eMedicine Specialties > Ophthalmology > Retina

Retinitis Pigmentosa

Author: David G Telander, MD, PhD, Assistant Professor, Department of Ophthalmology and Vision Science, Division of Vitreo-Retinal Diseases and Surgery, University of California Davis School of Medicine
Coauthor(s): Anthony de Beus, MD, PhD, Consulting Staff, Southwest Eye Centers; Kent W Small, MD, Director/President, Macular and Retinal Disease Center; President, Molecular Insight LLC; Consulting Surgeon, Glendale Eye Medical Group
Contributor Information and Disclosures

Updated: Aug 19, 2009

Introduction

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.

[ CLOSE WINDOW ]
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 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.


Usher syndrome with typical retinitis pigmentosa ...

Usher syndrome with typical retinitis pigmentosa appearance.

[ CLOSE WINDOW ]
Usher syndrome with typical retinitis pigmentosa ...

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.

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.1 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.

[ CLOSE WINDOW ]
Cone dystrophy.

Cone dystrophy.


Cone dystrophy demonstrating typical central macu...

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

[ CLOSE WINDOW ]
Cone dystrophy demonstrating typical central macu...

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.

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.2

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

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 develop 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).3 Choroideremia and gyrate atrophy typically present with large scalloped areas of peripheral retinal atrophy.

      Bull's eye maculopathy seen in cone dystrophy.

      Bull's eye maculopathy seen in cone dystrophy.

      [ CLOSE WINDOW ]
      Bull's eye maculopathy seen in cone dystrophy.

      Bull's eye maculopathy seen in cone dystrophy.

  • 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.4 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.

      Polydactyly seen in Bardet-Biedl syndrome (associ...

      Polydactyly seen in Bardet-Biedl syndrome (associated with retinitis pigmentosa).

      [ CLOSE WINDOW ]
      Polydactyly seen in Bardet-Biedl syndrome (associ...

      Polydactyly seen in Bardet-Biedl syndrome (associated with retinitis pigmentosa).

    • 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. As shown on these Web sites, over 196 different genes have been found that lead to retinal disease and vision loss.

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 15 different genes, whereas the autosomal recessive form of RP can be triggered by changes in more than 16 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. Over 45 genes have been found to cause these syndromic conditions, including 9 that cause Usher syndrome.

More on Retinitis Pigmentosa

Overview: Retinitis Pigmentosa
Differential Diagnoses & Workup: Retinitis Pigmentosa
Treatment & Medication: Retinitis Pigmentosa
Follow-up: Retinitis Pigmentosa
Multimedia: Retinitis Pigmentosa
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Cottet S, Schorderet DF. Mechanisms of apoptosis in retinitis pigmentosa. Curr Mol Med. Apr 2009;9(3):375-83. [Medline].

  2. Grover S, Fishman GA, Anderson RJ, et al. Visual acuity impairment in patients with retinitis pigmentosa at age 45 years or older. Ophthalmology. Sep 1999;106(9):1780-5. [Medline].

  3. Farrell DF. Unilateral retinitis pigmentosa and cone-rod dystrophy. Clin Ophthalmol. 2009;3:263-70. [Medline].

  4. Saihan Z, Webster AR, Luxon L, Bitner-Glindzicz M. Update on Usher syndrome. Curr Opin Neurol. Feb 2009;22(1):19-27. [Medline].

  5. Fishman GA, Gilbert LD, Fiscella RG, Kimura AE, Jampol LM. Acetazolamide for treatment of chronic macular edema in retinitis pigmentosa. Arch Ophthalmol. Oct 1989;107(10):1445-52. [Medline].

  6. Bastek JV, Heckenlively JR, Straatsma BR. Cataract surgery in retinitis pigmentosa patients. Ophthalmology. Aug 1982;89(8):880-4. [Medline].

  7. Neurotech. Results from Neurotech's NT-501 Phase 2 Retinitis Pigmentosa Studies Demonstrate Consistent Biological Effect on Photoreceptors. Neurotech. Available at http://www.neurotechusa.com/news_events/pr_2009-05-28.asp. Accessed May 28, 2009.

  8. Tsai D, Morley JW, Suaning GJ, Lovell NH. A wearable real-time image processor for a vision prosthesis. Comput Methods Programs Biomed. Sep 2009;95(3):258-69. [Medline].

  9. Humayun MS, Weiland JD, Fujii GY, et al. Visual perception in a blind subject with a chronic microelectronic retinal prosthesis. Vision Res. Nov 2003;43(24):2573-81. [Medline].

  10. Chow AY, Pardue MT, Perlman JI, et al. Subretinal implantation of semiconductor-based photodiodes: durability of novel implant designs. J Rehabil Res Dev. May-Jun 2002;39(3):313-21. [Medline].

  11. Smith AJ, Bainbridge JW, Ali RR. Prospects for retinal gene replacement therapy. Trends Genet. Apr 2009;25(4):156-65. [Medline].

  12. Acland GM, Aguirre GD, Bennett J, et al. Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness. Mol Ther. Dec 2005;12(6):1072-82. [Medline].

  13. Acland GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. May 2001;28(1):92-5. [Medline].

  14. Aleman TS, Duncan JL, Bieber ML, et al. Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci. Jul 2001;42(8):1873-81. [Medline].

  15. Amado RG, Chen IS. Lentiviral vectors--the promise of gene therapy within reach?. Science. Jul 30 1999;285(5428):674-6. [Medline].

  16. Balciuniene J, Johansson K, Sandgren O, Wachtmeister L, Holmgren G, Forsman K. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13. Genomics. Nov 20 1995;30(2):281-6. [Medline].

  17. Bateman JB, Philippart M. Ocular features of the Hagberg-Santavuori syndrome. Am J Ophthalmol. Aug 15 1986;102(2):262-71. [Medline].

  18. Baumgartner WA. Etiology, pathogenesis, and experimental treatment of retinitis pigmentosa. Med Hypotheses. May 2000;54(5):814-24. [Medline].

  19. Bemelmans AP, Kostic C, Crippa SV, et al. Lentiviral gene transfer of RPE65 rescues survival and function of cones in a mouse model of Leber congenital amaurosis. PLoS Med. Oct 2006;3(10):e347. [Medline].

  20. Bennett J. Gene therapy for retinitis pigmentosa. Curr Opin Mol Ther. Aug 2000;2(4):420-5. [Medline].

  21. Bennett J, Zeng Y, Bajwa R, Klatt L, Li Y, Maguire AM. Adenovirus-mediated delivery of rhodopsin-promoted bcl-2 results in a delay in photoreceptor cell death in the rd/rd mouse. Gene Ther. Sep 1998;5(9):1156-64. [Medline].

  22. Berson EL. Hereditary retinal diseases. In: Albert DM, Jakobiec FA. Principles and Practices of Ophthalmology. Philadelphia: WB Saunders; 1994:1181-1262.

  23. Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. Jun 1993;111(6):761-72. [Medline].

  24. Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. Sep 2004;122(9):1306-14. [Medline].

  25. Berson EL, Rosner B, Sandberg MA, et al. Vitamin A supplementation for retinitis pigmentosa. Arch Ophthalmol. Nov 1993;111(11):1456-9. [Medline].

  26. Bok D. Ciliary neurotrophic factor therapy for inherited retinal diseases: pros and cons. Retina. Dec 2005;25(8 Suppl):S27-S28. [Medline].

  27. Brod RD, Packer AJ, Van Dyk HJ. Diagnosis of neuronal ceroid lipofuscinosis by ultrastructural examination of peripheral blood lymphocytes. Arch Ophthalmol. Oct 1987;105(10):1388-93. [Medline].

  28. Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, Schuchard R. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol. Apr 2004;122(4):460-9. [Medline].

  29. Cogan DG, Rodrigues M, Chu FC, Schaefer EJ. Ocular abnormalities in abetalipoproteinemia. A clinicopathologic correlation. Ophthalmology. Aug 1984;91(8):991-8. [Medline].

  30. Dagnelie G, Zorge IS, McDonald TM. Lutein improves visual function in some patients with retinal degeneration: a pilot study via the Internet. Optometry. Mar 2000;71(3):147-64. [Medline].

  31. Dawson WW, Armstrong D, Greer M, Maida TM, Samuelson DA. Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease). Doc Ophthalmol. Aug 30 1985;60(2):163-71. [Medline].

  32. Delyfer MN, Leveillard T, Mohand-Said S, Hicks D, Picaud S, Sahel JA. Inherited retinal degenerations: therapeutic prospects. Biol Cell. May 2004;96(4):261-9. [Medline].

  33. Denman S, Weleber R, Hanifin JM, Cunningham W, Phipps R. Abnormal night vision and altered dark adaptometry in patients treated with isotretinoin for acne. J Am Acad Dermatol. Apr 1986;14(4):692-3. [Medline].

  34. Doonan F, Cotter TG. Apoptosis: a potential therapeutic target for retinal degenerations. Curr Neurovasc Res. Jan 2004;1(1):41-53. [Medline].

  35. Dyer DS, Wilson ME, Small KW, Pai GS. Alström syndrome: a case misdiagnosed as Bardet-Biedl syndrome. J Pediatr Ophthalmol Strabismus. Jul-Aug 1994;31(4):272-4. [Medline].

  36. Eiberg H, Gardiner RM, Mohr J. Batten disease (Spielmeyer-Sjøgren disease) and haptoglobins (HP): indication of linkage and assignment to chr. 16. Clin Genet. Oct 1989;36(4):217-8. [Medline].

  37. Fain GL. Why photoreceptors die (and why they don't). Bioessays. Apr 2006;28(4):344-54. [Medline].

  38. Fan BJ, Tam PO, Choy KW, Wang DY, Lam DS, Pang CP. Molecular diagnostics of genetic eye diseases. Clin Biochem. Mar 2006;39(3):231-9. [Medline].

  39. Fishman GA, Farber MD, Derlacki DJ. X-linked retinitis pigmentosa. Profile of clinical findings. Arch Ophthalmol. Mar 1988;106(3):369-75. [Medline].

  40. Fishman GA, Gilbert LD, Anderson RJ, Marmor MF, Weleber RG, Viana MA. Effect of methazolamide on chronic macular edema in patients with retinitis pigmentosa. Ophthalmology. Apr 1994;101(4):687-93. [Medline].

  41. Fishman GA, Kumar A, Joseph ME, Torok N, Anderson RJ. Usher's syndrome. Ophthalmic and neuro-otologic findings suggesting genetic heterogeneity. Arch Ophthalmol. Sep 1983;101(9):1367-74. [Medline].

  42. Fleischhauer J, Njoh WA, Niemeyer G. Syndromic retinitis pigmentosa: ERG and phenotypic changes. Klin Monatsbl Augenheilkd. Mar 2005;222(3):186-90. [Medline].

  43. Folz SJ, Trobe JD. The peroxisome and the eye. Surv Ophthalmol. Mar-Apr 1991;35(5):353-68. [Medline].

  44. Frasson M, Sahel JA, Fabre M, Simonutti M, Dreyfus H, Picaud S. Retinitis pigmentosa: rod photoreceptor rescue by a calcium-channel blocker in the rd mouse. Nat Med. Oct 1999;5(10):1183-7. [Medline].

  45. Gal A, Xu S, Piczenik Y, et al. Gene for autosomal dominant congenital stationary night blindness maps to the same region as the gene for the beta-subunit of the rod photoreceptor cGMP phosphodiesterase (PDEB) in chromosome 4p16.3. Hum Mol Genet. Feb 1994;3(2):323-5. [Medline].

  46. Gouras P, Carr RE. Electrophysiological studies in early retinitis pigmentosa. Arch Ophthalmol. Jul 1964;72:104-10. [Medline].

  47. Grant CA, Berson EL. Treatable forms of retinitis pigmentosa associated with systemic neurological disorders. Int Ophthalmol Clin. Winter 2001;41(1):103-10. [Medline].

  48. Heckenlively J. The frequency of posterior subcapsular cataract in the hereditary retinal degenerations. Am J Ophthalmol. Jun 1982;93(6):733-8. [Medline].

  49. Heckenlively JR. Retinitis Pigmentosa. XIV. Philadelphia: Lippincott; 1988.

  50. Herse P. Retinitis pigmentosa: visual function and multidisciplinary management. Clin Exp Optom. Sep 2005;88(5):335-50. [Medline].

  51. Hims MM, Diager SP, Inglehearn CF. Retinitis pigmentosa: genes, proteins and prospects. Dev Ophthalmol. 2003;37:109-25. [Medline].

  52. Hollyfield JG, Anderson RE, LaVail MM. Retinal Degenerative Diseases and Experimental Therapy. XIV. [1] leaf of col. plates. New York: Kluwer Academic/Plenum Publishers; 1999.

  53. Hossain P, Seetho IW, Browning AC, Amoaku WM. Artificial means for restoring vision. BMJ. Jan 1 2005;330(7481):30-3. [Medline].

  54. Hunter DG, Fishman GA, Mehta RS, Kretzer FL. Abnormal sperm and photoreceptor axonemes in Usher's syndrome. Arch Ophthalmol. Mar 1986;104(3):385-9. [Medline].

  55. Joshi AR, Mullen L, Small KW. The retina: genetic studies of several retinopathies located on the short arm of chromosome 17. Curr Opin Neurol. Feb 1997;10(1):31-5. [Medline].

  56. Kalloniatis M, Fletcher EL. Retinitis pigmentosa: understanding the clinical presentation, mechanisms and treatment options. Clin Exp Optom. Mar 2004;87(2):65-80. [Medline].

  57. Kaplan J, Gerber S, Bonneau D, et al. A gene for Usher syndrome type I (USH1A) maps to chromosome 14q. Genomics. Dec 1992;14(4):979-87. [Medline].

  58. Kennan A, Aherne A, Humphries P. Light in retinitis pigmentosa. Trends Genet. Feb 2005;21(2):103-10. [Medline].

  59. Kimberling WJ, Moller CG, Davenport S, et al. Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11. Genomics. Dec 1992;14(4):988-94. [Medline].

  60. Kimberling WJ, Moller CG, Davenport S, et al. Lutein and zeaxanthin exhibit photoprotective and anti-apoptotic activities in vitro. Invest Ophthalmol Vis Sci. 1998.

  61. Kimberling WJ, Weston M, Moller C. Clinical and genetic heterogeneity of Usher syndrome. In: Wright AF, Jay B. Molecular Genetics of Inherited Eye Disorders. Chur, Switzerland: Harwood; 1994:359-382.

  62. Kimura AE, Drack AV, Stone EM. Retinitis pigmentosa and associated disorders. In: Wright K, ed. Pediatric Ophthalmology and Strabismus. St. Louis: Mosby; In press.

  63. Marmor MF. The electroretinogram in retinitis pigmentosa. Arch Ophthalmol. Jul 1979;97(7):1300-4. [Medline].

  64. Marmor MF, Kessler R. Sildenafil (Viagra) and ophthalmology. Surv Ophthalmol. Sep-Oct 1999;44(2):153-62. [Medline].

  65. Masuno M, Shimozawa N, Suzuki Y, et al. Assignment of the human peroxisome assembly factor-1 gene (PXMP3) responsible for Zellweger syndrome to chromosome 8q21.1 by fluorescence in situ hybridization. Genomics. Mar 1 1994;20(1):141-2. [Medline].

  66. McLaughlin ME, Sandberg MA, Berson EL, Dryja TP. Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. Nat Genet. Jun 1993;4(2):130-4. [Medline].

  67. Miggiano GA, Falsini B. [Diet and management of degenerative diseases of the retina (retinitis pigmentosa)]. Clin Ter. Jul-Aug 2004;155(7-8):347-51. [Medline].

  68. Moosajee M. Genes and the eye. J R Soc Med. May 2005;98(5):206-7. [Medline].

  69. Moraes CT, DiMauro S, Zeviani M, et al. Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med. May 18 1989;320(20):1293-9. [Medline].

  70. Murakami A, Yajima T, Inana G. Isolation of human retinal genes: recoverin cDNA and gene. Biochem Biophys Res Commun. Aug 31 1992;187(1):234-44. [Medline].

  71. Naash ML, Peachey NS, Li ZY, et al. Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin. Invest Ophthalmol Vis Sci. Apr 1996;37(5):775-82. [Medline].

  72. Nadig MN. Development of a silicon retinal implant: cortical evoked potentials following focal stimulation of the rabbit retina with light and electricity. Clin Neurophysiol. Sep 1999;110(9):1545-53. [Medline].

  73. Naka H, et al. Ascorbic acid does not protect photic injury by blue light in the rat retina. Invest Ophthalmol Vis Sci. 1998.

  74. Nathans J, Hogness DS. Isolation and nucleotide sequence of the gene encoding human rhodopsin. Proc Natl Acad Sci U S A. Aug 1984;81(15):4851-5. [Medline].

  75. Newsome DA. Retinal fluorescein leakage in retinitis pigmentosa. Am J Ophthalmol. Mar 15 1986;101(3):354-60. [Medline].

  76. Norton EW. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. Nov 1993;111(11):1460; author reply 1463-5. [Medline].

  77. Paskowitz DM, LaVail MM, Duncan JL. Light and inherited retinal degeneration. Br J Ophthalmol. Aug 2006;90(8):1060-6. [Medline].

  78. Petersen-Jones S. Advances in the molecular understanding of canine retinal diseases. J Small Anim Pract. Aug 2005;46(8):371-80. [Medline].

  79. Phelan JK, Bok D. A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes. Mol Vis. Jul 8 2000;6:116-24. [Medline].

  80. Polak BC, Hogewind BL. Macular lesions in Alport's disease. Am J Ophthalmol. Oct 1977;84(4):532-5. [Medline].

  81. Radtke ND, Aramant RB, Seiler M, Petry HM. Preliminary report: indications of improved visual function after retinal sheet transplantation in retinitis pigmentosa patients. Am J Ophthalmol. Sep 1999;128(3):384-7. [Medline].

  82. Radtke ND, Aramant RB, Seiler MJ, Petry HM, Pidwell D. Vision change after sheet transplant of fetal retina with retinal pigment epithelium to a patient with retinitis pigmentosa. Arch Ophthalmol. Aug 2004;122(8):1159-65. [Medline].

  83. Radtke ND, Seiler MJ, Aramant RB, Petry HM, Pidwell DJ. Transplantation of intact sheets of fetal neural retina with its retinal pigment epithelium in retinitis pigmentosa patients. Am J Ophthalmol. Apr 2002;133(4):544-50. [Medline].

  84. Rivolta C, Sharon D, DeAngelis MM, Dryja TP. Retinitis pigmentosa and allied diseases: numerous diseases, genes, and inheritance patterns. Hum Mol Genet. May 15 2002;11(10):1219-27. [Medline].

  85. Rosenfeld PJ, Cowley GS, McGee TL, Sandberg MA, Berson EL, Dryja TP. A null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa. Nat Genet. Jun 1992;1(3):209-13. [Medline].

  86. Sankila EM, Pakarinen L, Kaariainen H, et al. Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q. Hum Mol Genet. Jan 1995;4(1):93-8. [Medline].

  87. Schachat AP, Maumenee IH. Bardet-Biedl syndrome and related disorders. Arch Ophthalmol. Feb 1982;100(2):285-8. [Medline].

  88. Schmidt-Erfurth U. Nutrition and retina. Dev Ophthalmol. 2005;38:120-47. [Medline].

  89. Schwendemann G, Elze KL, Koepp P, Lagenstein I, Steinhausen HC, Colmant HJ. Juvenile type of generalized ceroid-lipofuscinosis (Spielmeyer-Sjögren syndrome) I. Clinical findings. Neuropadiatrie. Feb 1978;9(1):3-27. [Medline].

  90. Shimozawa N, Tsukamoto T, Suzuki Y, et al. A human gene responsible for Zellweger syndrome that affects peroxisome assembly. Science. Feb 28 1992;255(5048):1132-4. [Medline].

  91. Small KW, Anderson WB Jr. Pigmented paravenous retinochoroidal atrophy. Discordant expression in monozygotic twins. Arch Ophthalmol. Oct 1991;109(10):1408-10. [Medline].

  92. Small KW, Letson R, Scheinman J. Ocular findings in primary hyperoxaluria. Arch Ophthalmol. Jan 1990;108(1):89-93. [Medline].

  93. Smith LE. Bone marrow-derived stem cells preserve cone vision in retinitis pigmentosa. J Clin Invest. Sep 2004;114(6):755-7. [Medline].

  94. Smith PR, Bain SC, Good PA, et al. Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation. Ophthalmology. Jun 1999;106(6):1101-8. [Medline].

  95. Smith RJ, Lee EC, Kimberling WJ, et al. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics. Dec 1992;14(4):995-1002. [Medline].

  96. Stojanovic A, Hwa J. Rhodopsin and retinitis pigmentosa: shedding light on structure and function. Receptors Channels. 2002;8(1):33-50. [Medline].

  97. Szlyk JP, Fishman GA, Alexander KR, Peachey NS, Derlacki DJ. Clinical subtypes of cone-rod dystrophy. Arch Ophthalmol. Jun 1993;111(6):781-8. [Medline].

  98. Szlyk JP, Seiple W, Laderman DJ, Kelsch R, Ho K, McMahon T. Use of bioptic amorphic lenses to expand the visual field in patients with peripheral loss. Optom Vis Sci. Jul 1998;75(7):518-24. [Medline].

  99. Takahashi M, Miyoshi H, Verma IM, Gage FH. Rescue from photoreceptor degeneration in the rd mouse by human immunodeficiency virus vector-mediated gene transfer. J Virol. Sep 1999;73(9):7812-6. [Medline].

  100. Takano Y, Ohguro H, Dezawa M, et al. Study of drug effects of calcium channel blockers on retinal degeneration of rd mouse. Biochem Biophys Res Commun. Jan 23 2004;313(4):1015-22. [Medline].

  101. Traboulsi EI, Green WR, Luckenbach MW, de la Cruz ZC. Neuronal ceroid lipofuscinosis. Ocular histopathologic and electron microscopic studies in the late infantile, juvenile, and adult forms. Graefes Arch Clin Exp Ophthalmol. 1987;225(6):391-402. [Medline].

  102. Travis GH, Brennan MB, Danielson PE, Kozak CA, Sutcliffe JG. Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature. Mar 2 1989;338(6210):70-3. [Medline].

  103. Travis GH, Hepler JE. A medley of retinal dystrophies. Nat Genet. Mar 1993;3(3):191-2. [Medline].

  104. van Soest S, Westerveld A, de Jong PT, Bleeker-Wagemakers EM, Bergen AA. Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol. Jan-Feb 1999;43(4):321-34. [Medline].

  105. Wang DY, Chan WM, Tam PO, et al. Genetic markers for retinitis pigmentosa. Hong Kong Med J. Aug 2005;11(4):281-8. [Medline].

  106. Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature. Mar 2 1995;374(6517):60-1. [Medline].

  107. Weiland JD, Liu W, Humayun MS. Retinal prosthesis. Annu Rev Biomed Eng. 2005;7:361-401. [Medline].

  108. Weleber RG. Stargardt's macular dystrophy. Arch Ophthalmol. Jun 1994;112(6):752-4. [Medline].

  109. Weleber RG, Denman ST, Hanifin JM, Cunningham WJ. Abnormal retinal function associated with isotretinoin therapy for acne. Arch Ophthalmol. Jun 1986;104(6):831-7. [Medline].

  110. Weleber RG, Gregory-Evans K. Retinitis pigmentosa and allied disorders. In: Ryan SJ. Retina. Vol I. 4th ed. Philadelphia: Elsevier/Mosby; 2006:395-498.

  111. Wright AF, Jay B, eds. Molecular Genetics of Inherited Eye Disorders. Vol 2. Chur, Switzerland: Harwood; 1994.

  112. Yamazaki H, Ohguro H, Maeda T, et al. Preservation of retinal morphology and functions in royal college surgeons rat by nilvadipine, a Ca(2+) antagonist. Invest Ophthalmol Vis Sci. Apr 2002;43(4):919-26. [Medline].

  113. Zeviani M, Moraes CT, DiMauro S, et al. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology. Sep 1988;38(9):1339-46. [Medline].

  114. Zylbermann R, Silverstone BZ, Brandes E, Drukker A. Retinal lesions in Alport's syndrome. J Pediatr Ophthalmol Strabismus. Jul-Aug 1980;17(4):255-60. [Medline].

[ CLOSE WINDOW ]

Keywords

retinitis pigmentosa, RP, night blindness, tunnel vision, peripheral vision, retinal dystrophies, hereditary dystrophies of the retinal pigment epithelium, retinal pigment epithelium, RPE, congenital stationary night blindness, CSNB, rod-cone dystrophies, cone-rod dystrophies, nyctalopia, loss of night vision, tunnel vision, loss of peripheral vision, Usher syndrome, Bardet-Biedl syndrome, Kearns-Sayre syndrome, Batten-Mayou disease, Vogt-Spielmeyer disease, retinal dystrophies, cystic macular edema, bull's eye maculopathy, Mizuo-Nakamura effect, choroideremia, gyrate atrophy, myopic degeneration, retinitis punctata albescens, ocular albinism, Waardenburg syndrome, Alström syndrome, Alport syndrome, Refsum disease, Lawrence-Moon syndrome, Hurler syndrome, Scheie syndrome, Sanfilippo syndrome, ptosis, external ophthalmoplegia, heart block, Gass adult foveal macular dystrophy, pattern dystrophy, Stargardt disease, Stargardt-like disease, congenital stationary night blindness, retinal renal syndromes, Leber congenital amaurosis, mitochondrial myopathies, congenital rubella, mucopolysaccharidoses, renal-retinal dysplasia, anterior lenticonus, neuronal ceroid lipofuscinosis, Jansky-Bielschowsky disease, Vogt-Spielmeyer-Batten disease, Kufs syndrome, abetalipoproteinemia, peroxisomal disorders, Zellweger syndrome, phytanic acid storage disease, pseudo-Zellweger syndrome, mitochondrial disorders

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

David G Telander, MD, PhD, Assistant Professor, Department of Ophthalmology and Vision Science, Division of Vitreo-Retinal Diseases and Surgery, University of California Davis School of Medicine
David G Telander, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Cataract and Refractive Surgery, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Coauthor(s)

Anthony de Beus, MD, PhD, Consulting Staff, Southwest Eye Centers
Anthony de Beus, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Kent W Small, MD, Director/President, Macular and Retinal Disease Center; President, Molecular Insight LLC; Consulting Surgeon, Glendale Eye Medical Group
Kent W Small, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American College of Physician Executives, American Medical Association, American Medical Informatics Association, American Ophthalmological Society, American Society of Human Genetics, Association for Research in Vision and Ophthalmology, California Medical Association, Macula Society, Pan-American Association of Ophthalmology, and Retina Society
Disclosure: Nothing to disclose.

Medical Editor

Russell P Jayne, MD, Consulting Vitreoretinal Surgeon, The Retina Center at Las Vegas
Russell P Jayne, MD is a member of the following medical societies: American Medical Association, American Society of Cataract and Refractive Surgery, and American Society of Retina Specialists
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Adjunct Professor of Ophthalmology, Columbia College of Physicians & Surgeons; Clinical Professor Ophthalmology, Chinese University of Hong Kong
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Club Jules Gonin, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting; OptiMedica Ownership interest Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.