This article is from November/December 2006 and may contain outdated material.
Retinitis pigmentosa is a group of heritable disorders of the retinal pigment epithelium (RPE) and photoreceptors that cause progressive visual field constriction and nyctalopia. Arteriolar narrowing, hyalinization and “waxy” optic disc pallor are found in almost all cases. Pigmentary changes are often found but may be absent or mild, especially early in the course of the disease. Typical pigment changes include diffuse granularity or stippling, pigment clumping and “bone spicule” deposits; these changes represent degeneration of the photoreceptors, atrophy of the outer retina and pigment epithelium, and migration of RPE cells into the retina.
Prevalence and History
The prevalence of RP worldwide is approximately one in 4,000. The prevalence increases during the first four decades of life and stabilizes over the next two to three decades. While up to one-quarter of all patients with RP will become legally blind in both eyes, it is rare to lose all vision. More than half of all patients with RP have visual acuity of 20/40 or better in at least one eye.
Most commonly, patients have RP as a result of multifactorial genetics, de novo development of an autosomal dominant gene or incomplete penetrance. Typically, they have no family history.
However, RP can exhibit autosomal dominant, autosomal recessive, X-linked recessive and indeterminate patterns of inheritance. The age of onset and the severity of disease vary, depending on the inheritance pattern. The autosomal dominant variant generally demonstrates milder clinical findings, with preservation of central vision into the sixth through eighth decades of life. The X-linked recessive form is the least common and most severe, with affected males having significant visual impairment usually by the fourth decade.
RP is usually an isolated finding, but rarely it may be associated with a systemic disorder. The association of RP with congenital sensorineural hearing loss in the absence of other systemic involvement is termed Usher’s syndrome. Hearing loss in patients with Usher’s syndrome is almost invariably nonprogressive. It is important to reassure patients with RP who have been hearing-impaired since birth that they are unlikely to become deaf, even though their vision may deteriorate.
Several other systemic associations with RP-like fundus patterns include mental retardation and obesity in Bardet-Biedl and Laurence-Moon syndromes, and external ophthalmoplegia and heart block in Kearns-Sayre syndrome.
Causes of Vision Loss
The common causes of vision loss in patients with RP include progression of retinal degeneration to the macula, cystoid macular edema and posterior subcapsular cataracts.
Retinal degeneration. The loss of photoreceptor and RPE function in RP progresses posteriorly and may lead to loss of visual acuity from macular involvement as well as to decreased visual function due to visual field constriction. Of all causes of visual loss in macular disease in RP, macular degeneration is the most common. Macular atrophy of the RPE and mottled angiographic transmission defects are more common in patients with a long duration of disease or with extensive peripheral degenerative changes.
Cystoid macular edema. Other macular lesions that occur in patients with RP include CME, macular hole and epiretinal membrane. Approximately 20 percent of patients with RP will develop CME. The mechanism of CME formation in RP is unknown; blood-retinal barrier breakdown and retinal edema secondary to chronic low-grade intraocular inflammation may lead to the development of CME.
Posterior subcapsular cataracts. RP is commonly associated with the development of PSC cataracts. About half of all patients with RP will develop PSC cataracts. Even small lens opacities may be significantly disabling in patients with RP, due to the preexisting visual field constriction and difficulties in low ambient light settings. As with CME, the development of cataracts in RP patients may be related to low-grade chronic inflammation.
Inflammation. While “retinitis” is considered a semantically incorrect term in RP, some evidence of chronic mild inflammation has nevertheless been shown. Manifestations of inflammation include vitreous cells, aqueous flare, CME and PSC cataracts. Laboratory analyses have identified heterogenous leukocytes, including macrophages and CD4, CD8, activated T, suppressor T and B cells, in eyes with RP while controls demonstrate only rare macrophages.
Other visual problems. Myopia, astigmatism and higher-order wavefront aberrations may be more prevalent in patients with RP. They also may have vitreous degenerative changes and may be aware of floaters due to vitreous cells, clumps and posterior vitreous detachment. Retinal detachment is an infrequent complication; its incidence in RP patients is similar to that in the general myopic population. Open-angle glaucoma occurs in patients with RP at a rate similar to that seen in the general population. Although optic disc pallor is observed almost universally in patients with RP, it does not necessarily denote optic atrophy, as the inner retinal layers remain intact until the late stages of the disease. Thus, optic disc atrophy is not considered a common cause for visual loss in RP patients; however, it may make examination of the optic disc for glaucomatous changes a challenge.
Treatment
It is important to follow patients with RP on a yearly basis and to watch for the development of potentially reversible causes of vision loss. Unfortunately, there is no effective treatment for macular degeneration; however, both CME and PSC cataracts are amenable to treatment.
Macular degeneration. There is no effective therapy for macular degeneration in RP. Vitamin A therapy is controversial, not having been shown to improve visual field, visual acuity or dark adaptation in multiple controlled trials. A large double-masked, randomized trial failed to demonstrate improvement in visual field or visual acuity in patients who received chronic daily oral vitamin A (15,000 IU/day) vs. controls.1 However, the study demonstrated a slower rate of decline in cone electroretinogram amplitude in patients receiving vitamin A vs. controls over a four- to six-year period. This has led to the recommendation by some professionals that vitamin A may be offered as a treatment to slow the progression of macular degeneration. However, the long-term administration of high-dose vitamin A is associated with the risk of hepatotoxicity, teratogenicity and mortality.
The same study found that oral vitamin E supplementation was associated with more rapid worsening of electroretinogram amplitudes vs. controls.
Other treatments such as topical 50 percent dimethyl sulfoxide eye drops and light deprivation therapy have demonstrated no improvement of visual acuity or decrease in the rate of progression of macular degeneration. Current research on therapies for RP includes ciliary neurotrophic factor encapsulated- cell technology2 and adenovirus-mediated gene therapy.3
Cystoid macular edema. Loss of visual acuity due to CME formation in patients with RP may be reversed with the administration of systemic carbonic anhydrase inhibitors such as acetazolamide (Diamox). Daily oral acetazolamide was shown to result in decreased central macular thickness and CME on serial OCT examinations.4 In general, acetazolamide is more effective in treating macular edema in diseases with diffuse RPE degeneration than in vascular diseases such as diabetic retinopathy and venous occlusive disease. Acetazolamide increases fluid transport through the RPE by active ion transport and acidification of the RPE. Macular edema due to low-grade inflammation may respond better to this mechanism than diffuse loss of endothelial tight junctions, as occurs in diabetes. Topical carbonic anhydrase inhibitors have a lower rate of systemic side effects than acetazolamide, but are less efficacious. CME that is refractory to acetazolamide treatment usually leads to permanent visual acuity loss, although some investigators have tried intravitreal corticosteroid injections for recalcitrant CME.
Cataracts. The risks of cataract surgery in patients with RP may be greater than in healthy controls; these risks include progression of outer layer macular retinal atrophy, macular edema, phototoxicity, posterior capsular opacification and anterior capsular phimosis.
In spite of these risks, cataract extraction in RP patients is often successful. In a retrospective study of 142 eyes with RP that underwent cataract extraction between 1985 and 1997, visual acuity improved in 77 percent of eyes and worsened in only 2.5 percent.5 There was an unexpectedly low incidence of postoperative macular edema overall, and a higher-than-average incidence of posterior capsular opacification compared with the risk in healthy eyes. Failure of visual acuity to improve following cataract extraction was attributed to macular edema in most eyes.
Only 37 percent of eyes in the study underwent phacoemulsification, with the remainder undergoing extracapsular cataract extraction; results were not analyzed by these subgroups. Thus cataract surgery is usually successful in RP patients, even with nonphacoemulsification techniques. Surgical outcomes may be even more favorable when phacoemulsification is used in all cases.
Low Vision Therapy
Low vision services may be very helpful for patients with RP, who experience multiple visual disabilities, including reduced contrast sensitivity, poor dark adaptation, glare and poor color vision. These disabilities may lead to difficulties with walking, recognizing objects, searching in cabinets, preparing food and other activities of daily living.
RP patients often develop a scanning pattern with distance vision in order to adapt to a diminishing visual field. This allows their functional vision to be much greater than a visual field test would measure. Unfortunately, this need to scan often means that distance visual acuity aids such as telescopes are poorly accepted. (It is important to document the extent of formal visual field in assessing the ability to drive; the states each have their own requirements for maintaining a legal driver’s license.)
For dark-adaptation difficulties, a simple penlight is useful for searching in dark cabinets or finding a keyhole at night. Near visual aids such as lighted magnifiers and closed-circuit televisions are helpful for reading and writing.
Patients with RP walk more slowly and are more likely to suffer a fall, especially in unfamiliar surroundings, than individuals with normal vision of the same age. Occupational therapy is often helpful, as well as orientation and mobility services such as guide dogs.
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1 Berson, E. L. et al. Arch Ophthalmol 1993;111:761–772.
2 Tao, W. et al. Invest Ophthalmol Vis Sci 2002;43:3292–3298.
3 Smith, A. J. et al. Mol Ther 2003;8:188–195.
4 Apushkin, M. A. et al. Ophthalmology 2004;111:1899–1904.
5 Jackson, H. et al. Br J Ophthalmol 2001;85:936–938.
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Dr. Schartman is chief resident of ophthalmology, and Dr. Scott is professor of ophthalmology and residency program director. Both are at Pennsylvania State University in Hershey.