Age-related Macular Degeneration (AMD) may now be less common than in the past

Age-related macular degeneration (AMD) is the leading cause of severe visual impairment in persons over 65 years of age, a group that is growing in numbers because of increased life expectancy.  AMD affects the center of the retina, the macula, where collection of fluid, fatty deposits, pigmentary changes, and blood, may cause significant visual impairment in about 10% of patients affected by ‘wet’ AMD. The rest 90% suffer from the non-progressive type of AMD, referred to as ‘dry’ AMD, where the features do not progress, and the vision largely remains stable, or deteriorates slowly.

AMD was considered to be more common in the Caucasian (or white) population, though recent studies from India indicate that the prevalence in India may be almost equal to the western population.

In the west, the prevalence was considered to be about 9.4 percent of US patients, based on a 1988-1994 Third National Health and Nutrition Examination Survey. But a recent study indicates the prevalence to be 6.5 percent in patients aged 40 and older, lower than the 9.4 percent reported earlier.

The new study involved 5,533 US adults, aged 40 years of older, who participated in the 2005-2008 National Health and Nutrition Examination Survey. Based on the digital photographs taken of both eyes, the researchers found that 6.5 percent of the participants had signs of some level of AMD, including tiny yellow or white deposits in the retina, pigment changes and deterioration of the retina and surrounding tissue. Less than one percent had the ‘wet’ disease, the advanced stage in which eyesight is more severely affected.

Extrapolating these new figures, an estimated 7.2 million people in the U.S. having any degree of AMD, with about 890,000 of these with advanced ‘wet’ disease. If that rate was correct and remained unchanged, it would mean about 18 million Americans should demonstrate signs of AMD. The new estimates represent a reduction of more than 30 percent in rates of AMD. The reasons for such a decrease in numbers is not very clear. The researchers feel it could reflect changes in time in smoking, diet and use of medications (anti-oxidant vitamins and zinc). A better understanding of the reduction of AMD in older population could help point to new prevention strategies that could lead to further reduction in numbers.

If we extrapolate the same percentage to Indian population, as some studies have indicated that the prevalence of AMD in Indian patients matches those of the western world, we have about 65 million patients in India. 

Source: Archives of Ophthalmology Jan 2011. Click here for the paper.

Breakthrough in possible treatment for dominant form of Retinitis Pigmentosa

Scientists have made a breakthrough in tackling a common form of retinitis pigmentosa (RP), which can eventually lead to blindness.

The breakthrough tackles the rhodopsin gene alteration that causes this inherited form of RP. Rhodopsin-linked RP is variable and at least 150 different alterations in the gene have been identified in RP families worldwide. This makes developing a gene-based therapy very complex, if not impossible, if the treatment targets the specific alteration.

Researchers in the Smurfit Institute of Genetics at the Trinity College of Dublin have been working for 20 years to identify the genes and find a potential treatment for RP. The paper has been published in the Molecular Therapy. The research is funded by Science Foundation Ireland, Fighting Blindness Ireland and the National Neurovision Research Institute, USA.

The rhodopsin-linked form of RP is caused by a mutant form of the rhodopsin gene. The therapy works by switching off both copies of the gene, the normal and the altered copies. Simultaneously, a replacement rhodopsin gene is introduced which has been subtly altered so it cannot be suppressed. It encodes normal protein, which allows the photoreceptors to work normally. The research restored visual function in mice with a dominant rhodopsin-linked form of RP exactly replicating the form of the disease, which affects humans.

The scientists hope that this basic research will move into more preclinical work, including a larger mammal, and eventually move on to human clinical trials.

The scientists believe that the research’s implications stretched far beyond RP, and may be applicable to a lot of dominant diseases. The key to finding a cure is to suppress the mutant gene causing the problems. Since this is the dominant gene, it is harder to treat, and hence the success of this research is important to treat those dominant diseases where the mutant protein drives the disease process.

Physician scientists and researchers can access the article here.

A new chip enables rapid detection of retinal disease genes defects

Researchers at the Netherlands Institute for Neuroscience have designed a custom resequencing chip that can detect known and new sequence changes in about 90 retinal disease genes using a new high-throughput strategy with a high sensitivity and specificity for one tenth of the cost of conventional direct sequencing, as reported in the recent issue of Ophthalmology journal.

The developed amplification strategy allows for the pooling of multiple patients with non-overlapping phenotypes, enabling many patients to be analyzed simultaneously in a fast and cost-effective manner.
This chip accurately and efficiently identified novel and known mutations in retinal disease genes in the study that included 60 patients.

The chip offers rapid analysis with high sensitivity and specificity, at about one-tenth the cost of conventional direct sequencing. The developed amplification strategy allows for the multiple patients to be pooled together with non-overlapping phenotypes, enabling many patients to be analyzed simultaneously in a fast and cost-effective manner.

The investigators designed a custom 300-kb Affymetrix resequencing chip that affords direct sequencing of 265,000 double-stranded bases of retinal disease genes. The study included patients with retinal disorders such as Leber's congenital amaurosis, ocular albinism, optic atrophy, glaucoma, pseudoxanthoma elasticum, retinitis pigmentosa and Stargardt's disease.

Direct sequencing of forward and reverse strands in relevant disease genes was performed to verify the presence of mutations in the DNA of the pooled patient sample. The investigators identified 87 known pathogenic and polymorphic sequence changes from 25 retinal disease genes. They developed primer sets for 1,445 amplicons representing genes tested on the chip.

Study results showed a detection rate of 99% and reproducibility rate of 100%, with no false positives. But the chip is not able to detect deletions of genetic material, and hence, it can be used to prescreen patients to improve the efficiency of subsequent formal DNA testing.

Source: Ophthalmology