Clinical Assessment of Patients with Inherited Retinal Degenerations
Publication Date: November 1, 2022
Last Updated: November 10, 2022
Summary of Recommendations
Clinical Evaluation: Inherited Retinal Degenerative Diseases
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| Assessment | Initial Visit | Follow Up Visit Every 1-2 Years |
| History | ||
| Ocular (including current needs) | 1-4a | 1-4 |
| Medical (including current medications and history of retinotoxic medication use) | ||
| Family history of vision problems | ||
| Pedigree | ||
| Pedigree | 1-4 | 1-4 |
| Clinical eye examination | ||
| Best corrected visual acuity: Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol (or equivalent) | 1-4 | 1-4 |
| Color vision testing (optional) | ||
| Slit lamp biomicroscopy | ||
| Intraocular pressure | ||
| Indirect ophthalmoscopy | ||
| Imaging | ||
| Color fundus photos* | 1-4 | 1-4 |
| Spectral Domain Optical Coherence Tomography | 1-4 | |
| Fundus autofluorescence: Short wavelength with reduced illumination when possible | 1-4 | 1-4 |
| Infrared Reflectance or autofluorescence (when available) | 1,3, 4 | 1, 3, 4 |
| Visual fields | ||
| Kinetic | 1-4 | 1-4 |
| Static | 1-3b | 1-3b |
| Microperimetry | 1-4b | 1-4b |
| Electroretinography | ||
| Full-field ERGc (when appropriate) | 1-4 | 1-3 |
| Multifocal ERGd (when appropriate) | 2, 4 | 2, 4 |
| FST (useful with unsteady fixation or when ERG is non recordable) | ||
| Genetic Diagnostic Testing | ||
| Single gene vs gene panel testing | 1-4 | 1-4 (if earlier visits did not provide conclusive results) |
| Exome Sequencing | ||
| Genome sequencing (usually research) | ||
Legend:
a) Numbers refer to clinical phenotypes:
1. Rod-cone degenerations, such as retinitis pigmentosa. Those with stationary rod-cone dysfunction, such as congenital stationary night blindness, should be evaluated similarly at baseline, then followed with clinical eye examinations only.
2. Cone-rod degenerations. Conditions affecting cones that are traditionally considered stationary, such as achromatopsia, should also be evaluated similarly at baseline, then followed with eye examination annually as some cases may progress slowly, warranting ongoing follow up.
3. Chorioretinal degenerations, such as CHM-associated retinal degeneration (choroideremia) and gyrate atrophy.
4. Inherited dystrophies that involve the macula, such as cone degeneration, X-linked retinoschisis, ABCA4-associated macular degeneration (Stargardt disease), and PRPH2-associated macular degeneration (pattern dystrophy).
b) Static perimetry and microperimetry are of uncertain value for patients with advanced disease as they may have unstable, eccentric fixation that makes interpretation difficult.
c) Full-field ERG is not necessary in Best disease, North Carolina macular dystrophy or in cases of pattern dystrophy limited to the macula. However, if electro-oculogram testing is not available, full-field ERG should be normal in Best disease. A full-field ERG is appropriate for a patient with macular changes for whom one is considering cone or cone-rod dystrophy in the differential diagnosis. Also, a non-detectable ERG is not recommended to be repeated.
d) Multifocal ERG is of uncertain value in patients when central acuity is significantly reduced or fixation is unstable, as mentioned above.
*Fundus photos should be used sparingly in Stargardt disease and other maculopathies due to potential light toxicity, thus consideration should be given to limiting their use.
a) Numbers refer to clinical phenotypes:
1. Rod-cone degenerations, such as retinitis pigmentosa. Those with stationary rod-cone dysfunction, such as congenital stationary night blindness, should be evaluated similarly at baseline, then followed with clinical eye examinations only.
2. Cone-rod degenerations. Conditions affecting cones that are traditionally considered stationary, such as achromatopsia, should also be evaluated similarly at baseline, then followed with eye examination annually as some cases may progress slowly, warranting ongoing follow up.
3. Chorioretinal degenerations, such as CHM-associated retinal degeneration (choroideremia) and gyrate atrophy.
4. Inherited dystrophies that involve the macula, such as cone degeneration, X-linked retinoschisis, ABCA4-associated macular degeneration (Stargardt disease), and PRPH2-associated macular degeneration (pattern dystrophy).
b) Static perimetry and microperimetry are of uncertain value for patients with advanced disease as they may have unstable, eccentric fixation that makes interpretation difficult.
c) Full-field ERG is not necessary in Best disease, North Carolina macular dystrophy or in cases of pattern dystrophy limited to the macula. However, if electro-oculogram testing is not available, full-field ERG should be normal in Best disease. A full-field ERG is appropriate for a patient with macular changes for whom one is considering cone or cone-rod dystrophy in the differential diagnosis. Also, a non-detectable ERG is not recommended to be repeated.
d) Multifocal ERG is of uncertain value in patients when central acuity is significantly reduced or fixation is unstable, as mentioned above.
*Fundus photos should be used sparingly in Stargardt disease and other maculopathies due to potential light toxicity, thus consideration should be given to limiting their use.
Examinations for Patients with Inherited Retinal Degenerations
Patient evaluations aim to:
- Establish a clinical diagnosis so the patient receives appropriate care (prognosis, monitoring for co-morbidities, and assessment of other organs that may be affected in syndromic conditions). Other non-genetic causes of retinal degeneration should be considered and excluded.
- Provide information on the genetic nature and inheritance of the disease and communicate the implications to other relevant family members.
- Provide information about ongoing or future clinical trials and novel treatments.
- Help the patient and family cope with and prepare for progressive visual impairment (low vision consultation, employment accommodations, and emotional support).
What should be done
- A thorough ocular/medical history and pedigree documenting family history of eye disease should be obtained at the initial visit and updated during subsequent visits.
- Understanding the patient's mood and affect is important, being sensitive to signs of depression that may accompany progressive vision loss.
- Molecular genetic testing (genotyping) of the patient can be valuable to confirm the diagnosis and optimize management.
- Clinical evaluation:
- best-corrected visual acuity with manifest refraction using standardized eye charts,1
- biomicroscopy with measurement of intraocular pressure (assessment of cataracts and anterior segment anomalies),
- dilated ophthalmoscopy to document features potentially related to vision loss (optic nerve and other retinal diseases, deposits, vessels, atrophy, schisis and macular edema)
Imaging
- Standard color or wide-field fundus photography may be performed at the initial visit to provide documentation of disease state and provide the context to align and compare data from other fundus modalities such as fundus autofluorescence (AF) images.
- For patients with nyctalopia and/or peripheral visual field loss, wide-field imaging has advantages since the primary site of disease is not in the macula in early disease.
- Fundus photos should be used sparingly in Stargardt disease and other maculopathies due to the risk of light toxicity. A test should be ordered only if it will be useful to monitor disease progress or determine if a patient is eligible for a clinical trial.
- Macular or wide-field AF fundus imaging using reduced illumination (25%), longer exciting wavelengths, infrared AF or near infrared fundus reflectance are good alternatives to short-wavelength AF in patients with retinitis pigmentosa and Stargardt disease to possibly reduce the risk of phototoxicity, although near-infrared imaging provides distinct information.2, 3
- Near infrared fundus reflectance is a separate imaging modality from short-wavelength AF that also provides insight on RPE health.
- Optical Coherence Tomography (OCT) provides cross-sectional imaging of the photoreceptors, retinal pigment epithelium, and inner retinal layers including the retinal nerve fiber layer.
- High-density volume scans with documentation of central retinal thickness provide a useful baseline for monitoring progression in structural features and helping to monitor CME, epiretinal membranes or macular schisis.
Visual field testing
Visual field testing is important to document the functional extent of vision from central to the far periphery. This is essential for determination of legal blindness, disability, and to counsel patients on visual limitations.
-
- Static visual field testing has advantages of automated indices of sensitivity loss and performance parameters to assess reliability.
- Newer perimeters test the entire field, and digital data can be exported into other applications for specific purposes such as modeling of sensitivity, which is useful for quantitative measurement in clinical trials.
- Although static perimetry using the Humphrey visual field (HVF) 30-2 protocol is acceptable in the federal registry for the determination of legal blindness and vision-related disability, there are perimeters that allow static testing well beyond the 60-degree range.
- This document does not advocate for any specific company’s instrument or product.
- Kinetic perimetry is the most common method used to assess peripheral vision and for licensing requirements for driving, disability evaluations, and legal blindness status.
- Fundus-guided perimeters (microperimeters) are particularly useful for measuring macular function in patients with eccentric fixation due to maculopathy and to investigate structure-function correlations.4
- Static visual field testing has advantages of automated indices of sensitivity loss and performance parameters to assess reliability.
Electrophysiology
- The full-field electroretinogram (ERG) is is important for diagnosis and staging of diffuse photoreceptor disease, evaluating the retina-wide function of rods and cones.5
- Delays in cone b-wave implicit times are an early sign of disease and reflect retina-wide involvement.
- Young patients with disease that appears to be limited to the macula benefit from full-field ERGs to rule out retina-wide disease.
- Multifocal or pattern ERG testing can be useful for detection and monitoring disease progression for diseases that primarily affect the macula.6 However, its accuracy can be limited in those patients with notable loss of central vision who are unable to maintain steady fixation.
- ISCEV (International Society for Clinical Electrophysiology of Vision) has published and updated standards that enable recordings to be compared between institutions and examiners (http://link.springer.com/article/10.1007/s10633-014-9473-7).7, 8
- Although it is not a test that uses electrophysiology, the full-field stimulus test (FST)9,10 can be useful when retinal function can no longer be reliably documented by ERG and provides a test that can measure rod- and cone-mediated visual function, but does not require stable fixation or electrode contact with the eye.
Recommendation Grading
Overview
Title
Clinical Assessment of Patients with Inherited Retinal Degenerations
Authoring Organization
American Academy of Ophthalmology
Publication Month/Year
November 1, 2022
Last Updated Month/Year
August 9, 2023
Supplemental Implementation Tools
Document Type
Consensus
Country of Publication
US
Document Objectives
Patients with inherited retinal degenerations will benefit from evolving knowledge that may influence their outcome. Special attention to aspects of the history and ophthalmic examination, tests of retinal structure and function, and genetic testing all help to determine an accurate diagnosis. Clinical and genetic testing of patients with IRDs go hand in hand, and one should not be interpreted without the other to ensure accuracy. This Clinical Statement aims to guide Academy members and care providers to optimize evaluations at baseline and during ongoing care of patients with IRDs.
This Academy Clinical Statement provides recommendations and clinical genetic assessments of patients with inherited retinal degenerations (IRDs). Various testing procedures and the timing at which they are recommended are described for patients within 4 broad classes of IRD (rod-cone degenerations, cone-rod degenerations, chorioretinal degenerations and inherited macular dystrophies). Pediatric patients not infrequently require modified testing regimens or sedation for accurate assessment. Genetic testing and genetic counseling are essential components of the management of patients with IRDs as genetic testing may confirm the diagnosis, provide information to optimize management of the patient and family members, and potentially confirm eligibility to participate in clinical trials. For example, genetic testing is required to determine eligibility of patients for approved gene therapies such as voretigene neparvovec-rzyl for RPE65-related IRD. This document is intended to provide guidelines for the management of patients with IRDs and provides information to support and educate patients with IRD. As always, final decisions are the responsibility of the individual treating physicians and are based on the needs of individual patients.
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Infant, Older adult
Health Care Settings
Ambulatory
Intended Users
Genetics, nurse, nurse practitioner, optometrist, physician, physician assistant
Scope
Counseling, Diagnosis, Assessment and screening
Diseases/Conditions (MeSH)
D012162 - Retinal Degeneration
Keywords
Inherited retinal degenerations