para>Leber congenital amaurosis characterized by reduced vision from birth and impaired electroretinogram responses from both cones and rods. ‚
Geriatric Considerations
Late-onset RP is asymptomatic and generally unrecognized until >40 years of age.
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ETIOLOGY AND PATHOPHYSIOLOGY
- Mutations in the rhodopsin gene account for ~30% of cases of autosomal dominant RP.
- Another 4 " “6% of autosomal dominant RP is caused by a mutation in the gene for a photoreceptor protein peripherin/RDS.
Genetics
- Autosomal dominant: 20%
- Autosomal recessive: 37%
- X-linked recessive: 4.5%
- Sporadic: 38.5%
RISK FACTORS
Family history ‚
GENERAL PREVENTION
- Genetic counseling
- No conclusive evidence demonstrates that the amount of light modifies the course of RP. A study in which one eye was covered with an opaque lens did not show any difference in disease progression compared with the fellow eye.
- Ultraviolet (UV)-absorbing sunglasses and brimmed hats are recommended when patients are at the beach or in the snow.
COMMONLY ASSOCIATED CONDITIONS
With systemic disorders ‚
- Usher syndrome: RP and congenital sensorineural hearing impairment
- Laurence-Moon-Biedl syndrome (also called Bardet-Biedl syndrome): Autosomal recessive disorder associated with retinal dystrophy, mental retardation, obesity, hypogonadism, and postaxial polydactyly.
- Cockayne syndrome: autosomal recessive disorder in which children at the age of 1 to 2 years present with retinal dystrophy, sensorineural deafness, cerebellar dysfunction, dementia, and UV light photosensitivity
DIAGNOSIS
HISTORY
- Headache and light flashes are the most common initial complaints.
- Night blindness (nyctalopia)
- Progressive visual field loss
- Central visual acuity is usually preserved until the end stages.
PHYSICAL EXAM
- Bone spicule pigmentation in the retina
- Retinal arteriolar narrowing
- Optic nerve head pallor, "waxy pallor " ¯
- Most patients are myopic.
- Posterior subcapsular cataracts are common in all forms.
- Cystoid macular edema
- Optic nerve head drusen
- Electroretinogram changes
- Retinal neovascularization
- RP is associated with an exudative retinal vasculopathy; fundus findings include serous retinal detachment, lipid deposition in the retina, and telangiectatic vascular anomalies.
- Variants of RP exist with unusual or regional distribution, including the following:
- Sectorial RP
- Pigmented paravenous atrophy
- Unilateral RP
DIFFERENTIAL DIAGNOSIS
- Bone spicule-like retinal pigmentation and retinal atrophy are nonspecific findings and may result from conditions other than RP.
- Infections
- Syphilis
- Rubella
- Inflammation (severe uveitis)
- Choroidal vascular occlusion
- Toxicity (chloroquine or thioridazine)
- Choroideremia
- Gyrate atrophy of choroid and retina (10- to 20-fold elevation of plasma ornithine levels)
- Systemic metabolic disorders such as Refsum disease and abetalipoproteinemia
- Kearns-Sayre syndrome: usually presents in adolescents; characterized by progressive external ophthalmoplegia " ”the first sign usually being ptosis " ”pigmentary degeneration of the retina, and a cardiac conduction defect that may cause complete heart block.
- Cone-rod dystrophy: characterized by bilateral and symmetric loss of cone function in the presence of reduced rod function
- Cone dystrophy: characterized by marked abnormality in cone function with some or no rod involvement
- Congenital stationary night blindness
- Oguchi disease
- Fundus albipunctatus
- Trauma
DIAGNOSTIC TESTS & INTERPRETATION
- Electroretinography: Photoreceptors generate reduced-amplitude A and B waves in RP. Rod and cone responses may be undetectable in advanced RP.
- Visual field testing: A ring scotoma in the midperiphery may be identified. The ring scotoma generally starts as a group of isolated scotomas in the area 20 to 25 degrees from fixation. Long after the entire peripheral field is gone, a small island of intact central visual field remains.
- Fluorescein angiography can demonstrate cystoid macular edema.
- Fundus photography documents the status of the retina.
- Hearing tests in patients complaining of hearing loss, such as those with Usher syndrome (RP with hearing loss)
- Optical coherence tomography can be used to detect and monitor cystoid macular edema.
- An abnormal hyperautofluorescent ring surrounding the fovea may be present on fundus autofluorescence imaging (FAF). In addition, spectral-domain optical coherence tomography (SD-OCT) has demonstrated a decrease in retinal thickness in the area of the hyperautofluorescent ring in RP patients with loss of the inner segment/outer segment (IS/OS) junction.
- Abnormal FAF precedes loss of retinal function and is helpful for monitoring disease progression (1)[C].
Initial Tests (lab, imaging)
Follow-Up Tests & Special Considerations
- Elevated plasma levels of phytanic acid in Refsum disease
- Acanthocytosis of RBCs in peripheral blood smear in abetalipoproteinemia, an autosomal recessive disorder in which apolipoprotein B is not synthesized, leading to fat malabsorption and deficiencies of fat-soluble vitamins; therapy with vitamins A and E may improve retinal function.
- Syphilitic neuroretinitis can be diagnosed by performing a fluorescent treponemal antibody absorption or microhemagglutination Treponema pallidum test.
- Elevated plasma ornithine levels in gyrate atrophy of the choroid and retina; usually a 10- to 20-fold elevation of plasma ornithine levels
Test Interpretation
- Disappearance of the rods, cones, and outer nuclear layers of the retina
- Bone spicule formation in the retina is secondary to the migration of retinal pigment epithelial cells into the overlying retina.
TREATMENT
GENERAL MEASURES
- Supportive care
- Genetic counseling
- Low-vision aids
- Patient education
MEDICATION
- Vitamin A 15,000 IU/day (retinal degeneration slowed, as measured by electroretinogram/visual fields); ˇ ²-carotene is not a suitable substitute; has not been studied in patients <18 years of age.
- Vitamin E 400 IU/day results in faster retinal degeneration and is not recommended.
- Lutein supplementation at a dose of 12 mg/day slowed visual field loss among nonsmoking adults with RP taking vitamin A (2)[B].
- Acetazolamide may be of benefit in the treatment of cystoid macular edema, which may occur in RP; 500 mg/day in a sustained-release capsule was found to be more effective than 250 mg/day.
- Topical dorzolamide may be of benefit in the treatment of cystoid macular edema associated with RP in those unable to tolerate systemic effects of acetazolamide.
- Intravitreal bevacizumab and ranibizumab injection may be of benefit in the treatment of cystoid macular edema associated with RP.
- Contraindications: Women who are pregnant or considering pregnancy should not take >8,000 IU/day of vitamin A. There is an increased incidence of birth defects in babies born to women who ingest higher dosages of vitamin A during pregnancy. Women should consult their obstetrician.
- Precautions: Avoid vitamin A supplement dosages >15,000 IU/day because higher dosages may cause liver damage.
- Oral docosahexaenoic acid has not been shown to be effective in slowing the loss of cone or rod ERG function in patients with X-linked RP (3)[B].
- Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants showed no therapeutic benefit (4)[B].
Pregnancy Considerations
Risk of teratogenicity with a high intake of vitamin A during pregnancy
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SURGERY/OTHER PROCEDURES
- The efficacy of the "Cuban therapy " ¯ " ”electric stimulation, autotransfused ozonized blood, and ocular surgery " ”has not been proven.
- Macular grid laser photocoagulation may be of benefit in patients with cystoid macular edema secondary to RP.
- Research is being done on photoreceptor and retinal pigment epithelium transplantation, gene therapy, and implantation of a visual prosthesis. The inner retinal neurons may be preserved after death of photoreceptors in RP, which could make some of these experimental procedures feasible.
- Patients who are blind from RP showed improvement in visual tasks with the Argus II retinal prosthesis (5)[B].
- Gene therapy has been successful in treating patients with Leber congenital amaurosis due to defects in the RPE65 gene (6)[C].
- Zonular instability can be noted in RP patients; therefore, care must be taken during cataract surgery (7)[B].
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Caution should be exercised because of reduced peripheral vision and poor night vision. ‚
Patient Monitoring
- Ophthalmic examinations every 1 to 2 years
- Check for complications (e.g., cataracts).
DIET
A diet rich in omega-3 fatty acids (primarily docosahexaenoic acid), when taken in combination with 15,000 IU/day of vitamin A, may slow the rate of visual acuity loss in patients with RP. A recent study has casted doubt on this claim. ‚
PATIENT EDUCATION
- Counsel patients to help them understand RP and its genetics.
- RP is a slowly progressive chronic disease; patients do not go blind rapidly, and total blindness is not a frequent end point of this disease.
- RP Foundation Fighting Blindness, Executive Plaza One, Suite 800, 11350 McCormick Road, Hunt Valley, MD 21031-1014 (800) 683-5555
- The American Academy of Ophthalmology, 655 E. Beach Street, San Francisco, CA 94109-1336 (415) 561-8540
PROGNOSIS
- Reassure about the slow course of RP.
- Most of the deafness in Usher syndrome is congenital. It is unlikely that an RP patient who is not born deaf will become deaf later in life.
- RP severity varies with inheritance pattern.
- Autosomal recessive form has an early age of onset, and patients may have severely constricted visual fields by age 20 years. Tends toward more rapid progression compared with autosomal dominant RP; also increased incidence of cataracts
- X-linked RP is similar in clinical presentation to autosomal recessive RP.
- Autosomal dominant RP generally has less severe findings initially than does autosomal recessive RP; symptoms may not occur until age 30 years.
- Good central vision is usually preserved. If the central visual field radius is >30 degrees, >90% of patients will have visual acuities of 20/40 or better. If the central visual field radius is <10 degrees, 30% of patients will have a visual acuity of 20/40 or better.
COMPLICATIONS
- Cataract
- Cystoid macular edema
- Loss of visual field
- Poor night vision
- Blindness
REFERENCES
11 Ogura ‚ S, Yasukawa ‚ T, Kato ‚ A, et al. Wide-field fundus autofluorescence imaging to evaluate retinal function in patients with retinitis pigmentosa. Am J Ophthalmol. 2014;158(5):1093 " “1098.22 Berson ‚ EL, Rosner ‚ B, Sandberg ‚ MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010;128(4):403 " “411.33 Hoffman ‚ DR, Hughbanks-Wheaton ‚ DK, Pearson ‚ NS, et al. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial. JAMA Ophthalmol. 2014;132(7):866 " “873.44 Birch ‚ DG, Weleber ‚ RG, Duncan ‚ JL, et al. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa. Am J Ophthalmol. 2013;156(2):283 " “292.e1.55 Rizzo ‚ S, Belting ‚ C, Cinelli ‚ L, et al. The Argus II Retinal Prosthesis: 12-month outcomes from a single-study center. Am J Ophthalmol. 2014;157(6):1282 " “1290.66 Bainbridge ‚ JW, Smith ‚ AJ, Barker ‚ SS, et al. Effect of gene therapy on visual function in Leber 's congenital amaurosis. N Engl J Med. 2008;358(21):2231 " “2239.77 Dikopf ‚ MS, Chow ‚ CC, Mieler ‚ WF, et al. Cataract extraction outcomes and the prevalence of zonular insufficiency in retinitis pigmentosa. Am J Ophthalmol. 2013;156(1):82 " “88.e2.
ADDITIONAL READING
- Berson ‚ EL, Rosner ‚ B, Sandberg ‚ MA, et al. ¸ ‰-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012;130(6):707 " “711.
- Chen ‚ RW, Greenberg ‚ JP, Lazow ‚ MA, et al. Autofluorescence imaging and spectral-domain optical coherence tomography in incomplete congenital stationary night blindness and comparison with retinitis pigmentosa. Am J Ophthalmol. 2012;153(1):143 " “154.e2.
CODES
ICD10
H35.52 Pigmentary retinal dystrophy ‚
ICD9
362.74 Pigmentary retinal dystrophy ‚
SNOMED
- Retinitis pigmentosa (disorder)
- X-linked retinitis pigmentosa (disorder)
- Autosomal dominant retinitis pigmentosa (disorder)
CLINICAL PEARLS
- Characterized by poor night vision, constricted visual fields, bone spicule-like pigmentation of the fundus, and electroretinographic evidence of photoreceptor cell dysfunction
- Avoid vitamin E, as it results in faster retinal degeneration and is not recommended; Vitamin A is recommended.
- RP severity varies with inheritance pattern.