nw2016 retinitis pigmentosa

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Retinitis Pigmentosa : A BriefNawat WatanachaiAugust 2016

Retinitis PigmentosaRetinitis pigmentosa (RP) is a group of genetic disorders that affect the retinas ability to respond to lightslow loss of visionbegin with nyctalopialoss of peripheral vision blindness+/- photopsia

characteristicshereditaryrate of progression and degree of visual loss varies from person to personMost RP are legally blind by age 40central visual field of less than 20 degrees XRmales : more often and more severefemales : carry the genes and experience vision loss less frequently.

Eye Testsvisual field testingMost useful for follow-up care Goldmann (kinetic) perimetry is recommended

Color testingCommonly, mild blue-yellow axis color defectsDark adaptation studyDisproportionately reduced contrast sensitivity relative to VA

Genetic subtyping

Eye Testsoptical coherence tomography (OCT)not useful in diagnosing RP

may help in CME

Eye TestsFluorescein angiography (FA, FFA)rarely useful in diagnosing RP

may help in CME

Eye TestsElectroretinogram (ERG)Most critical diagnostic test for RP Electro-oculogram (EOG)Not helpful in diagnosing RPbut can identify Best vitelliform macular dystrophycentral macular changesnormal ERG, and abnormal EOG

Systemic diseases that related to RPhearing loss and RPUsher syndromeWaardenburg syndromeAlport syndromeRefsum disease Kearns-Sayre syndromeExternal ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy AbetalipoproteinemiaFat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and pigmentary retinal degeneration Mucopolysaccharidoses Hurler syndrome, Scheie syndrome, Sanfilippo syndromeBardet-Biedl syndromePolydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy Neuronal ceroid lipofuscinosisDementia, seizures, and pigmentary retinopathyinfantile form is known as Jansky-Bielschowsky diseasejuvenile form is Vogt-Spielmeyer-Batten diseaseadult form is Kufs syndrome

management : medicalAcetazolamide

Macular edema (Fishman et al and Cox et al)oral acetazolamide helpsTopical acetazolamide less helps

Adverse effects:fatigue, renal stonesloss of appetite, hand tinglingelectrolyte imbalance, anemia

steroid for macular edema may be useful but has not been well studied

management : medicalPharmacotherapy?Fat-soluble vitaminsvitamin A, C, ECa-channel blockersiltiazemCarbonic anhydrase inhibitors acetazolamide, methazolamideDocosahexaenoic acid (DHA)Lutein, Zeaxanthin

medications with potential adverse effects in RP:Isotretinoin (Accutane) Sildenafil (Viagra) High-dose vitamin E

management : surgicalcataract cataract extractionRetinaretinal implantgene therapystem cell therapyothers : RPE transplantation, surgical growth factors placement

retinal prosthesis

ARGUS II prosthesis : U of southern californiaAlpha IMS

Microsystem-based visual prosthesis (MIVP)spiral cuff electrode around the optic nerveimplantable miniature telescopeHarvard/MIT retinal implantartificial silicon retina (ASR)Photovoltaic retinal prosthesisBionic vision australiadobelle eyeintracortical visual prosthesis

retinal prosthesis

ARGUS II prosthesis :U of southern california60 electrodesapprovedEU 2011US 2013

retinal prosthesis

Alpha IMSTubingen, GERsubretinal prosthesiscollect incident lighttransform to electrical signalsstimulate ganglion cells1500 electrodes

retinal prosthesis

Alpha IMS

gene therapy

under investigationto 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 seealso effective in a mouse model of Leber congenital amaurosis

Trials have also begun for RP, although currently only for MERTK gene mutationproblems : 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 cellsCell transplantation to treat retinal disease (including cells derived from stem cells) to replace damaged RPE or photoreceptor cellsadult bone marrowderived stem cells and embryonic stem cells2011, Advanced Cell Technology (ACT)human trial of a stem-cellderived therapy for ARMD, Stargardt diseasestem cells were differentiated into cells with an RPE phenotype PPVinjected under the retinaInitial results demonstrated safety and a trend toward visual improvement in 18 patients over 3-12 monthsRPE cell transplants (not derived from stem cells)placed into the subretinal space to rescue photoreceptors in animal models of RP