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