
● Current Developments in Laser Refractive Surgery, July 1990
● Opportunities for Collaboration, September, 1990
● An Evaluation of a New Eyeglass Lens Molding Process, Phase I: Technology Overview, September 1990
● Overview of High-Index Plastic Eyeglass Lens Materials, November 1990
● Background Information on the Contact Lens Industry, December, 1990
● Profitability in the Ophthalmic Industry, December, 1990

1991
● Contact Lens and Care Product Overview, January, 1991
● Current Developments in Laser Refractive Surgery, March 1991
● An Overview of the U.S. IOL Industry, April 1991
● Ophthalmic Industry Overview, August 1991
● Overview of Current Developments in Refractive Surgery, August 1991
● Technology Overview: Phoenix Laser Systems, October 1991
● Overview of the IOL Industry, September 1991

1992
● Excimer Lasers in Surgery, February 1992
● Current Developments in Laser Refractive Surgery, March 1992, updated July 1992
● New Ophthalmic Laser Technologies, June 1992
● Historical Overview of Ophthalmic Lasers in the Mid-1980s (legal case), July 1992
● Medical Laser Technology Alert Reports, monthly, July 1992 - April 1993

1993
● Technology Overview and Strategic Partnering for Unique Medical Laser Product Company, September 1993
● The Outlook for Refractive Surgery Centers, September 1993
● A Cost Comparison of Refractive Surgery vs. Eyeglasses and Contact Lenses, October 1993
● An Overview of Current Developments in Refractive Surgery, December 1993

1994
● An Assessment of a Laser-based Method to Alleviate Heart Attacks, February 1994
● The Outlook for a Laser-based Technique to Cure Psoriasis, March 1994
● Current Developments in Laser Refractive Surgery, August 1994, updated April 1995
● An Assessment of an Unique Laser-based Technique to Diagnose Severe Burns, August 1994

1995
● Estimated Market for a New Mid-IR Laser Delivery Fiber, February 1995
● The Outlook for Refractive Surgery, March 1995
● An Analysis of the Hawaii PRK Market, May 1995

1996
● Potential Laser (and non-laser) Sources for Activating Photofrin, March 1996
● Search for a Diode Laser Source for Activating Photofrin, April 1996
● A White Paper -- Laser Hair Removal: An Application Whose Time has Come, October 1996
● Worldwide Market Overview of Ophthalmic and Dermatologic Lasers, December 1996

1997
● U.S. Market Opportunities for ICON Centers for Cosmetic Surgery, March 1997
● Refractive & Cosmetic Surgery -- Any Synergies?, November 1997
● An Overview of the Medical Laser Industry, December 1997

1998
● Worldwide Medical Laser Marketplace, May 1998
● An Investigation into the Use of "Bermuda Cards", July 1998
● Review of Photodynamic Therapy for Treating ARMD, December 1998

1999
● Update: Trends in Refractive and Cosmetic Laser Surgery, November 1999
● An Evaluation of ThermoLase's Technologies, December 1999

2000
● A Look at the Future of Refractive Surgery, February 2000

2001
● A Brief Overview of the Opportunities for a 3 micron Medical Laser System, July 2001
● Adoption Rates of Soft Contact Lenses, IOLs, and Refractive Surgery, September 2001