AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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.

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 100 different genes. 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: 20-25% is autosomal dominant, 15-20% is autosomal recessive, and 5-10% is X linked, while the remaining 45-50% 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.

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.

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. The phenotypic variation is very significant because over 100 genes can cause RP.

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 over 100 gene 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.

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.⁴¹

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.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Presenting symptoms of RP vary, but the classic symptoms include the following:
• Nyctalopia: The earliest symptom in RP is most commonly night blindness and is considered a hallmark of the disease.
• • Patients might report difficulties with tasks at night or in dark places, such as trouble walking in dim lit rooms (eg, movie theaters). Patients may report difficulties driving in low light, at dusk, or in foggy conditions.
  • Patients may also report a prolonged period of time needed to adapt from light to dark.

• Visual loss: Peripheral vision loss is often asymptomatic; however, some patients notice this vision loss and report it as tunnel vision.
• • Patients may report bumping into furniture or doorframes or difficulties with sports requiring peripheral vision (eg, tennis, basketball).
  • The loss of vision is painless and slow to progress.

• Photopsia: Many patients with RP report seeing flashes of light (photopsia) and describe them as small, shimmering, blinking lights similar to the symptoms of an ophthalmic migraine. However, in contrast to the patient with an ophthalmic migraine, the photopsia may be continuous rather than episodic.
• A careful family history with pedigree and possible examination of family members can be useful.
• Drug history is essential to rule out phenothiazine/thioridazine toxicity.

Physical

• Ocular examination: Because RP is a collection of many inherited diseases, significant variability exists in the physical findings. Interestingly, even patients with the same genetic defect can have different clinical manifestations of the disease. The most common findings are described below.
• • Vision: Snelling visual acuity can vary from 20/20 to light perception, but it is usually preserved until late in the disease.
  • Pupils: Pupil reaction can be normal with or without afferent pupillary defect.
  • Anterior segment: Patients can develop posterior subcapsular cataracts; up to 50% of adult patients with RP have this type of cataract.
  • Fundus: The retina can appear unaffected early in the disease.
    • Typical key findings include the following:
      • Bone spicules - Midperipheral retinal hyperpigmentation in a characteristic pattern

      • Optic nerve waxy pallor

      • Atrophy of the RPE in the mid periphery of the retina

      • Retinal arteriolar attenuation

    • The presence of vitreous cells is common. Patients can have a loss of the foveolar reflex or an abnormal vitreoretinal interface. A subset of patients with RP develops cystoid macular edema with an associated more rapid and potentially reversible loss of vision.

    • Retinitis punctata albescens, a variant of RP, presents with yellow deposits deep in the retina rather the normal increased pigmentation of the peripheral retina.
  • Cone-rod retinal degenerations present with central macular pigmentary changes (bull's eye maculopathy). Choroideremia and gyrate atrophy typically present with large scalloped areas of peripheral retinal atrophy.

• Systemic evaluation: A physical examination can be helpful to rule out syndromic RP, which are conditions that have pigmentary retinopathy and mimic RP. There are many syndromes; the more common and severe types are described below.
• • Usher syndrome is a form of RP with hearing loss. As many as 10% of patients with RP can have hearing loss, and most of these patients have Usher syndrome. Hearing loss in this syndrome can be congenital with complete hearing loss or can occur in middle age with less profound changes in hearing. Most cases of Usher syndrome are autosomal recessive, and mutations have been found in more than 12 genetic loci and 8 identified genes.
  • RP and hearing loss are also associated with Waardenburg syndrome, Alport syndrome, and Refsum disease, all of which have their own systemic manifestations.
  • Kearns-Sayre syndrome consists of external ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy. This syndrome is caused by a mitochondrial genetic defect, and vision loss tends to occur later in life with moderate visual field loss and night vision difficulties. The cardiac conduction block can be life-threatening; therefore, an electrocardiogram (ECG) is essential to help rule out this syndrome in patients.
  • Abetalipoproteinemia is a condition caused by the lack of apolipoprotein B, leading to fat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and pigmentary retinal degeneration. High-dose therapy with vitamins A and E can prevent or limit the extent of the retinal degeneration.
  • The mucopolysaccharidoses (eg, Hurler syndrome, Scheie syndrome, Sanfilippo syndrome) may be affected with pigmentary retinopathy like RP.
  • Bardet-Biedl syndrome consists of polydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy. In this autosomal recessive condition, intelligence is usually subnormal, and vision loss occurs in the second decade and progresses to severe vision loss by middle age. Renal dysfunction can be severe and life-threatening, requiring full evaluation with initial diagnosis.
  • Neuronal ceroid lipofuscinosis is characterized by dementia, seizures, and pigmentary retinopathy. Progressive vision loss occurs in early-onset cases. These disorders have been categorized clinically in relation to the age of onset and the temporal relation of vision loss to neurologic symptoms.
    • Onset of the infantile form is at age 8-18 months. The infantile disease is characterized by optic atrophy, macular pigmentary changes with mottling of the periphery, and low or absent electrophysiologic findings (electroretinogram [ERG] and visual-evoked response [VER]). In the infantile forms, the retinal changes can lead to confusion with Leber congenital amaurosis.

    • Onset of the late infantile form (Jansky-Bielschowsky disease) is age 2-4 years, and onset of the juvenile form (Vogt-Spielmeyer-Batten disease) is age 4-8 years. These forms more prominently show macular granularity or bull's eye maculopathy, and the appearance can be mistaken for a primary retinal dystrophy, such as Stargardt disease.

    • The adult form is known as Kufs syndrome. This form often does not have ophthalmologic manifestations, but electrophysiologic changes that are indicative of inner retinal and RPE damage have been observed.

Causes

RP is a collection of many different genetic diseases that lead to progressive photoreceptor loss and associated vision loss; therefore, the etiology is remarkably variable. As discussed in Pathophysiology, the final common pathway of all these diseases is photoreceptor cell death (predominantly rod photoreceptors). Research has shown that photoreceptor death can be induced by different pathways.

There have been so many important contributions by so many groups around the world that even cataloging them is a formidable task. Fortunately, the authors can refer the reader to the online version of McKusick's classic Mendelian Inheritance of Man (OMIM). Dr. Stephen Daiger also maintains a superb up-to-date Web site called RetNet that is dedicated to the molecular genetics of inherited retinal diseases.

This article will not discuss all the genetic defects; however, some of the main defects, including several examples of how characteristic protein defects lead to vision loss and photoreceptor death, are discussed below.

• In the United States, about 30% of autosomal dominant RP cases are caused by a mutation of the gene for rhodopsin, and approximately 15% of these cases are from a single point mutation. This single amino acid alteration in the protein rhodopsin then leads to photoreceptor cell death.
• The autosomal dominant form of RP can be caused by mutations in at least 12 different genes, whereas the autosomal recessive form of RP can be triggered by changes in more than 60 different genes. X-linked RP is caused by mutations in only 2 known genes, with 75% of cases caused by a mutation of the RPGR gene.
• Photoreceptors are sensitive to light and have been placed in a high oxygen environment. As such, they are sensitive to genetic changes in multiple pathways, which can lead to their demise.
• For example, some mutations in genes that control phototransduction and vitamin A delivery are expressed in the RPE (eg, RPE65, RBP, RDH5), but these RPE mutations cause the photoreceptors to die as bystanders, while the RPE initially stays healthy. Alternatively, mutations of the rhodopsin gene are expressed in the photoreceptor itself, which then leads directly to its own death.
• Another interesting example is the mutation of the ABCA4 gene, which can cause both RP and Stargardt disease. This mutation affects a membrane protein called a flippase, which is found in the photoreceptor outer segments, and, as it moves, phototransduction molecules (eg, all-trans retinaldehyde) throughout the membrane. Defects in this protein cause a buildup of a toxic molecule that the RPE cells ingest when they phagocytosize the photoreceptor's outer segment. This leads to the death of the RPE. Since the photoreceptor requires the RPE for survival, it then in turn dies as well.
• Another major class of mutations in RP affects the RDS/peripherin gene, which is found on chromosome arm 6p. Mutations in this gene also are found in pseudo-RP diseases, such as Gass adult foveal macular dystrophy, pattern dystrophy, and Stargardt-like disease. Therefore, classifying pigmentary retinopathies and dystrophies of the RPE by clinical appearance is problematic.
• Mutations in beta-phosphodiesterase, an important protein in the phototransduction cascade, also have been linked to some cases of autosomal recessive RP. Many animal models of RP in dogs and mice demonstrate these and other defects. Underscoring the dichotomy between clinical presentation and genetic defect, a beta-phosphodiesterase mutation also has been linked to a congenital stationary night blindness.
• Each syndromic form of RP has genetic defects that lead to photoreceptor death in addition to systemic complications.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Infectious causes: Toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (TORCH); congenital rubella; syphilis

Inherited: Choroideremia, gyrate atrophy, Stargardt/fundus flavimaculatus, North Carolina macular dystrophy (NCMD), Bietti syndrome, pattern dystrophies, ocular albinism, cystinosis

Toxicity: Thioridizine toxicity, oxalosis

Neoplasm: Cancer-associated retinopathy (CAR)

Inflammatory: Serous uveitis

Metabolic: Refsum disease, abetalipoproteinemia

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• The tests described below are useful in excluding masquerading diseases or in detecting conditions that are associated with RP.
• Infectious lab tests
• • Syphilis
    • Venereal Disease Research Laboratory (VDRL) test

    • Fluorescent treponemal antibody absorption (FTA-ABS) test
  • Toxoplasmosis (when suspected) – Serum immunoglobulin G (IgG)

• Inherited/syndromic disease lab tests
• • 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
  • Abetalipoproteinemia - Lipid profile with possible protein electrophoresis

• Neoplasm related lab 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 (EOG)
• • Findings 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 (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 subtyping
• • Because of the wide variety of subtypes of so-called RP or related pigmentary retinopathies, the definitive test for diagnosis is identifying the particular defect.
  • 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.

  • Medical insurance will not always pay for 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.

TREATMENT

Section 6 of 11  

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Medical Care

The diagnosis of RP can be overwhelming to many patients. While therapies are limited, physicians should emphasize the therapies that are available to help patients. Perhaps, most importantly, it is essential to help patients maximize the vision they do have with refraction and low-vision evaluation. Many devices are available to help patients with night vision difficulties, and most low-vision clinics are aware of these devices.

The authors believe that patients should have annual examinations, including visual field testing and periodic (every 2-3 y) ERG evaluations. Changes in examination findings can help guide patients in their activities and can help with prognosis. Often, these examinations can provide reassurance that the changes are slow. In addition, regular examinations can ensure patients have appropriate community and legal assistance. Finally, as new therapies emerge, routine evaluation can keep patients informed of clinical trials and new treatments.

• Vitamin A/beta-carotene
• • Antioxidants may be useful in treating patients with RP, but no evidence in favor of vitamin supplementation exists; slight evidence to the contrary may even exist.
  • A recent comprehensive epidemiologic study concluded that very high daily doses of vitamin A palmitate (15,000 U/d) slow the progress of RP by about 2% per year. The effects are modest; therefore, this treatment must be weighed against the uncertain risk of long-term adverse effects from large chronic doses of vitamin A.
  • Annually check liver enzymes and vitamin A levels. Beta-carotene doses of 25,000 IU have been recommended.
• Docosahexaenoic acid (DHA)
• • DHA is an omega-3 polyunsaturated fatty acid and antioxidant.
  • Studies have shown a correlation of ERG amplitudes with patients' erythrocyte-DHA concentration. Others studies reported trends of less ERG change in patients with higher levels of DHA. However, a recent study compared DHA plus vitamin A to vitamin A alone in patients with RP over 4 years. In this study, the benefit of DHA was not seen. Further clinical trials must be done to determine DHA benefit.
• Acetazolamide
• • Macular edema can reduce vision in the later stages of RP. Of the many therapies tried, oral acetazolamide has shown the most encouraging results with some improvement in visual function. Studies by Fishman et al and Cox et al have demonstrated improvement in Snelling visual acuity with oral acetazolamide for patients who have RP with macular edema.³²
  • Topical acetazolamide has not been found to be as effective as oral therapy.
  • Adverse effects, including fatigue, renal stones, loss of appetite, hand tingling, and anemia, may limit its use.
  • The use of corticosteroids for macular edema may be useful but has not been well studied.
• Calcium channel blockers
• • Calcium channel blockers, such as diltiazem, are medications commonly used in cardiac disease.
  • Calcium channel blockers have shown some benefit in some animal models of RP, but they have been ineffective in other models.
  • No current recommendations exist regarding the use of calcium channel blockers in patients with RP.
• Lutein/zeaxanthin
• • Lutein and zeaxanthin are macular pigments that the body cannot make but instead come from dietary sources.
  • Lutein is thought to protect the macula from oxidative damage, and oral supplementation has been shown to increase the macular pigment.
  • A National Institutes of Health (NIH) clinical trial, the Age-Related Eye Disease Study II (AREDS II), is beginning to test the effectiveness of lutein and zeaxanthin to slow age-related macular degeneration. Their ability to prevent cone photoreceptor cell death (such as what occurs in RP) has not been shown.
  • Doses of 20 mg/d have been recommended.
• Medications with potential adverse effects in RP
• • Isotretinoin (Accutane): A medication used to treat acne has been reported to worsen night vision, ERG response, and dark adaptation. As its safety in patients with RP is not known, many physicians do not recommend isotretinoin use for their patients.
  • Sildenafil (Viagra)
  • • A medication to treat erectile dysfunction has been shown to cause reversible ERG and vision changes. Sildenafil is an inhibitor of PDE5 and less so PDE6. Mutations of the PDE6 gene are known to cause autosomal recessive RP. Therefore, physicians have suggested that this medication may not be safe for patients with RP, including carriers of the PDE6B gene mutation.
    • Some users of sildenafil have experienced blue photopsias, suggesting that the drug is active in the retina at a physiological level.
  • Vitamin E: Reports have suggested that high doses of vitamin E (400 U/d) may be modestly deleterious in patients with RP, but doses as high as 800 IU/d have been recommended.
• Other medications
• • Although doses of 1000 mg/d ascorbic acid have been recommended, no evidence exists that ascorbic acid is helpful.
  • Although bilberry is recommended by some practitioners of alternative medicine in doses of 80 mg, no controlled studies exist that document its safety or efficacy in treating patients with RP.
  • In patients who present with antiretinal antibodies, immunosuppressive agents (including steroids) have been used with anecdotal success.

Surgical Care

• Cataract extraction
• • Cataract surgery can often be beneficial in the later stages of RP. Bastek et al studied 30 patients with RP; 83% of them improved by 2 lines on the Snellen visual acuity chart with cataract surgery.⁶
  • Perioperative use of corticosteroids is recommended to prevent postoperative cystoid macular edema.
  • Educating patients about reasonable expectations of cataract surgery is essential.


• Growth factors
• • Ciliary neurotrophic factor (CNTF) has been shown to slow retinal degeneration in a number of animal models.
  • Phase II clinical trials are underway using an encapsulated form of RPE cells producing CNTF (Neurotech Inc). These encapsulated cells must be surgically placed into the eye. Phase I clinical trial results have been encouraging.


• Transplantation
• • Small patches of retinal or RPE tissue have been transplanted, and this technique could be helpful in the following RP forms: when RP is based on an RPE defect, when RP with primary defects exists in the outer segments, if the disease is driven by an overload of the phagocytic activity of the RPE, or if the RPE cannot provide sufficient nutritional support to the outer segments.
  • RPE cell transplants have been placed into the subretinal space to rescue photoreceptors in animal models of RP. One approach that may prove useful is ex vivo modification of these cells to provide trophic factors.
  • Stem cells are being actively investigated as a potential source to replace damaged RPE or photoreceptor cells. Both adult bone marrow–derived stem cells and embryonic stem cells are being used in animal models with the goal to investigate how to induce appropriate cell integration and differentiation.
  • No current investigational protocols exist in humans for this type of intervention.


• Retinal prosthesis
• • A retinal prosthesis or phototransducing chip placed on the retinal surface has been investigated for several years. The healthy ganglion cell layer of the retina can be stimulated, and implants in animal models have long-term stability.
  • In a study by Humayun et al, this has been shown to be beneficial in human subjects.⁴⁸ One patient who had no light perception from RP was able to see and localize a flashlight after the prosthesis. With this prosthesis, an external camera (placed in the patient's eyeglasses) transmits to the retinal prosthesis.
  • Chow et al placed subretinal microphotodiodes (prosthesis) in patients with severe RP.¹⁹ These patients had subjective improvement; however, the improvement was delayed and occurred in retinal areas outside of where the chip was placed. Therefore, the effect was thought to be an indirect benefit to adjacent cells.
  • Currently, no retinal prosthesis is available for clinical use, and this technology remains investigational.


• Gene therapy
• • Gene therapy is under investigation, with the hope to replace the defective protein by using DNA vector (eg, adenovirus, lentivirus).
  • Gene therapy was successful in providing the missing protein to a dog with Leger congenital amaurosis. Using adeno-associated virus (AAV), the Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the functional protein, thereby allowing the dog to see.
  • More recently, this technique of gene therapy also restored vision and prevented photoreceptor degeneration in a mouse model of Leber congenital amaurosis.
  • Phase I clinical trials are soon to be underway to investigate this treatment in human patients.
  • Because of the wide heterogeneity of defects in RP, gene therapy must be targeted specifically to each mutation.
  • It is not known which, if any, of the RP forms will show reversibility (even with a nondestructive reinsertion of the appropriate gene in the appropriate locus with appropriate regulation).

Consultations

• Clearly, RP is associated with several systemic diseases. Because of the severity of the systemic illness and its early presentation in most patients, the ophthalmologist may act as the consultant to an internist.
• Low-vision specialists can provide magnifying devices and field-expanding lenses for patients with RP who have poor central vision.

Diet

• Many practitioners recommend a well-balanced diet with adequate leafy green vegetables that contain the aforementioned supplements in nontoxic doses.
• No evidence exists that particular foods in excess are helpful or harmful.

Activity

• Light exposure
• • Stressful light exposure, which generates free radicals and strains the regenerative capacity of the eye, might put dystrophic retinas at a disadvantage. However, little direct or epidemiologic evidence exists that the disease is modified by light.
  • A specific form of RP, the Pro23His mutation in rhodopsin, has been shown to have increased retinal damage with increased light exposure.
  • UV-absorbing lenses are recommended, particularly in rhodopsin mutation varieties of RP, and patients with cone degeneration frequently benefit from tinted lenses.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Vitamins and antioxidants

May delay RPE degeneration.

Drug Category: Alternative medicines/herbal medications

Anecdotal testimonials only, believed to slow visual deterioration by advocates.

Drug Category: Calcium channel blockers

Reduce toxic levels of cyclic GMP in the RPE.

Drug Category: Carbonic anhydrase inhibitors

Reduce cystoid macular edema associated visual loss from RP.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
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• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Outpatient Care

• Annual patient examinations usually are sufficient to measure Goldmann visual field and visual acuity.
• • If medical treatment is initiated, more frequent visits and laboratory blood work may be indicated.
  • Patients with systemic conditions that are associated with RP may require closer follow-up care.

In/Out Patient Meds

• See Medical Care and Medication.

Prognosis

• See Mortality/Morbidity.

Patient Education

• To help them make wise decisions about driving or vocational rehabilitation, educate patients about their field defects.
• Family pedigrees and, when available, genetic subtyping can be helpful in genetic counseling. Patients should understand that the visual degeneration, which usually occurs over 30-40 years, slowly progresses and varies with the type of RP.
• Patients with Usher syndrome should understand that progressive hearing loss to deafness is not expected.

MISCELLANEOUS

Section 9 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• As with all bilateral, chronic causes of vision loss (both central and peripheral), carefully advise patients about their ability to drive a motor vehicle.

MULTIMEDIA

Section 10 of 11  

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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Usher syndrome with typical retinitis pigmentosa appearance.
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Media file 2:  Choroideremia.
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Media file 3:  Bull's eye maculopathy seen in cone dystrophy.
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Media file 4:  Polydactyly seen in Bardet-Biedl syndrome (associated with retinitis pigmentosa).
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Media file 5:  Cone dystrophy.
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Media file 6:  Gross pathology of an eye in a man with retinitis pigmentosa.
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Media file 7:  Leber congenital amaurosis.
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Media file 8:  Female carrier of choroideremia.
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Media file 9:  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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Media file 10:  Representative electroretinograms of patients with healthy eyes and X-linked retinoschisis. Courtesy of Dr. Nusinowitz, Jules Stein Eye Institute.
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Media file 11:  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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Media file 12:  Fellow eye of Image 11, 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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Media file 13:  Higher resolution image of typical bone spicule formation.
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Media file 14:  Cone dystrophy demonstrating typical central macular atrophy found in this condition.
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Media file 15:  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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Media file 16:  Retinitis pigmentosa progresses over decades. Associated cataract also is relevant, as seen in this image.
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Media file 17:  Pigmentary changes are not always seen in retinitis pigmentosa but frequently are observed, as in this patient with Alström disease.
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Media file 18:  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.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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