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  • Retinitis pigmentosa Presenter SAAD ALDAHMASH, MD

  • Background Retinitis pigmentosa (RP) should be regarded as a phenotypic description of several related, yet distinct, dystrophies of the photoreceptors and the pigment epithelium. Like many areas of medicine, new knowledge of the underlying genetic mechanisms has revealed surprising findings; several conditions that previously were considered identical or closely related actually are caused by completely different mechanisms, and apparently dissimilar conditions may be varying expressions of a single genetic defect.

  • BackgroundAs with many genetic disorders, autosomal dominant (heterozygous) varieties generally have a milder course than autosomal recessive (homozygous) varieties. Traditionally, disorders are grouped by their clinical appearance. The increasing incursion of genetic testing in the clinic may completely change classification in the future.

  • Pathophysiology With these cautionary remarks in mind, RP generically can be described as a progressive cause of visual loss, which is attributed to the loss of viable photoreceptors .RP usually is associated with pigmentary changes in the retinal pigment epithelium (RPE), which may be primary or secondary to the photoreceptor loss .

  • PathophysiologyThe photoreceptors that predominantly are affected may be rods or cones, and the RPE mostly may be affected centrally or peripherally. Given the number and distribution of rods and cones in the retina, prognostic information about the patient's visual loss depends on whether the process is primarily a rod-cone or cone-rod dystrophy. Patients with rod-cone dystrophies present with ring scotoma and night vision problems, which progress to a slow loss of all peripheral vision; central vision is spared the longest..

  • PathophysiologyPatients with cone-rod or pure-cone dystrophies present with visual acuity loss, color discrimination loss, and day vision problems.RP is a progressive disorder by definition; stationary dystrophies commonly are lumped into the category of congenital stationary night blindness (CSNB).

  • PathophysiologyThe inclusion or exclusion of different conditions for consideration is somewhat arbitrary, given the ill-defined nature of RP. The rod-cone or cone-rod dystrophies primarily are considered, either in isolated form (primary RP) or in association with a systemic condition.

  • PathophysiologySystemic conditions associated with pigmentary retinopathy are numerous; e.g.Usher, Alport, Alstrm, Jansky-Bielschowsky, Vogt-Spielmeyer-Batten, Zellweger, Refsum, and Kearns-Sayre.

  • Frequency In the US: The incidence of primary RP is approximately 1 in 4000. To date, more than 70 different genetic defects have been identified, including the following: X-linked (9%), autosomal recessive (16%), and autosomal dominant (22%); the remaining cases are primary RP or RP simplex. Internationally: Worldwide incidence is same as in the United States.

  • FrequencySex: Usually, no sexual predilection exists. However, because of X-linked varieties, men may be affected slightly more than women. Age: The age of onset varies depending on the disorder. RP usually is diagnosed in young adulthood, although it can occur anywhere from infancy to mid 30s to 50s.

  • Mortality/MorbidityA recent 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.

  • Clinical featuresSymptoms :Presenting symptoms of retinal dystrophies vary as much as the spectrum of disorders. Nyctalopia (loss of night vision) and tunnel vision (loss of peripheral vision) are classic complaints of RP, principally rod-cone disease

  • Clinical features When obtaining historical information, ask about adaptation to darkness.Patients may report difficulty driving in low light, at dusk, or in fog.Dark stairwells, movie theaters, and restaurants are situations where the transition between bright illumination and semidarkness present difficulties to some patients

  • Clinical featuresRing scotoma or loss of peripheral vision may be profound before the patient explicitly recognizes it.Symptoms may include bumping into furniture or doorframes or difficulty in playing games (eg, tennis, basketball, baseball).Pain or abnormal sensation is not reported.The loss of vision should be reasonably bilaterally symmetric and, once recognized, slow in onset or progression.

  • Clinical featuresIn contrast, cone-rod dystrophies and macular and pattern dystrophies present as bilateral, painless central visual loss.Vision is often worse under bright lighting with loss or color discrimination.Some cases of rod-cone degenerations are part of a systemic disorder with its own signs and symptoms (eg, Usher syndrome, Bardet-Biedl syndrome, Kearns-Sayre syndrome, Batten-Mayou disease, Vogt-Spielmeyer disease).

  • Clinical featuresPhysical: OcularThe external appearance and anterior segment of the eyes is generally normal in most of these retinal dystrophies.Late appearance of posterior subcapsular cataracts is observed in RP.Depending on the stage and type of disorder, visual acuity may range from normal (20/20) to no light perception.Pupillary response may be normal or abnormal with or without afferent pupillary defect

  • Clinical featuresThe vitreous may show fine cells.The typical features of rod-cone RP may include RPE hyperpigmentation in the form of "bone spicules" that alternate with atrophic regions, attenuation of the arterioles, and waxy pallor of the optic nerve head.Cystic macular edema may be observed in severe cases of RP.

  • Fine dust-like pigmentationArteriolar attenuation

  • Anterior and peripheral spreadUnmasking of large choroidal vessels

  • Perivascular bone-spicule pigmentation

    Initially mid-peripheral

  • Optic disc pallor


  • Quadrantic

  • Sectorial

  • Pericentri

  • Paravenous

  • Ocular associations of retinitis pigmentosa


  • Keratoconus

  • Vitreous degeneration

  • Optic disc drusen

  • Open-angle glaucoma

  • Myopia

  • Clinical featuresCone-rod disease may present with a bull's eye maculopathy. By contrast, scalloped areas of atrophy may be seen in choroideremia, gyrate atrophy, or myopic degeneration; a tapetal, transient sheen is seen in some X-linked CSNB (the Mizuo-Nakamura effect).Yellow flecks or dots are seen in a wide variety of disorders; most of them are not RP. Retinitis punctata albescens is a form of RP with numerous flecks, whereas fundus albipunctatus is a form of CSNB with a similar appearance

  • Systemicassociations

    Systemic findings are important in diagnosing pigmentary retinopathies.Patients with Usher syndrome have hearing loss, which may be profound or partial with a congenital or late onset.RP and hearing loss also are associated with Waardenburg syndrome, Alstrm syndrome, Alport syndrome, Refsum disease, and other systemic conditions, which all have their own systemic manifestations

  • SystemicassociationsShort stature, renal dysfunction, and polydactyly are some signs of Bardet-Biedl syndrome or Lawrence-Moon syndrome when associated with pigmentary retinopathy.The mucopolysaccharidoses may be associated with RP (eg, Hurler syndrome, Scheie syndrome, Sanfilippo syndrome), as well as the mitochondrial disorder, Kearns-Sayre syndrome, which manifests as ptosis, external ophthalmoplegia, and heart block

  • Differentials ARMD, nonexuditive Chloroquine , hydroxychloroquine toxicity Central serious chorioretinopathyNeuroretinitis Best diseaseToxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex (TORCH)Cancer-associated retinopathy (CAR) Ocular albinism

  • Lab Studies

    Venereal Disease Research Laboratory (VDRL) test and fluorescent treponemal antibody absorption (FTA-ABS) testSerum phytanic acid when other neurologic abnormalities are presentOrnithine levels in patients where a diagnosis of gyrate atrophy may be confused with RPECG to rule out heart block in patients with suspected Kearns-Sayre syndromeLipid profile with possible protein electrophoresis in patients with suspected abetalipoproteinemia

  • Lab StudiesAntibodiesAntiretinal antibodies, particularly antirecoverin antibodies, may be observed, especially in CAR or in severe cases of RP. Commercial tests are available.Recoverin is part of the phototransduction cascade in cone cells.

  • Imaging Studies Although fluorescein angiography is rarely useful to the clinician in diagnosing RP, cystoid macular edema might be appreciated more easily than with biomicroscopy.

  • Other Tests

    ElectroretinogramERG is the most critical diagnostic test for RP because it provides an objective measure of rod and cone function across the retina. 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 in infancy or early childhood, except for some of the very mild and regional forms of RP.

  • ERGBy contrast, the diagnosis for cone dystrophies is aided in part by these clinical findings but more definitively by the ERG. Severe and selective loss of cone function occurs with varying degrees of rod abnormality.

  • EOGElectro-oculogramElectro-oculogram (EOG) findings are always a