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Genetic testing is essential for patients with Leber congenital amaurosis or retinitis pigmentosa and those interested in gene therapy trials.
It is becoming increasingly necessary for optometrists to keep up-to-date on the most recent advances in genetic testing and genomics research as scientific knowledge regarding the genetic causes of ocular disease and gene therapy continues to expand.
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Patients with inherited retinal disease (IRD) can benefit from genetic testing to achieve a more accurate genetic diagnosis, gain a more precise prognosis, and facilitate gene-specific medication and management. Patients with retinitis pigmentosa (RP) or Leber's congenital amaurosis require confirmation of pathogenic RPE65 gene mutations to be eligible for Luxturna (Spark Therapeutics) gene therapy. Numerous ongoing interventional clinical trials require genetic diagnosis confirmation, including gene therapy, gene editing, and antisense oligonucleotide-based therapy. Patients and their families can also benefit from genetic counseling and referrals to helpful resources, such as support groups and low-vision rehabilitation.
Genetic Testing
Obtaining a saliva sample and submitting it to a lab is the beginning of a comprehensive genetic testing procedure. In contrast to a COVID test, which produces a simple positive or negative result, additional elements are involved in hereditary retinal illnesses.
In 2014, the Task Force on Genetic Testing of the American Academy of Ophthalmology (AAO) issued Recommendations for Genetic Testing of Inherited Eye Diseases. For illnesses for which the causative gene(s) have been identified, the paper recommends ordering testing through a Clinical Facility Improvement Amendments (CLIA)-accredited laboratory. Consumer-direct testing should be avoided. In addition, the document describes five components of genetic testing: " the clinical determination that a genetic eye disease is likely present, the molecular investigation of genomic DNA samples, the analysis of the resulting molecular data in the context of relevant published literature and public databases using appropriate statistical methods, the interpretation of the data in the context of the clinical findings, and the counseling of the patient regarding the interpretation."
If optometrists consider incorporating genetic testing into their clinical practice, they should have the plan to cover certain components.
Part 1: clinical exam. The initial examination is required to establish a tentative diagnosis or many differential diagnoses. Additional tests such as imaging, visual fields, and electroretinography may be performed depending on the eye condition. The Recommendations on Clinical Assessment of Patients with Inherited Retinal Degenerations of the American Academy of Ophthalmology provide an excellent summary of clinical testing for IRDs.
Using clinical examination and differential diagnosis is crucial to choose the proper genetic test panel. The panel should consist of genes related to the differential diagnosis. For instance, a patient suspected of having X-linked RP should be examined with a panel containing several genes associated with RP. Check if the panel includes the RPGR gene responsible for most X-linked RP cases.
However, checking additional genes is not always advantageous. For a patient with clinical symptoms of inherited retinal dystrophy, ordering an inherited retinal dystrophy panel rather than whole-exome sequencing is recommended. Ordering the right panel raises the likelihood of obtaining a clinically relevant result while decreasing the likelihood of unrelated secondary findings.
Parts 2 and 3: Parts 2 and 3 include sample collecting and laboratory testing. There are numerous facilities and testing panels from which to choose, and working with a CLIA-accredited laboratory is crucial advice. The Blueprint Genetics Retinal Dystrophy Panel and the Invitae Inherited Retinal Disorders Panel are two regularly utilized test panels. Both include about 330 genes linked to hereditary retinal diseases. In addition to alternatives for self-payment and insurance billing, these panels are supported by no-cost testing initiatives.
Minimal specialized equipment is required for in-office genetic testing, and clinical personnel can immediately request specimen-collecting kits from testing laboratories. In optometric practice, saliva and buccal swab samples are the most frequently acquired. The patient must spit into a tube for saliva samples, whereas numerous cheek swabs are required for buccal samples. Patients should abstain from eating, drinking, and chewing gum before saliva collection.
Testing in the laboratory may take two to four weeks. The ordering practitioner and patient may get access to the results via the website of the particular laboratory.
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