Clinical diagnosis
Steps to achieving a full diagnosis in IRD
Diagnosing IRD
Retinal dystrophies can be categorized in several ways including if they are syndromic (those affecting other organ systems, e.g., Usher syndrome), or non-syndromic (those where the symptoms are solely vision-related) and by the subtype of cell that is predominantly affected.1-4
In conditions where rod cells are more severely affected, nighttime or low-light and peripheral vision will be affected before degeneration of the central macula and colour vision. In those where cone cells are primarily affected, the primary signs may be photophobia, poor central vision, and impaired colour vision before further visual impairment becomes apparent.3
Adapted from Fighting Blindness Canada Website and Atlas of Inherited Retinal Diseases.2,5
In babies and young children
- Nystagmus (uncontrolled eye movements)3
- Failure to fix and follow3
- Photophobia (sensitivity to light)3
- Undetectable ERG recording3
- Reduced visual field and/or reduced light sensitivity3
- Problems with hearing and balance (associated with Usher syndrome)3
In older children, teenagers and adults
- Loss of visual acuity1
- Nyctalopia (loss of night vision)1,3
- Problems seeing in dim or low light1
- Slow eye response when switching from bright to dim light7
Electroretinogram
Using a skin electrode in young children or contact lens electrodes with older children and adults. Flash, pattern, and flicker light stimuli are used to detect photoreceptor response and function.2,8,9
Fundus autofluorescence
Lipofuscin, a fluorophore, is stored in the retinal pigment epithelium and can act as a surrogate marker of photoreceptor activity that can be picked up by fundus autofluorescence. Different patterns of fluorescence can indicate particular diagnoses.2
Optical coherence tomography (OCT)
OCT uses light reflection to visualize the structure of different layers of the retina in fine detail. It can be used to measure retinal thickening and to determine the level of progression of retinal dystrophies.2,10
Genetic testing
Previously, diagnosis of IRD has relied heavily on clinical testing. More recently there has been the development of new screening methods, and increasing interest in specific gene mutations.3,8
What is genetic testing?
Genetic testing is a medical test that studies human DNA to discover genetic changes or mutations that could lead to genetic disease. Genetic testing is performed on samples of DNA, usually from blood or saliva, and involves DNA sequencing to identify mutations. Most genetic testing looks at a panel of a few hundred genes that are known to be mutated in IRDs.2,11
Deciding if genetic testing would be appropriate for your patient
Genetic testing is appropriate for most patients with presumed genetically-caused retinal degeneration.8
Consider testing if:
Patient exhibits signs and symptoms of an IRD
Other systems/organs:
- Some IRDs can be syndromic and may affect other system/organs
- E.g., Usher Syndrome also results in hearing loss3
- E.g., Usher Syndrome also results in hearing loss3
Has a diagnosis of an inherited retinal dystrophy, or a family history of IRD8,11
Once your patient is suspected of having an IRD, consider ordering a genetic test as soon as possible. The wait times for genetic tests may be up to 1 to 2 years.
Genetic testing provides more information about your patient's IRD and is the only way of confirming which genes are affected, and can help with diagnosis.2,8,11 Patients may benefit from access to a genetic counsellor when receiving a genetic diagnosis. The process for ordering a genetic test can differ across provinces and may be complex, but is generally as follows: 3,5
1. An ophthalmologist or another physician specializing in medical genetics arranges for testing following a preliminary diagnosis. Click on the link below for a list of centers where genetic testing may be requested based on your location along with the associated referral forms:
Genetic testing centers by province:
https://www.cagc-accg.ca/index.php?page=225&id=
2. A genetic counsellor works with patients helping them to understand the purpose, benefits, risks, limitations, and the results of their genetic test.
3. DNA samples are taken with either blood or saliva; testing and counseling may take several months to years, depending on the province.
4. If initial gene panel test results are inconclusive, whole exome sequencing can be used to improve the likelihood of a genetic diagnosis, as there are a number of genes associated with IRDs.
