Genetic testing can give insight into an individual’s risk for retinal disorders that run in their family, yet many ophthalmologists do not routinely perform genetic tests on all their patients.

Researchers aim to enhance how doctors utilize genetic information to predict macular degeneration risk. Their goal is to develop an approach combining epidemiological data, clinical phenotype and molecular genetics as well as nutrition and lifestyle advice into one comprehensive framework.

Genes involved

Genetic testing can identify your risk for wet or dry macular degeneration and determine your likelihood of having either form. Dry macular degeneration causes central vision to break down, with fluid-filled deposits known as drusen appearing under the retina and fluid leakage into it from abnormal blood vessels forming abnormally, along with dry macular degeneration affecting peripheral vision as well. It’s best to address both forms early so genetic testing can identify your chances.

Researchers have discovered a number of genes which could contribute to macular degeneration; among these is CFH for early-onset macular degeneration; CFAR and LMNA may play roles; the former two can cause wet forms while the latter two may cause dry types.

Genetic screening has not only identified specific genes associated with macular degeneration, but has also discovered “candidate protective variants”. While they cannot yet guarantee disease protection, they provide useful indicators of one’s genetic risk for developing it.

Retinal specialists often recommend genetic testing for those with a family history of macular degeneration or clinical features suggestive of macular degeneration such as extensive intermediate drusen or wet AMD. Results from predictive genetic testing can help inform treatment strategies such as diet changes and lifestyle interventions, or enrollment in patient registries and clinical trials that test out new therapies such as gene therapy and cell therapies.

Doctors should avoid offering genetic testing routinely for eye diseases; rather, this type of test should only be utilized when necessary and appropriate. Predictive tests can be costly and psychologically distressful; their accuracy cannot be guaranteed either.

Physicians seeking to conduct genetic testing for eye diseases that run in families should carefully consider each patient’s family history before selecting certified laboratories that adhere to stringent confidentiality standards. Furthermore, physicians should avoid direct-to-consumer genetic testing services and discourage patients from seeking them themselves.

Predictors of disease

Researchers have made considerable strides toward understanding the genetics behind common inherited diseases like AMD. Unfortunately, mutations at single loci do not always cause disease on their own and environmental factors also play a part in its progression; as such, it’s vitally important that individuals understand their risk for AMD as well as ways they can alter lifestyle behaviors to mitigate it.

If a patient possesses a variant of the CFH gene that increases her risk five to tenfold for wet macular degeneration, a clinician should discuss and advise her of strategies to decrease it such as healthy diet, regular exercise, and taking supplements such as vitamins C and zinc.

Many genes involved in retinal degeneration also play a part in other conditions such as glaucoma. Therefore, it is crucial for patients with clinical features of glaucoma to undergo screening with GEDi-O which simultaneously screens all eight known high-risk genes at once for confirmation or disproval, and identification of patients who could benefit from clinical treatment trials with novel drugs or therapies.

Genetics can also provide valuable insight into the inheritance pattern of conditions, making it easier for ophthalmologists to recognize and counsel appropriate patients. For example, researchers studying hereditary optic atrophy have identified mutations in oPA1 (inherited as either dominant or recessive traits) and mitochondrial DNA (inherited from mother) that contribute to Kjer optic atrophy or Leber hereditary optic neuropathy. Furthermore, GEDi-O tests offer screening capabilities that allow early-onset glaucoma screening.

Clinicians are increasingly using genetic testing to identify individuals eligible to enroll in clinical trials of gene-based and cellular therapies to treat retinal degeneration and other ocular disorders, such as My Retina Tracker study recruiting patients for predictive genetic testing for AMD while counseling them about lifestyle changes they can implement to lower their risk.

Testing options

Genetic tests can identify specific changes in genes or chromosomes associated with macular degeneration and other eye disorders inherited from mother to daughter, such as macular dystrophy. There are various genetic tests available, and healthcare providers will select an appropriate one depending on patient medical history and exam findings. When suspected AMD symptoms exist, a large panel screening for mutations across multiple genes is often employed; but in many instances targeted genetic tests alone will suffice in diagnosing this disease.

If a genetic test indicates that an individual has an increased risk for retinal disease, genetic counseling could be useful. Genetic counselors specialize in collecting detailed family histories and reviewing molecular testing options with their clients; additionally they can coordinate testing among family members as well as enroll in research or patient registries or discuss clinical trials with them.

Soon, genetic tests that predict susceptibility to future illness based on both genes and environmental factors will become widely available, giving doctors more accurate pictures of an individual’s risk for common diseases like diabetes, heart disease, Alzheimer’s and cancer. These “predictive” genetic tests may offer benefits over current screening methods by offering more complete insights.

Genetic testing can be extremely costly and not all health insurance plans cover it. Patients considering genetic testing should check with their provider first before scheduling an appointment to discuss possible coverage before scheduling their appointment.

Researchers are exploring how genetic information can improve both the effectiveness and safety of drugs. One such field of laboratory research known as pharmacogenomics examines how genes and other factors influence people’s responses to different drugs; eventually pharmacogenomics should allow doctors to know whether a given medicine will work for any particular patient based on blood or saliva samples alone; ultimately this would reduce adverse reactions which occur with about 50% of prescriptions – helping physicians, patients and state Medicaid agencies find out which genetic services are covered under individual policies.

Results

Identification of genetic variants associated with eye diseases can aid clinicians in providing appropriate therapies. The GEDi-R panel tests 250 genes known to cause retinal degenerations; this approach allows more efficient testing than testing one gene at a time and may detect large deletions and insertions that would not otherwise be detected through conventional Sanger sequencing alone.

Initial advances in eye disorders were achieved through family-based linkage studies of affected and discordant siblings, later using Genome Wide Association Studies to identify genomic regions which had significant effects on complex phenotypes like age-related macular degeneration.

However, the mechanisms underlying many phenotypes remain unknown. Of particular note is how variants in non-coding regions and pathways impact disease risk; additionally complex phenotypes like age-related maculopathy may result from interactions among multiple genes with differing effects.

As well as genetic testing, various techniques exist for assessing the effect of gene-environment interactions on disease risk. Combining epidemiological data describing clinical phenotype, molecular genetics and lifestyle factors with epidemiological observations can provide valuable insight into long-term prevention and therapy strategies.

Studies have demonstrated that one-time gene therapy treatments can significantly slow or stop progression of wet AMD. These interventions involve injecting the mutant gene into induced pluripotent stem cells and then transplanting them back into the eye where they can act to replace the mutant protein that destroys retinal support layers. Trial results have been encouraging, though more research must be completed to develop effective and sustainable therapies for age-related macular degeneration. Individuals should abide by their healthcare provider’s recommendations regarding lifestyle modifications that can benefit vision health; such as wearing sunglasses and brimmed hats when outdoors; not smoking; and taking vitamins.