1. Introduction
2. Materials and Methods
2.1. Treatment and Testing Schedule
2.2. Electrophysiological Methods
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
STG/FF | Stargardt disease/fundus flavimaculatus |
S | Saffron |
P | Placebo |
ERG | electroretinogram |
fERG | focal electroretinogram |
FERG | high-frequency flicker ERG |
RPE | retinal pigment epithelium |
FF | fundus flavimaculatus (FF) |
PE | phosphatidylethanolamine |
ETDRS | Early Treatment Diabetic Retinopathy Study chart |
SSCP | single-strand conformation polymorphism |
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Patient # Sex | Acuity | Baseline | 1st CONTR | 2nd CONTR | Mutation I Allele | Mutation II Allele | |
---|---|---|---|---|---|---|---|
OD | OS | ||||||
2. F, 14 | 0.2 | 0.2 | B 11.04.11 | A 24.10.11 | 18.06.12 | IVS35 + 2t > c | IVS40 + 5g > a |
3. M, 11 | 0.1 | 0.1 | B 11.04.11 | A 10.10.11 | 16.04.12 | c432A > G; | Q767d > a G1961e |
4. F, 35 | 0.1 | 0.1 | A 11.04.11 | B 11.10.11 | 16.04.12 | c.52C > T; p.Arg18Trp | C7671 > A; p.Val767Asp |
5. F, 14 | 0.3 | 0.3 | A 18.04.11 | B 24.10.11 | 23.04.12 | c.1622T > C; p.Leu541Pro | ------ |
6. M, 12 | 0.3 | 0.3 | A 18.04.11 | B 24.10.11 | 23.04.12 | c.1622T > C; p.Leu541Pro | ------ |
8. M, 56 | 0.1 | 0.5 | B 18.04.11 | A 24.10.11 | 18.05.12 | Arg653His | Arg653His |
9. M, 61 | 0.9 | 0.9 | B 18.04.11 | A 24.10.11 | 18.05.12 | Arg653His | Arg653His |
11. M, 12 | 0.2 | 0.2 | A 02.05.11 | B 25.11.11 | 08.05.12 | c.5882G > A; p.Gly1961glu | c.6764G > T, p.Ser2255Ile |
12. F, 16 | 0.2 | 0.2 | B 09.05.11 | A 08.11.11 | 22.05.12 | c.3602T > G; p.Leu1201Arg | c.5530G > T; Gly1844Cys c.5722G > T; p.Glu1908X |
14. F, 78 | 0.1 | 0.1 | B 16.05.11 | A 28.11.11 | 21.05.12 | c.4793C > AAla1598Asp | (c.6184_6188delGTCT; p.Val2062fsX2113) |
18. F, 34 | 0.8 | 0.8 | B 20.06.11 | A 19.12.12 | 21.06.12 | c.2099G > A; p. W700X | c.4561C > T; P1486L |
19. F, 47 | 1.0 | 1.0 | A 11.07.11 | B 09.01.12 | 09.07.121 | c.2690C > T; p.Thr897Ile | ------ |
20. M, 43 | 0.1 | 0.1 | A 11.07.11 | B 09.01.12 | 09.07.12 | c.2690C > T; p.Thr897Ile | ------ |
21. M, 12 | 0.1 | 0.1 | B 11.07.11 | A 09.01.12 | 09.07.12 | c.4139C > T; Pro1380Leu | c.6005+1G > C |
23. M, 34 | 0.1 | 0.1 | B 20.06.11 | A 19.12.11 | 25.06.12 | c.61C > T; p.Gln21Ter | c.5882G > A; p.Gly1961Glu |
24. M, 16 | 0.1 | 0.9 | A 12.10.11 | B 23.04.12 | 29.10.12 | c.2461T > A; p.Trp821Arg c.2459A > G; p.Tyr850Cys | c.5882G > A; p.Gly1961Glu |
25. M, 29 | 0.1 | 0.1 | A 07.11.11 | B 02.05.12 | 12.11.12 | C768G > T; p.Val256splice | c.4437G>A;p.Trp1479X |
26. M, 32 | 0.1 | 0.1 | B 07.11.11 | A 28.05.12 | 03.12.12 | 5714 + 5G-A | 6088C > T |
27. F, 29 | 0.2 | 0.2 | A 08.11.11 | B 04.06.12 | 17.01.13 | Thr977Pro | IVS40 + 5G-A |
28. M, 27 | 0.2 | 0.2 | B 21.11.11 | A 21.05.12 | 22.11.12 | c.5065T > C; p.S1689P | c.5882G > A; p.G1961E |
29. F, 22 | 0.1 | 0.5 | A 13.12.11 | B 18.06.12 | 20.12.12 | 4709-4711delA | Gly1961Glu |
30. M, 42 | 0.1 | 0.2 | A 23.01.12 | B 27.06.12 | 07.01.13 | R152Q | R653C |
31. M, 10 | 0.2 | 0.2 | B 13.02.12 | A 06.08.12 | 11.02.13 | c.4200C>A;p.Tyr1400X | c.686T>C;p.Leu229Pro |
32. M, 17 | 0.3 | 0.3 | A 20.02.12 | B 03.09.12 | 18.03.13 | R18W | C1490Y |
33. M, 22 | 0.4 | 0.4 | B 21.02.12 | A 10.09.12 | 09.03.13 | c.5882G>A;p.Gly1691Glu | (c.3994_4017dup;p,.Gln1332_cys1339dup) Val2062ThrfsX52 |
38. M, 15 | 0.2 | 0.2 | B 03.04.12 | A 15.10.12 | 22.04.13 | c.2791G>A;p.Val931Met | ------ |
39. M, 21 | 0.1 | 0.2 | A 04.04.12 | B 29.10.12 | 13.05.13 | Ser1064Pro | IVS35+2t>c |
42. F, 21 | 0.3 | 0.3 | B 17.04.12 | A 08.10.12 | 11.04.13 | Ivs13+1g>a | Ivs40+5g>40 |
43. M, 52 | 0.1 | 0.5 | B 23.04.12 | A 12.11.12 | 16.05.13 | c.3323G>A;p.Arg1018His | c.5882G>A;p.Gly1961Glu |
44. M, 35 | 0.4 | 0.4 | A 17.05.12 | B 13.12.12 | 20.06.13 | GlY1961Glu | IVS45+1g>c |
45. F, 56 | 0.8 | 0.1 | B 21.5.12 | A 05.11.12 | 02.05.13 | c.2549>G;P.Tyr850Cys c.2875A>G;p.Thr959Ala | c.5882G>A;p.Gly1961Glu |
Baseline | SN1 | Noise I | 1st period | SN1 | Noise I | 2nd Period | SN1 | Noise I | |
---|---|---|---|---|---|---|---|---|---|
Pat. ID | Amp (ph) OD; OS | OD OS | OD OS | Amp (ph) OD; OS | OD OS | OD OS | Amp (ph) OD; OS | OD OS | OD OS |
2. | 0.63: 0.30 −160.5; −69.0 | 15.70 9.26 | 0.10 0.10 | 0.40; 0.49 −5.8; −177.3 | 0.86 6.12 | 0.17 0.27 | 0.24; 0.28 −67.3; 148.0 | 8.16 18.55 | 0.09 0.03 |
3. | 0.14; 0.50 −51.1; 10.7 | −11.61 10.93 | 0.54 0.13 | 0.12; 0.07 −108.4; 146.1 | −4.23 −10.51 | 0.20 10.23 | 0.09; 0.28 152.1; −86.6 | −1.05 4.43 | 0.10 0.17 |
4. | 0.33; 0.35 23.6; 163.0 | 6.30 3.09 | 0.16 0.25 | 0.13; 0.55 10.6; 44.6 | 13.49 11.21 | 0.03 n.c. | 0.39; 0.05 −32.1; 20.5 | 7.19 −8.92 | 0.17 0.13 |
5. | 0.97;0.71 27.1; −161.4 | 4.41 n.c. | 0.29 n.c. | 0.70; 0.63 19.6; −132.9 | 21.56 14.17 | 0.06 0.12 | 0.84; 0.84 48.0; −164.6 | 13.32 14.73 | 0.18 0.15 |
6. | 0.8; 0.858 2.0; −146.0 | 9.92 n.c. | 0.28 n.c. | 0.90; 0.92 42.1; −129.1 | 22.73 14.98 | 0.06 0.11 | 0.32; 0.61 42.2; 150.6 | 12.78 14.98 | 0.07 0.11 |
8. | 0.34; 0.17 −53.1; 30.2 | 9.04 1.70 | 0.12 0.10 | 0.12; 0.06 −179.2; 113.2 | −1.00 8.18 | 0.04 0.02 | 0.09; 0.08 −103.6; 70.9 | 10.57 2.64 | 0.01 0.04 |
9. | 0.63; 0.65 −54.1; −173.3 | 9.73 4.05 | 0.21 0.41 | 0.28; 0.23 −80.5; −175.8 | 6.79 −1.39 | 0.13 0.27 | 0.04; 0.11 −153.5; 115.0 | −11.34 −2.65 | 0.13 0.14 |
11. | 0.79; 0.70 −173.0; 18.5 | 14.86 10.57 | 0.14 0.21 | 0.75; 0.32 12.6; −177.8 | 10.47 4.35 | 0.23 0.19 | 0.40; 0.33 22.4; −142.2 | 10.70 10.07 | 0.12 0.10 |
12. | 0.18; 0.33 −139.3; 116.7 | −0.04 7.10 | 0.18 0.15 | 0.19; 0.18 99.1; −36.5 | 9.00 9.54 | 0.07 0.06 | 0.20; 0.38 −124.2; −124.5 | 19.63 12.61 | 0.02 0.09 |
14. | 0.24; 0.33 140.0; 176.5 | 4.53 2.75 | 0.14 0.24 | 0.41; 0.20 −89.7; −42.6 | 1.12 −0.76 | n.c. n.c. | 0.37; 0.40 145.2; −133.5 | 17.16 0.77 | 0.05 0.37 |
18. | 0.10; 0.28 −33.7; 167.4 | −5.02 17.98 | 0.11 0.03 | 0.13; 0.03 −40.1; 135.2 | 7.83 −5.87 | 0.05 0.07 | 0.11; 0.19 −47.9; −0.9 | 7.02 17.08 | 0.05 0.03 |
19. | 1.33; 1.86 −3.3; −174.4 | n.c. 20.35 | n.c. 0.18 | 1.22; 1.01 −9.5; −159.8 | 21.99 16.39 | 0.07 0.15 | 0.70; 0.48 110.4; −81.0 | 23.78 18.27 | 0.05 0.06 |
20. | 0.1; 0.089 3.6; 56.9 | 2.93 9.98 | 0.13 0.25 | 0.32; 0.16 −20.3; 19.5 | 11.61 −5.72 | 0.08 0.30 | 0.20; 0.07 −36.5; −25.6 | 4.49 −6.04 | 0.12 0.14 |
21. | 0.37; 0.46 −9.4; −173.6 | 11.85 11.55 | 0.10 0.12 | 0.89; 0.26 −15.3; −144.8 | 10.01 13.00 | 0.28 0.06 | 0.05; 0.12 −47.9; 127.6 | 5.25 0.20 | 0.01 0.05 |
23. | 0.50; 0.53 41.6; −141.6 | 9.34 22.92 | 0.17 0.04 | 0.57; 0.53 −11.7; −177.4 | 7.33 16.68 | 0.25 0.08 | 0.23; 0.28 −60.1; 137.7 | 10.32 16.82 | 0.07 0.04 |
24. | 0.10; 0.20 −55.4; 163.3 | 1.50 7.72 | 0.08 0.08 | 0.24; −9.0 0.13; −141.1 | 6.45 6.69 | 0.12 0.06 | 0.21; 0.05 −30.6; 85.1 | 23.02 −3.01 | 0.01 0.07 |
25. | 0.14; 0.16 −121.4; 146.4 | −0.02 −2.6 | 0.14 0.10 | 0.15; 0.17 26.7; −80.2 | 4.94 6.98 | 0.09 0.07 | 0.09; 0.06 29.8; 64.9 | 1.92 −4.92 | 0.08 0.10 |
26. | 0.32; 0.21 12.5; 84.4 | 2.93 −0.36 | 0.23 0.22 | 0.10; 0.02 −12.3; −53.3 | −536 −13.28 | 0.18 0.11 | 0.04; 0.11 −159.6; −90.5 | −8.29 5.79 | 0.11 0.06 |
27. | 0.46; 0.15 48.7; −124.1 | 6.60 1.69 | 0.23 0.12 | 0.16; 0.20 −43.7; 142.4 | 10.77 −3.07 | 0.05 0.06 | 0.34; 0.04 −0.4; 42.1 | 8.41 0.46 | 0.13 0.04 |
28. | 0.59; 0.37 35.3; −120.8 | 18.07 22.20 | 0.07 0.03 | 0.29; 0.08 −171.2; −12.6 | 14.59 4.81 | 0.05 0.05 | 0.31; 0.18 −53.3; 104.6 | 10.66 11.73 | 0.10 0.05 |
29. | 0.57; 0.45 32.9; −155.2 | 12.33 3.98 | 0.14 0.28 | 0.49; 0.18 −46.8; 167.1 | 18.43 3.78 | 0.06 0.12 | 0.19; 0.18 16.4; 70.6 | 2.43 −3.11 | 0.15 0.26 |
30. | 0.22; 0.07 49.4; 172.2 | 11.65 7.71 | 0.06 0.03 | 0.15; 0.11 −63.9; 148.0 | 16.07 7.63 | 0.02 0.04 | 0.22; 0.07 49.4; 172.2 | 11.65 7.71 | 0.06 0.03 |
31. | 0.45; 0.46 34.7; −126.2 | 13.83 12.98 | 0.09 0.12 | 0.21; 0.18 −35.7; 165.8 | 10.43 14.03 | 0.06 0.04 | 0.29; 0.27 −18.2; 170.6 | 9.68 10.01 | 0.10 0.08 |
32. | 0.30; 0.20 −42.0; 135.5 | 9.26 −0.96 | 0.10 0.22 | 0.18; 0.12 −95.9; 85.9 | 10.72 4.90 | 0.05 0.07 | 0.38; 0.33 −92.2; 118.0 | 7.84 4.85 | 0.16 0.19 |
33. | 0.07; 0.16 −3.22; −9.3 | 0.60 4.32 | 0.06 0.10 | 0.20; 0.07 −17.4; −87.7 | 12.79 2.59 | 0.05 0.05 | 021; 0.10 −61.8; 136.7 | 4.76 7.40 | 0.12 0.04 |
38. | 0.57; 0.40 −17.4; 137.2 | 14 n.c. | 12 n.c. | 0.35; 0.24 −20.0; −149.0 | 12.18 11.13 | 0.09 0.07 | 0.65; 0.57 −76; −84 | 26.77 11.13 | 0.03 0.15 |
39. | 0.20; 0.17 −145.8; −68.8 | −3.99 6.96 | 0.32 0.08 | 0.16; 0.17 47.0; 67.5 | 6.41 0.94 | 0.08 0.15 | 0.44; 0.35 −36.1;−22.2 | 14.02 16.3 | 0.09 0.06 |
42. | 0.07; 0.09 34.7; −47.9 | 2.73 2.38 | 0.04 0.07 | 0.21; 0.18 −20.1; 127.0 | 4.14 8.12 | 0.09 0.07 | 0.27; 0.21 −48.9; −157.9 | 3.89 3.67 | 0.17 0.14 |
43. | 0.34; 0.27 −71; −140 | 12.50 n.c. | 0.08 n.c. | 0.32; 0.30 −2.7; −29 | 4.31 12.69 | 0.20 0.07 | 0.17; 0.41 −41.7; −28.5 | 15 20.5 | 0.03 0.04 |
44. | 0.49; 0.46 −157; −142 | 10.31 30.1 | 0.08 0.01 | 0.16; 0.28 −87.6; −6.6 | 20.66 6.83 | 0.01 0.10 | 0.39; 0.30 −20.9; −10.6 | 4.31 11.11 | n.c. 0.11 |
45. | 0.16; 0.31 13.4; −168.1 | 11.13 17.47 | 0.04 0.08 | 0.27; 0.08 −27.9; −84.6 | 21.91 −4.51 | 0.02 −0.13 | 0.17; 0.18 −80.9; −57 | 25.21 11.43 | 0.01 0.06 |
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