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Case: 30 year old Caucasian Male
Retinitis Pigmentosa Sine Pigmento Desiree Cadiz, OD VA Palo Alto Health Care System
POV: comprehensive eye exam CC: light sensitivity HPI: gradual onset since ~2005, OD>OS, worse in the daylight, recent decrease in BCVA • Personal Ocular Hx: unremarkable • Systemic Hx: h/o head injury in 2006, (-) brain imaging/TBI dx • Social Hx: denies smoking • Family Oc Hx: unremarkable
Examination Findings • BCVA
• CT:
Right -4.00 +3.50 x093 20/25+1 Left -3.00 +2.75 x100 20/20-2 cc: ortho at distance and near
• PUPILS:
Reactivity (1-4): 4 both eyes Pupil size (dark/light): 5/3 both eyes RAPD: 1+ right RAPD
Examination Findings • Ishihara Color Vision Test : 17/17 plates OD/OS
• Red Cap Desaturation: OS brighter than OD
• EOM's: full and smooth both eyes • FIELDS:
OD very constricted fields in all quadrants OS FTFC
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Slit Lap Examination • Lids/Lashes:
mild meibomitis OU
• Conjunctiva:
clear and white OU
• Cornea:
clear OU
• Angles:
4/4 OU
• A/C:
deep and quiet OU
• Iris:
flat, avascular OU
• Lens:
RE: trace PSC, LE: clear
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Differential Diagnoses • • • •
Gyrate Atrophy Artery Occlusion Choroideremia Deferoxamine Retinopathy • Chlorpromazine & Thioridiazine Retinopathy • Retinitis Pigmentosa Sine Pigmento
Types of Retinitis Pigmentosa • Non-syndromic • • • • •
Classic retinitis pigmentosa (RP) Cone-rod dystrophy Retinitis punctata albescens Sector retinitis pigmentosa Retinitis pigmentosa sine pigmento (RPSP)
Retinitis Pigmentosa • a group of hereditary pigmentary retinal dystrophies • characterized by primary degeneration of rod photoreceptors secondary degeneration of cones (rod-cone dystrophy) • Prevalence: • Affects 1:3000 to 1:7000 worldwide • US & Europe: 1:3500 to 1:4000
• Most common hereditary fundus dystrophy
Clinical Presentation of RP • Onset: ~2nd-3rd decades • Symptoms • • • •
Nyctalopia Poor dark adaptation Restricted visual fields Photophobia
• Syndromic • Usher Syndrome • Bardet-Biedl Syndrome (BBS)
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Clinical Findings
Mid-stage changes: • Gradual increase in pigment density • Tessellated fundus/RPE atrophy
Classic Triad: 1. Arteriolar attenuation 2. Retinal bone-spicule pigmentation 3. Waxy disc pallor Early Changes: • Subtle mid-peripheral RPE atrophy • Mild arteriolar narrowing • Mid-peripheral perivascular bone-spicule pigmentation changes
Kanski, 2011
End-stage: • Severe arteriolar narrowing • Waxy pallor of ONH • Macular may show atrophy Kanski, 2011
Visual Acuity usually preserved until later disease Kanski, 2011
Sine Pigmento
Sine Pigmento
• (+) signs/symptoms of RP • (-) bony-spicules or pigment migration
• Overall Incidence: 22% (Pearlman, et al)
• May be mild/early classic RP
• Less functional vision loss, ?milder form of disease
• Pigment can develop as disease progresses
• Highest incidence: duration of symptoms less than 3 years (50%) • Lower incidence: increased symptom duration, 15 years (16.5%)
• 50% had recordable ERGs vs 8.9% of classic RP patients
• True Sine Pigmento – never develops pigment • Must be confirmed by ERG
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Diagnostic Testing • Pupils: normal or mild RAPD (unilateral/asymmetric disease) • Color vision: normal or acquired tritanopia (severe disease) • Visual Fields • Electroretinogram (ERG) • Optical Coherence Tomography (OCT)
Visual Field Testing • Goldmann Perimetry • Mid-peripheral scotomas • Small islands of vision peripherally and centrally (moderate-advanced disease)
http://people.ece.cornell.edu/ http://www.optiboard.com/
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Optical Coherence Tomography (OCT)
Electroretinograms (ERG) • Measures electrical response of the retina to flashes of light • Recorded by contact lens electrode
• Blue light flash = rod response • White light flash = rod + cone response • Flickering white light = isolated cone response Mitamura, 2012
Gold standard for diagnosis of RP Hartong, 2006
Ocular Associations
Inheritance
• Posterior Subcapsular Cataracts • Macular Edema • 10-20% of RP patients • Tx: Systemic CAIs
• Myopia • Open-angle glaucoma • ~3% of cases
• ONH drusen • Coats-like disease • Lipid deposition in peripheral retina
Kanski, 2011
• Posterior vitreous detachment
Hartong, 2006
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Inheritance • X-Linked: worse prognosis • Autosomal Recessive: • Retention of central vision until 5-6th decade
• Autosomal Dominant: • Best prognosis: preservation of central vision 6th decade
• 90% of patients do not find causative mutations • 2013: AD mutation on RP1 identified for RPSP
Hartong, 2006
Pathophysiology • Rod photoreceptors cell death • Dictated by affected gene/protein product
Treatment • Vitamin A and E • A randomized trial of vitamin A and E supplementation for RP (Berson, et al) • High dose vitamin A: slowed decline of cone ERG amplitudes • No effect on visual field or acuity
• Biochemical pathways affected: • • • • •
Phototransduction cascade Vitamin A metabolism Structural/cytoskeletal Cell-cell signaling Trafficking of intracellular proteins • pH regulation
• High dose vitamin E: negative effect
• Recommendation: 15000 IU oral vitamin A • Increase risk for hip fractures/osteoporosis • Enhanced risk for birth defects
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Future Considerations • • • •
Gene-specific therapies Transplantation to replace lost retinal tissue Implanted electrical devices Stem cell therapy
Summary • Consider retinitis pigmentosa sine pigmento in cases of visual field loss with vessel attenuation in the absence of RPE pigmentary changes • ERG = gold standard for diagnosis of RP • Diagnostic imaging can be useful in making dx
• Management: • Limited treatment options • Genetic testing not necessary, but genetic counseling may be useful • Extensive counseling/early low vision rehabilitation
References Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol. 1993 Jun;111(6):761-72. PubMed PMID: 8512476. Berson EL. Retinitis pigmentosa without pigment. Arch Ophthalmol. 1969 Apr;81(4):453. PubMed PMID: 5777754. Berson EL. Retinitis pigmentosa and allied diseases: applications of electroretinographic testing. Int Ophthalmol. 1981 Aug;4(1-2):7-22. PubMed PMID: 7028651.
References Ma L, Sheng XL, Li HP, Zhang FX, Liu YN, Rong WN, Zhang JL. Identification of a novel pR1443W mutation in RP1 gene associated with retinitis pigmentosa sine pigmento. Int J Ophthalmol. 2013;6(4):430-5. PubMed PMID: 23991373; PubMed Central PMCID: PMC3755298. Mitamura Y, Mitamura-Aizawa S, Nagasawa T, Katome T, Eguchi H, Naito T. Diagnostic imaging in patients with retinitis pigmentosa. J Med Invest. 2012;59(1-2):1-11. PubMed PMID: 22449988. Musarella MA, Macdonald IM. Current concepts in the treatment of retinitis pigmentosa. J Ophthalmol. 2011;2011:753547. PubMed PMID: 21048997; PubMed Central PMCID: PMC2964907. Pagon RA. Retinitis pigmentosa. Surv Ophthalmol. 1988 Nov-Dec;33(3):137-77. PubMed PMID: 3068820.
Bird AC. Investigation of retinitis pigmentosa. Aust J Ophthalmol. 1982 May;10(2):99-106. PubMed PMID: 7049143. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809. PubMed PMID: 17113430. JACOBSON JH, STEPHENS G. Unilateral retinitis pigmentosa sine pigmento. Arch Ophthalmol. 1962 Apr;67:456-8. PubMed PMID: 14036508. Kanski, J.J. (2011) Clinical Ophthalmology A Systematic Approach (7th ed.) China: Butterworth Heinemann Elsevier. Krawczyński MR, Dmeńska H, Witt M. Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa and a hearing loss. J Appl Genet. 2004;45(1):107-10. PubMed PMID: 14960774.
Pearlman JT, Saxton J, Hoffman G. Unilateral retinitis pigmentosa sine pigmento. Br J Ophthalmol. 1976 May;60(5):354-60. PubMed PMID: 952804; PubMed Central PMCID: PMC1042728. Pearlman JT, Flood TP, Seiff SR. Retinitis pigmentosa without pigment. Am J Ophthalmol. 1976 Apr;81(4):4179. PubMed PMID: 1083673. Pearlman JT, Saxton J, Flood TP, Seiff SR. The clinical significance of retinitis pigmentosa without pigment: a computer assisted analysis. Adv Exp Med Biol. 1977;77:31-5. PubMed PMID: 322461. Prokofyeva E, Troeger E, Wilke R, Zrenner E. Early visual symptom patterns in inherited retinal dystrophies. Ophthalmologica. 2011;226(3):151-6. PubMed PMID: 21832827. Rayapudi S, Schwartz SG, Wang X, Chavis P. Vitamin A and fish oils for retinitis pigmentosa. Cochrane Database Syst Rev. 2013 Dec 19;12:CD008428. PubMed PMID: 24357340. Weiland JD, Humayun MS. Retinal prosthesis. IEEE Trans Biomed Eng. 2014 May;61(5):1412-24. PubMed PMID: 24710817.
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