Antiangiogenic Drugs Are Stopping Neovascularization in Wet Macular Degeneration

(Updated 3/12/22)

A substance in the body called Vascular Endothelial Growth Factor (VEGF) is responsible for the growth of new blood vessels. It promotes this growth by stimulating the endothelial cells, which form the walls of the vessels and transport nutrients and oxygen to the tissues. Evidence shows that when the retinal pigment epithelial (RPE) cells begin to wither from lack of nutrition (a condition called “ischemia”), the VEGF goes into action to create new vessels. This process is called “neovascularization,” and it acts as a restorative function in other parts of the body. In the retina, however, the vessels do not form properly, and leaking results. This leakage causes scarring in the macula and eventual loss of central vision.

Antiangiogenic drugs prevent the VEGF from binding with the receptors on the surface of the endothelial cells. In most cases, the drugs are injected into the vitreous of the eyeball, then pass into the subretinal space, where the vessels proliferate. Neovascularization is then blocked, preventing bleeding into the retina.

New research is looking for less invasive and burdensome introduction of the drugs by way of topical eye drops, implanted timed release capsules, and implanted ports of delivery. The most recent breakthrough is FDA approval of Susvimo. This procedure continuously delivers a form of ranibizumab (Lucentis), offering an alternative to anti-VEGF eye injections. The tiny implant is surgically inserted into the eye during a one-time outpatient procedure and refilled every six months. More about Susvimo.
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Here is information on current anti-angiogenic drugs being studied or already being used in the clinics:

In clinic use:
Macugen (pegaptanib sodium) [approved 2004]
Lucentis (ranibizumab) [approved 2006]
EYLEA (aflibercept) [approved 2011]
Avastin (bevacizumab) [available off-label since 2007]
Brolucizumab (RTH-258) [approved 2019]
Byooviz (ranibizumab-nuna) [approved 2021]
Faricimab (Vabysmo) [approved 2022]

Under study:
Abicipar
AKST4290 (oral)
AR-13503
EYP-1901
GB-102
IBI302
ICON-1
KSI-301
OPT-302
PAN-90806
RBM-007
RGX-314
X-82 (oral)


Macugen (pegaptanib sodium)
Macugen, made by OSI EyeTech Pharmaceuticals, was the first antiangiogenic drug to gain FDA approval. Pegaptanib is a chemically synthesized strand of genetic material that bonds with VEGF cells to block replication. A large trial of Macugen on 1,196 patients at 117 centers around the world was completed in 2003. In November of that year, data presented to the American Academy of Ophthalmology (AAO) showed that Macugen stabilized or improved vision in 33% of the patients in the trials, while the same results occurred in 23% of a control group not given Macugen. As many as 71% of the patients given Macugen lost less than three lines of vision during the year, compared with 55% in the control group. The drug is injected directly into the eye every six weeks, or about nine times a year.
Working in conjunction with Pfizer Ophthalmics, Macugen gained FDA approval on December 17, 2004, and was ready for public use beginning in 2005.

Lucentis
Genentech, Inc. announced on May 23, 2005 that a Phase III clinical study of the investigational drug Lucentis (ranibizumab) met its primary efficacy endpoint of maintaining vision in patients with wet AMD. Approximately 95 percent of patients maintained or improved vision (defined as a loss of less than 15 letters in visual acuity) at one year when treated with Lucentis injections compared to approximately 62 percent of those treated in the control arm. Vision improvement was an unexpected result that had not been seen at a significant level in other antiangiogenic drug trials. Lucentis is approved for use in the European Union, Switzerland, India, Canada and the United States. A regulatory decision in Australia is expected before the end of 2007.
On January 14, 2006, one-year data from the second pivotal Phase III study of Lucentis were presented at the Macula 2006 meeting in New York. Data showed that, for the second time in a large, Phase III study, Lucentis improved vision in patients with wet AMD.
On November 13, 2006, several new findings were presented at the 2006 AAO meeting:
Elias Reichel, M.D. reported that in the MARINA trials, there was improvement at all visual acuity levels, but there was not a big difference if the patient’s baseline vision was either low or excellent. This “floor-to-ceiling” effect is not unusual with this kind of study, but it is useful information for patient communicating with patients about expectations.
Nancy Holekamp, M.D., discussed key anatomic endpoints in the MARINA trials, in particular, the total lesion area over time (no growth of the lesion area was noted in the treated patients), the mean area of leakage (the amount of decrease was statistically significant) and the mean foveal retinal thickness (treated eyes showed a significant thinning of the retina). The bottom line is that all anatomic outcomes from the trial favored Lucentis, and the treatment is so effective over a long period of time without any signs of toxicity, there is no indication that anything in lieu of Lucentis should be used to treat wet AMD.
Peter Kaiser, M.D., reported on subgroup analysis of Genentech’s PIER study. The primary endpoint was met, showing a difference of 16 letters visual acuity between the treated group and the sham group. Further, the dosing regimen was effective, but the visual acuity benefit was not as robust when injections went from monthly to quarterly. The persistence of monthly injections may depend upon who has dry lesions and who has wet lesions at the 5th month. The dry lesion group did better than the wet lesion group with quarterly dosing. This data is pointing toward better prediction of dosage outcomes for individual patients.
On February 15, 2007, Dr. Kaiser reported two-year results of the Phase 3 ANCHOR trial comparing Lucentis with photodynamic therapy (PDT) for wet AMD. The study showed that Lucentis helps maintain vision, with few adverse effects, significantly better than PDT. 89.9% of patient randomised to Lucentis in a head-to-head comparison with Visudyne for photodynamic therapy (PDT) lost fewer than 15 letters on a visual acuity chart at 24 months compared to 65.7% of those treated with PDT. 78% of the Lucentis-treated group maintained their baseline visual acuity or gained letters, compared to only 29% of the PDT group. Overall, patients randomised to Lucentis had a 20.5 letter benefit at 24 months (+10.7 EDTRS letters) compared to those treated with PDT (-9.8 letters). This was similar to visual acuity seen at 12 months (+11.3 letters with Lucentis vs -9.6 letters with PDT).
On February 23, 2008, the final results from Cohort 1 of the Phase IIIb SAILOR study of Lucentis in patients with wet AMD were presented on February 23, 2008 at the Bascom Palmer Eye Institute’s Angiogenesis meeting by Dr. David Boyer (Retina-Vitreous Associates Medical Group, Los Angeles). The final, one-year data support the long-term safety and efficacy profile of Lucentis.
The study, titled “Ranibizumab (Lucentis) Safety in Previously Treated and Newly Diagnosed Patients with Neovascular Age-related Macular Degeneration (AMD): The SAILOR Study,” was designed to evaluate the safety of two different doses of Lucentis (0.5 mg, the FDA-approved dose, and 0.3 mg) administered once a month for three months and thereafter as needed based on re-treatment criteria.
For more detail in all of these areas of study, see www.lucentis.com.

EYLEA (aflibercept injection, formerly VEGF Trap-Eye)
In August 2008, Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG announced that patients with wet AMD receiving EYLEA (aflibercept injection) in a Phase 2 extension study on an “as needed” dosing schedule continued to show highly significant improvements in retinal thickness and vision gain at 52 weeks. There were no drug-related serious adverse events, and treatment was generally well-tolerated.
For all dose cohorts combined, there was a 5.3 mean letter gain in visual acuity at the end of 52 weeks. The mean decrease in retinal thickness was 130 microns versus baseline. During weeks 12 to 52, patients from all dose groups combined received, on average, only two additional injections. This supported Regeneron’s expectation that, with EYLEA treatment, patients’ visual acuity would improve over time without the need for monthly intravitreal injections.
A phase 3 study, VIEW 1, began enrolling patients in late 2007. The VIEW 1 study compared EYLEA and Lucentis. A phase 2 study in diabetic macular edema (DME) was also completed. EYLEA injected into the eye every two months was found to be as effective as monthly doses of Lucentis, and monthly monitoring of patients receiving EYLEA was not necessary.
On June 17, 2011, the Food and Drug Administration advisory panel voted unanimously to recommend EYLEA as a treatment for wet AMD. The advisers also said the injected drug could be given once every two months. This was an improvement upon the typical 4-6 week dosings of both Lucentis and Avastin.
Finally, on November 18, 2011, Regeneron announced that the FDA had approved EYLEA for treatment of patients with wet AMD. Recommended dose is 2 mg every four weeks for the first 12 weeks, followed by 2 mg every eight weeks. EYLEA offers less frequent injections than either Lucentis (4 weeks) or Avastin (6 weeks), and there are no monitoring requirements.
Since September 2012, Eylea has also gained approval in the U.S., Europe, and Japan for use in treating wet AMD, diabetic macular edema, and neovascular myopic degeneration. For more information, see www.regeneron.com.

Avastin (bevacizumab)
Avastin (bevacizumab), has been shown in preliminary off-label studies to stop blood vessel growth and leakage in the retinas of patients with macular degeneration. Testing began in March 2005 at the Bascom Palmer Eye Institute in Miami under the leadership of Dr. Philip Rosenfeld. In July 2005, Dr. Peter Campochiaro followed with subjects at the Johns Hopkins Medical Center in Baltimore. Potential side effects, according to Rosenfeld, are increased risk of stroke or heart attack in patients taking chemotherapy, and elevation of blood pressure. Systemic infusions of Avastin, he said would be needed every few months.
On February 15, 2007, Elias Reichel, M.D. reported to Hawaiian Eye/Retina 2007 that Avastin has shown good results in a small retrospective case series for treatment of neovascularization from myopic degeneration. 15 eyes studied showed a mean improvement in acuity of 3 lines, central foveal thickness decreased an average of 93 micrometers and no complications.
In May 2011, first year results of the Comparison of AMD Treatments Trial (CATT) were announced. The report focused on the relative safety and efficacy of Lucentis and Avastin. After one year, the two compounds have been found to be extremely similar in their improvement of mean visual acuity and the occurrence of adverse events. Five related trials were also undertaken in the UK and Europe.
At the end of the 2-year comparison study, The National Institutes of Health reported that both drugs improved vision when administered monthly or on an as needed basis. Patients receiving Lucentis, however, fully maintained first-year vision gains with an average 5.7 injections in the second year. In contrast, patients treated with Avastin experienced a greater decline in vision despite receiving significantly more injections over the two year period. In addition, secondary anatomical outcomes were significantly better with Lucentis. For more information, see www.nih.gov/news/health/apr2012/nei-30a.htm

Faricimab (Vabysmo)
A global Phase III program for faricimab in wet AMD began in 2019. The efficacy of faricimab administered at 12- and 16-week intervals was evaluated against ranibizumab every 4 weeks. At week 24, researchers reported in May 2020 that 65% of faricimab-treated patients were disease activity-free. By January 2021, further research had shown that people receiving faricimab injections at fixed intervals of up to every 16 weeks achieved visual acuity outcomes as effective as those receiving Regeneron’s aflibercept (Eylea) injections every eight weeks. More information.

PAN-90806
PAN-90806 is a topical eye drop for the treatment of neovascular AMD, diabetic retinopathy, and potentially diabetic macular edema (DME). It is being developed by Panoptica and began a phase 1 clinical trials in early 2014, a 2-month open-label study of approximately 30 patients at 15 to 20 sites in the U.S. The study was completed in May 2016. More information.

OPT-302
OPT-302 is soluble receptor developed by Opthea Pty Ltd. It is a derivative of VGX-300 which has been optimised for local ocular administration. OPT-302 potently and specifically blocks VEGF-C and VEGF-D from binding and activating VEGFR-2 and VEGFR-3.
On August 6, 2019, Opthea announced positive Phase 2b results demonstrating that OPT-302 combination therapy showed improvements across multiple secondary endpoints at 24 weeks. Compared to Lucentis monotherapy, OPT-302 (2.0 mg) combination treatment showed improvements that included a higher proportion of patients with stable vision (defined as ≤ 15 letter loss from baseline), and those gaining ≥10 and ≥15 letters of visual acuity. On March 15, 2021, Opthea announced that, based upon the positive Phase 2 results, the first patient has now been enrolled in the Phase 3 trial. More information

ICON-1
The EMERGE study examined the hypothesis that a protein called Tissue Factor (TF), when out of control, initiates inflammation and angiogenesis, resulting in wet AMD. ICON-1 is thought to block the protein and reverse the progression of the disease, both alone and in combination with Lucentis.
Phase 2a results showed that ICON-1 was well tolerated and that in combination with anti-VEGF therapy treated both the symptoms and the underlying process driving inflammation and CNV. The combination effectively reduced CNV lesion size, increased the durability of effect and improved removal of pathologic fluid from the retina. Based on these positive results, the company initiated a Phase 2b study of ICON-1 in combination with anti-VEGF treatment in 2018. More information

RGX-314
Regenxbio’s RGX-314 differs from current therapeutics in that it includes a gene vector (NAV AAV8) which encodes an antibody fragment designed to neutralize VEGF (vascular endothelial growth factor) activity. This modifies the pathway for formation of new leaky blood vessels which lead to retinal fluid accumulation and vision loss.
In August 2019, Regenxbio reported positive phase 1/2a results in patients with wet age-related macular degeneration, and that the drug is continuing to be well tolerated across five dose cohorts.
Investigation of RGX-314 with a phase IIb trial (AAVIATE) is proceeding, with dosing of the first patient using suprachoroidal delivery. As of December 31, 2020, suprachoroidal delivery of RGX-314 was reported to be generally well-tolerated, with no evidence of inflammation.

More information

Brolucizumab (RTH258)
Novartis announced on October 8, 2019 that the US Food and Drug Administration (FDA) approved BEOVU® (brolucizumab-dbll) injection for the treatment of wet age-related macular degeneration (wet AMD).  BEOVU® carries a recommended dosing schedule of monthly for the first three doses followed by one dose every 8-12 weeks. More information.

Abicipar
Allergan trials have demonstrated that the biological drug Abicipar is equal to Genentech’s Lucentis (ranibizumab), with the added benefit that Abicipar treatments are effective at up to 12-week dosages. This is longer than Lucentis (4 weeks), Avastin (6 weeks), and Eylea (8 weeks), the three currently available drugs for treatment of wAMD. Trials are ongoing. More information

KSI-301
Kodiak trials showed good results for treatment of diabetic macular edema. Twelve weeks after a single dose of KSI-301 saw improvement of almost two lines (9 eye chart letters) and retinal edema of 121 microns. Unfortunately, Phase 3 results showed that, although KSI-301 demonstrated strong durability and was safe and well tolerated, it did not meet the primary efficacy endpoint of showing non-inferior visual acuity gains for subjects dosed on extended regimens compared to aflibercept given every eight weeks. More information.

GB-102
Graybug Vision’s novel investigational depot approach is designed to continuously inhibit activity of all VEGF receptors for the treatment of wet AMD. In Phase 1 trials, GB-102 was well-tolerated with no dose limiting toxicities, drug-related serious adverse events or inflammation. 88% and 68% percent of evaluable patients were maintained only on a single dose of GB-102 at 3- and 6-months, respectively. Patients with wet-AMD require intravitreal injections every 6 to 8 weeks, on average, with the current standard-of-care.

Graybug Vision’s Phase 2b ALTISSIMO study of GB-102, was completed in January 2021. Topline data are expected to be announced in the second quarter of this year, and full results presented in the later part of 2021 at a medical conference.

Graybug announced in April 2022 that it plans to proceed with a Phase 2 clinical trial of an optimized formulation of GB-102 in wet AMD patients following successful demonstration of improved performance in an extensive battery of novel in vitro stress tests. This decision, supported by a significantly more favorable competitive landscape following recent readouts of other long-acting vascular endothelial growth factor (VEGF) inhibitors, is anticipated to result in a six-month data readout available in the third quarter of 2023.

More information

X-82 (Oral)
Under study by Tyrogenex, Inc., this oral medication is intended for use in combination with anti-VEGF injections. The expectation is that the combination therapy will reduce the number of injections required for stabilizing the retina. Phase 2 trials began in 2017. More information.

AKST4290 (Oral)
Alkahest Inc. has reported that AKST4290, an oral medication for treatment of wet AMD, was shown in trials to be safe, effective, and “extremely promising”. Two Phase 2a clinical trials for AKST4290 were recently completed: one in naïve patients and one in refractory wet AMD patients. Results are pending. More information

IBI302
In April 2019, Innovent Biologics announced that it had dosed the first patient in a phase 1 trial of IBI302, the company’s wet AMD treatment candidate. A single intravitreal injection of IBI302, a recombinant fully human bispecific fusion protein targeting VEGF and complement proteins, will be evaluated in 36 patients with wet AMD in the open-label, single-center, dose escalation clinical trial. More information

AR-13503

In August 2019,  Aerie Pharmaceuticals, Inc. (Aerie), began patient dosing in their first human clinical trial of a sustained release implant in patients with wet macular degeneration or diabetic macular edema. The polymer implant provides controlled release of AR-13503, an injectable drug that inhibits blood vessel growth in the retina, while potentially reducing the treatment burden associated with more frequent intravitreal injection. More information

RBM-007
RBM-007 is a novel oligonucleotide-based aptamer with potent anti-FGF2 (fibroblast growth factor 2) activity. A Phase 2 Study assessing the safety, efficacy and durability of RBM-007 is underway. More information

Byooviz (ranibizumab-nuna)
The first biosimilar to ranibizumab injection for wet AMD. Also approved to treat macular edema and myopic choroidal neovascularization. More information.

EYP-1901
A potential twice-yearly sustained delivery intravitreal anti-VEGF treatment for wet age-related macular degeneration (wAMD). More information

Summary of Research and Developments in Macular Degeneration: 2009-2010

by Dan Roberts
June 10, 2010
Introduction
If I were to describe the past twelve months in a word, it would be “progress.” No spectacular breakthroughs have occurred during that time to make big news in the AMD world, but a lot of persistent work has been reaping promising results. moving us ever closer to effective treatments. Even the cure we hope for is now being thought of more in terms of “sooner” than “later.”
This summary is a brief overview of the news that has been of interest to us during the period of June 2009 through May 2010. More details about the reports from the 2009 Meeting of the American Academy of Ophthalmology (AAO) may be found on this site. Other reports in this summary are annotated with sources for further reference.
I’ll begin by mentioning two studies in the area of nutrition, since nutraceuticals are currently our most immediate hope for slowing the progression of vision loss from AMD.
NUTRACEUTICAL
1. Omega-3 Lowers AMD Risk
For the past couple of years, we have been made aware of the benefits of Omega-3 fatty acids in our diet, and nutritionists have been recommending several servings of fish each week or supplementation with fish oil. To further confirm these benefits, 671 subjects in the 2009 ALIENOR Study were given eye examinations seven years after plasma fatty acid measurement. As hoped, lower risk of geographic atrophy (advanced dry AMD) was associated with higher plasma levels of total omega-3 fatty acids, in accordance with previous studies of dietary intake.
Ref: AAO 2009 Paper: “Plasma Omega 3 Fatty Acids and Risk for Age-Related Maculopathy: The ALIENOR Study” (Presenting Author: Jean-Francois Korobelnik MD)
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2. Saffron Improves Vision
Another interesting finding was reported in March 2010, when clinical trials in Italy and Australia showed that the spice, saffron, can improve vision in people with AMD.
Subjects experienced up to 2 lines of improvement in their vision while taking saffron pills, but the effect quickly disappeared when the dose was discontinued. This indicates that it may improve the vision function of surviving cells but it does not reverse the damage that is already present.
If you intend to add saffron to your diet, be sure you are actually purchasing saffron, not safflower, which is sold as saffron by some unscrupulous dealers.
Ref: www.mdsupport.org/library/saffron.html
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SURGICAL
Seven surgical procedures headed the news during these past 12 months.
1. FDA Considering Approval of IMT
The investigational implantable miniature telescope (IMT), discussed here last year, is designed to be a solution for moderate to profound vision loss due to advanced, end-stage forms of AMD that have no current surgical or medical treatment options.
If you remember, the telescope prosthetic device, which is smaller than a pea, is implanted in one eye during an outpatient surgical procedure. In the implanted eye, the device renders enlarged central vision images over a wide area of the retina to improve central vision, while the non-operated eye provides peripheral vision for mobility and orientation. On March 27, 2009, the FDA Ophthalmic Devices Advisory Panel unanimously recommended that the FDA approve, with conditions, the premarket application of the IMT for End-Stage AMD. The device has received CE Mark approval in Europe, but we are still waiting for approval in the US at this time. No explanation has yet been given for the delay.
Ref: AAO 2009 Session: “Implantable Miniaturized Telescope” (Presenter: Mark R. Wilkins, MD)
Ref: www.mdsupport.org/library/imt.html
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2. LMI Approved in Europe
In 2007, Optolight Vision Technology announced success from implantation of the LMI, which is a second generation of the implantable miniature telescope. They reported that the LMI may be an effective solution for optical rehabilitation of patients with ARMD or other macular pathology by increasing the central image on the retina while preserving peripheral vision. This preservation of the peripheral field is the main difference between the LMI and the IMT, allowing it to be implanted in both eyes.
On June 17, 2009, OptoLight Vision Technology announced that it received CE mark approval in Europe, which allowed OptoLight to immediately begin marketing the implant in Europe and other markets outside of the United States.
Ref: www.mdsupport.org/library/lmi.html
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3. Skin Cells Changed Into Retina Tissue
In August 2009, scientists at the University of Wisconsin-Madison reported that they had reprogrammed skin cells and turned them into different kinds of retinal cells. The work added to a growing weight of evidence that stem cells made by reprogramming have similar, if not the same, abilities as the more controversial embryonic stem cells.
Scientists may now be able to take a skin biopsy from someone with a vision ailment, create retinal cells, and observe how the disease unfolds and how the cells die over time. They hope to also use reprogramming as a way to generate damaged or diseased cells on which pharmaceutical companies can test their drugs and to find ways to correct genetic defects.
Farthest off, but most exciting to many researchers, is the possibility of using reprogramming to produce healthy cells that can replace those that have died.
Ref: “Skin Cells Changed Into Retina Tissue,” by Mark Johnson (Journal Sentinel Online.
August 24, 2009)
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4. UCI Researchers Create Retina
As recently as the end of May 2010, University of California Irvine scientists have created an eight-layer animal retina from human embryonic stem cells. This is the first three dimensional tissue structure to be made from stem cells, and it could be a big step toward retina replacement in eyes affected by macular degeneration. It is an advancement over creation of single cell layers, since the multi-layered human retina might then be replaced in its entirety in one procedure.
The researchers are testing the early-stage retinas in animal models, in hopes that success will lead to human clinical trials.
Ref: today.uci.edu
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5. Brachytherapy May Improve Vision
Epimacular brachytherapy involves radiation treatment delivered by a small plaque sewn to the sclera (the white covering of the eyeball). In November 2009, NeoVista, Inc. announced results from a study designed to examine the company’s brachytherapy procedure when used in patients undergoing anti-VEGF drug injections for wet AMD.
Preliminary study results suggest that a single procedure of epimacular brachytherapy can further improve visual acuity in a majority of this patient population while decreasing the number of injections required. Most importantly, they researchers reported, 63% of patients enrolled in the study experienced improvement in their visual acuity, while 50% of patients gained 5 or more letters of visual acuity at 6 months.
Ref: www.neovistainc.com/meritage.html
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6. New Radiation Treatment Under Study
Another radiation therapy system entering trials this past year was the Oraya IRay system. This delivers a robotically controlled dose of low-energy X-ray radiation to the retina.
Oraya Therapeutics, Inc. began enrolling patients at seven European sites to demonstrate the safety and effectiveness of radiation therapy for the treatment of wet AMD. According to the company, the radiation dosages close inflammation mediated capillaries and further stop the inflammatory process that leads to wet AMD. In this study, the procedure is used in conjunction with anti-VEGF injections.”
Ref: www.orayainc.com/clinicaltrials.asp
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7. Tinted IOLs May Slow AMD
A 2009 study showed that implantation of a blue light-filtering intraocular lens (IOL) at the time of cataract surgery increases macular pigment in the retina. This increase may provide protection against the development and/or progression of AMD.
Macular pigment is thought to protect against AMD by absorbing blue light before it reaches the photoreceptors in the retina. The retina is exposed to as much as six times the amount of blue light in a person having the lowest level of macular pigment when compared to a person with the highest level. This gives rise to the belief that blocking blue light with replacement IOLs and other types of protective lenses may help slow down the disease process.
Ref: Macular Pigment Research Group: www.mprg.ie
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PHARMACEUTICAL
The pharmaceutical industry leads the way this year, with nine newsworthy headlines.
1. Fenretinide Granted Fast-Track Status
Fenretinide (ST-602), a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, has been found to also slow the production and accumulation of a toxin called A2E that leads to buildup of lipofuscin (waste deposits) in the retina, resulting in vision loss in people with dry AMD. If the drug proves effective with dry AMD patients, it may then also be used off-label for treatment of Stargardt’s disease, a juvenile form of macular degeneration.
The trials, which began in 2006, were granted fast-track designation in April 2009, based upon strong results from phase 2.
Ref: ARVO 2009 Paper: “Fenretinide for the Treatment of Geographic Atrophy in Patients with AMD: One-Year Interim Analysis” (Presenting Author: Roger Vogel MD)
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2. Lucentis Still the Gold Standard
Incidence of ocular and non-ocular safety events continues to be low and consistent with prior Lucentis trials. For 600 patients who received Lucentis in prior trials, the most common ocular adverse events over 2 years have been worsening macular degeneration (35%), retinal hemorrhage (25%), and conjunctival hemorrhage (25%). Lucentis is still showing excellent results, and it is still considered the gold standard for treatment of wet AMD.
Ref: AAO 2009 Paper: “Safety Outcomes Over 2 Years in the HORIZON Extension Trial of Ranibizumab (Lucentis) in Neovascular AMD” (Presenting Author: Matthew S Benz MD)
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3. POT-4 Found Safe and Effective
POT-4 is a synthetic peptide that has been found to inhibit a genetic process that can lead to local inflammation, tissue damage (as in dry AMD) and the resulting blood vessel growth in wet AMD. Inflammation is thought to be the cause of AMD in as many as 50% of cases, so a good deal of research is being done in this area.
It was reported in 2009 that phase 1 studies found POT-4 to be well tolerated, safe, and effective in improving macular edema.
Ref: AAO 2009 Paper: “Phase 1 Results of the Complement C3 Inhibitor POT-4 in AMD” (Presenting Author: Philip J Rosenfeld MD PhD)
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4. VEGF Trap-Eye Completes Phase 2
AAO 2009 Poster: “VEGF Trap-Eye Vision-Specific Quality of Life Through 52 Weeks in Patients With Neovascular AMD in CLEAR-IT 2: A Phase 2 Clinical Trial” (Presenting Author: Allen C Ho MD)
VEGF Trap-Eye is a molecule which has been shown to block choroidal neovascularization (blood vessel growth) in eyes with wet AMD. Two studies were reported in 2009 to have been successful in both improvement of the affected retina and improvement in patients’ quality of life.
AAO 2009 Poster: “OCT and Fluorescein Angiography Outcomes Through 1 Year for a Phase 2 Study of Intravitreal VEGF Trap-Eye in Neovascular AMD” (Presenting Author: Peter K Kaiser MD)
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5. Oral Drug For Dry AMD Enters Phase 2
Following the success of the Phase I clinical trial, Acucela Inc. has begun recruiting participants with dry AMD for a Phase II study of the oral drug ACU-4429 for dry AMD. Known as the ENVISION Clarity Trial, Acucela is planning to enroll at least 56 participants at multiple sites throughout the U.S. Participants will receive either the drug or a placebo.
Ref: www.medicalnewstoday.com/articles/149919.php
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6. Alzheimer’s Disease Treatment May Benefit AMD Patients
Copaxone (glatiramer acetate) injections are given in Alzheimer’s disease to decrease destructive beta-amyloid deposits. These deposits are similar to the proteins seen in
drusen found in dry AMD, so researchers are trying copaxone for treatment of dry AMD. In week 12 of a small preliminary study, 4 eyes (3 patients) treated with copaxone showed a total reduction of drusen area from baseline of 66%. Two eyes receiving sham injection had essentially no significant change in drusen area.
Ref: www.medscape.com/viewarticle/564015_2
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7. MC-1101 Eye Drop For Wet AMD Proves Safe
MC-1101 is an eye drop which affects the blood flow in the choroid, hopefully stopping the progression of AMD. So far, a small Phase 1 study by MacuCLEAR, Inc. has established the safety of seven dosages over three days, and plans for further trials are underway.
Ref: www.macuclear.com
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8. Aspirin May Aggravate AMD
We have been told that aspirin might help to inhibit the inflammation process, thereby slowing the progression of AMD. But here is frustrating news of a study just completed that suggests aspirin might actually be somehow associated with progression of the disease. 4691 patients 65 years and older were asked about their use of aspirin and about other possible risk factors for aging macula disorders. The results showed that odds ratios for all grades of early aging macula disorder rose with increasing aspirin intake frequency for subjects who reported daily use. The researchers, therefore, concluded that frequent aspirin use seems to be harmful for aging macula disorder in older populations.
Study leader Dr. Paulus de Jong said, however, that patients with cardiovascular disease should not stop taking aspirin. “But if they are taking it as a pain killer, there are other medications they can use.”
Of course, more study is needed before definite conclusions can be drawn, and other studies have shown no correlation, even beneficial correlations, between aspirin and macula disorders. But moderate intake of aspirin might be something we need to consider until more is known.
Ref: Association for Research in Vision and Ophthalmology (AAO) 2010 Annual Meeting: Abstract 1620. Presented May 3, 2010.
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9. Studies Show Lucentis and Avastin to be Equal
In February 2010, investigators at Kaiser Permanente Southern California in Pasadena reported that Avastin and Lucentis performed equally. Of 452 patients treated for wet AMD, 22.9 percent of Avastin patients and 25.0 percent of Lucentis patients attained visual acuity better than or equal to 20/40 after a year of treatment. Similar numbers of patients in each
group also showed some degree of vision improvement at 12 months.
The Kaiser Permanente study is one of several comparing the two drugs. The largest, and probably most definitive, study is the National Eye Institute’s ongoing Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT), with results expected next year. Avastin, originally designed as a cancer drug, is administered off-label, but research like the Kaiser study has been showing it to be at least as safe and effective as Lucentis for use in treatment of wet AMD.
We should remember that the comparison trials will not lead to FDA approval of Avastin for treatment of wet AMD. It may or may not confirm what we already know, but the drug will, in either case, remain on off-label status. Since large scale Avastin trials by the parent company, Genentech, are not likely, this will still be considered a safety issue.
Ref: Ophthalmology (Feb 2010)
Ref: www.mdsupport.org/library/catt.html
Drugs Under Study For Wet AMD
Here is a list of drugs currently under study for treatment of wet AMD. Three of them (Macugen, Lucentis and Avastin) have already entered clinical use, but followup studies continue to confirm their safety and efficacy.
Macugen
Lucentis (ranibizumab)
Avastin (bevacizumab)
Verteporfin PDT (in combination)
Tryptophanyl-tRNA synthetase (TrpRS)
AdPEDF
VEGF-TRAP-EYE
AG-013958
JSM6427
TG100801
ATG3
Perceiva
Endostatin
Pazopanib
siRNA
Ref: www.mdsupport.org/library/anti-angio.html
_______________________
Drugs Under Study For Dry AMD
Here is a shorter list, but still encouraging, of drugs under study for potential treatment of the dry form of AMD:
ACU-4429
Copaxone
Fenretinide (ST-602)
Iluvian (fluocinolone acetonide)
MC-1101
OT-551
POT-4
Retinylamine
Ref: www.mdsupport.org/library/treatments.html
_______________________
So there are at least 23 chances for treatments or cures from the pharmaceutical industry.If I haven’t mentioned them in this summary, it’s because most are still in the trial process, with no significant findings to report as yet. We may not hear very much about this work in the daily news, but rest assudred that the race is on, and no matter who reaches the finish line first, we, the patients–or at least our children and grandchildren–are going to be the eventual winners.
GENETICS
A great deal of research is being carried out in the field of genetics, as this is very likely where the cures for most diseases will be found. Two developments have stood out during the past 12 months.
1. RPE65 Gene Therapy Showing Promise
First, three young adults who received gene therapy for Leber congenital amaurosis (LCA), a blinding eye condition, remained healthy and maintained previous visual gains one year later. One patient also noticed a visual improvement that helped her perform daily tasks.
In this study, researchers injected healthy copies of the RPE65 gene under a healthy area of the retina in an attempt to repair the visual cycle. One year after the procedure, evidence shows that the newly introduced gene is functional and is increasing the light sensitivity of the retina.
This is the first study that reports the one-year safety and effectiveness of successful gene therapy for LCA. It paves the way for similar techniques, which can eventually be applied to other genetic diseases such as AMD.
Ref: www.mdsupport.org/library/breakthrough.html
________________________
2. PEG-POD: A New Gene Delivery Tool
The second bit of news came in January 2010, when researchers reported having developed a new tool for gene therapy which significantly increases gene delivery to cells in the retina compared to other carriers and DNA alone.
A peptide called PEG-POD provides a safe and effective vehicle for transferring DNA into cells without using a virus, currently the most common means of DNA delivery. PEG-POD protects DNA from damage in the bloodstream, allowing for gene therapy treatments that can be administered through an IV and directed to many other parts of the body.
The researchers found that gene expression in specimens injected with PEG-POD was 215 times more effective than two other carriers tested.
Ref: www.mdsupport.org/library/PEG-POD.html
_________________________
Envisioning A Cure For AMD (by Rick Trevino, OD)
I would like to quote from an article by Dr. Rick Travino, who is active in our online community and who hosts one of the most informative web sites about vision research and developments. In his commentary, “Envisioning A Cure For AMD,” he wrote:
“One of the most exciting developments in the field of AMD research has been the discovery of a relatively small number of genes that seems to control a large amount of the risk of developing the disease.
“Most of the genes that are known to influence the risk of developing AMD involve various components of the complement cascade. Most prominent among these is complement factor H (CFH); however, variants in genes coding for other components of the complement system have also been discovered and shown to be associated with AMD risk and protection. The complement system is very important in regulating the body’s immune system and directing inflammatory processes. Several lines of evidence suggest that dysregulation of inflammation plays a key role in the development of AMD.
“Now, thanks to these discoveries, we are beginning to see treatments that are specifically tailored to address abnormalities in the complement system. This raises the very real possibility of a truly preventative treatment, or even a cure, for the disease. . . Many . . . complement pathway-modulating compounds are currently being considered for, and/or are under, preclinical development for possible use in AMD.
“One could imagine a day when persons are screened at an early age to determine whether they harbor the genes that will ultimately lead them to develop AMD later in life. Then, based upon their specific genetic make-up, persons could take medications, or perhaps undergo gene therapy, that will prevent AMD from ever occurring. In this scenario, the eradication of AMD is a real possibility.”
Thank you, Dr. Trevino for reinforcing our hope for the future.
Ref: www.myvisiontest.com
GOOD NEWS
Incidence of AMD Declining
And finally, to continue on a positive note, I reported last year that a recent study found a lower 5-year incidence of early AMD in patients born or examined more recently, compared to similarly aged persons born or examined in an earlier period. That study included 2,968 participants with early AMD and 3,588 participants with late stage AMD, all of whom were examined at 5-year intervals between 1988 and 2005 as part of the Beaver Dam Eye Study.
Now we have more good news along those same lines. A new study reported this year has shown a 68% lower incidence of macular degeneration in the Baby Boom population. The research suggests that improvements in environment, behaviors, and other such modifiable factors may have contributed to the results. The “birth cohort” effect remained even after adjusting for AMD risk factors such as obesity, heavy drinking, and sunlight exposure.
More study is necessary as the younger population continues to age, but the results further emphasize the importance of environmental and lifestyle factors to retinal health.
Source: Karen J. Cruickshanks, MD (University of Wisconsin School of Medicine and Public Health in Madison) and reported at the Association for Research in Vision and
Ophthalmology (AAO) 2010.
____________________
Conclusion
One of the worst aspects of living with macular degeneration is that there is little we can do about our inevitable loss of vision. To alleviate some of the frustration that causes, we want to leave no stone unturned in our daily battle to maintain our healthiest eyesight.
I hope our news updates and annual summaries are serving that purpose by providing you with some comfort in knowing about all the good research being done. With this kind of information in hand, we no longer have to say, “Why didn’t someone tell me?”
Now, please accept the challenge of passing this information along. Educating others is one of the best ways to keep from being victimized by this disease, and your help is greatly appreciated!

Summary of Research and Developments in Macular Degeneration: 2005-2006

by Dan Roberts
This is a compilation of significant research in the field of macular degeneration during the period May 2005 through May 2006, beginning with new findings as presented at the 2006 meeting of the Association for Research in Vision and Ophthalmology (ARVO).
Triple therapy found to be effective for wet AMD

Triple therapy with a combination of intravitreal Kenalog, photodynamic therapy (PDT), and intravitreal Macugen (pegaptanib sodium) has been found to be safe and effective for treatment of wet AMD. Improvements in visual acuity and in macular thickness in sixteen patients were reported at the ARVO meetings by JM Colina-Luquez MD, ophthalmologist, New England Retina Associates, Hamden, Connecticut
7.9% of those who had had prior therapy had an improvement in visual acuity of 3 lines or more, compared to 33% of those with newly diagnosed disease. This is an improvement in acuity from 20/200 to 20/50.
(Poster presentation: Prospective and Preliminary Study Evaluating Triple Therapy of Intravitreal Triamcinolone, Photodynamic Therapy and Pegaptanib Sodium for Choroidal Neovascularization)
Macugen may present risk of increased IOP

Optometrist Allison Toler, OD (East Florida Eye Institute, Stuart, Florida) and ophthalmologist Ronald Frenkel, MD, Bascom Palmer Eye Institute, University of Miami, Miami, Florida) reported to the ARVO meeting that treatment with pegaptanib sodium (Macugen) may run the risk of significantly increased intraocular pressure (IOP). In a study of eight patients, mean pre-injection IOP was 12.9 mm Hg and mean post-injection IOP was 39.4 mm Hg. The IOP returned to normal in most cases within 30 minutes of the injection, and eventuially all patients showed normal IOP levels.
The researchers then compared Macugen injection to Avastin (bevacizumab) injection. The spikes in IOP were similar, but IOP decreased faster in patients who underwent Avastin treatment. As a result of these findings, physicians were cautioned to closely monitor IOP levels in glaucoma patients who are also being treated with Macugen.
(Poster presentation: IOP Effects of Macugen in Glaucoma Patients]
Intravitreal injections affect the fellow eye

S.D. Martin et al (Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Center, Louisville, KY) reported to the ARVO meeting that intravitreal injections of anti-VEGF drugs (i.e. Macugen and Avastin) also have an effect in the fellow eye. This is possibly the result of systemic absorption. Conclusions were drawn from analysis of pre- and post-injection ocular coherence tomography (OCT) graphs of 29 patients over a six-week period. Intravitreal use of these drugs, therefore, should be done with caution, since such absorption might also affect other systemic functions of the body. The researchers suggested that lower dosages of Macugen may be wise.
(Poster presentation: Intravitreally Injected Anti-VEGF Drugs Exert a Biological Effect in the Fellow Eye)
No association between cataracts and macular degeneration

Susan Bressler, MD (Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland) reported to ARVO that analyses of data from the Age Related Eye Disease Study (AREDS) has shown “no clear evidence of an association between cataract surgery and neovascular age-related macular degeneration,” and that “most patients undergoing cataract surgery can probably be reassured that surgery will not markedly increase their risk for progression to neovascular age-related macular degeneration.” The conclusion was drawn from checking outcomes after 1,704 cataract surgeries and 543 neovascular ARMD events after baseline among 8,152 eyes with a median follow-up of nine years.
(Poster presentation: The Effect of Cataract Surgery on the Development of Neovascular Age-Related Macular Degeneration)
New Lutein Findings
    The Melbourne Collaborative Cohort Study presented evidence to ARVO that neither lutein nor zeaxanthin are protective against the progression of AMD. This is contradictory to previous studies showing the opposite.
The same study of over 41,000 subjects showed an association between high intake of unsaturated fats and development of AMD, and that olive oil intake may be beneficial.
At the same meeting, a second multicenter study of 300 subjects showed that daily supplementation with 18 mg lutein and 2.4 mg zeaxanthin over six months resulted in a slight increase in macular pigment density.
Blue light risk
    Research from the University of Chicago has confirmed that the blue light wavelength peaking at 440 nm causes retinal damage through photochemical change and apoptotic cell death. The study authors repeated the recommendation stressed by MD Support at the 2005 ARVO meeting that blue blocking lenses be worn to protect the retina from direct exposure to strong blue light (i.e. sunlight, either natural or artificial).
(See “Artificial Lighting and the Blue Light Hazard” at www.mdsupport.org/library/hazard.html.)
Statins, smoking and wet AMD
    A scientific poster presentation at the 2005 AAO meeting, “Reduced Risk of Progression to Exudative ARMD with Statin Use” (Gregory R Nettune, MPH, et al) presented research finding that “the risk of exudative AMD was increased by smoking and reduced by use of statins. Further, the duration of statin use up to four years was associated with an increasing degree of protection.” The study also found that current smoking or smoking within the past 20 years led to a 6-fold increase in risk of conversion from dry to wet AMD. No difference was found in subjects who had not smoked in 20 years.
As reported at the 2006 ARVO meeting, research from Duke and Vanderbilt University Medical Centers (published in the online edition of the American Journal of Human Genetics, March 6, 2006) has discovered that a version of the LOC387715 gene significantly increases the risk of developing ARMD in tobacco smokers. This is an unusual instance wherein genetics and environment can combine to create a disease risk. The other example related to ARMD is the CFH gene and how its effects are related to the body’s immune system (see below). 

VEGF Trap 

Regeneron Pharmaceuticals reported to ARVO positive results after at the sixth week in its Phase I dose-escalation study of intravitreal anti-angiogenic drug VEGF Trap. 21 patients received a single injection of one of six doses, from 0.05mg to 4mg, and were monitored for 12 weeks.
Ocular coherence tomography (OCT) useful in determining need for Lucentis treatment
A study is being conducted at the Bascom Palmer Eye Institute (University of Miami) to evaluate the use of optical coherence tomography (OCT) for determining when patients needed an injection of Lucentis. The PrONTO Study (Prospective Optical Coherence Tomography Imaging of Patients with Neovascular Age-Related Macular Degeneration Treated with Intra-Ocular Lucentis) has shown good results at the end of its first year under principle investigator Philip Rosenfeld, MD. The results were reported to the 2006 meeting of ARVO.
“By using OCT in this uncontrolled study”, said Dr. Rosenfeld, “we were able to give fewer injections into the eye and observed vision improvement for most of our forty patients.” Intermittent injections were given every 3 to 4 months as determined using OCT. After 1 year, 17.5% of patients needed no further injections, and 20% needed only one additional injection. In spite of such individual differences, Dr.Rosenfeld said that the need for treatment was easily monitored using OCT.
__________________________________________________________
The following research was published throughout the past 12-month period on the MD Support site. For complete information, visit the library at www.mdsupport.org/library.html.
Gene replacement therapy successful in early trials
      Researchers at Johns Hopkins University Medical Center have used gene replacement therapy to halt (at least temporarily) retinal bleeding in patients with the wet form of age-related macular degeneration (AMD). This was done by single injections of a PEDF (pigment epithelial derived factor) gene into the eyes of patients during a phase I clinical trial just completed.
The methodology used in this research can also be applied to treating other types of gene-related retinal diseases, such as retinitis pigmentosa, Usher’s syndrome, and choroideremia.
New drugs are stopping retinal bleeding

Drugs called “anti-angiogenics” are stopping retinal bleeding in patients with wet AMD. The first to be approved was Macugen in February 2005. Another drug, Avastin, is being used off-label by doctors who consider it to be more effective than Macugen.
If all goes well in the trials, a third drug, Lucentis, will soon follow. This drug has shown very high success rates in trials. Doctors are saying that, if it is approved later this year, Lucentis will probably become their first choice. At least seven other drugs are also being tested, both alone and in combination with others. Due to this research, vision loss from wet AMD may soon become a thing of the past.
Drusen fragments may lead to wet AMD

Drusen are cellular waste deposits in the retina that are associated with development of macular degeneration. In research sponsored by the National Eye Institute, fragments of two known components of drusen (named C3a and C5a) have been identified that may be the cause of dry age-related macular degeneration (AMD) progressing to the wet form. As a result of this new finding, the fragments can serve as markers for predicting which patients are at high risk for progression to the wet stage. The next step is to develop a substance that can block C3a and C5a, essentially halting the progression from dry to wet. That is not to say that drusen are the only cause of CNV, but this is research worth following.
Two genes shown to lead to AMD

In 2005, the first suspect protein was discovered by three separate research centers. Called Complement Factor H (CFH), it may be a cause of AMD in as many as 50% of cases. CFH helps to control the body’s immune response and inflammation. In a later study, the question arose as to why 29% of the subjects who had a variation in Factor H did not develop AMD. This led to discovery of a second gene, Factor B, which explains the analomy. While Factor H stops the immune response, Factor B activates it. The two opposites can, therefore, balance one another and prevent AMD from developing in some cases.
The two genes are now connected to development of AMD in three out of four people who have the disease. The next step is to learn how to control the body’s immune response that sets off inflammation. Once the viral or bacterial cause has been identified, that knowledge in combination with the newly-discovered genetic markers will make it possible to develop effective therapies for the prevention of the disease.
Other genes that have been recently found to be associated with AMD are ABCR4, FBLN5, FBLN6, LOC387715 and MTTL1. More than 50 genes have been linked to AMD so far.
Clinical Trial for Wet AMD

Genentech is enrolling patients in its Phase IIIb clinical study of Lucentis for patients with all subtypes of new or recurrent active subfoveal wet AMD. Called SAILOR (Safety Assessment of Intravitreal Lucentis for AMD), the one-year study will evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for three months and thereafter as needed based on criteria-based re-treatment options. The study is being conducted at over 70 sites in the United States and will enroll approximately 5,000 patients. To inquire about participation, call 1-888-662-6728.
Encapsulated Cell Technology (ECT)–A New Drug Delivery System

    A means of delivering drugs into the retina on a time release basis has been developed and proven safe and effective. The NT-501 uses encapsulated cell technology (ECT) to manufacture and secrete a drug called ciliary neurotrophic factor (CNTF) into the vitreous of the eye. CNTF is produced by genetically modified cells contained in the ECT, which is implanted inside the eyeball. The device acts, therefore, like a miniature factory for production and distribution of the drug. The device may prove to be safer, more effective and more convenient than injection.
Results from Phase I showed not only that the ECT device works and is safe, but that CNTF is a potentially effective drug treatment for slowing down all forms of hereditary retinal diseases such as macular degeneration and retinitis pigmentosa.
New gene thought to increase AMD risk in smokers

Research from Duke and Vanderbilt University Medical Centers has discovered that a version of the LOC387715 gene significantly increases the risk of developing ARMD in tobacco smokers. This is an unusual instance wherein genetics and environment can combine to create a disease risk.
Stem Cells Promise Cure
    Stem cell transplantation is showing promise as a potential cure for retinal disease. Here is a summary of an article that appeared April 19th in Science Magazine regarding this exciting research:

Stem Cells Promise Cure For Vision Loss

Dr Rajender Prasad Centre for Opthalmic Sciences at AIIMS has been studying the effect of stem cells in patients who suffer from degenerative vision disorders. The study is being conducted on fifty patients who are severely affected by age-related macular degeneration or retinitis pigmentosa.
According to Dr Atul Kumar, Professor of Opthalmology and head of the team undertaking the research, significant improvement has been noticed in vision of the patients after one month of injecting stem cells. There is further improvement after a gap of three months.
The researchers are using autologous (derived from patient’s own body) bone marrow derived stem cells and injecting them into a loose tissue near the cornea. Follow-ups are then done after one, three, six and 12 months.
[end article summary]
This study is still in early phase I of clinical trials. Dr. Atul Kumar has had success over the past several years with corneal regeneration using stem cells, and now he is testing his theory that retinal regeneration might also occur. So far the results are promising. He is testing only dry AMD patients age 50+ and retinitis pigmentosa patients age 18+, with best corrected acuity of 20/400 in both cases.
OccuLogix Reports Positive MIRA-1 Analysis Results

New analysis of data from the MIRA-1 trials shows significant vision improvement in dry AMD patients treated with the RHEO procedure, a blood filtration treatment currently available in Canada, but not yet approved in the United States.
On March 9, OccuLogix, Inc. announced that eyes treated with the RHEO procedure showed that 50% of patients with vision worse than 20/40 improved after treatment to 20/40 or better and would be able to qualify for a drivers license. This compares to 20% of patients in the placebo group.
“Prior to the development of the RHEO procedure,” said Dr. Lawrence Yannuzzi (Columbia University and Manhattan Eye, Ear and Throat Hospital), “there hasn’t been a potential treatment for Dry AMD beyond vitamin therapy. These results, while not yet conclusive, are very encouraging and may offer patients living with Dry AMD hope for the future.”
OccuLogix plans on meeting with the FDA soon to discuss the study results. Further study will likely be required before approval for marketing in the United States. We will continue to provide further updates as they become available. For more information about the study or the RHEO procedure, see: www.occulogix.com and www.rheo.com.
Eye Drops May Treat Wet AMD

On April 5, 2006, TargeGen, Inc. (San Diego) announced that a “prodrug” called TG100801 may be effective as an eye drop treatment for wet macular degeneration. TG100801 converts to the active drug TG100572 as it penetrates the eye. TG100572 was shown to stop neovascularization and to decrease inflammation, both of which are characteristics of wet macular degeneration. TargeGen plans to initiate human clinical trials with TG100801 prior to the end of 2006.
Dr. Shiyin Yee of TargeGen presented the preclinical data last month at The 6th International Symposium on Ocular Pharmacology and Therapeutics in Berlin, Germany. Collaborating laboratories are Johns Hopkins University School of Medicine.
Fenretinide may slow vision loss from Stargardt disease

Fenretinide, a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, has been found to also slow the production and accumulation of a toxin that leads to vision loss in Stargardt’s patients. The toxin, called A2E, is a byproduct of vitamin A, the formation of which encourages production of waste deposits called lipofuscin. These deposits accumulate in the retinal pigment epithelium (RPE), interfering with the RPE’s ability to nourish the photoreceptors.
The efficacy study was conducted by Sytera and collaborators at The Jules Stein Eye Institute. Researchers found that A2E accumulation was decreased by 60% in mouse models after 28 days of treatment with fenretinide.
Since accumulation of lipofuscin is also a condition of eyes affected by age-related macular degeneration (AMD), Sytera is planning clinical trials using AMD patients as subjects. This will provide a larger population for the study than the relatively small number of Stargardt’s patients available. If the drug proves effective with dry AMD patients, it may then be used off-label for treatment of Stargardt’s disease.
Implantable miniature telescope helps improve visual acuity

On October 19, 2005, Isaac Lipshitz, M.D. announced positive results from VisionCare’s Phase I/III clinical trials of the IMT. After one year, subjects showed a mean improvement of over 3 lines in both distance and near visual acuity. 90% exceeded the primary endpoint of the trial with a 2-line improvement. Significant improvement in quality of life and daily living activities was also measured. A 2-year follow-up has revealed no serious safety issues, and the company now looks forward to completing the regulatory review process on the way to marketing the IMT for public use.
Bacterial infection linked to AMD
Further evidence has shown that the bacterium Chlamydia pneumoniae may lead to a higher risk of age-related macular degeneration. The evidence was presented in a study published in the November issue of the journal Graefe’s Archive for Clinical and Experimental Ophthalmology (Massachusetts Eye and Ear Infirmary, Dr. Murat Kalayoglu, lead author). That study found C. pneumoniae in the diseased eye tissue of five of nine people with wet AMD but not in the eyes of 20 people without AMD.
The researchers found that “C. pneumoniae is capable of modifying the function of important cell types involved in regulating normal eye function,” and that “C. pneumoniae infection led to increased production of vascular endothelial growth factor (VEGF), the key protein involved in wet AMD.” This, they hypothesized, could partially explain the increased VEGF levels in many AMD patients, and that C. pneumoniae may be acting as an accelerant of inflammation in AMD patients who have variations in their complement factor H (CFH) gene.
Lucentis maintained or improved vision in approximately 95% of patients in phase III study
On January 14, 2006, Genentech, Inc. announced positive one-year results from its second pivotal Phase III study of the investigational drug Lucentis (ranibizumab) in patients with wet age-related macular degeneration (AMD). Data from the ANCHOR study comparing Lucentis to verteporfin (Visudyne¨) photodynamic therapy (PDT) showed a difference in mean change in visual acuity of 18 letters for patients treated with 0.3 mg of Lucentis and 21 letters for patients treated with 0.5 mg of Lucentis from study entry compared to those treated with PDT at 12 months.
AdPEDF protein halts development of ocular blood vessels

In January 2006, Researchers at Johns Hopkins University Medical Center announced that they were able to halt (at least temporarily) choroidal neovascularization (CNV) with single injections of the PEDF gene into the eyeballs of patients during a phase I clinical trial.
AdPEDF is a protein produced naturally in the eye to promote survival of retinal and other nerve cells. It also regulates the growth of ocular blood vessels, as in patients with wet MD. The PEDF (pigment epithelium-derived factor) gene produces the AdPEDF protein. By injecting the PEDF gene into the eye, the researchers are able to elevate the level of AdPEDF, thereby halting the development of blood vessels.
Macugen update
    David Guyer, M.D., (Eyetech Pharmaceuticals, now OSI) reported that after 40,000 treatments to date, Macugen has shown no safety problems. He stressed that it is very important that doctors treat as early as possible and follow the treatment regimen exactly as outlined in the protocol. Data has shown that starting the injections too late into the progression of the disease and/or stopping the treatment early (before four injections) may prevent improvement.
Recent studies with negative or insignificant results
The following studies did not reach their primary endpoints during the past year:

      • Submacular surgery
      •Transpupillary thermotherapy
      • Radiation therapy
      • Comparison of anecortave acetate (Retaane 15 mg) with verteporfin PDT in patients with predominantly classic subfoveal CNV.
    • Visudyne VIO for occult AMD

EVIZON with Visudyne
Genaera announced that its Phase II clinical trial of EVIZON (formerly squalamine lactate) to treat wet AMD met its goal of demonstrating safety when dosed with Visudyne for PDT. The 40mg EVIZON treatment, combined with the PDT, was well tolerated, with approximately 90% of subjects maintaining vision at 29 weeks.
AREDS II
A second age-related eye disease study (AREDS), now in planning stages, might include lowering the amount of zinc, eliminating beta-carotene, and including the carotenoids lutein, zeaxanthin, and DHA/Omega 3 (fish oil). These changes are based upon new findings since the late 90’s and recommendations from nutritionists. AREDS II will study 4000 subjects using various combinations of the above supplements.
Vitamin E found to be safe
    Vitamin E in doses less than or equal to 400IU (as found in most supplements) is of no concern, despite recent misleading reports that high doses could be fatal.
The above information was gathered from four sources at the annual meeting of the American Academy of Ophthalmology: 1) an instructional course titled “New and Investigational Therapies for ARMD, 2005,” 2) a seminar titled “ARMD: Evolving Treatment Options,” 3) a symposium on “Pharmacotherapy for Macular Diseases” and 4) private discussions between this writer and researchers. 

Summary of Research and Developments in Macular Degeneration: 2005-2006

by Dan Roberts
This is a compilation of significant research in the field of macular degeneration during the period May 2005 through May 2006, beginning with new findings as presented at the 2006 meeting of the Association for Research in Vision and Ophthalmology (ARVO).
Triple therapy found to be effective for wet AMD
Triple therapy with a combination of intravitreal Kenalog, photodynamic therapy (PDT), and intravitreal Macugen (pegaptanib sodium) has been found to be safe and effective for treatment of wet AMD. Improvements in visual acuity and in macular thickness in sixteen patients were reported at the ARVO meetings by JM Colina-Luquez MD, ophthalmologist, New England Retina Associates, Hamden, Connecticut
7.9% of those who had had prior therapy had an improvement in visual acuity of 3 lines or more, compared to 33% of those with newly diagnosed disease. This is an improvement in acuity from 20/200 to 20/50.
(Poster presentation: Prospective and Preliminary Study Evaluating Triple Therapy of Intravitreal Triamcinolone, Photodynamic Therapy and Pegaptanib Sodium for Choroidal Neovascularization)
Macugen may present risk of increased IOP
Optometrist Allison Toler, OD (East Florida Eye Institute, Stuart, Florida) and ophthalmologist Ronald Frenkel, MD, Bascom Palmer Eye Institute, University of Miami, Miami, Florida) reported to the ARVO meeting that treatment with pegaptanib sodium (Macugen) may run the risk of significantly increased intraocular pressure (IOP). In a study of eight patients, mean pre-injection IOP was 12.9 mm Hg and mean post-injection IOP was 39.4 mm Hg. The IOP returned to normal in most cases within 30 minutes of the injection, and eventuially all patients showed normal IOP levels.
The researchers then compared Macugen injection to Avastin (bevacizumab) injection. The spikes in IOP were similar, but IOP decreased faster in patients who underwent Avastin treatment. As a result of these findings, physicians were cautioned to closely monitor IOP levels in glaucoma patients who are also being treated with Macugen.
(Poster presentation: IOP Effects of Macugen in Glaucoma Patients]
Intravitreal injections affect the fellow eye
S.D. Martin et al (Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Center, Louisville, KY) reported to the ARVO meeting that intravitreal injections of anti-VEGF drugs (i.e. Kenalog, Macugen and Avastin) also have an effect in the fellow eye. This is possibly the result of systemic absorption. Conclusions were drawn from analysis of pre- and post-injection ocular coherence tomography (OCT) graphs of 29 patients over a six-week period. Intravitreal use of these drugs, therefore, should be done with caution, since such absorption might also affect other systemic functions of the body. The researchers suggested that lower dosages of Macugen may be wise.
(Poster presentation: Intravitreally Injected Anti-VEGF Drugs Exert a Biological Effect in the Fellow Eye)
No association between cataracts and macular degeneration
Susan Bressler, MD (Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland) reported to ARVO that analyses of data from the Age Related Eye Disease Study (AREDS) has shown “no clear evidence of an association between cataract surgery and neovascular age-related macular degeneration,” and that “most patients undergoing cataract surgery can probably be reassured that surgery will not markedly increase their risk for progression to neovascular age-related macular degeneration.” The conclusion was drawn from checking outcomes after 1,704 cataract surgeries and 543 neovascular ARMD events after baseline among 8,152 eyes with a median follow-up of nine years.
(Poster presentation: The Effect of Cataract Surgery on the Development of Neovascular Age-Related Macular Degeneration)
New Lutein Findings
The Melbourne Collaborative Cohort Study presented evidence to ARVO that neither lutein nor zeaxanthin are protective against the progression of AMD. This is contradictory to previous studies showing the opposite.
The same study of over 41,000 subjects showed an association between high intake of unsaturated fats and development of AMD, and that olive oil intake may be beneficial.
At the same meeting, a second multicenter study of 300 subjects showed that daily supplementation with 18 mg lutein and 2.4 mg zeaxanthin over six months resulted in a slight increase in macular pigment density.
Blue light risk
Research from the University of Chicago has confirmed that the blue light wavelength peaking at 440 nm causes retinal damage through photochemical change and apoptotic cell death. The study authors repeated the recommendation stressed by MD Support at the 2005 ARVO meeting that blue blocking lenses be worn to protect the retina from direct exposure to strong blue light (i.e. sunlight, either natural or artificial).
(See “Artificial Lighting and the Blue Light Hazard” at www.mdsupport.org/library/hazard.html.)
Statins, smoking and wet AMD
A scientific poster presentation at the 2005 AAO meeting, “Reduced Risk of Progression to Exudative ARMD with Statin Use” (Gregory R Nettune, MPH, et al) presented research finding that “the risk of exudative AMD was increased by smoking and reduced by use of statins. Further, the duration of statin use up to four years was associated with an increasing degree of protection.” The study also found that current smoking or smoking within the past 20 years led to a 6-fold increase in risk of conversion from dry to wet AMD. No difference was found in subjects who had not smoked in 20 years.
As reported at the 2006 ARVO meeting, research from Duke and Vanderbilt University Medical Centers (published in the online edition of the American Journal of Human Genetics, March 6, 2006) has discovered that a version of the LOC387715 gene significantly increases the risk of developing ARMD in tobacco smokers. This is an unusual instance wherein genetics and environment can combine to create a disease risk. The other example related to ARMD is the CFH gene and how its effects are related to the body’s immune system (see below).
VEGF Trap
Regeneron Pharmaceuticals reported to ARVO positive results after at the sixth week in its Phase I dose-escalation study of intravitreal anti-angiogenic drug VEGF Trap. 21 patients received a single injection of one of six doses, from 0.05mg to 4mg, and were monitored for 12 weeks.
Ocular coherence tomography (OCT) useful in determining need for Lucentis treatment
A study is being conducted at the Bascom Palmer Eye Institute (University of Miami) to evaluate the use of optical coherence tomography (OCT) for determining when patients needed an injection of Lucentis. The PrONTO Study (Prospective Optical Coherence Tomography Imaging of Patients with Neovascular Age-Related Macular Degeneration Treated with Intra-Ocular Lucentis) has shown good results at the end of its first year under principle investigator Philip Rosenfeld, MD. The results were reported to the 2006 meeting of ARVO.
“By using OCT in this uncontrolled study”, said Dr. Rosenfeld, “we were able to give fewer injections into the eye and observed vision improvement for most of our forty patients.” Intermittent injections were given every 3 to 4 months as determined using OCT. After 1 year, 17.5% of patients needed no further injections, and 20% needed only one additional injection. In spite of such individual differences, Dr.Rosenfeld said that the need for treatment was easily monitored using OCT.
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The following research was published throughout the past 12-month period on the MD Support site. For complete information, visit the library at www.mdsupport.org/library.html.
Gene replacement therapy successful in early trials
Researchers at Johns Hopkins University Medical Center have used gene replacement therapy to halt (at least temporarily) retinal bleeding in patients with the wet form of age-related macular degeneration (AMD). This was done by single injections of a PEDF (pigment epithelial derived factor) gene into the eyes of patients during a phase I clinical trial just completed.
The methodology used in this research can also be applied to treating other types of gene-related retinal diseases, such as retinitis pigmentosa, Usher’s syndrome, and choroideremia.
New drugs are stopping retinal bleeding
Drugs called “anti-angiogenics” are stopping retinal bleeding in patients with wet AMD. The first to be approved was Macugen in February 2005. Another drug, Avastin, is being used off-label by doctors who consider it to be more effective than Macugen.
If all goes well in the trials, a third drug, Lucentis, will soon follow. This drug has shown very high success rates in trials. Doctors are saying that, if it is approved later this year, Lucentis will probably become their first choice. At least seven other drugs are also being tested, both alone and in combination with others. Due to this research, vision loss from wet AMD may soon become a thing of the past.
Drusen fragments may lead to wet AMD
Drusen are cellular waste deposits in the retina that are associated with development of macular degeneration. In research sponsored by the National Eye Institute, fragments of two known components of drusen (named C3a and C5a) have been identified that may be the cause of dry age-related macular degeneration (AMD) progressing to the wet form. As a result of this new finding, the fragments can serve as markers for predicting which patients are at high risk for progression to the wet stage. The next step is to develop a substance that can block C3a and C5a, essentially halting the progression from dry to wet. That is not to say that drusen are the only cause of CNV, but this is research worth following.
Two genes shown to lead to AMD
In 2005, the first suspect protein was discovered by three separate research centers. Called Complement Factor H (CFH), it may be a cause of AMD in as many as 50% of cases. CFH helps to control the body’s immune response and inflammation. In a later study, the question arose as to why 29% of the subjects who had a variation in Factor H did not develop AMD. This led to discovery of a second gene, Factor B, which explains the analomy. While Factor H stops the immune response, Factor B activates it. The two opposites can, therefore, balance one another and prevent AMD from developing in some cases.
The two genes are now connected to development of AMD in three out of four people who have the disease. The next step is to learn how to control the body’s immune response that sets off inflammation. Once the viral or bacterial cause has been identified, that knowledge in combination with the newly-discovered genetic markers will make it possible to develop effective therapies for the prevention of the disease.
Other genes that have been recently found to be associated with AMD are ABCR4, FBLN5, FBLN6, LOC387715 and MTTL1. More than 50 genes have been linked to AMD so far.
Clinical Trial for Wet AMD
Genentech is enrolling patients in its Phase IIIb clinical study of Lucentis for patients with all subtypes of new or recurrent active subfoveal wet AMD. Called SAILOR (Safety Assessment of Intravitreal Lucentis for AMD), the one-year study will evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis administered once a month for three months and thereafter as needed based on criteria-based re-treatment options. The study is being conducted at over 70 sites in the United States and will enroll approximately 5,000 patients. To inquire about participation, call 1-888-662-6728.
Encapsulated Cell Technology (ECT)–A New Drug Delivery System
A means of delivering drugs into the retina on a time release basis has been developed and proven safe and effective. The NT-501 uses encapsulated cell technology (ECT) to manufacture and secrete a drug called ciliary neurotrophic factor (CNTF) into the vitreous of the eye. CNTF is produced by genetically modified cells contained in the ECT, which is implanted inside the eyeball. The device acts, therefore, like a miniature factory for production and distribution of the drug. The device may prove to be safer, more effective and more convenient than injection.
Results from Phase I showed not only that the ECT device works and is safe, but that CNTF is a potentially effective drug treatment for slowing down all forms of hereditary retinal diseases such as macular degeneration and retinitis pigmentosa.
New gene thought to increase AMD risk in smokers
Research from Duke and Vanderbilt University Medical Centers has discovered that a version of the LOC387715 gene significantly increases the risk of developing ARMD in tobacco smokers. This is an unusual instance wherein genetics and environment can combine to create a disease risk.
Stem Cells Promise Cure
Stem cell transplantation is showing promise as a potential cure for retinal disease. Here is a summary of an article that appeared April 19th in Science Magazine regarding this exciting research:
Stem Cells Promise Cure For Vision Loss
Dr Rajender Prasad Centre for Opthalmic Sciences at AIIMS has been studying the effect of stem cells in patients who suffer from degenerative vision disorders. The study is being conducted on fifty patients who are severely affected by age-related macular degeneration or retinitis pigmentosa.
According to Dr Atul Kumar, Professor of Opthalmology and head of the team undertaking the research, significant improvement has been noticed in vision of the patients after one month of injecting stem cells. There is further improvement after a gap of three months.
The researchers are using autologous (derived from patient’s own body) bone marrow derived stem cells and injecting them into a loose tissue near the cornea. Follow-ups are then done after one, three, six and 12 months.
[end article summary]
This study is still in early phase I of clinical trials. Dr. Atul Kumar has had success over the past several years with corneal regeneration using stem cells, and now he is testing his theory that retinal regeneration might also occur. So far the results are promising. He is testing only dry AMD patients age 50+ and retinitis pigmentosa patients age 18+, with best corrected acuity of 20/400 in both cases.
OccuLogix Reports Positive MIRA-1 Analysis Results
New analysis of data from the MIRA-1 trials shows significant vision improvement in dry AMD patients treated with the RHEO procedure, a blood filtration treatment currently available in Canada, but not yet approved in the United States.
On March 9, OccuLogix, Inc. announced that eyes treated with the RHEO procedure showed that 50% of patients with vision worse than 20/40 improved after treatment to 20/40 or better and would be able to qualify for a drivers license. This compares to 20% of patients in the placebo group.
“Prior to the development of the RHEO procedure,” said Dr. Lawrence Yannuzzi (Columbia University and Manhattan Eye, Ear and Throat Hospital), “there hasn’t been a potential treatment for Dry AMD beyond vitamin therapy. These results, while not yet conclusive, are very encouraging and may offer patients living with Dry AMD hope for the future.”
OccuLogix plans on meeting with the FDA soon to discuss the study results. Further study will likely be required before approval for marketing in the United States. We will continue to provide further updates as they become available. For more information about the study or the RHEO procedure, see: www.occulogix.com and www.rheo.com.
Eye Drops May Treat Wet AMD
On April 5, 2006, TargeGen, Inc. (San Diego) announced that a “prodrug” called TG100801 may be effective as an eye drop treatment for wet macular degeneration. TG100801 converts to the active drug TG100572 as it penetrates the eye. TG100572 was shown to stop neovascularization and to decrease inflammation, both of which are characteristics of wet macular degeneration. TargeGen plans to initiate human clinical trials with TG100801 prior to the end of 2006.
Dr. Shiyin Yee of TargeGen presented the preclinical data last month at The 6th International Symposium on Ocular Pharmacology and Therapeutics in Berlin, Germany. Collaborating laboratories are Johns Hopkins University School of Medicine.
Fenretinide may slow vision loss from Stargardt disease
Fenretinide, a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, has been found to also slow the production and accumulation of a toxin that leads to vision loss in Stargardt’s patients. The toxin, called A2E, is a byproduct of vitamin A, the formation of which encourages production of waste deposits called lipofuscin. These deposits accumulate in the retinal pigment epithelium (RPE), interfering with the RPE’s ability to nourish the photoreceptors.
The efficacy study was conducted by Sytera and collaborators at The Jules Stein Eye Institute. Researchers found that A2E accumulation was decreased by 60% in mouse models after 28 days of treatment with fenretinide.
Since accumulation of lipofuscin is also a condition of eyes affected by age-related macular degeneration (AMD), Sytera is planning clinical trials using AMD patients as subjects. This will provide a larger population for the study than the relatively small number of Stargardt’s patients available. If the drug proves effective with dry AMD patients, it may then be used off-label for treatment of Stargardt’s disease.
Implantable miniature telescope helps improve visual acuity
On October 19, 2005, Isaac Lipshitz, M.D. announced positive results from VisionCare’s Phase I/III clinical trials of the IMT. After one year, subjects showed a mean improvement of over 3 lines in both distance and near visual acuity. 90% exceeded the primary endpoint of the trial with a 2-line improvement. Significant improvement in quality of life and daily living activities was also measured. A 2-year follow-up has revealed no serious safety issues, and the company now looks forward to completing the regulatory review process on the way to marketing the IMT for public use.
Bacterial infection linked to AMD
Further evidence has shown that the bacterium Chlamydia pneumoniae may lead to a higher risk of age-related macular degeneration. The evidence was presented in a study published in the November issue of the journal Graefe’s Archive for Clinical and Experimental Ophthalmology (Massachusetts Eye and Ear Infirmary, Dr. Murat Kalayoglu, lead author). That study found C. pneumoniae in the diseased eye tissue of five of nine people with wet AMD but not in the eyes of 20 people without AMD.
The researchers found that “C. pneumoniae is capable of modifying the function of important cell types involved in regulating normal eye function,” and that “C. pneumoniae infection led to increased production of vascular endothelial growth factor (VEGF), the key protein involved in wet AMD.” This, they hypothesized, could partially explain the increased VEGF levels in many AMD patients, and that C. pneumoniae may be acting as an accelerant of inflammation in AMD patients who have variations in their complement factor H (CFH) gene.
Lucentis maintained or improved vision in approximately 95% of patients in phase III study
On January 14, 2006, Genentech, Inc. announced positive one-year results from its second pivotal Phase III study of the investigational drug Lucentis (ranibizumab) in patients with wet age-related macular degeneration (AMD). Data from the ANCHOR study comparing Lucentis to verteporfin (Visudyne¨) photodynamic therapy (PDT) showed a difference in mean change in visual acuity of 18 letters for patients treated with 0.3 mg of Lucentis and 21 letters for patients treated with 0.5 mg of Lucentis from study entry compared to those treated with PDT at 12 months.
AdPEDF protein halts development of ocular blood vessels
In January 2006, Researchers at Johns Hopkins University Medical Center announced that they were able to halt (at least temporarily) choroidal neovascularization (CNV) with single injections of the PEDF gene into the eyeballs of patients during a phase I clinical trial.
AdPEDF is a protein produced naturally in the eye to promote survival of retinal and other nerve cells. It also regulates the growth of ocular blood vessels, as in patients with wet MD. The PEDF (pigment epithelium-derived factor) gene produces the AdPEDF protein. By injecting the PEDF gene into the eye, the researchers are able to elevate the level of AdPEDF, thereby halting the development of blood vessels.
Macugen update
David Guyer, M.D., (Eyetech Pharmaceuticals, now OSI) reported that after 40,000 treatments to date, Macugen has shown no safety problems. He stressed that it is very important that doctors treat as early as possible and follow the treatment regimen exactly as outlined in the protocol. Data has shown that starting the injections too late into the progression of the disease and/or stopping the treatment early (before four injections) may prevent improvement.
Recent studies with negative or insignificant results
The following studies did not reach their primary endpoints during the past year:

  • Submacular surgery
  • Transpupillary thermotherapy
  • Radiation therapy (multiple negative studies)
  • Comparison of anecortave acetate (Retaane 15 mg) with verteporfin PDT in patients with predominantly classic subfoveal CNV.
  • Visudyne VIO for occult AMD

EVIZON with Visudyne
Genaera announced that its Phase II clinical trial of EVIZON (formerly squalamine lactate) to treat wet AMD met its goal of demonstrating safety when dosed with Visudyne for PDT. The 40mg EVIZON treatment, combined with the PDT, was well tolerated, with approximately 90% of subjects maintaining vision at 29 weeks. For more about EVIZON, see www.mdsupport.org/library/anti-angio.html.
AREDS II
A second age-related eye disease study (AREDS), now in planning stages, might include lowering the amount of zinc, eliminating beta-carotene, and including the carotenoids lutein, zeaxanthin, and DHA/Omega 3 (fish oil). These changes are based upon new findings since the late 90’s and recommendations from nutritionists. AREDS II will study 4000 subjects using various combinations of the above supplements.
Vitamin E found to be safe
Vitamin E in doses less than or equal to 400IU (as found in most supplements) is of no concern, despite recent misleading reports that high doses could be fatal.
The above information was gathered from four sources at the annual meeting of the American Academy of Ophthalmology: 1) an instructional course titled “New and Investigational Therapies for ARMD, 2005,” 2) a seminar titled “ARMD: Evolving Treatment Options,” 3) a symposium on “Pharmacotherapy for Macular Diseases” and 4) private discussions between this writer and researchers.