One theory of the origins of age-related macular degeneration (AMD) proposes that wet AMD is the product of excessive vascular endothelial growth factor (VEGF) secretion by the retinal pigment epithelium (RPE) and, conversely, dry AMD is caused by insufficient VEGF being produced by a dysfunctional RPE.

If this theory is correct, then one might expect that dry AMD could be induced by inhibiting the secretion of VEGF. And that is exactly what scientists have just accomplished.

Writing in the Proceedings of the National Academy of Science, scientists were able to produce a condition similar to geographic atrophy, the end stage of dry AMD, in genetically engineered mice that contain a RPE that does not secrete VEGF.

This is both good and bad news.

The good news is that we may be on the verge of understanding what causes geographic atrophy, and hence in a much better position to develop treatments for it.

The bad news is that continuous blockage of VEGF, as may occur with the chronic use of anti-VEGF medications, such as Lucentis and Avastin, may trigger or worsen dry AMD. anti-VEGF medications currently under development, such as VEGF-Trap, are much more potent than currently available drugs. We know that most of the 10% of patients that lose vision while on Lucentis therapy do so not because of macular fluid but because of progression of dry AMD. It remains to be determined whether this is caused by or independent of the action of Lucentis.

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Consumption of 2 to 4 egg yolks per day for 5 weeks increased macular pigment in older adults with low macular pigment who were also taking cholesterol-lowering statins.

Lutein and zeaxanthin accumulate in the macula, and are collectively referred to as macular pigment (MP). Macular pigment acts as a blue-light filter that may reduce the risk of dry AMD. Low macular pigment may be associated with increased risk of AMD. Egg consumption significant increases serum lutein and zeaxanthin concentrations and may increased MP optical density (MPOD).

In this study, 37 subjects consumed foods containing 2 egg yolks/d, followed by 4 egg yolks/d for 5 wk each, with a 4-wk egg-free period at baseline and between the 2 interventions.

Changes in MPOD with egg yolk consumption were inversely associated with baseline MPOD. Subjects with low-baseline MPOD showed increases of 50% with 4 egg yolks. MPOD increased by 31% at a retinal eccentricity of 0.5 degree with 2 egg yolks. The nonresponsiveness of subjects with high baseline MPOD may indicate saturation of the macula.

Serum HDL cholesterol increased by 5% after consumption of 2 and 4 egg yolks. Serum LDL cholesterol did not change with either egg yolk treatment.

A decrease in MPOD was observed after the 4-wk washout phase in the low-baseline MPOD subgroups. This is a valuable finding because previous reports suggest that MPOD stays high for a long time after supplementation.

To summarize, consumption of 2 and 4 egg yolks/d for 5 wk significantly improved MPOD at a retinal eccentricity of 0.5 degree, whereas consumption of 4 egg yolks/d improved MPOD at all retinal eccentricities in an older population with low MPOD who were taking statins.

WHAT IT MEANS TO YOU: Eggs are not as bad for you as you may think. Many people are concerned about cholesterol, and egg yolks do contain a large amount of cholesterol. But, as illustrated in this study, heavy egg consumption leads to only HDL ("good") cholesterol going up. Other studies have confirmed this observation. So, eating eggs may actually be good for you - especially if you have low macular pigment.

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Low-fluence photodynamic therapy (LFPDT) is safe and effective for CNV secondary to pathologic myopia (PM), according to a new study.

PDT is performed by intravenous administration of a drug know as verteporfin, then activating the drug within the retina using a laser. When verteporfin is activated by laser light, it generates singlet oxygen and free radicals, leading to thrombosis and occlusion of the CNV. Because of concerns regarding vision loss following PDT, investigators have attempted to improve outcomes by reducing the amount of laser energy used during the procedure. This is known as low-fluence photodynamic therapy. Concurrent intravitreal steroid injection has also been investigated as a means to improve to PDT outcomes.

Pathologic myopia may result in degenerative changes of the retina. These degenerative changes may lead to complications such as retinal detachment and macular degeneration. Degenerative changes affecting the macula include lacquer crack lesions, atrophy, and CNV.

In the current study, 25 eyes with CNV secondary to PM underwent LFPDT, with a standard dose of verteporfin and timing but fluence and irradiance rates reduced to 25 mJ/cm2 and 300 mW/cm2, respectively.

After a mean follow-up of 13.4 months, and 1.37 treatments (range: 1-3), BCVA was stable in 29 (91%) eyes. Two (6%) patients gained more than three lines and one (3%) eye lost more than three lines. Mean greatest linear dimension of the CNV did not change significantly at the end of follow-up. RPE depigmentation was present in six eyes (18%) and no patient showed RPE atrophy.

The investigators conclude that LFPDT is an effective and safe treatment for CNV secondary to PM, stabilizing visual acuity and lesion size and producing only mild RPE changes.

WHAT IT MEANS TO YOU: The present study found that low-fluence PDT can stabilize myopia CNV over a 1 year period. Previous studies found that PDT had a beneficial effect on myopia CNV at 1 year, but was not significantly better than placebo after 2 years. Research has also found that Avastin is more effective than standard-fluence PDT for myopic CNV. The present study would suggest that low-fluence PDT may be a viable alternative to standard-fluence PDT for myopic CNV, but anti-VEGF therapy remains the only therapy with the potential to improve, rather than just stabilize, vision in patients with myopic CNV.

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Intravitreal triamcinolone acetonide (ITA) does not improve the visual outcome of verteprofin photodynamic therapy (PDT) for neovascular AMD.

After the introduction of verteporfin for the treatment of subfoveal choroidal neovascularization (CNV), consideration was given to improving the efficacy of this therapy via the concomitant use of intraocular steroids. It was thought that visual acuity improvement and a reduced number of PDT treatments might be possible with the combined administration of PDT and ITA.

One hundred individuals over the age of 50 were randomized 1:1 to either to PDT alone or combined PDT and ITA in this multicenter, 2-year, double-blind, randomized controlled trial. Participants all received full-fluence PDT and were randomly assigned to either (1) a same-day injection of 4 mg ITA or (2) a sham intraocular injection.

Combination therapy with PDT and ITA when compared with PDT therapy alone resulted in no significant difference in final visual acuity at 1 year. Subjects receiving ITA required significantly fewer retreatments over the course of the study (1.28 vs 1.94, respectively). Although elevated intraocular pressures were noted in a larger proportion of subjects receiving ITA, all of these individuals were managed successfully with topical ocular antihypertensive agents.

The investigators conclude that there was no visual benefit to the addition of intravitreal triamcinolone to PDT. Combination therapy, however, can reduce the number of PDT treatments required by subjects who have predominantly classic CNV owing to AMD.

WHAT IT MEANS TO YOU: Concomitant intravitreal steroid injection reduces the need for retreatment but does not improve the visual outcome of PDT at 1 year. Because the visual outcome is the same with or without steroids, it is truly elective. The patient can decide whether he wants to assume the risk and cost of an intravitreal steroid injection (PDT does not itself entail intravitreal injection), in the hope that it will decrease the frequency of retreatment.

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Binocular visual field loss is a risk factor for bone fractures in older women, according to a new study.

Using data from the Study for Osteoporotic Fractures (SOF) for 1997 to 2008, researchers examined the associations between vision loss and fractures in 4773 women at least 65 years old.

Overall, 1773 women (37%) had no visual field loss, 2015 (42%) had mild loss, 485 (10%) had moderate loss, and 500 (11%) had severe loss.

Over a mean follow-up of 8 years, 424 (9.3%) women suffered a first hip fracture, for an incidence rate of 11.4 per 1000 person-years. Women with a first hip fracture missed a mean of 8.3 points on the visual field test, compared to a mean of 6.1 missed points among those without any fractures (p < 0.001).

The highest risk of hip fracture was found in women with the most severe visual field loss (hazard ratio [HR] 1.66). Risks were lower among those with mild (HR 1.49) and moderate (HR 1.25) visual field loss.

In the analysis of non-spine, non-hip fracture, 770 (19.9%) women had fractures. Here again, the risk of fracture was highest in women with severe visual field loss (HR 1.59) and lower with mild and moderate loss (HR 0.88 and 1.18, respectively).

The researchers conclude that future guidelines for the care of older patients should consider recommending evaluations of the visual fields in patients at heightened risk of fractures.

WHAT IT MEANS TO YOU: Vision loss is a well-recognized risk factor for falls. There are a number of things that can be done around the house that will help to guard against falls. These include making sure that rugs and shower/bath/tub mats are slip-proof, secure railings so that they are not loose, and making sure hallways and stairs are properly lit.

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A new report from the AREDS group finds that cataract surgery benefits patients with all stages of AMD, from mild to advanced.

This study involved a total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD.

Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery.

This study found a statistically significant gain of visual acuity in patients with AMD after cataract surgery. This gain in visual acuity was seen in all levels of AMD, including advanced cases with central geographic atrophy or neovascular changes.

The findings of this study are particularly important in light of epidemiologic studies that suggest a harmful effect of cataract surgery on the acceleration of AMD progression. Data from AREDS suggest that there is little evidence of effect of cataract surgery on the risk of progression to advanced AMD.

The investigators conclude that, on average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months.

WHAT IT MEANS TO YOU: Recent studies of the effect that cataract surgery has on AMD confirms that cataract extraction does not accelerate the progression of macular degeneration. Now, this report from AREDS provides even more good news about cataract surgery in persons with AMD - that regardless of severity of AMD, a significant and lasting visual acuity benefit can be expected. This study removes any lingering doubts about the value of removing a mature cataract from patients with AMD.

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In a study on laboratory rats, orally administrated doxycycline, an inexpensive and widely used broad-spectrum antibiotic, was found to reach the choroid and effectively hampered progression of experimental CNV.

Doxycycline, a member of the tetracycline antibiotics group, has broad antimicrobial properties. New uses of doxycycline are being reported. Studies have found that doxycycline is a potent matrix metalloproteinase (MMP) inhibitor. MMPs can facilitate endothelial cell migration during angiogenesis. Furthermore, MMP-2 and MMP-9 can inhibit the activity of pigment epithelium-derived factor (PEDF), a potent antiangiogenic factor.

Doxycycline was orally administered to rats; nontreated animals were used as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At 7 days after induction, animals were euthanatized, and eyes were collected.

CNV lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/d caused a 70% inhibition of CNV volume compared with control animals. Doxycycline elevated PEDF levels in plasma. Enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline.

This study found that doxycycline effectively inhibits the progression of CNV, inhibits the activity of MMP-2 and MMP-9, and increases the levels of PEDF. The investigators state that doxycycline can shift the balance between proangiogenic and antiangiogenic factors to inhibit the progression of CNV.

WHAT IT MEANS TO YOU: Doxycycline is a safe and widely used antibiotic that, not unlike aspirin, has many surprising beneficial effects. Human studies are needed to know if doxycycline can effectively inhibit CNV in persons with AMD. But, in the meanwhile, it worth considering placing patients with recalcitrant CNV on doxycycline while other attempts to control the disease are undertaken.

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The CLEAR-IT 2 trial was a phase 2 study of VEGF Trap-Eye in patients with neovascular AMD. Below are the results of the CLEAR-IT 2 and 6-month data from the extension stage as reported by Retina Today. Patients were randomly assigned to receive monthly or quarterly injections for an initial 3-month fixed-dose period, after which they received it on an as needed basis at monthly visits out to 1 year. At 1 year, patients who received three monthly doses followed by as-needed dosing had greater average vision improvement than patients who received initial quarterly dosing. All patients received VEGF Trap-Eye on an as-needed basis in the extension stage of the study. The mean gain in BCVA from baseline was 7.3 letters at 3-months in the original study, 8.4 letters at 1 year, and 7.1 letters at month 6 of the extension study. Patients received a mean of 3.5 injections of VEGF Trap-Eye over the 15-month course of the PRN dosing phase.

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A retrospective study of the visual and refractive outcome of visually impaired myopic adults treated with refractive surgery (photorefractive keratectomy [PRK] or laser-assisted in situ keratomileusis [LASIK]) finds that refractive surgery improved the best spectacle-corrected visual acuity in visually impaired patients.The researchers searched a database for mildly visually impaired patients who had undergone either PRK or LASIK. The investigators found that refractive surgery improves best spectacle-corrected visual acuity in visually impaired patients, possibly through plastic changes in the visual cortex. They comment that refractive surgery may be used successfully for the treatment of visually impaired adults to enhance their visual acuity. The study appears in Acta Ophthalmologica.

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Scientists have confirmed that blindness causes structural changes in the brain, indicating that the brain may reorganize itself functionally in order to adapt to a loss in sensory input, according to a Medical News Today report. Researchers found that visual regions of the brain were smaller in volume in blind individuals than in sighted ones. However, for non-visual areas, the trend was reversed - they grew larger in the blind. For example, the frontal lobes, which are involved with, among other things, working memory, were found to be abnormally enlarged, perhaps offering an anatomical foundation for some of blind individuals' enhanced skills. This, the researchers say, suggests that the brains of blind individuals are compensating for the reduced volume in areas normally devoted to vision.

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Lucentis is ineffective in treating avascular pigment epithelial detachment (PED) secondary to AMD over a 1 year follow-up period, according to a study published in the journal Eye. A PED occurs when fluid enters the space between the RPE and choroid. There is currently no effective treatment for PED. In this prospective case series, the first group of six patients received three and the second group of six patients received six intravitreal injections of Lucentis at monthly intervals. The mean baseline PED volume of 1.33 mm3 decreased significantly by 42% at month 6 (-0.55 mm3, P<0.05). Compared to baseline no significant change was observed at months 9 and 12. The investigators conclude that treatment with intravitreal injections of Lucentis may temporarily decrease the volume of avascular PED secondary to AMD, however this effect was not maintained over the 1-year study period. The treatment was ineffective for improving retinal function as measured with BCVA and microperimetry.

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Lucentis produces a significantly better visual outcome than focal/grid laser in diabetic macular edema (DME), according to the READ-2 six months results published in the journal Ophthalmology. Focal/grid laser therapy is currently standard of care and the gold standard with which new treatments are compared. In this phase 2 clinical trial a total of 126 patients with DME were randomized 1:1:1 to receive Lucentis, focal/grid laser photocoagulation, or a combination of Lucentis and laser. At month 6, the mean gain in visual acuity was significantly greater in the Lucentis-only group compared with the laser-only group. The vision change of the Lucentis-only group was not significantly different than that of the combination group. The investigators conclude that during a span of 6 months, Lucentis injections had a significantly better visual outcome than focal/grid laser treatment in patients with DME.

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Intravitreal Avastin is effective in the treatment of CNV resulting from presumed ocular histoplasmosis syndrome. This study is a retrospective review of consecutive cases in which intravitreal Avastin (1.25 mg) was injected into 24 eyes with CNV resulting from presumed ocular histoplasmosis syndrome. Patients' mean age was 43 years and mean follow-up was 31.8 weeks. The average number of Avastin injections was 6.8 injections/year. After 12 months, visual acuity improved from mean logMAR 0.86 to mean logMAR 0.34. Fourteen (58.3%) eyes had final visual acuity of 20/40 or better compared with 5 (20.8%) eyes at baseline. Ten patients (41.6%) had visual acuity of 20/200 or worse at baseline compared with 5 (20.8%) eyes at the final visit. The investigators conclude that intravitreal Avastin seems to be an effective treatment for choroidal neovascularization resulting from presumed ocular histoplasmosis syndrome. The study was published in the journal Retina.

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Advanced Cell Technology (ACT), Inc. announced that it filed an Investigational New Drug (IND) Application with the US Food and Drug Administration (FDA) to initiate a Phase I/II multicenter study using embryonic stem cell derived retinal cells to treat patients with Stargardt's Macular Dystrophy (SMD). The Phase I/II trial will be a prospective, open-label study that is designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation to advanced patients with SMD. A total of twelve patients will be enrolled into the study at three clinical sites, including Portland, Oregon; Worcester, Massachusetts; and Newark, New Jersey.

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