Laboratory Studies
The tests described below are useful in excluding masquerading diseases or in detecting conditions that are associated with retinitis pigmentosa (RP).
Infectious laboratory tests include the following:
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Syphilis: Venereal Disease Research Laboratory (VDRL) test; fluorescent treponemal antibody absorption (FTA-ABS) test
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Toxoplasmosis (when suspected): Serum immunoglobulin G (IgG)
Inherited/syndromic disease laboratory tests include the following:
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Refsum disease: Serum phytanic acid in the presence of other neurologic abnormalities
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Gyrate atrophy: Ornithine levels
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Kearns-Sayre syndrome: ECG to help rule out heart block
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Abetalipoproteinemia: Lipid profile with possible protein electrophoresis
Neoplasm related laboratory tests: Antiretinal antibodies, particularly antirecoverin antibodies, may be observed, especially in CAR or in severe cases of RP. Commercial tests are available.
Imaging Studies
Although fluorescein angiography is rarely useful to the clinician in diagnosing RP, the presence of cystoid macular edema can be confirmed by this test.
Optical coherence tomography (OCT) can be helpful to document the extent and/or presence of cystoid macular edema. OCT is not useful in helping to establish a diagnosis of RP.
Other Tests
Electroretinogram
ERG is the most critical diagnostic test for RP because it provides an objective measure of rod and cone function across the retina and is sensitive to even mild photoreceptor impairment.
The full-field ERG in RP typically shows a marked reduction of both rod and cone signals, although rod loss generally predominates.
A and b waves are reduced since the primary site of disease is at the photoreceptors or RPE.
The ERG is usually abnormal by early childhood, except for some of the very mild and regional forms of RP.
By contrast, the diagnosis for cone dystrophies is aided in part by clinical findings but more definitively by the ERG. Severe and selective loss of cone function occurs with varying degrees of rod abnormality.
In fundus albipunctatus, ERG recordings have absent rod function; after 3-4 hours of dark adaptation, ERG findings may be normal.
Congenital stationary night blindness displays a negative waveform on ERG.
Electro-oculogram
Electro-oculogram (EOG) fndings are always abnormal when ERG findings are abnormal; therefore, EOG is not helpful to the clinician in diagnosing RP.
Central macular changes, normal ERG findings, and abnormal EOG findings suggest Best vitelliform macular dystrophy.
Visually evoked cortical potentials
Visually evoked cortical potentials (VECPs) rarely provide additional information to the clinician when diagnosing RP.
Formal visual field
Progressive loss of peripheral vision is a major symptom along with visual acuity changes; therefore, this test is the most useful measure for ongoing follow-up care of patients with RP.
Goldmann (kinetic) perimetry is recommended, as it can more easily detect progressive visual field changes.
Midperipheral scotomas develop early in RP. These visual field defects can join together to form a ring scotoma. Patients can go on to develop constricted visual fields or tunnel vision. Some patients progress to being legally blind with central vision intact, but peripheral vision is limited to less than 20°.
Color testing
Mild blue-yellow axis color defects are common, although most patients with RP do not clinically complain of major difficulty with color perception.
Dark adaptation
Contrast sensitivity often is reduced out of proportion to visual acuity in patients with RP. Patients are usually sensitive to bright light.
Patients with fundus albipunctatus have poor dark adaptation but may have normal results after 3-4 hours of adaptation.
Genetic testing
Because of the wide variety of subtypes of so-called RP or related pigmentary retinopathies, the definitive test for diagnosis is identifying the particular genetic defect. RP including rod dystrophies and rod-cone dystrophies are often monogenetic conditions in which change in one genetic locus is the cause of the retinal pathology.
Genetic subtyping will become more useful as therapies begin to target specific genetic subtypes. In addition, identifying the gene may prove helpful in determining the prognosis and in providing genetic counseling. Genetic testing will be essential for gene therapy, and many gene therapy clinical trials are already underway for the treatment for retinal dystrophies such as Leber congenital amaurosis, Usher syndrome, Stargardt disease, and RP due to mutations in MERTK gene.
Medical insurance will not always cover the costs of genetic testing; however, the cost of these tests continues to decrease.
Histologic Findings
Histology is not clinically helpful. Because of the general good health of patients with RP and the chronic nature of the disease, histology usually has been obtained only on chronically atrophic retinas. Nonspecific atrophy of the sensory retina with hyperplastic changes in the RPE is observed. Animal studies of experimental RP models show cellular apoptosis in some varieties; in others, abnormalities of the rod outer segments are observed.
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Usher syndrome with typical retinitis pigmentosa appearance.
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Choroideremia.
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Bull's eye maculopathy seen in cone dystrophy.
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Polydactyly seen in Bardet-Biedl syndrome (associated with retinitis pigmentosa).
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Cone dystrophy.
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Gross pathology of an eye in a man with retinitis pigmentosa.
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Leber congenital amaurosis.
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Female carrier of choroideremia.
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Representative electroretinograms of patients with healthy eyes, rod-cone dystrophy, and congenital stationary night blindness. Courtesy of Dr. Nusinowitz, Jules Stein Eye Institute.
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Representative electroretinograms of patients with healthy eyes and X-linked retinoschisis. Courtesy of Dr. Nusinowitz, Jules Stein Eye Institute.
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Retinitis pigmentosa pigmentation pattern demonstrated with ultrawide fundus imaging using the scanning laser ophthalmoscope (Optomap; Optos PLC, Dunfermline, Scotland, United Kingdom).
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Fellow eye of same patient as in the image above, again demonstrating a typical retinitis pigmentosa pigmentation pattern demonstrated with ultrawide fundus imaging using the scanning laser ophthalmoscope (Optomap; Optos PLC, Dunfermline, Scotland, United Kingdom).
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Higher resolution image of typical bone spicule formation.
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Cone dystrophy demonstrating typical central macular atrophy found in this condition.
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Retinitis pigmentosa, rubella, a history of retinal detachment, and syphilis all may result in a hyperpigmented retinal pigment epithelium (RPE) with bone spicule appearance, restricted visual field and/or poor vision, and atrophic vessels.
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Retinitis pigmentosa progresses over decades. Associated cataract also is relevant, as seen in this image.
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Pigmentary changes are not always seen in retinitis pigmentosa but frequently are observed, as in this patient with Alström disease.
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Genetic screening may be helpful in identifying patients who are at risk, in counseling, and in directing treatment as new knowledge is acquired. Some varieties of retinitis pigmentosa may have increased vulnerability to environmental hazards; for example, one might avoid light exposure in some rhodopsin mutations or sildenafil in phosphodiesterase mutations. Patients with retinitis pigmentosa may have other findings. This patient with Alström disease shows acanthosis.
