Nw2016 retinitis pigmentosa
-
Upload
nawat-watanachai -
Category
Health & Medicine
-
view
274 -
download
0
Transcript of Nw2016 retinitis pigmentosa
Retinitis Pigmentosa : A Brief
Nawat WatanachaiAugust 2016
Retinitis Pigmentosa
• Retinitis pigmentosa (RP) is • a group of genetic disorders
that affect the retina’s ability to respond to light
• slow loss of vision• begin with nyctalopia• loss of peripheral vision • blindness• +/- photopsia
characteristics
• hereditary• rate of progression and degree of visual loss varies from person to person• Most RP are legally blind by age 40• central visual field of less than 20 degrees • XR• males : more often and more severe• females : carry the genes and experience vision loss less frequently.
Eye Tests
• visual field testing• Most useful for follow-up care • Goldmann (kinetic) perimetry is recommended
• Color testing• Commonly, mild blue-yellow axis color defects
• Dark adaptation study• Disproportionately reduced contrast sensitivity relative to VA
• Genetic subtyping
Eye Tests
• optical coherence tomography (OCT)• not useful in diagnosing
RP
• may help in CME
Eye Tests
• Fluorescein angiography (FA, FFA)• rarely useful in diagnosing RP
• may help in CME
Eye Tests• Electroretinogram (ERG)
• Most critical diagnostic test for RP
• Electro-oculogram (EOG)• Not helpful in diagnosing RP• but can identify Best vitelliform
macular dystrophy• central macular changes• normal ERG, and abnormal
EOG
Systemic diseases that related to RP
• hearing loss and RP• Usher syndrome• Waardenburg syndrome• Alport syndrome• Refsum disease
• Kearns-Sayre syndrome• External ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy
• Abetalipoproteinemia• Fat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and
pigmentary retinal degeneration • Mucopolysaccharidoses
• Hurler syndrome, Scheie syndrome, Sanfilippo syndrome• Bardet-Biedl syndrome
• Polydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy • Neuronal ceroid lipofuscinosis
• Dementia, seizures, and pigmentary retinopathy• infantile form is known as Jansky-Bielschowsky disease• juvenile form is Vogt-Spielmeyer-Batten disease• adult form is Kufs syndrome
management : medical
• Acetazolamide
• Macular edema (Fishman et al and Cox et al)• oral acetazolamide helps• Topical acetazolamide less helps
• Adverse effects:• fatigue, renal stones• loss of appetite, hand tingling• electrolyte imbalance, anemia
• steroid for macular edema • may be useful but has not been well studied
management : medical• Pharmacotherapy?
• Fat-soluble vitamins• vitamin A, C, E
• Ca-channel blockers• iltiazem
• Carbonic anhydrase inhibitors• acetazolamide, methazolamide
• Docosahexaenoic acid (DHA)• Lutein, Zeaxanthin
• medications with potential adverse effects in RP:• Isotretinoin (Accutane) • Sildenafil (Viagra) • High-dose vitamin E
management : surgical• cataract • cataract extraction
• Retina• retinal implant• gene therapy• stem cell therapy• others : RPE transplantation, surgical growth factors
placement
retinal prosthesis• ARGUS II prosthesis : U of southern california• Alpha IMS
• Microsystem-based visual prosthesis (MIVP)• spiral cuff electrode around the optic nerve
• implantable miniature telescope• Harvard/MIT retinal implant• artificial silicon retina (ASR)• Photovoltaic retinal prosthesis• Bionic vision australia• dobelle eye• intracortical visual prosthesis
retinal prosthesis• ARGUS II prosthesis :
• U of southern california• 60 electrodes• approved
• EU 2011• US 2013
retinal prosthesis• Alpha IMS
• Tubingen, GER• subretinal prosthesis
• collect incident light• transform to electrical signals• stimulate ganglion cells
• 1500 electrodes
retinal prosthesis
• Alpha IMS
gene therapy
• under investigation• 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 (LCA)• adeno-associated virus (AAV)• Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the
functional protein, thereby allowing the dog to see• also effective in a mouse model of Leber congenital amaurosis
• Trials have also begun for RP, although currently only for MERTK gene mutation• problems : wide heterogeneity of defects in RP
• Jacobson et al found that gene therapy is acceptably safe and effective in the extrafoveal retina for LCA caused by RPE65 mutations; however, no benefit and some risk was noted in treating the fovea. Age-dependent effects were not evident.[18]
• 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).
stem cells• Cell transplantation to treat retinal disease (including cells derived from stem cells)
• to replace damaged RPE or photoreceptor cells• adult bone marrow–derived stem cells and embryonic stem cells
• 2011, Advanced Cell Technology (ACT)• human trial of a stem-cell–derived therapy • for ARMD, Stargardt disease• stem cells were differentiated into cells with an RPE phenotype
• PPV• injected under the retina
• Initial results demonstrated safety and a trend toward visual improvement in 18 patients over 3-12 months
• RPE cell transplants (not derived from stem cells)• placed into the subretinal space to rescue photoreceptors in animal models of RP