Retinitis Pigmentosa

Updated: Feb 17, 2015
  • Author: David G Telander, MD, PhD; Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

Practice Essentials

Retinitis pigmentosa (RP) is a group of inherited disorders characterized by progressive peripheral vision loss and night vision difficulties (nyctalopia) that can lead to central vision loss. See the image below.

Gross pathology of an eye in a man with retinitis Gross pathology of an eye in a man with retinitis pigmentosa.

Essential update: FDA approves first retinal implant for advanced adult RP

The US Food and Drug Administration (FDA) has approved the first retinal implant, the Argus II Retinal Prosthesis System, for adults aged 25 years or older with advanced RP. [1] Although this device will not restore vision to patients, it replaces the function of degenerated cells in the retina and may improve a patient’s performance of basic activities by improving their ability to perceive images and movement. [1]

The implant includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU), and an implanted retinal prosthesis (artificial retina). The VPU transforms images from the video camera into electronic data that are wirelessly transmitted to the retinal prosthesis. About two thirds of patients had no adverse events related to the device or the procedure; however, over one third of patients had a total of 23 serious adverse events, including conjunctival erosion, dehiscence, retinal detachment, inflammation, and hypotony. [1]

Signs and symptoms

Presenting signs and symptoms of RP vary, but the classic ones include the following:

  • Nyctalopia (night blindness): Hallmark; most commonly the earliest symptom in RP
  • Visual loss, usually peripheral; in advanced cases, central visual loss
  • Photopsia (seeing flashes of light)

A careful family history with pedigree and possible examination of family members can be useful. In addition, a drug history is essential to rule out phenothiazine/thioridazine toxicity.

See Clinical Presentation for more detail.

Diagnosis

Because RP is a collection of many inherited diseases, significant variability exists in the physical findings. Ocular examination involves assessment of visual acuity and pupillary reaction, as well as anterior segment, retinal, and funduscopic evaluation.

Systemic examination for RP can be helpful to rule out syndromic RP, which are conditions that have pigmentary retinopathy and mimic RP, such as the following:

  • Syndromes associated with RP and hearing loss: Usher syndrome, [2] Waardenburg syndrome, Alport syndrome, Refsum disease
  • Kearns-Sayre syndrome: External ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy
  • Abetalipoproteinemia: Fat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and pigmentary retinal degeneration
  • Mucopolysaccharidoses (eg, Hurler syndrome, Scheie syndrome, Sanfilippo syndrome): Can be affected with pigmentary retinopathy
  • Bardet-Biedl syndrome: Polydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy
  • Neuronal ceroid lipofuscinosis: Dementia, seizures, and pigmentary retinopathy; infantile form is known as Jansky-Bielschowsky disease, juvenile form is Vogt-Spielmeyer-Batten disease, and adult form is Kufs syndrome

Testing

The following laboratory tests are useful in excluding masquerading diseases or in detecting conditions that are associated with RP:

  • Infectious studies for syphilis (VDRL, FTA-ABS), toxoplasmosis (when suspected; serum IgG)
  • Inherited/syndromic disease studies for Refsum disease (serum phytanic acid in the presence of other neurologic abnormalities), gyrate atrophy (ornithine levels), Kearns-Sayre syndrome (ECG to help rule out heart block), and abetalipoproteinemia (lipid profile with possible protein electrophoresis)
  • Neoplasm related studies for antiretinal antibodies (particularly antirecoverin antibodies), especially in cancer-associated retinopathy (CAR) or in severe RP

Other studies that may be helpful include the following:

  • Electroretinogram (ERG): Most critical diagnostic test for RP
  • Electro-oculogram (EOG): Not helpful in diagnosing RP, but central macular changes, normal ERG findings, and abnormal EOG findings suggest Best vitelliform macular dystrophy (Best disease)
  • Formal visual field testing: Most useful measure for ongoing follow-up care of patients with RP; Goldmann (kinetic) perimetry is recommended
  • Color testing: Commonly, mild blue-yellow axis color defects, although most patients with RP do not clinically complain of major difficulty with color perception
  • Dark adaptation study: Disproportionately reduced contrast sensitivity relative to visual acuity in RP; bright-light sensitivity
  • Genetic subtyping: Definitive test for diagnosis to identify the particular defect

Imaging tests

Fluorescein angiography is rarely useful in diagnosing RP; however, the presence of cystoid macular edema can be confirmed by this test. Likewise, although optical coherence tomography (OCT) is not useful in helping to establish a diagnosis of RP, this imaging study can be helpful to document the extent and/or presence of cystoid macular edema.

Procedures

Biopsy for histologic examination in patients with RP is not clinically helpful, owing to the general good health of these patients and the chronic nature of the disease. Generally, specimens are obtained only on chronically atrophic retinas.

See Workup for more detail.

Management

There is currently no cure for RP; therefore, therapies are limited. Nonetheless, it is essential to help patients maximize the vision they do have with refraction and low-vision evaluation.

Pharmacotherapy

Medications used in the management of RP include the following:

  • Fat-soluble vitamins (eg, vitamin A, vitamin E, ascorbic acid)
  • Calcium-channel blockers (eg, diltiazem)
  • Carbonic anhydrase inhibitors (eg, acetazolamide, methazolamide)

The following are medications with potential adverse effects in RP:

  • Isotretinoin (Accutane)
  • Sildenafil (Viagra)
  • High-dose vitamin E

Surgery

Surgical management of RP generally involves cataract extraction. However, following FDA approval in February 2013 for the first retinal implant in adults with severe cases of RP, implantation of this device may become a viable treatment option. [1]

Investigational procedures with potential in managing RP include the following:

  • Surgical placement of growth factors
  • Transplantation of retinal or retinal pigment epithelial (RPE) tissue
  • Placement of retinal prosthesis or phototransducing chip
  • Subretinal gene therapy

See Treatment and Medication for more detail.

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Background

Retinitis pigmentosa (RP) is a group of inherited disorders characterized by progressive peripheral vision loss and night vision difficulties (nyctalopia) that can lead to central vision loss.

Gross pathology of an eye in a man with retinitis Gross pathology of an eye in a man with retinitis pigmentosa.

With advances in molecular research, it is now known that RP constitutes many retinal dystrophies and retinal pigment epithelium (RPE) dystrophies caused by molecular defects in more than 40 different genes for isolated RP and more than 50 different genes for syndromic RP. Not only is the genotype heterogeneous, but patients with the same mutation can phenotypically have different disease manifestations. In this article, the clinical manifestations for diagnosis, the new molecular understandings of the pathogenesis, and the latest therapeutic options for patients are reviewed.

RP can be passed on by all types of inheritance: approximately 20% of RP is autosomal dominant (ADRP), 20% is autosomal recessive (ARRP), and 10% is X linked (XLRP), while the remaining 50% is found in patients without any known affected relatives. RP is most commonly found in isolation, but it can be associated with systemic disease. The most common systemic association is hearing loss (up to 30% of patients). Many of these patients are diagnosed with Usher syndrome. Other systemic conditions also demonstrate retinal changes identical to RP.

Usher syndrome with typical retinitis pigmentosa a Usher syndrome with typical retinitis pigmentosa appearance.

RP is a misnomer, as the word retinitis implies an inflammatory response, which has not been found to be a predominant feature of this condition. As molecular understanding increases, RP will be further characterized by the specific protein/genetic defect. This characterization will have increasing importance in the determination of a prognosis and will likely allow clinicians to use gene-targeted therapies.

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Pathophysiology

RP is typically thought of as a rod-cone dystrophy in which the genetic defects cause cell death (apoptosis), predominantly in the rod photoreceptors; less commonly, the genetic defects affect the RPE and cone photoreceptors. [3] RP has significant phenotypic variation, as there are many different genes that lead to a diagnosis of RP, and patients with the same genetic mutation can present with very different retinal findings.

Cone dystrophy. Cone dystrophy.
Cone dystrophy demonstrating typical central macul Cone dystrophy demonstrating typical central macular atrophy found in this condition.

Histopathologic changes in RP have been well documented, and, more recently, specific histologic changes associated with certain gene mutations are being reported. The final common pathway remains photoreceptor cell death by apoptosis. The first histologic change found in the photoreceptors is shortening of the rod outer segments. The outer segments progressively shorten, followed by loss of the rod photoreceptor. This occurs most significantly in the mid periphery of the retina. These regions of the retina reflect the cell apoptosis by having decreased nuclei in the outer nuclear layer. In many cases, the degeneration tends to be worse in the inferior retina, thereby suggesting a role for light exposure.

The final common pathway in RP is typically death of the rod photoreceptors that leads to vision loss. As rods are most densely found in the midperipheral retina, cell loss in this area tends to lead to peripheral vision loss and night vision loss. How a gene mutation leads to slow progressive rod photoreceptor death can occur by many paths, as illustrated by the fact that so many different mutations can lead to a similar clinical picture.

Cone photoreceptor death occurs in a similar manner to rod apoptosis with shortening of the outer segments followed by cell loss. This can occur early or late in the various forms of RP.

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Epidemiology

Frequency

United States

The prevalence of typical RP is reported to be approximately 1 in 4000 in the United States. The carrier state is believed to be approximately 1 in 100. The highest reported frequency of occurrence for RP is among the Navajo Indians at 1 in 1878.

International

Worldwide prevalence of RP is approximately 1 in 5000. The frequency of occurrence for RP has been reported to be as low as 1 in 7000 in Switzerland.

Mortality/Morbidity

A multicenter population study by Grover et al of patients with RP who were at least 45 years or older found the following findings: 52% had 20/40 or better vision in at least one eye, 25% had 20/200 or worse vision, and 0.5% had no light perception. [4]

Sex

Usually, no sexual predilection exists. X-linked RP is expressed only in males; therefore, because of these X-linked varieties, men may be affected slightly more than women.

Age

The age of onset can vary. RP usually is diagnosed in young adulthood, although it can present anywhere from infancy to the mid 30s to 50s.

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