Researchers examining data from the National Health and Nutrition Examination Survey (NHANES) report that the prevalence of age-related macular degeneration (AMD) is declining in the United States.

The NHANES program, part of the Centers for Disease Control, began in the early 1960s and conducts a series of surveys focusing on different population groups or health topics. The survey examines a nationally representative sample of about 5,000 persons each year.

Eye health was assessed by NHANES between the years 2005 and 2008. Previously, eye health was included in NHANES between the years 1988-1994. This makes it possible to compare findings from the 1988-1994 surveys with the more recent surveys and to then draw conclusions about changes in eye health over that roughly 15 year period.

Using data from the 2005-2008 NHANES, the researchers determined that the total prevalence of AMD in the United States is 6.5%, which is 30.8% lower than the 9.4% prevalence rate reported in NHANES from 1988 to 1994.

The researchers, writing in the January edition of Archives of Ophthalmology, state that this may reflect changes in smoking behavior, diet, physical activity, and blood pressure control, each of which has been associated with AMD risk.

These data, and those reported below from the Women's Health Initiative Observational Study, provide convincing evidence that lifestyle plays a major role in the development of AMD. This, I believe, represents a major victory in the fight against AMD.

While we cannot change our genetic predisposition to certain diseases, we can make healthy lifestyle choices. And when it comes to AMD, these choices appear to make a very big difference.

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Selective retina therapy (SRT) speeds recovery of acute central serous chorioretinopathy (CSC), according to a new study.

Selective retina therapy (SRT) is a new laser procedure for retinal diseases thought to be associated with an abnormality of the retinal pigment epithelium (RPE). The aim of the therapy is to selectively damage the RPE without affecting the surrounding retina and choroid. Goal is to stimulate RPE cell migration and proliferation and hence improve RPE metabolism at the diseased sites. Previous research found SRT was not effective for dry AMD. A related technique, subthreshold diode micropulse laser treatment, has been used effectively for CSC and diabetic macular edema.

Thirty eyes of 30 patients with CSC of at least a 3 months' duration were recruited. 14 eyes were randomized to an SRT group and 16 eyes to a control group. After 3 months of follow-up, patients in the control group with persistence of subretinal fluid (SRF) were allocated to a cross-over group, treated with SRT and followed up for a further 3 months.

At 3 months of follow-up, the average improvement of BCVA was significantly greater after SRT than in the control group: 12.7 versus 6.3 letters. SRF had decreased significantly more after SRT as compared with the control group: 203 µm versus 41 µm. In eight eyes allocated to the cross-over group, the mean BCVA had increased during 3 months of follow up before SRT by 1.4 letters and continued to increase during 3 months following SRT by 7.4 letters, while SRF increased by 39.5 µm before SRT and decreased by 151.5 µm after SRT.

The researchers conclude that SRT appears to expedite functional recovery and the re-absorption of SRF as compared with that in untreated controls.

WHAT IT MEANS TO YOU: The search continues for a safe and effective means of speeding the resolution of acute CSC. Because most cases of acute CSC will resolve fully without intervention, it is imperative that any treatment that is undertaken have a very low risk of adverse effects. Safety-enhanced photodynamic therapy is currently the most appealing of the available treatment options for acute CSC, but is still far from ideal. Newer laser procedures such as subthreshold diode micropulse and now selective retina therapy offer very promising possibilities.

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Modifying diet, smoking, and physical activity may reduce the risk of AMD as much as 3-fold, according to a new study.

This research studied 1313 women aged 55-74 years in the Women's Health Initiative Observational Study. Scores on a food frequency questionnaire were analyzed. Physical activity and lifetime smoking history were also queried. Stereoscopic fundus photographs were taken to assess the presence and severity of AMD; it was present in 202 women, 94% of whom had early AMD, the primary outcome.

In multivariate models, women whose diets scored in the highest quintile compared with the lowest quintile on the modified 2005 Healthy Eating Index had 46% lower odds for early AMD.

Women in the highest quintile compared with those in the lowest quintile for physical activity (in metabolic energy task hours per week) had 54% lower odds for early AMD.

Although smoking was not independently associated with AMD on its own, having a combination of 3 healthy behaviors (healthy diet, physical activity, and not smoking) was associated with 71% lower odds for AMD compared with having high-risk scores.

The investigators conclude that modifying lifestyles might reduce risk for early AMD as much as 3-fold, lowering the risk for advanced AMD in a person's lifetime and the social and economic costs of AMD to society.

WHAT IT MEANS TO YOU: Smoking is the behavior that most strongly and consistently associated with AMD. The fact that this study did not find smoking to be independently associated with AMD makes me approach their other results with caution. Is it possible that smoking does not increase the risk of AMD in women, but only in men? I am not aware of any study that would support that hypothesis. Despite the curious smoking results, the other major findings, that a healthy diet and regular exercise can reduce the risk of AMD, are significant. The large positive benefit of both diet and exercise send a strong message that a healthy lifestyle can play a large role in preventing the development of AMD.

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Prophylactic use of intraocular pressure (IOP)-lowering medication is ineffective in reducing the IOP spikes that often occur after intravitreal injections of Macugen (pegaptanib), Avastin (bevacizumab), and Lucentis (ranibizumab), according to a recent study.

Seventy-one patients with exudative AMD received intravitreal injections of 1 of 3 anti-VEGF medications: 30 patients received Macugen (0.09 mL), 47 patients received Avastin (0.05 mL), and 42 patients received Lucentis (0.05 mL). Glaucoma medication, 1 hour prior to the injection, was used 63%, 74%, and 66% of the time in eyes that received Macugen, Lucentis, and Avastin, respectively. Intraocular pressure was measured prior to injection, within 1 minute after injection, and every 5 to 10 minutes until the pressure was reduced to a safe level.

All 3 intravitreal injections caused significant initial IOP spikes (mean IOP of 38.5 mm Hg in the Macugen group, 37.75 mm Hg in the Lucentis group, and 34.88 mm Hg in the Avastin group). The IOP reduced to less than 30 mm Hg in all 3 groups within 20 minutes. Prophylactic medication did not prevent post-injection IOP spikes. Patients with and without glaucoma showed a similar rate of IOP normalization over time in all 3 groups.

The researchers conclude that intraocular pressure spikes after intravitreal injection of Macugen, Lucentis, and Avastin are common and in most cases transient. Routine prophylactic use of IOP-lowering medications is essentially ineffective in preventing IOP spikes after intravitreal injection of Macugen, Lucentis, and Avastin and therefore not necessary before the injection.

WHAT IT MEANS TO YOU: Very high IOP following intravitreal injection is a common and serious problem. Even transient pressure spikes can cause serious damage to the eye, and the risk is compounded by the necessity for repeated monthly injections. When a patient's IOP shoots up very high following an injection, fluid can be removed from the eye to rapidly return the pressure to normal, a procedure known as paracentesis. However, this necessitates another injection and all the risk, discomfort and inconvenience that entails. Some doctors have tried to decrease the necessity for post-injection paracentesis by giving the patient some glaucoma eye drops before the procedure. This study clearly demonstrates the ineffectiveness of this approach.

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Intravitreal injections of Lucentis (ranibizumab) given every 90 days results in visual outcomes that are inferior to those achieved when the injections are given every 30 days, according to results reported by the EXCITE study.

The EXCITE study was a Phase IIIb, multicenter, active-controlled, double-masked clinical trial in which patients were randomized to 3-monthly loading doses of 0.3 or 0.5 mg Lucentis followed by quarterly injections or 0.3 mg monthly injections through 12 months follow-up.

In this study 120 patients received 0.3 mg quarterly (after 3 initial monthly doses of 0.3 mg), 118 patients received 0.5 mg quarterly (after 3 initial monthly doses of 0.5 mg), and 115 patients received 0.3 mg monthly. Everyone enrolled in the EXCITE study had AMD with subfoveal choroidal neovascularization (CNV).

At the end of the study, the mean best-corrected visual acuity (BCVA) improvement was 4.9 letters with 0.3 mg/quarter, 3.8 letters with 0.5 mg/quarter -- and 8.3 letters with 0.3 mg/month.

From baseline to month three (when all the groups were getting monthly injections), the increases were 6.8, 6.6, and 7.5 letters, respectively. But from month three to month 12, mean BCVA fell in both quarterly groups, while the monthly group had a mean increase of 0.8 letters.

Although the proportion of patients who lost fewer than15 letters during the study was similar across the treatment groups, more patients gained at least 15 letters with 0.3 mg/month (28.7%) than with 0.3 mg/quarter (14.2%) or 0.5 mg/quarter (17.8%).

The investigators conclude that after 1 year of treatment, BCVA gain in the monthly regimen was higher than that of the quarterly regimens.

WHAT IT MEANS TO YOU: EXCITE was one of the major clinical trials designed specifically to determine whether quarterly injections of Lucentis was as effective as monthly treatment. To date, every study that has looked at this question has found that anything less than monthly injections will produce vision outcomes that are below those that can be achieved with monthly treatment. This is a major drawback of Lucentis therapy. New drugs in the pipeline, such as VEGF-Trap, are more potent than Lucentis and will hopefully permit less frequent injections without sacrificing vision.

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Cataract and cataract surgery are not associated with AMD, according to new data from the Beijing Eye Study.

The population-based Beijing Eye Study included 4,439 subjects (age: 40+ years). Using photographs, the amount of AMD and cataract were assessed using standardized grading systems. Photographs with sufficient quality were available for 3,826 (86.2%) participants with a mean age of 55.3 years (range: 40-90 years).

The asymmetry (side difference) in presence of macular drusen, early AMD and late AMD was not significantly associated with the inter-eye difference in the presence or amount of cataract.

As a corollary, unilateral pseudophakia or aphakia was not significantly associated with inter-eye differences in the number of drusen, and overall presence of early or late AMD.

The researchers conclude that inter-eye difference in any characteristics of AMD was not significantly associated with either any type of cataract or in pseudophakia. This suggests that the development of cataract or cataract surgery did not markedly influence the development of AMD.

WHAT IT MEANS TO YOU: There is continuing controversy regarding what, if any, risk cataract surgery conveys toward the development of AMD. The concern regarding cataract surgery stems largely from the fact that more blue light will reach the retina after a cataract is removed, and blue light has a higher potential to cause oxidative damage. Most studies that have examined the actual risk of cataract surgery on AMD development have found little or no risk, but they have, for the most part, been short-term studies. The value of this study is that it examined a very large group of people, and for each person compared one eye to the other eye. By doing so, the researchers are able to draw conclusions about the effect of specific differences between the eyes, for example, the effect of having cataract surgery on one eye but not the other eye. It turns out that in persons that have had cataract surgery in one eye but not the other there is the same amount of AMD in both eyes.

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Researchers studied choroidal neovascularization recurrence interval times in patients with neovascular AMD after intravitreal anti-VEGF therapy.

Individualized anti-VEGF dosing that aims to avoid recurrent CNV activity as well as to reduce the number of injections and office visits would aim to perform the injection immediately prior to the next recurrence. This would require the ability to determine or predict the recurrence interval for an individual patient. In this study, researchers analyzed the recurrence intervals of patients undergoing anti-VEGF therapy for neovascular AMD to determine whether predictable, regular recurrence patterns were present for individual patients

The records of patients who received intravitreal Lucentis injections for neovascular AMD at a university eye clinic were retrospectively reviewed. All patients were treated on an as-needed (PRN) basis. All eyes showing at least two documented recurrences of CNV activity during follow-up were included in this analysis. Recurrence intervals were deemed to be regular or periodical if the difference between recurrence interval times was less than 50 days.

Twenty-nine eyes of 28 patients met the inclusion criteria. Two to six recurrences were detected per case (mean 2.8 recurrences). Recurrence intervals ranged from 41 days to 523 days (mean 165 days).

Twenty-two eyes (76%) showed periodical recurrence intervals and seven eyes (24%) showed irregular recurrence intervals. Of eyes with periodic recurrence, 41% had all of their recurrences at regular intervals.

All eyes with classic CNV showed at least two periodical recurrence intervals. Eyes with occult CNV showed periodical recurrence intervals in 61% of cases.

The researchers conclude that periodical recurrences of CNV activity may be seen in eyes with neovascular AMD undergoing anti-VEGF therapy. Knowledge of individual recurrence interval times may allow for the development of an individualized treatment plan and prophylactic therapy.

WHAT IT MEANS TO YOU: There is a general impression among retinal specialists that some patients tend to go longer between recurrences than other patients. What is less clear is whether these intervals are consistent enough to be a basis for treatment decisions. If we knew that patient A tended to recur every 6 weeks and patient B tended to recur every 12 weeks, then we could have patient A return for an injection every 5 weeks and patient B could return every 11 weeks. Unfortunately, things are not so clear cut in the real world. This study found that 76% of patients tended to recur at about the same time, and in 24% of patients it was more erratic. However, regular was defined very generously, within a 50 day interval. In clinic, waiting 50 days after recurrence to get an injection could cost you some vision. So, the bottom line here is that although recurrence intervals are fairly consistent in 76% of patients, they are too variable to be useful in guiding retreatment.

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Advanced Cell Technology, Inc (ACT) announced that it has won U.S. Food and Drug Administration (FDA) approval to test human embryonic stem cells for treating dry AMD. It is the second FDA-approved trial for ACT's stem cell product and the third for the controversial and powerful stem cells. ACT said it would start recruiting patients with dry AMD using retinal pigment epithelial (RPE) cells, which ACT makes from human embryonic stem cells. In October, Geron Corp enrolled the first patient in the first ever approved study of human embryonic stem cells, to treat people with spinal cord injuries. In November, ACT won FDA approval for a clinical trial of human embryonic stem cells to treat people with Stargardt's macular dystrophy. There are no good treatments for advanced cases of dry AMD, which causes an estimated 85% of cases of macular degeneration, according to the U.S. National Eye Institute. Last year, the Obama administration overturned restrictions on using federal funds for embryonic stem cell research, but last summer two researchers challenged the policy. A U.S. appeals court has ruled that funding could continue while the court battles are continuing.

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The incidence of rhegmatogenous retinal detachment (RD) after intravitreal injection is a very low 0.014%, or about 1 in every 7188 injections, according to a new study published online in Acta Ophthalmologica. The risk of serious adverse events reported after intravitreal injection is low. Endophthalmitis, which is infection inside the eye, is perhaps the most serious complication of injection. Endophthalmitis has a reported incidence of 0.2% per injection. In this study a total of 35,942 consecutive intravitreal anti-VEGF injections were performed at 6 retina clinics over a 36 month period. Five RDs were reported, between 2 and 6 days after the injection. Of the affected eyes, four were myopic -1.75 to -5.50 D. The incidence rate of rhegmatogenous RD was 0.013% (5/35,942) per injection. The investigators conclude that the incidence of RD was very low (1 per 7188 injections). All RDs occurred within 1 week of the injection procedure. The risks of RD can be minimized by a careful injection technique.

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Bayer HealthCare and Regeneron Pharmaceuticals announced initiation of a new Phase III clinical trial investigating the efficacy and safety of VEGF Trap-Eye (aflibercept) in patients with CNV as a result of pathologic myopia. The trial, named MYRROR, has started in Japan and will start in other Asian countries, including China, Korea Singapore and Taiwan. Myopia is highly prevalent in Asian countries such as Singapore and Japan, where around 40% of adults have myopia and nearly 10% of these have high myopia. Currently, there is no well-established treatment for myopic CNV. VEGF Trap-Eye has demonstrated efficacy for neovascular AMD. "With this study, we hope to show the efficacy of VEGF Trap-Eye in combating yet another important cause of vision loss, myopic choroidal neovascularization," said Rupert Sandbrink, Vice President at Bayer. The study is scheduled to run until June 2013.

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The NHS in the United Kingdom has moved a step closer to approving Avastin for the treatment of AMD. The National Institute for Health and Clinical Excellence (NICE), which decides which drugs may be prescribed on the NHS, has decided to move towards an official appraisal of Avastin that has been widely and cheaply used off-label in the treatment of wet AMD. Avastin is licensed for bowel cancer, but ophthalmologists discovered that it could halt and even reverse the progress of wet AMD. Nice rarely appraises unlicensed drugs, but has decided that it will do so with Avastin. The Royal National Institute of Blind People opposed the appraisal, arguing that there was not enough evidence of Avastin's safety. But in a cash-strapped NHS, there are already primary care trusts (PCT) that have voted with their feet. Stockport PCT offers Avastin to patients at a private hospital, or Lucentis at an NHS hospital which has a waiting list of four to five weeks. Approval for an unlicensed use of Avastin could open the door for other unlicensed drugs to be appraised and used in the NHS.

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The European Commission has granted Novartis a new indication for Lucentis to treat patients with visual impairment due to diabetic macular edema (DME). Laser therapy, the current standard of care, can stabilize vision in many patients, but generally does not improve vision. Lucentis is the first licensed therapy to significantly improve both vision and vision-related quality of life in patients with visual impairment due to DME. The approval of Lucentis was based on data from two Novartis-sponsored clinical trials, RESTORE and RESOLVE, which showed that Lucentis was superior in providing rapid and sustained visual acuity gain versus sham (dummy) therapy or laser therapy, the current standard of care. Diabetic macular edema (DME) is a consequence of diabetic retinopathy, the most common diabetic eye complication. Visual impairment due to DME affects approximately 1-3% of patients with diabetes, and DME is a leading cause of blindness in the working-age population in most developed countries.

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Alimera Sciences announced that it received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA) for the investigational drug Iluvien. The FDA issued the CRL to communicate its decision that the NDA cannot be approved in its present form. The NDA seeks the approval to market Iluvien (fluocinolone acetonide intravitreal insert), Alimera's investigational, sustained drug delivery system that releases sub-microgram levels of fluocinolone acetonide for the treatment of diabetic macular edema (DME). Alimera conducted two Phase 3 pivotal clinical trials (collectively known as the FAME Study) for Iluvien. No new clinical studies were requested in the CRL. However, the FDA asked for data through month 36 of the FAME Study to further assess the relative benefits and risks of Iluvien. The NDA included data through month 24. The FDA also indicated that it had observed deficiencies in current good manufacturing practices during its facility inspections of two of Alimera's third-party manufacturers. Alimera's third-party manufacturers are in the process of resolving these deficiencies.

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