Hereditary Retinal Diseases Introduction and update !"#"$%&'()*+(),-./&01& 2)3,%&'4)+"%#"565&.7&8"+("9%,& 8"+("9%,&'6%6)&:,"*);5"6$&<.##)9)&.7&=>?%,&8)@"+",)&& A55"56%,6&B;.7)55.;&",&6()&'>;9);$&0)4%;6?),6& & Objectives • 2)*")C&56>@$&6..#5&7.;&();)@"6%;$&;)3,%#&@"5)%5)5& • 2)*")C&"?"6%6.;5&.7&A280& • 2)*")C&4.6),3%#&6;)%6?),6&7.;&();)@"6%;$&;)3,%#&@"5)%5)5& Inherited retinal diseases • <.?4;"5)&%&C"@)&;%,9)&.7&9),)3+%##$&%,@&4(),.6$4"+%##$& ()6);.9),).>5&@"5)%5)5&6(%6&5(%;)&",&+.??.,&4;.9;)55"*)&#.55&.7& 4(.6.;)+)46.;&7>,+3.,&%++.?4%,")@&D$&*"5>%#&#.55E& • 8%$&.++>;&",&"5.#%3.,&.;&%5&4%;6&.7&%&?>#3F5$56)?"+&+.,@"3.,& Retinal Degenerations/Dystrophies Macular Degenerations/ Dystrophies Retinitis Pigmentosa Cone Dysfunction Syndromes ABCA4 Spectrum North Carolina Stargardt/Fundus • Achromatopsia Flavimaculatus Macular Nonsyndromic RP • Oligocone Trichromacy - Macular Dysfunction Dystrophy • Rod-cone dystrophies • Blue cone monochromacy - Peripheral Cone • Cone-rod dystrophies • Enhanced S-cone syndrome - Peripheral Rod/Cone • Cone dystrophies Isolated Foveal Hypoplasia Leber’s Congential Amaurosis BEST1 Spectrum Rod Dysfunction Syndromes • AD Best Macular Dystrophy SECORD/Juvenile RP • Congenital Stationary Night Blindness X-Linked RP • Multifocal Vitelliform Albinism X-Linked • AOFPED AR RP Complete CSNB • Oculocutaneous AD RP • AR Best Macular Dystrophy Albinism Incomplete CSNB • ADVIRC Syndromic RP Autosomal Dominant • Ocular Albinism Ciliopathies RHO,GNAT1, PDE6B PRPH2 Spectrum • Usher's syndrome Autosomal Recessive • Pattern Dystrophy • Bardet – Beidl Syndrome GRM6, TRPM1, LRIT1 • Central Areolar Choroidal • Joubert Syndrome Dys. • Fundus albipunctatus (RDH5) • Senior Loken Syndrome • Oguchi Disease (ARR, GRK1) EFEMP1 Spectrum • Alstrom Syndrome Dominant Drusen Mitochondrial (Kearns-Sayre) X-linked Retinoschisis Doyne’s Honeycomb Peroxisomal (Zellweger, Refsum) Dystrophy Choroidal Degenerations Fleck Dystrophies Malattia Levintenese Choroderemia • Benign Familial Fleck Gyrate Atrophy Sorsby Macular Dystrophy • Retinitis Punctata Albescens Bietti Crystalline Dystrophy • Alport Occult Macular Dystrophy Late Onset Retinal Dystrophy A@%46)@&%,@&?.@"G)@&C"6(&4);?"55".,&.7&8%;-&B),,)5"/&80/&B(0& The Spectrum of Retinal Degenerations RP !"#$%&'(")$*+ /$"$0*+ •+ A0/&A2/&H!/&8"6.+(.,@;"%#& •& !"#$%& •& '()*%& 1-$+.2+3"0$'*+ •& +#,& •&I&J&$)%;&K&!<A& •& '+'#$& •&JFL&$)%;5&K&'M<120& •& +'-+& •&LFJN&$)%;5&K&H!2B& •&+')*.& •&ONFPN&$)%;5&K&A2&.;&A0&2B& •&Q&LL&$)%;5&F&A>6."??>,)& :5";%.<&)*+ 4(5$%*+ •&:5();&'$,@;.?)& •&R"6;).;)3,%#& •&S%;@)6F S)"@#& •&2)3,%#& •& T.>D);6&'$,@;.?)& •&2BM& •&'),".;F !.-),& •& <(.;".;)3,%#& •& 2)75>?& •&<(.;."@& •& A#56;.?& ,$-&."*+ •&8%+>#%& •& B);"+),6;%#& 3%-("$99$0*+ •&B.56);".;&B.#)& •&!$5.5.?)5& •&8"@F4);"4();$& •&B);.U"5.?)5& •&<.,+),6;"+& •&8"6.+(.,@;"%& •&B%,&2)3,%& •&<"#">?& 67")8."(9+4.00*+ •&<),6;".#)&&&&&&& •&2.@F<.,)&@$56;.4($& •&<.,)F2.@&0$56;.4($& •&<.,)&0$56;.4($& 2)4;.@>+)@&C"6(&4);?"55".,&.7&8%;-&B),,)5"/&80/&B(0& & How do we evaluate hereditary retinal diseases? • M2V& • 1<W& • R"5>%#&G)#@& • A>6.X>.;)5+),+)& • Y#>.;)5+)",&%,9".9;%?& • <.#.;&4(.6.5& • Y%?"#$&("56.;$& Electroretinogram • M#)+6;"+%#&4.6),3%#&9),);%6)@&D$&6()&;)3,%&",&;)54.,5)&6.&%&+(%,9)&",& "##>?",%3.,E& • 2)54.,5)&6.&X%5(&"5&%&5>??)@&%+3*"6$&.7&%##&;)3,%#&+)##5&%,@&+.,5"565& .7&.*);#%44",9&4.5"3*)&%,@&,)9%3*)&+.?4.,),6&4.6),3%#5&6(%6& .;"9",%6)&7;.?&@"Z);),6&56%9)5&.7&;)3,%#&4;.+)55",9& ERG equipment Multifocal ERG Visual field Fundus photography and autofluorescence OCT FA Color testing Family history taking • 0"@&%,$.,)&",&$.>;&7%?"#$&[D#..@&;)#%3*)5\&(%*)&*"5".,&4;.D#)?5&%6& $.>,9&%9)]& • 16();&6(%,&+%6%;%+65&%,@^.;&&,))@",9&9#%55)5]& Macular degenerations and dystrophies: pitfalls and close calls Differentiating AMD from Macular dystrophies • _.&4%6(.9,.?.,"+&+#","+%#&+(%;%+6);"53+5&7.;&A80& • S;.%@&4(),.6$4"+&54)+6;>?&.7&A80&%++.>,65&7.;&.*);#%4&C"6(& @$56;.4(")5& • Y#)+-5`0;>5),& • <(.;".;)3,%#&%6;.4($`V).9;%4("+&%6;.4($& • <_R& • 0"Z);),3%3.,&"5&"?4.;6%,6&D)+%>5)&.7&"?4#"+%3.,5&7.;&6()&4;.9,.5"5/& 9),)3+&+.>,5)##",9&%,@&4;)*),6%3*)&6();%4$& A word about Drusen and Drusen-like lesions =%70$"+ 69$)>0+ ?&'$99&2.%<+9$0&."0+ • Y.+%#&@)4.5"65&.7&)U6;%+)##>#%;& • e,&6()&@))4);&;)3,%#&#%$);5&",& • 2.>,@/&$)##.C"5(&#)5".,&6(%6& @)D;"5& 4.56);".;&4.#)& #..-5&#"-)&%,&)99&$.#-& • S)6C)),&D%5%#&#%?",%&.7&2BM& • R%;"%D#)&",&5"b)/&5(%4)&%,@& • e,6),5)&($4);%>6.YA& %,@&S;>+(a5&?)?D;%,)& @"56;"D>3.,& • =$4.X>.;)5+),+)&.,&YA& • <%;D.($@;%6)5/&b",+&%,@&%6&#)%56& • <%,&D)&",6);+.,,)+6)@&",&?"@F • A++>?>#%3.,&.7&($4);;)X)+3*)& JOc&4;.6)",5& 4);"4();$&6.&7.;?&;)3+>#%;& ?%6);"%#&D)6C)),&&6()& • Y>,@.5+.4$d&$)##.C"5(&,.@>#%;& 4%f);,& ,)>;.;)3,%&%,@&2BM& #)5".,&#.+%6)@&%6&6()&4.56);".;& 4.#)& • <>3+>#%;& • 2)3+>#%;& • <.##."@& Patient # 1 • gP&$E.E&?%#)&4;)5),65&7.;&)*%#>%3.,&.7&'6%;9%;@6&8%+>#%;&0$56;.4($&& • _.&*"5>%#&+.?4#%",65&& • B8=d&:#+);%3*)&+.#"35&5^4&+.#)+6.?$/&()%@%+()5/&%,)?"%/&,#&@")6& • Y1=Ud&[email protected])@& • 21'd&_)9%3*)& Exam ,&-#'+$5$++ 4$@+$5$+ ?&07(9+()7&'5++ ON^ON& ON^ON& !3A+ JP& JO& B,,+ h^h& h^h& 1"'$%&.%+0$-<$"'++ _.;?%#& _.;?%#& 1"'$%&.%+C&'%$.70+ _.&+)##& _.&+)##& Pattern dystrophy-PRPH2 • A0& • B;)5),6&",&?"@#"7)&C"6(&?"#@&+),6;%#&*"5".,& @"56>;D%,+)5& • S>f);X$& • 2)3+>#%;& • Y>,@>5&4>#*);>#),6>5& • B5)>@.F'6%;9%;@6& • Y#)+-5&",&6()&4.56);".;&4.#)&%,@&%;.>,@&*%5+>#%;& %;+%@)5& • B;)+)@)@&D$&?%+>#%;&4%f);,&@$56;.4($&.;& ,.,54)+"G+&7.*)%#&+(%,9)5& • YAY&5(.C5&("9(#$&",+;)%5)@&%>6.YA/&C("+(&)*.#*)& 6.C%;@&+.,X>),6&%6;.4("+&%;)%5&%,@&5(.C5&#%;9);& b.,)&.7&@)+;)%5)@&YAY&5"9,%#& Pattern vs AMD • <.,7>5".,&D)+%>5)& • <#","+%##$&*"5"D#)&5"9,5&4;)5),3,9&",&?"@#"7)&%,@&*"5>%#&+.?4#%",5&?%$&?%,"7)56& #%6);&& • ')+.,@%;$&+(%,9)5&5>+(&%5&<_R&.;&VA& • Y)%6>;)5&6(%6&()#4&@"Z);),3%6)& • 2)#%3*)#$&)%;#$&%9)& • B.5"3*)&7%?"#$&(U& • 8.;)&4;.,.>,+)@&%>6.YA& • B);"4();%#&;)3,%#&%D,.;?%#"3)5&C"6(&+.;;)54.,@",9&%D,.;?%#"3)5&ZM2V& • V),)3+&6)53,9& Patient # 2 • gi&$E.E&7)?%#)&4;)5),65&7.;&)*%#>%3.,&.7&'6%;9%;@6&8%+>#%;& 0$56;.4($&& • _.&*"5>%#&+.?4#%",65/&)U+)46&5()&@.)5&,.6&#"-)&6.&@;"*)&%6&,"9(6& • B8=d&_)9%3*)& • Y1=Ud&_)9%3*)& • 21'd&_)9%3*)& Exam ,&-#'+$5$++ 4$@+$5$+ ?&07(9+()7&'5++ ON^OL& ON^gN& !3A+ Jg& JO& B,,+ h^h& h^h& 1"'$%&.%+0$-<$"'++ B.56);".;&4.#%;&+%6%;%+6& B.56);".;&4.#%;&+%6%;%+6& 1"'$%&.%+C&'%$.70+ _.&+)##& _.&+)##& Stargardt disease—ABCA4 • A2& • Y";56&O&@)+%@)5&.7&#"7)& • B;.9;)55"*)&+),6;%#&*"5".,&#.55& • YAYd&$)##.C&X)+-&+.;;)54.,@&6.&",6),5)& %>6.YA/&5.?)&X)+-5&5>;;.>,@)@&D$&(%#.&.7& ($4.%>6.YA& • 0%;-&+(.;."@&",&iNj& • 1<W&5(.C5&($4);;)X)+3*)&6("+-),",9&.7&2BM& AMD vs Stargardt • <.,7>5".,&D)+%>5)&.7&& • !%6)&%9)&.7&.,5)6& • W()&4;)5),+)&.7&$)##.C&X)+-5/&+(.;".;)3,%#&%6;.4($&%,@&;%;)#$&<_R8& • Y)%6>;)5&6(%6&()#4&@"Z);),3%6)& • Y#)+-5&%;)&?.;)&";;)9>#%;#$&5(%4)@&6(%,&@;>5),& • e,6),5)&%>6.YA&C"6(&5>;;.>,@",9&(%#.&.7&@)+;)%5)@&AY& • 0%;-&+(.;."@& • 8>6%3.,&",&AS<AP&& Patient # 3 • hg&$E.E&7)?%#)&;)7);;)@&7.;&kX>"@l&",&6()&#)m&)$)& • _.3+)5&@)+#",)&",&RA&10& • B8=d&_.,+.,6;"D>6.;$& • B1=Ud&k,.&@"5)%5)&+%>5",9&*%;"%3.,5&",&20'l& Exam ,&-#'+$5$++ 4$@+$5$+ ?&07(9+()7&'5++ ON^iN& ON^PN& !3A+ JJ& JJ& B,,+ _^A& _^A& 1"'$%&.%+0$-<$"'++ _.;?%#& _.;?%#& 1"'$%&.%+C&'%$.70+ _.&+)##& _.&+)##& AOFPED • 1,)&.7&6()&4%f);,&@$56;.4(")5& • 8"#@&&RA&#.55&.;&?)6%?.;4(.45"%& • S"#%6);%#&5?%##&;.>,@&$)##.CFC("6)&#)5".,5&",&6()& 7.*)%&C"6(.>6&@;>5),& • YAYd&($4);AY& • YAd&0.6F%,@F=%#.&.;&k5.#%;&)+#"45)l&& • 1<W&#)5".,5&D)6C)),&,)>;.;)3,%&%,@&2BM/& %@*%,+)@&@"5)%5)&&4(.6.;)+)46.;5&%,@&2BM& D)+.?)&@"5;>46)@& • _.;?%#&.;&?"#@#$&%D,.;?%#&M1V& • V),)3+&+%>5)&",&?",.;"6$&.7&465& AOFPED vs AMD • <.,7>5".,&D)+%>5)&.7& • '?%##&;.>,@&$)##.C&C("6)&?%+>#%;&#)5".,&6(%6&?%$&D)&+.?4#"+%6)@&D$&<_R& • Y)%6>;)5&6(%6&()#4&@"Z);),3%3.,d& • R"6)##"7.;?&#)5".,&C"6(.>6&@;>5),& • 8%;-)@&%>6.YA& • !)5".,&+.;;)54.,@",9&6.&($4);;)X)+3*)&%++>?>#%3.,&%D.*)&6()&2BM& Take home points: • Y>,@.5+.4$/&%>6.YA/&1<W&%,@&)#)+6;.4($5".#.9$&%;)&)55),3%#&",& %44;.%+(",9&4%3),65&C"6(&?%+>#%;&@$56;.4(")5& • ="56.;$&6%-",9d& • '4)+"G+&5$?46.?5& • Y%?"#$&("56.;$& & Take home points: • Y>,@.5+.4$/&%>6.YA/&1<W&%,@&)#)+6;.4($5".#.9$&%;)&)55),3%#&",& %44;.%+(",9&4%3),65&C"6(&?%+>#%;&@$56;.4(")5& • ="56.;$&6%-",9d& • '4)+"G+&5$?46.?5& • Y%?"#$&("56.;$& & Fundus autofluorescence • W()&?.56&*%#>%D#)&@"Z);),3%3,9&6..#&6.&@"53,9>"5(&&@$56;.4(")5&7;.?& )%+(&.6();&%,@&7;.?&A80& • e,@";)+6&;)X)+3.,&.7&?)6%D.#"+&+(%,9)5&%,@&#"4.7>5+",&%++>?>#%3.,& %6&6()&#)*)#&.7&6()&2BM& Optical Coherence Tomography • '0F1<W&%##.C5&("9(F;)5.#>3.,&%,%#$5"5&.7&6()&%,%6.?"+%#&#.+%3.,&.7& 6()&@)4.5"65&%,@^.;&X)+-5&",&&.;&>,@);&6()&;)3,%&.;&B2M& Psychophysical and electrophysiological testing • ?7M2V&+%,&D)+.?)&%D,.;?%#&)%;#$&",&6()&+.>;5)&.7&6()&@"5)%5)& • !"?"6)@&*%#>)&",&@"Z);),3%#&@"%9,.5"5& • ZM2V&+%,&D)+.?)&4;.9;)55"*)#$&%D,.;?%#&",&5.?)&@"5)%5)5&C"6(&3?)& • M1V&;)X)+65&4%,;)3,%#&7>,+3.,&.7&2BM& Genetic testing • A80&"5&?>#37%+6.;"%#&@"5)%5)&C"6(&5)*);%#&9),)3+&%,@&),*";.,?),6%#& 7%+6.;5& • S)C%;)&.7&4(),.6$4"+&()6);.9),)"6$& • M54)+"%##$&()#47>#&",&4%3),6&C"6(&)%;#$&%,@&),@F56%9)&@"5)%5)& • A"@5&",&4;.*"@",9&%&+#","+%#&4;.9,.5"5&& Genetic Testing • V),)3+&6)565&%;)&6)565&.,&D#..@&%,@&.6();&355>)&6.&G,@&9),)3+& @"5.;@);5& • Y",@",9&9),)3+&@"5)%5)5&",&>,D.;,&D%D")5& • Y",@",9&.>6&"7&4).4#)&+%;;$&%&9),)&7.;&%&@"5)%5)&%,@&?"9(6&4%55&"6&.,&6.&6()";& +("#@;),& • '+;)),",9&)?D;$.5&7.;&@"5)%5)& • W)53,9&7.;&9),)3+&@"5)%5)5&",&%@>#65&D)7.;)&6()$&+%>5)&5$?46.?5& • 8%-",9&%&@"%9,.5"5&",&%&4);5.,&C(.&(%5&@"5)%5)&5$?46.?5& • Y"9>;",9&.>6&6()&6$4)&.;&@.5)&.7&%&?)@"+",)&6(%6&"5&D)56&7.;&%&+);6%",&4);5.,& • B).4#)&(%*)&?%,$&@"Z);),6&;)%5.,5&7.;&D)",9&6)56)@&.;&,.6&D)",9&