Summary of Research and Developments in Macular Degeneration, 2012-2013

by Dan Roberts
June 2013
This is a summary of reports about significant research and development in the field of macular degeneration and related diseases presented since June 2012 and May 2013. I will briefly describe the conclusions of 77 studies that have been presented in the areas of therapy, prevention, technology, nutrition and daily living. Reports on the new retinal prosthesis and prevalence of AMD will also be summarized.
For those who wish more detail, references to the original resources are provided. Those sources labeled “ARVO Presentation” refer to reports and posters presented at the May 2013 meeting of the Association for Research in Vision and Ophthalmology and posted on the Web at
After targeting the macula with a nano-second pulse laser called 2RT, results suggested a potentially clinically significant reduction in the odds of progression to advanced AMD at 12 months and at 24 months. Researchers concluded that the 2RT laser has the potential to slow the progression of early AMD. A large randomised controlled trial is currently underway.
Source: ARVO Presentation 4146: Novel Laser treatment for Early Age-related Macular Degeneration (Kate Brassington1, et al)
In 2008, Acucela Inc. announced that it had begun a Phase I trial for its lead compound ACU-4429, an oral drug developed for the treatment of dry age-related macular degeneration (AMD). It modulates the visual cycle by significantly reducing the accumulation of a by-product of the visual cycle called A2E. which is believed to damage retinal cells.
Phase 1 safety trials were successful, and the results of Acucela’s Phase 2a trial were announced at the ARVO meeting in May 2013. This study demonstrated that ACU-4429 does have the ability to modulate the visual cycle with minimal adverse events. Yhe compound continues to show promise as a treatment for geographic atrophy from dry AMD, and a long-term Phase 2b study is now underway.
Source: A Phase 2 Double-masked, Placebo-controlled, Dose Ranging Study of Emixustat Hydrochloride (ACU-4429) in Subjects with GA Associated with Dry AMD (Pravin U. Dugel1, et al)
A flavonoid called querectin has been found to protect against oxidative cellular injury and inhibit progression of AMD to the advanced wet form. It may, therefore, be of therapeutic value as an AMD treatment.
Source: ARVO Presentation 4123: Quercetin Protects Hydrogen Peroxide Damaged Human Retinal Pigment Epithelial (hRPE) Cells and Inhibits Vascular Endothelial Growth Factor (VEGF) Production (Andrew Kumar1, et al)
An antibiotic called minocycline has been seen in cell culture to also protect retinal cells from oxidative damage. This finding suggests that minocycline, too, may play a therapeutic role in the treatment of AMD.
Source: ARVO Presentation 4108: Minocycline protects retinal pigment epithelial cells from hypoxia (Joanna DaCosta)
A protein called Interleukin-17A (IL17A) is a driving force in chronic inflammation and its overexpression has been linked to AMD. One study found that an injection into the eye of a receptor named sIL17R could neutrilize that damaging protein. Based upon results of the study, the researchers believe this should be considered as another potential treatment for AMD.
Source: ARVO Presentation 1713: Interleukin-17 neutralization ameliorates retinal degeneration in Cx3cr1-/-/Ccl2-/-/Crb1rd8 mice (Daniel Ardeljan1, et al)
We know that lipid (fatty) deposits in the retina are important factors in development of AMD. Scientists have discovered that a peptide called D-4F, primarily developed to treat arthersclerosis, also reduces lipids in the retina after injection into the eye (Rudolf et al., IOVS 2010, 51: Abstract 2984). Now, this past year, we have learned that D-4F taken orally may be almost as effective as injections, and definitely safer and more pleasant.
Source: ARVO Presentation 1714: Oral administration of Apolipoprotein A-I mimetic peptide D-4F reduces lipid accumulation in murine Bruch’s membrane (BrM) (Martin Rudolf, et al)
The low vision community has shown an interest in the use of acupuncture as a means of slowing the progression of retinal diseases. No large scale clinical trials have been accomplished to measure safety and efficacy of acupuncture for this purpose, but a small study this past year did show interesting results.
Researchers applied electroacupuncture to the forehead and below the eyes, and acupuncture to the bodies of twelve retinitis pigmentosa (RP) patients over a period of two weeks. They found significant and lasting improvement in acuity, contrast, dark adaptation, and visual field, concluding that electro- and standard acupuncture entails minimal risk and may have measurable benefits for patients with RP. Further research may find that it might also be useful as a treatment for similar retinal diseases like macular degeneration. For now, it is still an alternative treatment which should be considered carefully by patients and their physicians.
Source: ARVO Presentation 4017: Visual Function Improvements following Electroacupuncture for Retinitis Pigmentosa (Ava K. Bittner1, et al)
A drug called antifactor D has been in trials since 2011, and results are expected in September of this year. It is injected into the eye to block an enzyme called complement factor D. Factor D is thought to be associated with dry AMD by genetic association.
Source: Genentech, Inc.
As usual, we have seen a great deal of effort to find more effective therapies for the wet form of macular degeneration in all of its forms, to include age-related MD, myopic degeneration, and diabetic retinopathy. Here, in no particular order, is a quick run down of most of the studies this past year.
Activation of the Stat3 gene is associated with new blood vessel growth (called neovascularization) and inflammation in the retina. An eye drop of an inhibitor of Stat3, called CLT-005, given to rabbit and rodent animal models, has been shown to reduce neovascularization and also prevent dramatic loss of contrast sensitivity in animals with dry AMD. Future studies may support topical CLT-005 as a stand alone therapy or in conjunction with other treatments.
Source: ARVO Presentation 1716: Eyedrop application of CLT-005, a Stat3 inhibitor, is efficacious in animal models of Wet and Dry Age-related Macular Degeneration (Rafal Farjo1, et al)
A follow up study of Lucentis has shown that the vascular endothelial growth factor, or VEGF, that causes neovascularization was suppressed for 2 months after the initial Lucentis injection in some eyes with AMD. This means that some patients may be able to go as long as two month between injections, rather than the one month originally recommended. (1)
Another study confirmed these results by evaluating the efficacy of bimonthly Lucentis injections. After six months, these researcher also concluded that bimonthly injection may be effective and could be an option. (2)
1. ARVO Presentation 3169: Aqueous Vascular Endothelial Growth Factor and Ranibizumab Concentrations after Monthly and Bimonthly Intravitreal Injections of Ranibizumab for Age-Related Macular Degeneration (Xiying Wang1, et al)
2. ARVO Presentation 3804: The efficacy of bimonthly injection of ranibizumab for age-related macular degeneration for six months (Tomoko Sawada, et al)
One pertinent study was designed to assess the efficacy of retreating proactively or reactively with the anti-VEGF drugs Lucentis or Eylea. In other words, is it better to continue injections on a regular schedule or wait until neovascularization occurs? In the study, a subset of patients lost vision after switching from proactive to reactive treatment with either drug. Since vision lost from nevascularization does not usually return, proactive treatment appeared to result in better visual outcomes than reactive.
Source: ARVO Presentation 3171: Subanalysis of Visual Acuity Outcomes in the Second Year of VIEW Studies (Michaella Goldstein, et al)
We reported here in 2010 that the Oraya IRay radiation therapy system entered trials to demonstrate the safety and effectiveness of radiation therapy for the treatment of wet AMD. The system delivers a robotically controlled dose of low-energy X-ray radiation to the retina. closing leaking vessels and further stopping inflammation. In this study, the procedure was used in conjunction with anti-VEGF injections. Results showed that patients undergoing radiotherapy may experience about a 50% reduction in the need for anti-VEGF injections, and that their visual acuity may also benefit. Eyes with active leaking and without significant scarring (25-50% of the study population) achieved the greatest benefits from the
Phase I trials were completed this past year evaluating another kind of radiation therapy for wet AMD using a novel episcleral brachytherapy device called SMD-1. This easily delivered brachytherapy approach was shown to be safe and tolerable, and it may prove to be an effective therapy alongside anti-VEGF drug injections. Larger phase I/II trials are planned.
Source: ARVO Presentation 3787: Novel Minimally-Invasive Episcleral Brachytherapy for the Treatment of Neovascular Age-Related Macular Degeneration (nAMD): Results of a Twelve Month Prospective Phase I Safety and Tolerability Evaluation (Kamaljit S. Balaggan, et al)
A report in late 2012 suggests that the current practice of injecting anti-VEGF drugs as a treatment for wet AMD may cause vision loss in the long run.
The researchers have shown that vascular endothelial growth factor (VEGF) is important to the health of the cone photoreceptor cells in the macula, and that removing the protein in mice retinas has led to atrophy of those cells.
Anti-VEGF drugs are effective in stopping neovascularization. We have now learned, however, that the drugs might actually be starving healthy cone cells by cutting off their nutrition supply. The researchers stress that this has not been an issue in humans during the seven years the drugs have been on the market, but that long-term safety studies have not yet been completed. In view of their findings, they recommend consideration of methods other than general blocking of VEGF. This is a long term adverse effect that merits further investigation.
Source: Journal of Clinical Investigation., November 2012 (Martin Friedlander, MD PhD, et al. The Scripps Research Institute, La Jolla, California)
The past several years have seen a confusing mixture of study results about the safety of aspirin use by people with AMD. The most recent input comes from Emily Chew, M.D. of the National Eye Institute. She reported in 2012 that, in spite of recent reports, evidence from observational studies and randomized, controlled clinical trials suggest there is no major harmful effect of aspirin use by AMD patients. She said that results from recent studies have shown no increased hemorrhage risk and no harmful association of aspirin with progression of AMD. Furthermore, she supports that aspirin may actually offer significant protection from the development of the disease.
A recent study supported Dr. Chew’s position by finding that aspirin may help to block unwanted blood vessel growth, and that it may not worsen neovascularization in people with wet AMD. (1)
Another new study, however, has concluded that long-term aspirin use may be found to actually enhance new blood vessel growth by increasing vascular density. (2) Past concern about aspirin has focused on the blood thinning issue, but this recent finding suggests that there may yet be more to consider.
Still, most physicians are recommending that, in light of aspirin’s benefit to the cardiovascular system, the best course of action for AMD patients is to consult with their physicians and take aspirin when it is clinically indicated.
1. ARVO Presentation 1715: Effect of Aspirin on human ARPE-19 cells and in Mouse Model of Choroidal Neovascularization (Sunali Goyal, et al)
2. Long-term Use of Aspirin and Age-Related Macular Degeneration. Barbara E. K. Klein, MD, et al. (JAMA. 2012;308(23):2469-2478. doi:10.1001/jama.2012.65406)
In the ongoing debate about which is the better drug for treating wet AMD, Lucentis or off-label Avastin, The National Institutes of Health has reported that, at the end of a 2-year comparison study, both drugs improve 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.
Source: NIH News online at
Scientists at Queen’s University in Kingston Ontario have found that patients who have gotten eye injections with Avastin have been 12 times more likely to develop pain and serious inflammation in the eye than those who have received Lucentis. Their study, After studying medical records of more than 1500 patients, they concluded that significant concern still exists regarding the safety of [Avastin], and that “patients receiving [Avastin] should be counselled regarding a possible increased risk for serious adverse events.”
Source: Rate of serious adverse effects in a series of bevacizumab and ranibizumab injections. Sanjay Sharma, MD, MSc, et al. Canadian Journal of Ophthalmology, June 2012)
A recall notice pertaining to off-label Avastin for wet AMD was posted on March 20, 2013 by the FDA. It applied to people being treated in Georgia, Louisiana, South Carolina, and Indiana. It resulted from contamination at a compounding pharmacy that serves clinics in those areas, where five cases of eye infection were reported. This follows previous contamination issues with Avastin in 2011 that led to stricter controls over the use of compounding pharmacies. It seems that contamination of the drug at the pharmacy level is still a problem calling for closer monitoring.
In August 2012, the FDA recommended Lucentis for treatment of diabetic macular edema (DME). DME is an eye condition in people with diabetes characterized by retinal swelling and blurred vision. It is a major cause of vision loss and blindness estimated to affect more than 560,000 people in the United States. The current standard of care for DME in the U.S. is laser surgery, which primarily serves to slow the progression of vision loss and help stabilize vision. Lucentis was first approved by the FDA for treatment of wet age-related macular degeneration in 2006 and for macular edema following retinal vein occlusion in 2010.
We know that our bodies can sometimes become resistant to long term use of certain drugs. We also know that not all systems react positively to the same drugs. For these reasons, doctors may consider switching from one product to another, and it is useful for them to share reports about how patients will respond.
In one study this past few months, Eylea, the newest drug treatment for wet MD, was been found to be effective in 20 patients who were unresponsive to Lucentis and Avastin.
Source: “The Effect of Eylea (Aflibercept) in Exudative AMD Patients Recalcitrant to Ranibizumab and Bevacizumab”. Vincent S Hau MD, et al. (Published online at
Another study compared increases in intraocular pressure (IOP) from injections of ucentis and Eylea, and found that Eylea patients had a lower incidence of increased IOP than Lucentis patients.
Source: IOP in Patients With Neovascular AMD Receiving Intravitreal Aflibercept or Ranibizumab Injection. K Bailey Freund, et al. (Published online at
Further research assessed the effect of switching from Avastin and/or Lucentis to Eylea in AMD patients. One group found that, on average, 41% had improved visual acuity, and 57% had a decrease in swelling of the retina. (1)
Another group found that, in the first twelve months after switching from Lucentis to Eylea, a patient on Eylea would likely experience more injections than on Lucentis, but there should be a large reduction in monitoring visits. (2)
A third group found that Eylea injections are a prudent alternative to Lucentis and Avastin where a patient has become unresponsive. This retrospective case study suggested that beginning Eylea rescue therapy can resolve blood vessel growth in 25% of eyes previously nonresponsive to the other drugs. The data also showed that 70% of eyes undergoing rescue therapy had maintained or gained acuity following the three rescue injections. Neovascularization, however, is unlikely to stop if it does not do so during the initial three rescue injections. (3)
1. ARVO Presentation 3827: The effects of aflibercept following bevacizumab or ranibizumab on visual acuity and central macular thickness in patients with age-related macular degeneration (Ambar Faridi, et al)
2. ARVO Presentation 3813: Impact of using the aflibercept dosing regimen for wet macular degeneration on numbers of injections and monitoring visits over three years (Niro Narendran, et al)
3. ARVO Presentation 3806: Eylea Rescue Therapy in Eyes with Proven Non-Response to Other anti-VEGF Molecules (Benjamin Guidry, et al)
Some researchers are finding that antibiotics may not be necessary after drug injections into the eyeball. One retinal surgeonreported that, after administering 15,029 injections using an antiseptic, but no topical antibiotic, only one case of infection occurred. The antiseptic Betadine was used in conjunction with all of the treatments.
Source: Eliminating Antibiotic Prophylaxis for Intravitreal Injections: A
Consecutive Series of 15,029 Injections by a Single Surgeon. Abdhish R Bhavsar MD (Published online at
A vitrectomy is a surgical operation that involves removal and replacement of the vitreous gel from the inside of the eyeball. Patients with wet AMD who have undergone vitrectomies have been noted to have a reduced response to anti-VEGF injections. Researchers looked into this and found that such patients do benefit from the treatments, but that the drugs seem to have a shorter half-life in the eye. The researchers concluded that these eyes may require more frequent injections, or more powerful drugs may be needed.
Source: ARVO Presentation 4135: Approach to Previously Vitrectomized Patients with Neovascular Age-Related Macular Degeneration with Reduced Response to Anti-vascular Endothelial Growth Factor Treatment (Mohammad Zubair Y. Arain, et al)
The media has recently reported a new finding about cholesterol and AMD. We have know for years that cholesterol buildup in the retina can lead to inflammation (i.e. wet AMD), and researchers have been working to find ways to treat it. Statin drugs have been considered, but with little success, and now we hear that restoring the function of our macrophage cells may someday be the way to go.
Macrophages are key immune cells that remove cholesterol and fats from tissues. As they begin to malfunction from age, however, excessive cholesterol builds up. These lipid deposits gradually become more numerous in the retina, destroying the macula and leading to loss of central vision.
Researchers speculate that drugs now being used to prevent artherosclerosis might be effective also in preventing wet macular degeneration. They have identified a protein that macrophages use to do their work, and they discovered how they might be able to improve the level of that protein in the aging macrophages. From this they think the drug might also prevent new blood vessel growth and leakage in AMD patients, since inflammation is a direct result of cholesterol buildup.
This is promising research, but macrophage restoration as a treatment for wet AMD is still a few years away.
Source: Apte RS et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metabolism, vol. 17(4), published online April 2, 2013
Myopic macular degeneration is the leading cause of vision impairment from neovascularization in people under 50 years old. Also called pathologic myopia, studies are being conducted to find treatments for the condition other than coagulation of the leaking vessels with a cool laser. This procedure, called photodynamic therapy (PDT), was a standard treatment for wet AMD before the advent of anti-VEGF drug injections in 2006. At least two studies compared PDT with Lucentis during the past year, both finding that. visual function was significantly improved in the subjects receiving Lucentis.
ARVO Presentation 1247: Twelve-month efficacy and safety of ranibizumab 0.5 mg(RBZ) versus verteporfin photodynamic therapy(vPDT) in the treatment of visual impairment(VI) due to choroidal neovascularization(CNV) secondary to pathologic myopia(PM) (Francesco Bandello. Ophthalmology, Univ Vita Salute-Scient Inst San Raffaele, Milan, Italy)
ARVO Presentation 1245: Impact of Ranibizumab on Patient-Reported Visual Functioning in Myopic Choroidal Neovascularization: 3- and 6-Month Results Kyoko Ohno-Matsui, et al)
Anti-VEGF drug injections are now the standard treatment for wet macular degeneration. The leading drugs are Lucentis, Eylea, and off-label Avastin. There is no doubt about their benefit to thousands of AMD patients, but some risks are also being noticed in follow up studies.
One concern has been the effect of blood thinning medication on of such drugs. That concern, however, has been alleviated in at least one study concluding that there was no significant increase in retinal hemorrhaging between patients with wet AMD taking blood thinners and those who were not
Source: ARVO Presentation 6309: Association of Systemic Anticoagulation and Rate of Intraocular Hemorrhage Following Intravitreal Anti-VEGF Therapy for Age-related Macular Degeneration (Joanna Olson, et al)
Another concern is that the blood vessel layer of the retina (the choroid) may grow thinner after multiple injections of anti-VEGF drugs. This is a sign of retinal atrophy, which can result in vision loss.
One study found a decrease in the thickness of the choroid after as few as 3 injections. The subjects already had thinner choroids with an average of 12 prior injections. Over the following 8 months, however, there was no statistically significant change with further treatments.(1)
A second study found reduction over time of thickness of the macula, as well. (2) These are only two of several reports on this issue, and not all of them agree, so further study is needed.
1. ARVO Presentation: Choroidal Thickness following Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration (Charlotte So, Zac Ravage)
2. ARVO Presentation 6265: Retinal and choroidal thickness changes over time in patients with neovascular age-related macular degeneration treated with anti-VEGF (Thais S. Mendes, et al)
A disturbing risk factor has arisen since anti-VEGF treatment began. It appears that some patients with wet MD are developing vision loss after successful regression of the blood vessels. The changes in the retina resemble the atrophy seen in advanced dry macular degeneration (geographic atrophy). (1) (2) Researchers have reported that sight cells appear to be injured in up to 20% of patients after prolonged anti-VEGF injections. (3) They recommend that larger studies be undertaken to determine if this could be a result of the drugs or if it is just part of the natural course of the disease.
1. ARVO Presentation 6284: Cellular Features of Retinal Pigment Epithelial Atrophy after Regression of Choroidal Neovascularization
(Mina M. Chung)
2. ARVO Presentation 6295: The Role of Anti-VEGF Therapy in the Development and Progression of Geographic Atrophy in Patients with Wet Age-Related Macular Degeneration (Justin Shaw, et al)
3. ARVO Presentation 3658: Geographic atrophy risk factors in participants of the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) (Juan E. Grunwald, et al)
According to two reports during the period, scarring of the retina is another concern associated with anti-VEGF treatment, no matter which drug or dosage schedule is used. The risk factors for scarring, which can permanently impair vision, may lead to development of treatments that decrease scarring caused by the damaging vessels.
1. ARVO Presentation 3661: Risk Factors for Scarring in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) (Ebenezer Daniel, et al)
2. ARVO Presentation 3659: Sustained Severe Visual Acuity Loss in the Comparison of AMD Treatments Trials (CATT) (Gui-Shuang Ying, et al)
Three drugs have been recently studied that hold promise as combination therapies for treatment of wet MD.
A new drug called Fovista completed phase 2 clinical trials this past year. Used in combination with an anti-VEGF drug, it blocks pericyte cells that hinder the effectiveness of the drugs. The makers of Fovista reported a 62% higher relative visual benefit when it was used in combination with Lucentis.
Another combination therapy is anti-VEGF injection along with photodynamic therapy (PDT), a low voltage laser applied to an injected drug (verteporfin) that coagulates existing blood vessels. Some patients were found to require no further treatment after this combination treatment, which inspired researchers to test it further. Five reports were found concluding that combining anti-VEGF injections with PDT treatment did result in longger-term closure and control of neovascularization. If proven successful in further research, this procedure could reduce the number of injections required for treatment of wet AMD. (1) (2) (3) (4) Similar good results were reported after this combination was applied to patients affected by a kind of sub-group of wet AMD called polypoidal choroidal vasculopathy (PCV) (5)
1. ARVO Presentation 4509: Long-Term and Lasting Outcomes of Combination Treatment for Age-Related Macular Degeneration with Photodynamic Therapy and Intravitreal Injection of Anti-Vascular Endothelial Growth Factor (Colleen M. McLellan, et al)
2. ARVO Presentation 3790: AURORE STUDY: a french multicenter retrospective study in wet AMD patients treated with Verteporfin PDT plus Ranibizumab in routine clinical practice (Franck Rumen1, et al)
4. ARVO Presentation 3792: Long-term Results of Combination Therapy with Half-time Reduced Fluence Photodynamic Therapy and Intravitreal Ranibizumab for Retinal Angiomatous Proliferation (Hirotaka Yokouchi, et al)
5. ARVO Presentation 3789: Photodynamic therapy, anti-vascular endothelial growth factor therapy, and combination therapy for polypoidal choroidal vasculopathy (Hae Min Kang, et al) _______________________________
Finally, treatment with a non-steroidal anti-inflammatory eye drop called Ketorolac has also been found to increase the effectiveness of Lucentis in treatment of wet AMD.
Source: ARVO Presentation 4175: Prospective randomized controlled trial of combination ranibizumab and ketorolac for wet age-related macular degeneration (Andrea Russo, et al)
Since the advent of anti-VEGF drug treatment in 2006, thousands of people have been able to retain their eyesight. One recent study showed that with strict monthly follow-up and prompt retreatment with Lucentis as needed, good vision can be achieved and maintained for a period as long as four years, with the need for retreatment seeming to decrease significantly after the first 12 months. (1)
2. This kind of response has been a lifesaver for many, but doctors are finding that more than 10% of patients do not respond completely to the treatment. Resistance to the drugs is suspected to account for many of these. In other words, some people may be developing an immunity to the very drug that is intended to help them. Researchers, for example, evaluated the characteristics of eyes with visual acuity loss at a two-year follow-up in patients with wet AMD who were initially treated with Lucentis. The number of patients losing visual acuity increased, especially after 12 months. (2)
3. Realizing that drug resistance might become a serious roadblock to effective treatment for wet MD, researchers are trying to develop ways to identify at-risk patients and to devise alternative methods for helping them. (3)
1. ARVO Presentation 3826: Four year results of visual outcome in Neovascular Age Related Macular Degeneration (AMD) treated with Ranibizumab (Anchal Kailey, et al)
2. ARVO Presentation 3795: Visual acuity loss at a two-year follow-up in patients with exudative age-related macular degeneration treated with ranibizumab and as needed retreatment basis (Takeya Kohno, et al)
3. ARVO Presentation 3170: Detection of anti-ranibizumab antibodies among exudative AMD patients (Nicolas Leveziel, et al)
Regeneron, the company that developed the newest anti-VEGF drug, Eylea, has received the most attention as a potential solution. Five studies found that patients who have developed resistance over time to Lucentis and off-label Avastin, are responding well when switched to Eylea. Those studies are listed here:
ARVO Presentation 6270: Aflibercept (Eylea) Effect on Macula Thickness and Visual Acuity in Exudative AMD Patients Recalcitrant to Ranibizumab and Bevacizumab (Vincent Hau, et al)
ARVO Presentation 4176: Aflibercept Rescue of Bevacizumab- or Ranibizumab-Resistant Choroidal Neovascularization in Age-Related Macular Degeneration (Cheryl A. Arcinue, et al)
ARVO Presentation 3833: Short-term Effectiveness of Intravitreal Aflibercept for Persistent Exudative Age-Related Macular Degeneration (Andrew A. Chang1, et al)
ARVO Presentation 3834: Visual And Anatomical Outcomes Following Intravitreal Aflibercept In Eyes With Recalcitrant Neovascular Age Related Macular Degeneration (Dilraj S. Grewal, et al)
ARVO Presentation 3828: Comparison of the Relative Efficacy of Aflibercept in the Treatment of Neovascular Age Related Macular Degeneration in Patients Previously Treated with Alternative Vascular Endothelial Growth Factor Inhibitors (Khushboo K. Agrawal, et al)
On the other hand, a large comprehensive study found that development of antibodies in patients undergoing Lucentis treatment for up to two years had no significant impact on their response to the drug.
Source: ARVO Presentation 3793: Analysis of 24 month data from the HARBOR study indicates that anti-therapeutic antibodies status had no significant impact on the treatment response to ranibizumab (Gary Sternberg, et al)
And another study concluded that there was no visual benefit seen by changing to Eylea in patients who were unresponsive to Lucentis and/or off-label Avastin
Source: ARVO Presentation 3801: Comparison of outcomes after switching treatment from intravitreal bevacizumab or ranibizumab to aflibercept in neovascular age-related macular degeneration (Frank X. Venzara1, et al)
As a side note, a single study found that switching stabilized patients to Eylea may lead to a temporary loss of visual acuity in some, with most of them recovering and improving after further treatment. This event, the researchers concluded, may or may not be different for those patients who have become resistant to the first drug.
Source: ARVO Presentation 3796: Short-term vision changes after switch to aflibercept therapy for age-related macular degeneration previously treated with other antiVEGF agents (Irene A. Barbazetto, et al)
Another attempt at solving the drug resistance problem has been to switch to either of the other anti-VEGF drugs. The results suggested that doing so may provide short-term benefits. (1)
Researchers have even suggested that alternating drugs, specifically Lucentis and Avastin, bi-weekly might be an answer. Their study showed this regimen to show significant improvement in so-called recalcitrant patients. (2)
1. ARVO Presentation 3823: Effect of anti-VEGF medication change on central macular thickness and visual acuity in patients with neovascular age-related macular degeneration (John P. Campbell, et al)
2. ARVO Presentation 3811: The Efficacy Of Biweekly Alternating Intravitreal Bevacizumab And Ranibizumab In Recalcitrant Choroidal Neovascularization Secondary To Age-Related Macular Degeneration (Radha Ram, et al)
Eye infection (endophthalmitis) from the injection protocol has also been a concern since the advent of anti-VEGF drug treatment. Recent research, however, has found that the incidence has been low, and that post-injection antibiotic drops do not appear to significantly reduce the risk of developing infection. If infection does occur, it can be easily treated with topical steroids, and in most cases, the condition will not result in vision loss. Patients should be cautioned to be vigilant about any evidence of infection for 24 hours after an injection, and to report any such evidence to their physician.
ARVO Presentation 1118: Meta-Analysis of Infectious Endophthalmitis After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor Agents (John Fileta, et al)
ARVO Presentation 1114: Incidence of Endophthalmitis after Anti-VEGF Injections and use of Anti-Microbials in the Comparison of AMD Treatments Trials (CATT) (Colin A. McCannel1, et al)
ARVO Presentation 1113: The role of antibiotic prophylaxis to prevent post-injection endophthalmitis (Philip P. Storey, et al)
ARVO Presentation 1104: The Incidence of Noninfectious Intraocular Inflammation after Intravitreal Aflibercept Injection (Kunjal K. Modi, et al)
One exciting potential therapy for macular degeneration and myopic degeneration is stem cell therapy. This involves transplanting stem cell-derived retinal tissue to replace dysfunctional tissue and maintain photoreceptor function. In trials so far, the procedure has been shown to be safe, and there has even been some success in restoring vision.
In July, Advanced Cell Technology, Inc. (ACT) treated the tenth and final patient in their Phase 1/2 clinical trial at Moorfields Eye Hospital in London. The outpatient transplant surgery was performed successfully without any complications, and the patient was reported to be recovering uneventfully. The company said that improvements in visual acuity initially reported had persisted for a year, and preliminary results indicated that the research is on the right track.
In February of this year, ACT that they had gained approval from the FDA to begin safety trials to evaluate the safety and tolerability of embryonic stem cell replacement in people with severe myopia. This refers specifically to degenerative myopia (aka “myopic
macular degeneration”), offering hope for people who have lost vision to this condition.
ACT press release:
Scientists are continuing to search for sources of stem cells that replicate the power of embryonic cells without confronting the ethical issues that have arisen. Two new sources have shown potential this past year, to include the skin of the patients themselves and human breast tissue.
“Stem cell trial to treat eye disease” by Simeon Bennett (San Francisco Chronicle, October 9, 2012)
“New Type of Pluripotent Cell Discovered In Adult Breast Tissue” by Elizabeth Fernandez (published online March 04, 2013 at
Researchers from the Miller School of Medicine have collaborated with an international team to locate more genes associated with AMD. So far, they have identified new locations near seven different genes. For a list of previously discovered genes associated with AMD, see Genetics Home Reference on the web site of the National Institutes of Health (NIH). More information about specific gene discoveries may also be found online in the MD Support Library.
Source: “Seven New Loci Associated with Age-Related Macular Degeneration,” (published online, in Nature Genetics, March 3, 2013)
Genetics is a fascinating science that can help identify pathologies of inherited diseases like AMD. By identifying the altered genes and replacing them, we could theoretically cure every condition. But it’s not as simple as it sounds, and the technology is not yet in place. And that’s why the American Academy of Ophthalmology (AAO) recommends that eye physicians and surgeons avoid genetic testing at this time for complex eye disorders until treatment or surveillance strategies can be shown to be of benefit.
Reporting to the AAO members at their annual meeting in 2012, Dr. Edwin Stone said current genetic tests for AMD are flawed and cannot reliably help predict clinical outcomes. Until such time as genetic testing becomes more reliable, he said, “combining a patient’s family history of eye disease with a standard eye exam will remain the best way to determine his or her risk for AMD.”
Source: Edwin Stone, MD. AAO presentation (Chicago, July 2012)
Hundreds of low vision devices are now on the market, with the quality of imaging and audio improving at enormous speed. The biggest news this past year, was approval in the United States of a retinal prosthesis that is allowing people with severe vision loss to see again. In September, the FDA Ophthalmic Devices Advisory Panel recommended market approval for Second Sight’s Argus II Retinal Prosthesis System.
The system converts video images captured by a miniature camera, housed in the patient’s glasses, into a series of small electrical pulses. These pulses are transmitted wirelessly to an array of microchips to stimulate the retina’s remaining cells resulting in perceptions of patterns of light in the brain. The resulting image is a simple pixelation of light and dark, but it is providing basic sight to patients who have had no light perception at all.
The Argus II received CE Mark approval in Europe last year, and on February 14 of this year, the FDA unanimously approved it for people who have lost significant vision from retinitis pigmentosa. As the technology advances, the system may someday be useful also for people with degenerative diseases of the macula.
Curcumin is found in the popular Indian spice turmeric. Scientists have learned from a study of rodents that curcumin can suppress neovascularization. Curcumin supplementation, therefore, and by extension, tumeric, is now being considered as a potential therapy for wet AMD.
Source: ARVO Presentation 1242: Suppression of experimental choroidal neovascularization by curcumin in mice (Ping Xie, et al)
A study published July 29, 2012 in American Journal of Epidemiology has concluded that drinking more than 20 g of alcohol per day was associated with an approximate 20% increase in the odds of early AMD when compared with those who reported no alcohol intake at baseline. A typical glass of wine contains about 15 g. The positive association, drawn by researchers at the Centre for Eye Research Australia, was apparent for wine, beer, and spirits.
This is interesting in light of previous research showing red wine to be beneficial to the retina for its antioxidant properties. It is not, however, the alcohol content that provides this benefit, so, as substantiated by these new findings, one glass per day should be the limit.
Researchers identified why, in addition to central field loss, adults with AMD have trouble recognizing and identifying people’s faces. They believe that it could largely be due to abnormal eye movement patterns and fixations associated with the condition.
The study found that AMD patients made more frequent eye movements compared to those with healthy vision. They believe it could have a lot to do with the way the brain coordinates eye movement. And that gives hope that eye movement control training and training of allocation of attention could improve face perception and eye scanning behavior in individuals with AMD.
Source: Optometry and Vision Science (January 2012)
A new Northwestern Medicine study shows that senior citizens are reporting fewer visual impairment problems than their counterparts from a generation ago. The researchers said that “improved techniques for cataract surgery and a reduction in the prevalence of macular degeneration may be the driving forces behind this change”.
From 1984 until 2010, the decrease in visual impairment in those 65 and older was highly statistically significant, while there was little change in visual impairments in adults under the age of 65. The study showed that in 1984, 23 percent of elderly adults had difficulty reading or seeing newspaper print because of poor eyesight. By 2010, there was an age-adjusted 58 percent decrease in this kind of visual impairment, with only 9.7 percent of elderly reporting the problem.
The researchers also reported a substantial decline in eyesight problems that limited elderly Americans from taking part in daily activities, such as bathing, dressing or getting around inside or outside of the home. They credited three likely reasons for the decline:

  • Improved techniques and outcomes for cataract surgery
  • Less smoking, resulting in a drop in the prevalence of macular degeneration
  • Treatments for diabetic eye diseases are more readily available and improved, despite the fact that the prevalence of diabetes has increased

Future studies should identify which treatment strategies help prevent vision in older adults and then make those treatments available to as many people as possible.
This concludes my summary for this year. I hope it will leave you with confidence in our future and the future of those who are following us. Please pass this information along to them. And if you don’t remember the details of the overwhelming amount of research being done (and who could?), just tell them things are getting better at an ever-quickening pace, thanks to the unceasing dedication of researchers and developers around the world..
Our hope lies with them and in the doctors who make the therapies and treatments available to us. We thank them for that, and I thank you for listening.

Aspirin and AMD

by Dan Roberts
Updated 12/19/12
This is an attempt to shed some light on the issue of aspirin and macular degeneration.
In the spring of 2005, a large study introduced some interesting new information about aspirin. The study was done using 39,876 women over a 10-year period in order to clarify the suspected differences between men and women in the way that aspirin affects the system.
To translate and summarize the conclusions of the study, 100 mg of aspirin every other day . . .

  • lowers the risk of stroke in women, but not in men
  • reduces the risk of cardiovascular problems in men, but not in women, EXCEPT women age 65 and older. (Information about men was not derived from this study, but from 5 other studies referenced)
  • has a greater benefit for people who don’t smoke
  • increases the risk of gastrointestinal hemorrhages (i.e. gastrointestinal bleeding and peptic ulcer) in women age 65 and older

The authors conclude by saying, “…any decision about the use of aspirin in primary prevention … must ultimately be made after [consulting a] physician or health care provider, so that the net absolute benefits and risks for the individual patient can be ascertained.” Here is the study, for those who wish to learn more:
Ridker, P.M., et al. “Low-dose aspirin in the primary prevention of cardiovascular disease in women.” (The New England Journal of Medicine. Vol 352 (March 31) Pgs 1293-1304. 2005. Read the original paper.
An earlier study that shed light on aspirin use in connection with AMD concluded that “therapy with … aspirin is associated with decreased rates of CNV [choroidal neovascularization] among AMD patients.” That study is:
“Statin and aspirin therapy are associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration.” (Wilson HL, Schwartz DM, Bhatt HR, McCulloch CE, Duncan JL. Department of Ophthalmology, UCSF School of Medicine, San Francisco, CA 94143, USA.)
This connection is made, because AMD has been shown to have causes in common with cardiovascular disease. In other words, treat the cardiovascular problem with aspirin, and you might also be helping to prevent AMD. Here is that study:
“Do age-related macular degeneration and cardiovascular disease share common antecedents?” (KK Snow, JM Seddon – Ophthalmic Epidemiology, 1999 –
Inflammation is now thought to be one of those commonalities, and we all know that aspirin is a good anti-inflammatory.
That having been said, here is a more recent conflicting study (Ref: AAO Annual Meeting: Abstract 1620, May 3, 2010) 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.
These 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.”
A 2012 report, “Long-term Use of Aspirin and Age-Related Macular Degeneration” by Barbara E. K. Klein, MD et al (JAMA. 2012;308(23):2469-2478. doi:10.1001/jama.2012.65406) concluded that “Among an adult cohort, aspirin use 5 years prior to observed incidence was not associated with incident early or late AMD. However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular AMD.” These results were derived from a 14.8 year followup of subjects in the Beaver Dam Eye Study.
It was reported here in November 2012 that Emily Chew, M.D. (deputy director, Division of Epidemiology and Clinical Applications, National Eye Institute) reported to Retina 2012 that evidence suggests there is no major harmful effect of aspirin use by AMD patients. Furthermore, she supported the opinion that aspirin may actually offer significant protection from the development of the disease.
The findings of the recent research by Dr. Klein et al, however, suggest that the mechanisms underlying the association of aspirin with late AMD may be different from its blood thinning properties. It might even be found to enhance new blood vessel growth, since it has been found in lab studies to increase vascular density. Dr. Chew based her comments on the blood thinning issue, but the recent findings suggest there may be more to to consider.
Dr. Chew recommends that, in light of aspirin’s benefit to the cardiovascular system, the best course of action for AMD patients is to consult with their physicians and take aspirin when it is clinically indicated. Until the results of this new research are substantiated by more studies, that is still good advice.

Summary of Research and Developments in Macular Degeneration, 2011-2012

by Dan Roberts
June 2012
Here is MD Support’s summary of the the past twelve months of significant research and development in the field of macular degeneration.
We begin with the field that has been making the most news: pharmacology.
SEP: Infection Risk From Repackaged Avastin
The big pharmaceutical news of the year surrounded anti-VEGF drugs for treatment of wet AMD. Anti-VEGF drugs are injected into the eyeball to halt the growth and leakage of blood vessels into the retina that can lead to quick central vision loss. The leading approved drugs are Lucentis and Eylea, while a similar drug, Avastin, is being used off-label for the same purpose at a much lower cost. Repackaging by a pharmacy, however, is required to prepare Avastin for injection at proper dosages.
In September, the FDA alerted the public that repackaged intravitreal injections of off-label Avastin caused a cluster of strep infections in twelve patients in Florida, where investigators traced the tainted drug to a single pharmacy. Soon after, contamination was also reported in Tennessee and California. This is a risk that Genentech, the maker of the drug, warned about when doctors began using the cancer drug Avastin in place of their approved drug, Lucentis.
Reacting quickly to the reports of infection, the Department of Veterans Affairs (VA) ceased using Avastin to treat wet AMD until it could investigate the problem. Then, in November, the VA announced the reinstatement of Avastin on three conditions: 1) that the physician use only one dose per patient from each manufacturer’s vial, 2) that patients be carefully screened before receiving treatment, and 3) that patients be fully informed of the health risks associated with off-label therapy.
Many patients contacted MD Support asking what they should do to ensure their safety. Our recommendation was to learn about the benefits and risks of all three available treatments, and then decide which is better in the patient’s individual case. It is the doctor’s obligation to ensure that the patient has a full understanding before agreeing to receivng Avastin off-label.
Ophthalmic use of Avastin has recently been shown to be generally as safe and effective as Lucentis. Since, however, both the Food an Drug Administration and the Center for Disease Control have established clear warnings and specific guidelines about repackaging drugs, and since those guidelines are generally being ignored in the use of off-label Avastin, a patient’s safest option is to stick with proven drugs that don’t require compounding by a second party. In his article, “The Misuse of Compounding By Pharmacists”, Bruce A. Bouts, MD recommends that our best practice would be to:
1. Avoid compounded agents when sterility is important (e.g., injectable or inhalation agents).
2. Avoid a compounded product when a generic or brand-name agent is readily available.
NOVEMBER: New Anti-VEGF Drug Approved
In November, our attention was drawn to FDA approval of the newest anti-VEGF drug, Eylea, as a treatment for wet AMD. In trials, Eylea injected into the eye every two months was found to be as effective as monthly doses of Lucentis. The most striking improvement is that monthly monitoring of patients receiving Eylea is not necessary. The longer time between injections (up to two months) helps relieve some of the treatment and cost burden of other anti-VEGF drugs.
This would seem to give Regeneron (the company that makes Eylea) the edge over Genentech, makers of Lucentis. And it did indeed take over a large share of the market within only a few months. Genentech and its European counterpart, Novartis, however, are remaining big players by working toward first approval of Lucentis for use in treatment of diabetic macular edema.
Another development from Genentech may soon be sustained long-term delivery of Lucentis via an implanted ocular device. This would replace the current procedure of periodically injecting the drug into the eyeball.
The device can be implanted into the eye in a 15 minute out-patient procedure. The implant can hold and release four months worth of Lucentis, and it can be resupplied through a permanent opening where it attaches to the sclera (the white outer shell of the eyeball). About 100 implants have been accomplished to date, and the results are consistent with the traditional injection procedure. According to Genentech, The patient would not be aware of the device, and it can be seen only upon examination through the dilated pupil. Trials are expected to begin soon, with clinical use possible in as little as two years.
MAY: MC-1101 for Dry AMD
In May of this year, a topically administered eye drop drug called MC-1101 was introduced as a potential for treating and stopping the progression of AMD from the dry form to the wet form. The drug, being tested by MacuCLEAR, Inc., works by increasing ocular blood flow in the choroidal vessels.
The company has completed a successful Phase 1 human clinical trial for MC-1101 which showed that the drug is safe and well tolerated. The next phase of the study will track visual improvement in 60 patients, with the hope that a treatment for dry AMD will soon make it to the clinics.
But now some disappointing news. Fenretinide, a drug that has been used to treat certain cancers, rheumatoid arthritis, acne, and psoriasis, was found several years ago to slow the production and accumulation of a toxin that leads to vision loss in a juenile form of macular degeneration called Stargardt disease. Trials showed that the drug also reduced the incidence of choroidal neovascularization by about 50 percent in patients with dry AMD.
This was promising news worth following, but the developer, Sirion Therapeutics, announced in February that the trials had been suspended. The FDA ruled that the Phase 2 results were flawed, and, at this point, the high cost of continuing the trials has halted further research.
NOV: Implantable Miniature Telescope
In the field of surgery this past year, we heard about approval of the implantable miniature telesope, ongoing stem cell research, and an interesting development in treatment for cataracts.
You may remember that the implantable miniature telescope (IMT) was approved by the FDA back in July 2010 for use as a prosthetic device in the eye. Then, in September 2011, VisionCare Ophthalmic Technologies, Inc. announced that outpatient facilities could obtain Medicare and Medicaid reimbursement for the procedure. Two months later, the company announced that the first patient had received the device.
The pea-sized telescope implant is designed to improve visual acuity. Eligible patients must have central vision blindness and have either stopped responding to AMD medications or have a form of the disease for which no treatment is available. The magnification provided by the implant reduces the impact of the blind spot caused by end-stage AMD. Patients and physicians can find more information about the IMT at
JAN: Stem Cell Study
Another bit of good news came in January of this year from Advanced Cell Technology, when the company reported the first use of human embryonic stem cells to treat macular degeneration in human beings.
The study began with one elderly patient and one young patient with different forms of macular degeneration that had led to severe vision loss. The transplants appeared safe after four months, and both patients had some improvement in vision. The future therapeutic goal will be to treat patients earlier in the disease process, in order to boost the prospects of improving or retaining sight in new patients.
The authors say that, in patients who begin with poor vision, it is difficult to ascertain definite improvements in vision unless such improvements are spectacular. While neither patient lost vision, some standard tests suggested vision had improved in both. The younger patient with Stargardt’s disease went from being able to see only hand movements at first to being able to see single finger movements.
The study is expected to continue into 2014, beginning with 12 patients and eventually including a much larger population. Clinical trial sites have been established so far at Jules Stein Eye Institute in Los Angeles, Wills Eye Institute in Philadelphia, Bascom Palmer Eye Institute in Miami, and Massachusetts Eye and Ear Infirmary in Boston.
FEB: Radiation Therapy
Five years ago, NeoVista, Inc. began trials to study the effects of radiation therapy in combination with Lucentis injection for treatment of wet AMD. The therapy was intended to complement the drug injection by extending the time between treatments. Unfortunately, the company reported in February that Phase III of the study did not meet it’s primary endpoint at two years, becoming the second major trial to fall by the wayside this past year.
FEB: HuCNS Cells
Returning to a more positive note, we heard good news in February about stem cell research from StemCells, Inc. They announced that the FDA authorized a trial of a new method using stem cells from the brain to prevent degeneration of the macula in dry AMD patients.
Purified human neural (HuCNS) stem cells will be administered by a single injection into the space beneath the retina. Patients’ vision will be evaluated over a one-year period, then followed for an additional four years in a separate observational study.
Preclinical data submitted by the Company demonstrated that the stem cell transplants significantly protect against the degeneration of the existing sight cells. Moreover, the number of cone cells (which are responsible for central vision) remains constant over an extended period. This approach is expected to offer a safe, effective and simple treatment that differs from approaches that aim to replace the sight cells.
APR: Cataract Surgery and Alzheimer’s
Our final report in the surgery department comes from a study showing that cataract surgery can relieve Alzheimer’s symptoms in some people.
As reported by the researchers in April, one in four patients showed improvements in thinking and memory skills after replacement with a clear lens. Many also showed an easing of symptoms of depression, and most of the participants also slept better after the surgery. They did not show improvements in day-to-day functioning, but all-in-all, that’s not bad, considering they could do all that and see better, too.
NOV: Vitamins and Aspirin
Moving on to developments in the field of eye health and nutrition, two studies published last year caused some concern in the low vision community about possible harm from vitamins and aspirin. We may be worrying more than necessary, however, due to the way the study results were reported.
One study concluded that “several commonly used dietary vitamin and mineral supplements may be associated with increased total mortality”. The other study revealed that frequent aspirin use is associated with early AMD and wet late AMD.
Both of these studies have three things in common: 1) use of terms like “associated”, 2) the absence of cause and effect in the study designs, and 3) media distortion of the facts.
We must remember that a certain intervention “may be associated” with macular degeneration, but it does not necessarily cause the disease or its progression. For example, a person may be taking regular dosages of aspirin to alleviate a cardiovascular problem. At the same time, that person may have macular degeneration caused by the same inflammatory response responsible for the cardiovascular condition. There would, therefore, appear to be an association between aspirin and macular degeneration.
The researchers are aware of this, which is why they have not said conclusively that either vitamins or aspirin are going to harm us. They simply say that an association has been found and that further study is necessary before making such claims. It is the media that often carries it to that next step. We must, therefore, think twice about such reports and consult with professionals before changing our course of treatment.
Since 2006, the National Institutes of Health (NIH) have been conducting a nationwide study to see if a modified combination of vitamins, minerals, and fish oil can further slow the progression of vision loss from AMD.
This new study, called the Age-Related Eye Disease Study 2 (AREDS2), builds upon results from the first AREDS research. That study, completed in 2001, found that high-doses of vitamins C and E, beta-carotene, zinc, and copper, taken by mouth, reduced the risk of progression to advanced AMD by 25 percent, and lowered the risk of moderate vision loss by 19 percent.
AREDS2 will refine the findings of the original study by adding the antioxidants lutein and zeaxanthin and the omega-3 fatty acids DHA and EPA to the formulation. The main objective is to determine if these nutrients will also help decrease a person’s risk of progression to advanced AMD. Previous observational studies have suggested that these nutrients may protect vision.
In addition to including these nutrients, the study is also looking at eliminating beta-carotene from the original formula, due to findings that it may be a risk for cancer in some people, and it is decreasing the amount of zinc. Findings from the study are expected in 2013, but manufacturers are already making the AREDS2 formula available based upon a preponderance of evidence in its favor.
In the area of gene replacement research, three events caught our attention during the past twelve months. We learned in November that investigators had identified a rare, high-risk mutation resulting in a loss of function of an important protein called Complement Factor H (CFH). CFH helps control the body’s immune response and inflammation, and mutation of this protein has been suspected for several years to be a cause of AMD in as many as 50% of cases. Now a newly-discovered mutation, more clearly links the CFH gene dysfunction to the disease and may lead to new and effective preventative treatments for high risk individuals.
APR: AVA-101
In April, we heard about a single injection of a new gene therapy treatment from Avalanche Biotech that could possibly stop blood vessel growth and leakage in the wet form of AMD for several years. An injection of a drug called AVA-101 creates a kind of BioFactory that continuously secretes a therapeutic protein over an extended period. This avoids the need for frequent injections, as is now the practice.
Based on preclinical studies, the therapeutic effect will be maintained for at least 18 months and has the potential to last for several years. Human clinical trials are currently underway.
MAY: IL-18
In May, a new finding made the news as yet another possible treatment for wet AMD. Inflammation in the retina results from blood vessel development, and the natural component named IL-18 has been found to keep the process under control. By injecting the chemical into the eye, or by injecting a gene that produces IL-18, the scientists are speculating that they can keep dry AMD from developing into wet AMD. In other words, it would be a preventative treatment, similar to a vaccination.
This discovery was the first step in a long road to clinical application. It must first be tested in animals, then go through human clinical trials, so we are looking at about 10 years of intensive lab work and fund raising. If results from other treatment experiments underway don’t come sooner, at least this offers another reason for hope.
New Vision Enhancement System
And finally, technology continues to make strides. One development is a new vision enhancement system that may one day provide something like sight for people who are blind or extremely visually impaired. The system is being developed as a result of military-related trauma research.
It involves computer technology, a cell phone, an auditory feedback device, and an eyeglass-mounted camera to capture objects in the user’s visual field. Information about the visual field is conveyed to the user wirelessly to assist in finding objects or avoiding hazards.
Developers say that, though the technology focuses on military vision trauma, it could also be used by people with age-related and other forms of macular degeneration.
And, of course, 2012 has brought the latest generation of the Apple iPad to market. The iPad3 has a higher screen resolution than the iPad2, a better camera, and stronger wi-fi (at extra cost). Other than that, it is essentially the same as it’s older brother, and the changes may be too negligible for you to upgrade. On the other hand, if you don’t already own an iPad, you can find really good deals on the older models for less than $350. Considering all of its accessible features for low vision people, it might be worth looking into.
Another exciting technological development is the self-driving automobile. It has been road tested now for thousands of miles, and it looks like it will actually become a reality in a few years. In case you think you couldn’t afford one (and how many people could?), don’t worry. They are being seriously considered for use as taxis, so they will be available to all of us. And we won’t have to talk to them about the weather, or why they drove a mile out of our way to get us to the grocery store on the next block. Just pick up a phone, say “pick me up”, and it will come right to your front door.
This kind of thing, along with vision restoration and cures, could conceivably become realities in our lifetimes. We are hearing about an ever-increasing number of such achievements in the areas of surgery, nutrition, pharmacology, and technology. We have also witnessed some failures, but failure often leads to better knowledge.
And remember, we are not only patients. We are also in a position to teach those who follow us. Please take every opportunity to pass along this information to family members and friends. And if they want to keep up through the year, invite them to join one of our live support groups, or tell them about our website at
Here’s to another year of promising work on behalf of our low vision community.

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

by Dan Roberts
June 10, 2010
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.
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)
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.
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)
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.
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)
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.
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.
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.”
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:
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)
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)
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)
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)
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.
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.
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.
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.
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)
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.
Lucentis (ranibizumab)
Avastin (bevacizumab)
Verteporfin PDT (in combination)
Tryptophanyl-tRNA synthetase (TrpRS)
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:
Fenretinide (ST-602)
Iluvian (fluocinolone acetonide)
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.
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.
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.
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.
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.
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!