2. Retinitis Pigmentosa
ā¢ Retinitis pigmentosa (RP) is
ā¢ a group of genetic disorders
that affect the retinaās ability to
respond to light
ā¢ slow loss of vision
ā¢ begin with nyctalopia
ā¢ loss of peripheral vision
ā¢ blindness
ā¢ +/- photopsia
3. characteristics
ā¢ hereditary
ā¢ rate of progression and degree of visual loss varies from person to person
ā¢ Most RP are legally blind by age 40
ā¢ central visual field of less than 20 degrees
ā¢ XR
ā¢ males : more often and more severe
ā¢ females : carry the genes and experience vision loss less frequently.
4. Eye Tests
ā¢ visual field testing
ā¢ Most useful for follow-up care
ā¢ Goldmann (kinetic) perimetry is recommended
ā¢ Color testing
ā¢ Commonly, mild blue-yellow axis color defects
ā¢ Dark adaptation study
ā¢ Disproportionately reduced contrast sensitivity relative to VA
ā¢ Genetic subtyping
5. Eye Tests
ā¢ optical coherence
tomography (OCT)
ā¢ not useful in diagnosing
RP
ā¢ may help in CME
6. Eye Tests
ā¢ Fluorescein angiography (FA, FFA)
ā¢ rarely useful in diagnosing RP
ā¢ may help in CME
7. Eye Tests
ā¢ Electroretinogram (ERG)
ā¢ Most critical diagnostic test for
RP
ā¢ Electro-oculogram (EOG)
ā¢ Not helpful in diagnosing RP
ā¢ but can identify Best vitelliform
macular dystrophy
ā¢ central macular changes
ā¢ normal ERG, and abnormal
EOG
8. Systemic diseases that related to RP
ā¢ hearing loss and RP
ā¢ Usher syndrome
ā¢ Waardenburg syndrome
ā¢ Alport syndrome
ā¢ Refsum disease
ā¢ Kearns-Sayre syndrome
ā¢ External ophthalmoplegia, lid ptosis, heart block, and pigmentary retinopathy
ā¢ Abetalipoproteinemia
ā¢ Fat malabsorption, fat-soluble vitamin deficiencies, spinocerebellar degeneration, and
pigmentary retinal degeneration
ā¢ Mucopolysaccharidoses
ā¢ Hurler syndrome, Scheie syndrome, Sanfilippo syndrome
ā¢ Bardet-Biedl syndrome
ā¢ Polydactyly, truncal obesity, kidney dysfunction, short stature, and pigmentary retinopathy
ā¢ Neuronal ceroid lipofuscinosis
ā¢ Dementia, seizures, and pigmentary retinopathy
ā¢ infantile form is known as Jansky-Bielschowsky disease
ā¢ juvenile form is Vogt-Spielmeyer-Batten disease
ā¢ adult form is Kufs syndrome
9. management : medical
ā¢ Acetazolamide
ā¢ Macular edema (Fishman et al and Cox et al)
ā¢ oral acetazolamide helps
ā¢ Topical acetazolamide less helps
ā¢ Adverse effects:
ā¢ fatigue, renal stones
ā¢ loss of appetite, hand tingling
ā¢ electrolyte imbalance, anemia
ā¢ steroid for macular edema
ā¢ may be useful but has not been well studied
10. management : medical
ā¢ Pharmacotherapy?
ā¢ Fat-soluble vitamins
ā¢ vitamin A, C, E
ā¢ Ca-channel blockers
ā¢ iltiazem
ā¢ Carbonic anhydrase inhibitors
ā¢ acetazolamide, methazolamide
ā¢ Docosahexaenoic acid (DHA)
ā¢ Lutein, Zeaxanthin
ā¢ medications with potential adverse effects in RP:
ā¢ Isotretinoin (Accutane)
ā¢ Sildenafil (Viagra)
ā¢ High-dose vitamin E
16. gene therapy
ā¢ under investigation
ā¢ to replace the defective protein by using DNA vector (eg, adenovirus, lentivirus)
ā¢ Gene therapy was successful in providing the missing protein to a dog with Leger congenital
amaurosis (LCA)
ā¢ adeno-associated virus (AAV)
ā¢ Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the
functional protein, thereby allowing the dog to see
ā¢ also effective in a mouse model of Leber congenital amaurosis
ā¢ Trials have also begun for RP, although currently only for MERTK gene mutation
ā¢ problems : wide heterogeneity of defects in RP
ā¢ 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]
ā¢ 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).
17. stem cells
ā¢ Cell transplantation to treat retinal disease (including cells derived from stem cells)
ā¢ to replace damaged RPE or photoreceptor cells
ā¢ adult bone marrowāderived stem cells and embryonic stem cells
ā¢ 2011, Advanced Cell Technology (ACT)
ā¢ human trial of a stem-cellāderived therapy
ā¢ for ARMD, Stargardt disease
ā¢ stem cells were differentiated into cells with an RPE phenotype
ā¢ PPV
ā¢ injected under the retina
ā¢ Initial results demonstrated safety and a trend toward visual improvement in 18 patients
over 3-12 months
ā¢ RPE cell transplants (not derived from stem cells)
ā¢ placed into the subretinal space to rescue photoreceptors in animal models of RP