According to popular legend, Juan Ponce de Leon, the famous Spanish explorer, discovered Florida while searching for the Fountain of Youth.

Today, researchers are continuing his search for the key to eternal youth, and some believe they have begun to find tantalizing clues that may someday lead to a cure for aging.

In the October 2010 edition of Investigative Ophthalmology and Vision Science, researchers report that the target of rapamycin (TOR) pathway plays a key role in regulating age-related changes in retinal pigment epithelial (RPE) cells. The researchers demonstrate that inhibition of TOR delays the aging process of the RPE.

Age-dependent degeneration of the RPE is a hallmark of age-related macular degeneration (AMD).

Currently, aging is an inevitable biological process that contributes to the pathogenesis of many diseases, including AMD. But the process of aging is believed to be determined by a genetically programmed molecular clock.

Our biological clock is subject to regulation by multiple pathways, including TOR. Therefore, it may be possible to slow down or maybe even stop the clock by manipulating TOR. Very recently, it has been shown that mice with genetically altered TOR experience increases in life span.

If inhibiting TOR can slow down the aging process of the RPE, it will become a promising therapeutic strategy to prevent and treat vision loss in people with AMD - a Fountain of Youth for our eyes.

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The high-density lipoprotein (HDL)-raising allele of the LIPC gene was associated with a reduced risk of AMD. Higher total cholesterol and LDL levels were associated with increased AMD risk, whereas higher HDL levels tended to reduce the risk of AMD.

Hepatic lipase (LIPC), a gene located on chromosome 15q22, recently was discovered to be associated with AMD. This genetic variant is known to affect serum HDL ("good") cholesterol levels.

Participants in this study were genotyped for 8 genetic variants associated with AMD, including LIPC. Fasting blood specimens were obtained and serum levels of total cholesterol, LDL, HDL, and triglycerides were determined.

The T allele of the LIPC gene was found to be associated with a reduced risk of AMD (odds ratio, 0.4) independent of HDL level. There was a significant trend for increasing HDL with increasing number of LIPC T alleles Mean level of HDL was lower and mean level of LDL was higher in cases of advanced AMD compared with controls. Higher total cholesterol levels were also associated with increased risk of AMD.

These results show that the TT genotype of the LIPC gene is significantly associated with a reduced risk of advanced AMD for both neovascular and geographic atrophy subtypes.

LIPC genotype was associated with AMD risk independent of HDL level. This suggests that HDL level may not mediate the association between LIPC and AMD. The LIPC association may not be the result of an effect on raising systemic HDL levels, but could represent a pleiotropic effect of the same functional unit.

In conclusion, HDL and LIPC genotype are independently associated with a reduced risk of advanced AMD, and LDL and total cholesterol are associated with an increased risk of AMD.

WHAT IT MEANS TO YOU: This is the first report to assess the LIPC gene together with lipid biomarkers and their associations with AMD. The researchers confirm that LIPC genotype can lower the risk of advanced AMD. It is not clear at this time how LIPC influences AMD, but it seems HDL levels are not the whole answer. Other, as yet undiscovered, influences of the LIPC gene appear to influence the development of AMD. Additional research is needed to clarify these mechanisms. In the meanwhile, this is yet another good reason to keep your cholesterol levels in check

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Among Chinese adults, myopic retinopathy is associated with higher age, worse best corrected visual acuity, deeper anterior chamber, larger optic disc and greater prevalence of open-angle glaucoma, according to a new study

The Beijing Eye Study included 4439 subjects age 40 years and greater.

Myopic retinopathy was present in 198 eyes of 132 participants (3.1%). Myopic retinopathy was significantly associated with higher age, worse best-corrected visual acuity, deeper anterior chamber, larger optic disc, less age-related macular degeneration, and greater prevalence of open-angle glaucoma.

The prevalence of myopic retinopathy increased significantly with increasing myopic refractive error, from 3.8% in eyes with a myopic refractive error of < -4.0 diopters to 89.6% in eyes with a myopic refractive error of at least -10.0 diopters.

Myopic retinopathy was not associated significantly with the level of education, rural versus urban region of residence. This may contradict the results of previous studies from highly urbanized regions in East Asia, which show a clear relationship between myopic refractive error and urbanization and a higher level of education.

The investigators conclude that myopic retinopathy was present in 3.1% of subjects aged 40+ years who resided in the Greater Beijing area.

WHAT IT MEANS TO YOU: The most interesting finding in this study is that myopic retinopathy in China is not associated with higher education or urban residence, contradicting most other studies. It is widely recognized that myopia is more common among persons with higher education, but this is not always the case with very high myopia, and those of the patients that will most often develop retinopathy. Urban dwellers are likely to engage in more indoor activities, such as reading and computer work - activities associated with higher risk for myopia, than rural dwellers. Because myopia is a leading cause of vision impairment in Asia, these finding have important public health significance. This study would suggest that greater urbanization and higher education in China may not lead to greater vision loss from myopia.

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A new study finds the combination of elevated C-reactive protein (CRP) levels and the high-risk genotype of the complement factor H (CFH) gene resulted in a super-additive risk for AMD progression.

C-reactive protein (CRP) is a general marker of systemic inflammation. It is a protein found in the blood. The level of CRP will rise in response to inflammation from any cause. Therefore, CRP levels can be used as a gauge for the amount of inflammation that is present in the body.

This study found an epidemiologic association between advanced AMD, elevated CRP levels and the high-risk genotype of the CFH gene.

In 2007, it was found that the binding affinity of CRP to CFH is influenced by the Y402H polymorphism. This provides a biologic basis for an interaction between these 2 risk factors. It is suggested that impaired binding of CRP to CFH could reduce the ability of CFH to inhibit inflammation, and thereby cause deterioration of the macula in individuals with initial signs of AMD.

The current study is in agreement with this hypothesis. The researchers found evidence of a synergistic, super-additive effect of the risk factors, thus supporting the notion of a biological interaction between complement factor H and CRP in relation to AMD.

By taking account of both CFH genotype and CRP levels it may be possible to identify those persons most at risk of progression and vision loss secondary to AMD.

WHAT IT MEANS TO YOU: It has long been recognized that elevated CRP levels are a risk factor for AMD. This study finds that elevated CRP levels together with the high-risk CFH genotype will combine to greatly increase the risk of AMD progression. Therefore, measurement of CRP levels are key to assessing one's true risk developing advanced AMD.

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Avastin (bevacizumab) and Lucentis (ranibizumab) use was not associated with increased risks of mortality, myocardial infarction, bleeding, or stroke compared with photodynamic therapy or Macugen (pegaptanib) use.

This study used a large Medicare claims database to examine associations between therapies for neovascular AMD and risks of all-cause mortality, incident myocardial infarction, bleeding, and incident stroke.

The researchers found the hazard of mortality was significantly lower with Lucentis therapy than with photodynamic therapy (hazard ratio, 0.85) or Macugen use (0.84), and the hazard of myocardial infarction was significantly lower with Lucentis use than with photodynamic therapy (0.73). There were no significant differences between Avastin use and the other therapies. The researchers found no statistically significant relationship between treatment group and bleeding events or stroke.

The investigators observed significantly lower hazards of all-cause mortality, incident myocardial infarction, and incident stroke with Lucentis therapy compared with Avastin therapy. The risk of systemic adverse events in this study was lowest with Lucentis use.

The researchers do not believe that Lucentis may be protective with respect to mortality and thromboembolic events. Rather, they suggest that recipients of Lucentis may have been healthier in ways this study could not measure. The substantial cost difference between Lucentis and Avastin suggests that Medicare beneficiaries with higher socioeconomic status, often associated with better overall health, may have been more likely to receive Lucentis.

In conclusion, this study found no evidence of increased risks of mortality, myocardial infarction, bleeding, or stroke among Medicare beneficiaries who received intravitreous Lucentis or Avastin for neovascular AMD.

WHAT IT MEANS TO YOU: This study reviewed the claims data of 146,942 Medicare beneficiaries. By studying such a large group of patients it is possible to find small outcome differences that are not apparent in much smaller clinical trials. The results of this study add to the large body of evidence that indicates that there are no serious adverse health effects of anti-VEGF therapy of AMD.

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Low macular pigment optical density (MPOD) may be a risk factor for chronic central serous chorioretinopathy (CSC).

Macular pigment is composed of three carotenoids (i.e., lutein, zeaxanthin, and meso-zeaxanthin). Lutein and zeaxanthin can be obtained only from food, and meso-zeaxanthin is synthesized mainly from retinal lutein.

In the present study researchers compared MPOD results in patients with CSC and normal subjects. MPOD was measured by autofluorescence spectrometry.

The researchers found that MPOD was 0.548 DU in normal subjects. Central retinal thickness (CRT) was moderately positively correlated with MPOD in normal subjects.

The investigators then evaluated the association between MPOD and CSC. The mean MPOD in all eyes with CSC was 0.456 DU, which differed significantly from the control eyes.

When compared between the control group and the CSC groups, MPOD in the affected and fellow eyes with chronic CSC was significantly lower than in the control eyes. The central retina in eyes with chronic and acute CSC was significantly thinner than in normal subjects.

Both affected and fellow eyes of patients with chronic CSC had significantly lower MPOD compared to normals, independent of CRT. This suggests that eyes with low MPOD are likely to develop chronic CSC. This hypothesis is supported by the finding of lower MPOD in fellow unaffected eyes of patients with chronic CSC, although the CRT was maintained.

In conclusion, low MPOD may be a risk factor for the development of chronic CSC, and a decrease in MPOD may be accelerated by a thinning central retina. The exact relationship between low MPOD and development of chronic CSC is unknown; however, this study suggests the possibility that supplementation of macular pigment may suppress the development or progression of chronic CSC.

WHAT IT MEANS TO YOU: The cause of CSC is not clearly understood, but there is good evidence that CSC is primarily a disease of the choroid. Imaging technology has revealed abnormal fluid leakage from choroidal blood vessels in patients with CSC. However, breakdown in retinal pigment epithelial (RPE) function may also play a role in the development of CSC. It is unclear whether (or how) MPOD deficiencies might contribute to this disease. It is possible that low MPOD might be an effect, rather than a cause of the disease. This is the first study to examine the possible relation between MPOD and CS, and as is so often the case, it raises more questions than it answers.

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The standard of care for retinal vein occlusion remained unchanged until 2009, when three separate clinical trial programs reported data challenging the status quo. (1) The SCORE Study supported the use of triamcinolone over observation for central retinal vein occlusion (CRVO) and confirmed the superior safety profile of laser in BRVO, (2) Allergan presented data on its dexamethasone-containing Ozurdex implant for both branch retinal vein occlusion (BRVO) and CRVO, (3) The BRAVO and CRUISE studies demonstrated the positive impact of Lucentis on BRVO and CRVO, respectively. Suddenly, retinal specialists had at their disposal a plethora of data on new and effective treatments for the second-leading cause of vision loss due to retinal vascular disorders. At the current time, there are no definitive answers as to how best to treat patients with occluded retinal veins, and several questions still remain. The sudden onset of new information for treating retinal vein occlusion, it seems, calls into question the current standard of care. But it also leaves open the question as to what the new standard should be.

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The average age at which neovascular AMD develops is getting older, according to a study in the September 2010 edition of Ophthalmologica. The medical records and fluorescein angiograms of patients diagnosed with wet AMD in 1986 and 2006 in a Paris, France eye clinic were analyzed to identify differences in age, gender and type of CNV. A total of 79 patients with CNV due to AMD were diagnosed in 1986, and 278 patients in 2006 were included. The patients diagnosed in 2006 were 4.7 years older than those diagnosed in 1986 (80.1 vs. 75.4 years). The main increase was in the percentage of patients over 85 years: 11.39% in 1986 versus 26.98% in 2006. There was no significant difference between the two groups as regards gender or type of CNV.

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Submacular hemorrhage (SMH) is the presence of subretinal blood below the macula. It is a relatively common problem in patients with wet AMD. The visual prognosis of these patients is usually poor. Unfortunately, the optimum management of SMH is uncertain. It has been proposed that patients with moderate-sized subfoveal SMH be treated with surgical displacement of the hemorrhage away from the fovea. Two techniques for displacing SMH away from the fovea have been described. Both procedures displace SMH away from the foveal area, without actual removal of the blood. The "expansile gas technique" utilizes intravitreal injection of an expansile gas bubble combined with clot lysis using intravitreal tissue plasminogen activator (tPA) and face downward posture postoperatively. An alternative technique, called the "vitrectomy technique", involves vitrectomy with subretinal tPA injection and air exchange. One advantage of the vitrectomy technique is less need for face-down posturing. The relative effectiveness of the two techniques is unknown. An important question is: how does hemorrhage displacement followed by anti-VEGF therapy compare to anti-VEGF therapy alone? One study found with expansile gas displacement, visual acuity improved in 80% of patients compared to 60% of patients with anti-VEGF treatment alone. Additional research is required to determine the optimum management of patients with SMH.

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Fenretinide , an oral retinol binding protein inhibitor, showed promising results in a phase 2 clinical trial for geographic atrophy. Fenretinide (ReVision Therapeutics) slowed the progression of advanced dry AMD and prevented the development of wet AMD, Jason Slakter, MD, said at a company-sponsored symposium during the American Academy of Ophthalmology meeting. Fenretinide inhibits the accumulation lipofuscin in the retina. The anti-inflammatory and anti-angiogenic properties of the drug are thought to provide an additional therapeutic benefit against development of wet AMD. The 2-year study included 246 patients with geographic atrophy. Results showed that patients who received fenretinide had about half the risk of progressing to wet AMD at 2 years compared with those who received placebo, Dr. Slakter said. At the conclusion of the two-year study, 43 percent of patients taking fenretinide had median atrophic lesion size growth of 30% from baseline, compared to 50% growth in the placebo arm. Visual acuity among patients taking fenretinide declined six letters, while patients taking placebo lost 11 letters. A phase 3 trial is scheduled to commence in 2011.

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Retina Implant AG, a leading developer of subretinal implants for the visually impaired, announced the presentation of findings obtained during their first human clinical trial in the form of two presentations at The Eye and the Chip 2010 Annual Meeting in Detroit, Mich. The first study presented by Eberhart Zrenner, M.D., of the University of Tuebingen, Germany includes findings from Retina Implant's first human clinical trial. During this clinical trial 11 patients received micro chips implanted below the retina. The researchers found that the micro chip can restore useful vision and the ability to read letters and form words. The second paper, presented by Walter-G. Wrobel, CEO of Retina Implant AG discusses the cost-benefit analysis of subretinal implants. "The primary goal of our first clinical trial was to provide useful vision to patients, but this study shows that such devices could be a cost-effective treatment for people blinded by retinal degeneration," Dr Wrobel said.

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Ongoing clinical trials exploring the use of complement inhibitors for treating dry AMD offer promise for a disease that has long been considered difficult to treat, according to a speaker at the joint meeting of the American Academy of Ophthalmology and the Middle East Africa Council of Ophthalmology. A number of recent studies have implicated the complement immune system in AMD, Philip J. Rosenfeld, MD, PhD, said at Retina Subspecialty day preceding the meeting. As a result, Dr. Rosenfeld said, human trials are determining whether complement inhibition is of any real clinical benefit. Several such trials are already underway. Alcon is currently investigating its POT-4 (AL-78898A) anti-C3 cyclic peptide in human trials. There is some evidence that POT-4 may also affect VEGF expression in the retina, Dr. Rosenfeld said. Separately, Genetech/Roche has an anti-factor D (FCFD4514S) that inhibits the C3 and C5 alternative pathway convertases. Phase 1 studies have been successfully completed with that agent, Dr. Rosenfeld said. Two separate C5 inhibitors are being studied: Eculizumab/Sollris (Alexion) and ARC1905, an anti-C5 aptamer (Ophthotech).

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