77:
543:
National
Hospital Episode Statistics, they calculated the annual incidence of anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus from 1999 to 2011. According to this study the incidence of congenital anophthalmia ranged from 2.4 (95% CI 1.3 to 4.0) per 100 000 infants in 1999 to 0.4 (0 to 1.3) in 2011. Parents that already have a child who has anophthalmia have a 1 in 8 chance of having another child with anophthalmia. Approximately 2/3 of all cases of anophthalmia are determined to be of genetic basis. Anophthalmia is one of the leading causes of
67:
29:
542:
had a combined average of 1 in every 10,000 births. The annual rate of occurrence of anophthalmia/microphthalmia in the United States is about 780 children born/year. The most extensive epidemiological survey on this congenital malformation has been carried out by
Dharmasena et al. and using English
495:
to have conformers fitted into the eye. Conformers are made of clear plastic and are fitted into the socket to promote socket growth and expansion. As the child's face grows and develops, the conformer will need to be changed. An expander may also be needed in anophthalmia to expand the socket that
435:
Genetic testing can include chromosomal microarray analysis, single-gene testing, or multigene-panel testing. Genomic testing including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing or use of a multigene panel fails to confirm a molecular
190:
mutation which predisposes the fetus to vitamin A deficiency (a known environmental risk factor for anophthalmia) during pregnancy. If
Vitamin A deficiency occurs during the first several months when the eye is developing, it may lead to anophthalmia. This form of anophthalmia is the first that may
511:
published in 2016 asked whether the type of material used to make the prosthetic eye affects the success of the operation. Prosthetic eyes can be made from two types of material; porous or non-porous material. "If the material is porous then the artificial eye can become integrated into the body
150:
is caused by a mutation in the Sox2 gene that does not allow it to produce the Sox2 protein that regulates the activity of other genes by binding to certain regions of DNA. Without this Sox2 protein, the activity of genes that is important for the development of the eye is disrupted. Sox2
512:
because new blood vessels can grow into the material. If the material is non-porous, then the artificial eye remains separate from the rest of the body's tissue." After assessing three studies, the review concluded that there wasn't enough evidence to conclude which material was better.
185:
has recently been linked to autosomal dominant form of anophthalmia. This form of anophthalmia has variable penetrance and a unique maternal inheritance effect that is rooted in pregnancy. Specifically, the disease only occurs when a mother and fetus both carry a
798:
Chowdhury, Fuad; Wang, Lei; Al-Raqad, Mohammed; Amor, David J.; Baxová, Alice; Bendová, Šárka; Biamino, Elisa; Brusco, Alfredo; Caluseriu, Oana; Cox, Nancy J.; Froukh, Tawfiq; Gunay-Aygun, Meral; Hančárová, Miroslava; Haynes, Devon; Heide, Solveig (July 2021).
520:
If the proper actions are not taken to expand the orbit, many physical deformities can appear. It is important that if these deformities do appear, that surgery is not done until at least the first two years of life. Many people get eye surgery, such as upper
76:
172:. There are at least 33 mutations in the Sox2 gene that have been known to cause anophthalmia. Some of these gene mutations will cause the Sox2 protein not to be formed, while other mutations will yield a non-functional version of this protein.
525:
surgery and lower eyelid tightening. These surgeries can restore the function of the surrounding structures like the eyelid in order to create the best appearance possible. This is more common with people who have degenerative anophthalmia.
1361:
1342:
303:
of chromosome 14 has been known to occasionally be the source of anophthalmia. The deletion of this region of chromosome has also been associated with patients having a small tongue, and high arched palate, developmental and
490:
Currently, there is not a treatment option for regaining vision by developing a new eye. There are, however, cosmetic options so the absence of the eye is not as noticeable. Typically, the child will need to go to an
388:, but it may not show a correct negative result. Amniocentesis can only diagnose anophthalmia when there is a chromosomal abnormality. Chromosomal abnormalities are only a minority of cases of anophthalmia.
155:
inheritance, but the majority of patients who have Sox2 anophthalmia are the first in their family history to have this mutation. In certain cases, one parent will possess the mutated gene only in their
191:
be intervened upon with vitamin A supplementation of retinyl esters during the first several months of pregnancy. This strategy exploits an RBP-independent pathway. Clinical research is underway. See
1261:
Kataev, MG; Filatova, IA; Verigo, EN; Kiriukhina, SL (2000). "Potentialities of conservative and surgical treatment of patients with congenital microphthalmia and anophthalmia".
469:
Aside from these associative conditions, anophthalmia in only one eye tends to be associated with complications in the other eye. These risks include a higher chance of having
608:
Wiese, K. GĂĽnter; Vogel, Martin; Guthoff, Rudolf; Gundlach, Karsten K.H. (1999). "Treatment of congenital anophthalmos with self-inflating polymer expanders: A new method".
345:
the eye starts to develop and for some reason stops, leaving the infant with only residual eye tissue or extremely small eyes which can only be seen under close examination.
1107:
862:
127:
can all cause anophthalmia. Anophthalmia is an extremely rare disease and is mostly rooted in genetic abnormalities. It can also be associated with other syndromes.
259:
Many environmental conditions have also been known to cause anophthalmia. The strongest support for environmental causes has been studies where children have had
1190:
836:
320:. The region that has been deleted is region q22.1-q22.3. This confirms that region 22 on chromosome 14 influences the development of the eye.
1438:
504:
should be avoided because it may damage the prosthetic eye. Children need to be checked regularly to ensure the fit and size is appropriate.
883:
372:
can be used to diagnose anophthalmia during gestation. Due to the resolution of the ultrasound, it is difficult to diagnose it until the
1236:
1211:
583:
1155:"Trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformation in England: Database study"
1004:
773:
236:
is also linked to anophthalmia, as well as causing myopia and microphthalmia. It is dominantly inherited. BMP4 interacts with the
1132:
534:
Anophthalmia has been reported to be present in 3 out of every 100,000 births. Many instances of anophthalmia also occur with
1103:
1308:
983:
858:
1029:
1443:
453:
408:
can be used to scan the brain and orbits. Radiologists use this to assess the internal structures of the globe, the
670:"Biochemical Basis for Dominant Inheritance, Variable Penetrance, and Maternal Effects in RBP4 Congenital Disease"
1054:
Schellini S, El Dib R, Silva LR, Farat JG, Zhang Y, Jorge EC (2016-11-07). Cochrane Eyes and Vision Group (ed.).
120:
1376:
99:
tissue are missing from the orbit. The absence of the eye will cause a small bony orbit, a constricted mucosal
647:
1305:– Charity offering support and information for people affected by microphthalmia, anophthalmia, and coloboma
959:
351:
the eye started to form and, for some reason, degenerated. One reason for this occurring could be a lack of
80:(a) Bilateral anophthalmia. (b) Bilateral microphthalmia. (c) Unilateral anophthalmia with shell (right eye)
552:
1154:
801:"Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities"
496:
is present. The conformer is changed every few weeks the first two years of life. After that, a painted
309:
500:
can be fitted for the child's socket. The prosthetic eye can be cleaned with mild baby soap and water.
112:
463:
300:
276:
223:
1365:
544:
413:
165:
66:
1319:
1182:
458:
369:
305:
244:
205:
SOX2 and RBP4 are not the only genes that can cause anophthalmia. Other important genes include
152:
1387:
1270:
1174:
1085:
939:
887:
828:
820:
755:
699:
668:
Chou CM, Nelson C, Tarle SA, Pribila JT, Bardakjian T, Woods S, Schneider A, Glaser T (2015).
625:
560:
497:
263:. These infections are typically viral. A few known pathogens that can cause anophthalmia are
124:
108:
92:
55:
1240:
910:"A case of deletion 14(q22.1→q22.3) associated with anophthalmia and pituitary abnormalities"
1166:
1153:
Dharmasena, Aruna; Keenan, Tiarnan; Goldacre, Raph; Hall, Nick; Goldacre, Michael J (2017).
1075:
1067:
975:
929:
921:
812:
745:
735:
689:
681:
617:
425:
373:
116:
60:
1215:
587:
556:
522:
508:
501:
474:
429:
272:
248:
1080:
1055:
1008:
934:
909:
777:
750:
723:
694:
669:
539:
535:
317:
237:
1370:
621:
87:(Greek: ἀνόφθαλμος, "without eye") is the medical term for the absence of one or both
1432:
1170:
1056:"Integrated versus non-integrated orbital implants for treating anophthalmic sockets"
385:
284:
227:
157:
1186:
1128:
1071:
352:
1416:
275:. Other known environmental conditions that have led to anophthalmia are maternal
1381:
444:
There are a few conditions that are associated with anophthalmia. These include:
409:
288:
1392:
971:
816:
685:
376:. The earliest time to detect anophthalmia this way is approximately 20 weeks.
1355:
1351:
1314:
1033:
448:
313:
264:
230:
inherited. Mutation effects vary in severity, and can include microphthalmia.
161:
100:
824:
800:
428:, can examine the child and give a correct diagnosis. Some will do molecular
1411:
548:
492:
88:
1274:
1178:
1089:
832:
759:
740:
703:
629:
943:
551:
in children. Anophthalmia and microphthalmia together make up 1.7-1.8% of
1294:– Support group for parents with anophthalmic and microphthalmic children
960:
http://www.cafamily.org.uk/medical-information/conditions/a/anophthalmia/
925:
470:
335:
is a complete absence of eye tissue due to a failure of the part of the
1298:
International
Children's Anophthalmia and Microphthalmia Network (ICAN)
979:
644:"SOX2 - SRY (sex determining region Y)-box 2 - Genetics Home Reference"
405:
268:
1334:
1346:
1237:"MCYSHN: Anophthalmia and Microphthalmia Health Condition Fact Sheet"
219:
104:
96:
774:"Summary of Results from Anophthalmia-Microphthalmia Genetics Study"
222:
expression. Mutations in these genes can cause a failure of retinal
643:
251:
is also known to result in anophthalmia among other abnormalities.
1291:
336:
280:
232:
207:
193:
143:
28:
1297:
1032:. International Children's Anophthalmia Network. Archived from
1315:
GeneReviews/NCBI/NIH/UW entry on anophthalmia / microphthalmia
401:
214:
538:. A recent study in the UK indicated that anophthalmia and
142:
The most common genetic cause for anophthalmia is mutated
1320:
NCBI/Molecular diagnosis of anophthalmia / microphthalmia
1303:
1302:
1007:. United States: National Eye Institute. Archived from
859:"Baby born without eyes due to rare genetic disorder"
1324:
432:to see if the cause is linked with gene mutations.
328:
There are three classifications for this condition:
1402:
1328:
1129:"CDC - Birth Defects, Data and Statistics - NCBDDD"
54:
40:
21:
1239:. Health.state.mn.us. 2010-11-16. Archived from
578:
576:
1005:"Facts About Anophthalmia and Microphthalmia"
908:Elliott, J; Maltby, E L; Reynolds, B (1993).
8:
955:
953:
722:Verma, Amit S; Fitzpatrick, David R (2007).
1104:"Prosthetic Eye - Fake Eye -Socket Surgery"
384:It is possible to diagnose prenatally with
1325:
218:. Each of these genes are an important in
65:
27:
18:
1079:
933:
749:
739:
693:
75:
1060:Cochrane Database of Systematic Reviews
610:Journal of Cranio-Maxillofacial Surgery
572:
717:
715:
713:
7:
547:blindness and accounts for 3-11% of
243:pathway and can cause anophthalmia.
1214:. Viscotland.org.uk. Archived from
974:. Radiopaedia.org. 3 October 2011.
36:Right-sided anophthalmia (MR image)
586:. Anophthalmia.org. Archived from
14:
728:Orphanet Journal of Rare Diseases
724:"Anophthalmia and microphthalmia"
1171:10.1136/bjophthalmol-2016-308952
1159:British Journal of Ophthalmology
168:it through that. This is called
1193:from the original on 2023-04-06
1135:from the original on 2018-06-18
1110:from the original on 2012-04-26
986:from the original on 2023-12-17
865:from the original on 2024-02-09
857:Steinbuch, Yaron (2024-02-08).
839:from the original on 2024-07-01
650:from the original on 2023-07-12
646:. Ghr.nlm.nih.gov. 2012-07-09.
261:gestational-acquired infections
1072:10.1002/14651858.CD010293.pub2
584:"Questions about Anophthalmia"
1:
886:. Macs.org.uk. Archived from
776:. Macs.org.uk. Archived from
622:10.1016/S1010-5182(99)80016-X
271:, and certain strains of the
1439:Congenital disorders of eyes
1309:National Eye Institute (NEI)
151:anophthalmia syndrome is an
914:Journal of Medical Genetics
1460:
817:10.1038/s41436-021-01129-6
686:10.1016/j.cell.2015.03.006
148:Sox2 anophthalmia syndrome
459:Goldenhar-Gorlin syndrome
424:Physicians, specifically
349:Degenerative anophthalmia
121:chromosomal abnormalities
35:
26:
1131:. Cdc.gov. 2011-09-19.
555:cases in laboratory of
553:reconstructive surgical
255:Environmental influence
201:Other influential genes
164:and the offspring will
884:"What is Anophthalmia"
741:10.1186/1750-1172-2-47
343:Secondary anophthalmia
197:for more information.
81:
416:, and brain anatomy.
79:
1263:Vestnik Oftalmologii
926:10.1136/jmg.30.3.251
805:Genetics in Medicine
464:Waardenburg syndrome
333:Primary anophthalmia
277:vitamin A deficiency
125:prenatal environment
1444:Medical terminology
414:extraocular muscles
392:Postnatal diagnosis
339:that forms the eye.
1403:External resources
980:10.53347/rID-15230
360:Prenatal diagnosis
310:undescended testes
306:growth retardation
287:, and exposure to
283:during gestation,
245:Haploinsufficiency
170:germline mosaicism
153:autosomal dominant
82:
1426:
1425:
561:ocular prostheses
117:Genetic mutations
109:palpebral fissure
74:
73:
16:Medical condition
1451:
1326:
1279:
1278:
1258:
1252:
1251:
1249:
1248:
1233:
1227:
1226:
1224:
1223:
1208:
1202:
1201:
1199:
1198:
1150:
1144:
1143:
1141:
1140:
1125:
1119:
1118:
1116:
1115:
1100:
1094:
1093:
1083:
1051:
1045:
1044:
1042:
1041:
1026:
1020:
1019:
1017:
1016:
1001:
995:
994:
992:
991:
968:
962:
957:
948:
947:
937:
905:
899:
898:
896:
895:
880:
874:
873:
871:
870:
854:
848:
847:
845:
844:
811:(7): 1234–1245.
795:
789:
788:
786:
785:
770:
764:
763:
753:
743:
719:
708:
707:
697:
665:
659:
658:
656:
655:
640:
634:
633:
605:
599:
598:
596:
595:
580:
516:Cosmetic surgery
426:ophthalmologists
374:second trimester
299:An interstitial
113:malar prominence
70:
69:
61:Medical genetics
47:anoftalama
31:
19:
1459:
1458:
1454:
1453:
1452:
1450:
1449:
1448:
1429:
1428:
1427:
1422:
1421:
1398:
1397:
1337:
1288:
1283:
1282:
1260:
1259:
1255:
1246:
1244:
1235:
1234:
1230:
1221:
1219:
1210:
1209:
1205:
1196:
1194:
1152:
1151:
1147:
1138:
1136:
1127:
1126:
1122:
1113:
1111:
1106:. Tabanmd.com.
1102:
1101:
1097:
1066:(6): CD010293.
1053:
1052:
1048:
1039:
1037:
1028:
1027:
1023:
1014:
1012:
1003:
1002:
998:
989:
987:
970:
969:
965:
958:
951:
907:
906:
902:
893:
891:
882:
881:
877:
868:
866:
856:
855:
851:
842:
840:
797:
796:
792:
783:
781:
772:
771:
767:
721:
720:
711:
667:
666:
662:
653:
651:
642:
641:
637:
607:
606:
602:
593:
591:
582:
581:
574:
569:
557:plastic surgery
532:
518:
509:Cochrane Review
502:Rubbing alcohol
488:
483:
475:detached retina
442:
422:
399:
394:
382:
367:
362:
326:
324:Classifications
297:
273:influenza virus
257:
224:differentiation
203:
180:
140:
133:
64:
50:
17:
12:
11:
5:
1457:
1455:
1447:
1446:
1441:
1431:
1430:
1424:
1423:
1420:
1419:
1407:
1406:
1404:
1400:
1399:
1396:
1395:
1384:
1373:
1358:
1338:
1333:
1332:
1330:
1329:Classification
1323:
1322:
1317:
1312:
1306:
1300:
1295:
1287:
1286:External links
1284:
1281:
1280:
1253:
1228:
1212:"anophthalmia"
1203:
1165:(6): 735–739.
1145:
1120:
1095:
1046:
1021:
996:
972:"Anophthalmia"
963:
949:
900:
875:
849:
790:
765:
709:
680:(3): 634–646.
660:
635:
600:
571:
570:
568:
565:
540:microphthalmia
536:microphthalmia
531:
528:
517:
514:
498:prosthetic eye
487:
486:Prosthetic eye
484:
482:
479:
467:
466:
461:
456:
451:
441:
438:
430:genetics tests
421:
418:
398:
395:
393:
390:
381:
378:
366:
363:
361:
358:
357:
356:
346:
340:
325:
322:
318:hypothyroidism
296:
293:
279:, exposure to
256:
253:
238:Sonic hedgehog
202:
199:
179:
174:
139:
134:
132:
129:
72:
71:
58:
52:
51:
49:
48:
44:
42:
38:
37:
33:
32:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1456:
1445:
1442:
1440:
1437:
1436:
1434:
1418:
1414:
1413:
1409:
1408:
1405:
1401:
1394:
1390:
1389:
1385:
1383:
1379:
1378:
1374:
1372:
1368:
1367:
1363:
1359:
1357:
1353:
1349:
1348:
1344:
1340:
1339:
1336:
1331:
1327:
1321:
1318:
1316:
1313:
1310:
1307:
1304:
1301:
1299:
1296:
1293:
1290:
1289:
1285:
1276:
1272:
1268:
1264:
1257:
1254:
1243:on 2012-08-07
1242:
1238:
1232:
1229:
1218:on 2012-04-26
1217:
1213:
1207:
1204:
1192:
1188:
1184:
1180:
1176:
1172:
1168:
1164:
1160:
1156:
1149:
1146:
1134:
1130:
1124:
1121:
1109:
1105:
1099:
1096:
1091:
1087:
1082:
1077:
1073:
1069:
1065:
1061:
1057:
1050:
1047:
1036:on 2012-07-12
1035:
1031:
1025:
1022:
1011:on 2012-07-18
1010:
1006:
1000:
997:
985:
981:
977:
973:
967:
964:
961:
956:
954:
950:
945:
941:
936:
931:
927:
923:
919:
915:
911:
904:
901:
890:on 2012-07-28
889:
885:
879:
876:
864:
860:
853:
850:
838:
834:
830:
826:
822:
818:
814:
810:
806:
802:
794:
791:
780:on 2012-07-28
779:
775:
769:
766:
761:
757:
752:
747:
742:
737:
733:
729:
725:
718:
716:
714:
710:
705:
701:
696:
691:
687:
683:
679:
675:
671:
664:
661:
649:
645:
639:
636:
631:
627:
623:
619:
615:
611:
604:
601:
590:on 2012-07-28
589:
585:
579:
577:
573:
566:
564:
562:
558:
554:
550:
546:
541:
537:
529:
527:
524:
523:eyelid ptosis
515:
513:
510:
505:
503:
499:
494:
485:
480:
478:
476:
472:
465:
462:
460:
457:
455:
454:Lenz syndrome
452:
450:
447:
446:
445:
439:
437:
433:
431:
427:
419:
417:
415:
411:
407:
403:
396:
391:
389:
387:
386:amniocentesis
380:Amniocentesis
379:
377:
375:
371:
364:
359:
354:
350:
347:
344:
341:
338:
334:
331:
330:
329:
323:
321:
319:
315:
311:
307:
302:
295:Chromosome 14
294:
292:
290:
286:
285:solvent abuse
282:
278:
274:
270:
266:
262:
254:
252:
250:
246:
242:
239:
235:
234:
229:
225:
221:
217:
216:
211:
209:
200:
198:
196:
195:
189:
184:
178:
175:
173:
171:
167:
163:
159:
154:
149:
145:
138:
135:
130:
128:
126:
122:
118:
114:
110:
106:
102:
98:
94:
90:
86:
78:
68:
62:
59:
57:
53:
46:
45:
43:
41:Pronunciation
39:
34:
30:
25:
20:
1410:
1386:
1375:
1360:
1341:
1266:
1262:
1256:
1245:. Retrieved
1241:the original
1231:
1220:. Retrieved
1216:the original
1206:
1195:. Retrieved
1162:
1158:
1148:
1137:. Retrieved
1123:
1112:. Retrieved
1098:
1063:
1059:
1049:
1038:. Retrieved
1034:the original
1024:
1013:. Retrieved
1009:the original
999:
988:. Retrieved
966:
920:(3): 251–2.
917:
913:
903:
892:. Retrieved
888:the original
878:
867:. Retrieved
852:
841:. Retrieved
808:
804:
793:
782:. Retrieved
778:the original
768:
731:
727:
677:
673:
663:
652:. Retrieved
638:
613:
609:
603:
592:. Retrieved
588:the original
533:
530:Epidemiology
519:
506:
489:
468:
443:
440:Associations
436:diagnosis.
434:
423:
400:
383:
368:
353:blood supply
348:
342:
332:
327:
298:
260:
258:
240:
231:
213:
206:
204:
192:
187:
182:
181:
176:
169:
147:
141:
136:
85:Anophthalmia
84:
83:
22:Anophthalmia
1311:– Resources
1269:(6): 9–13.
1030:"Treatment"
616:(2): 72–6.
420:Examination
410:optic nerve
370:Ultrasounds
365:Ultrasounds
355:to the eye.
289:thalidomide
91:. Both the
1433:Categories
1388:DiseasesDB
1247:2012-07-17
1222:2012-07-17
1197:2020-08-31
1139:2012-07-17
1114:2012-07-17
1040:2012-07-17
1015:2012-07-17
990:2012-07-17
894:2012-07-17
869:2024-02-09
843:2024-02-09
784:2012-07-17
654:2012-07-17
594:2012-07-17
567:References
545:congenital
481:Treatments
449:Trisomy 13
314:micropenis
265:Toxoplasma
228:dominantly
226:. OTX2 is
162:sperm cell
107:, reduced
1412:eMedicine
825:1098-3600
549:blindness
493:ocularist
56:Specialty
1275:11196218
1191:Archived
1187:27880982
1179:27601422
1133:Archived
1108:Archived
1090:27820878
984:Archived
863:Archived
837:Archived
833:33824499
760:18039390
704:25910211
648:Archived
630:10342141
471:glaucoma
301:deletion
103:, short
95:and the
1417:oph/572
1382:D000853
1081:6465188
944:7682620
935:1016311
751:2246098
695:4409664
312:with a
269:rubella
220:retinal
210:, CHX10
166:inherit
105:eyelids
1273:
1185:
1177:
1088:
1078:
942:
932:
831:
823:
758:
748:
734:: 47.
702:
692:
628:
397:MRI/CT
316:, and
281:X-rays
146:gene.
131:Causes
123:, and
101:socket
97:ocular
63:
1393:29617
1371:743.0
1356:Q11.1
1352:Q11.0
1183:S2CID
473:or a
337:brain
249:PRR12
241:(SHH)
93:globe
1377:MeSH
1366:9-CM
1292:MAPS
1271:PMID
1175:PMID
1086:PMID
940:PMID
829:PMID
821:ISSN
756:PMID
700:PMID
674:Cell
626:PMID
559:and
412:and
404:and
402:MRIs
233:BMP4
212:and
208:OTX2
194:RBP4
188:RBP4
183:RBP4
177:RBP4
144:SOX2
137:SOX2
111:and
89:eyes
1362:ICD
1343:ICD
1267:116
1167:doi
1163:101
1076:PMC
1068:doi
976:doi
930:PMC
922:doi
813:doi
746:PMC
736:doi
690:PMC
682:doi
678:161
618:doi
406:CTs
247:of
215:RAX
160:or
158:egg
1435::
1415::
1391::
1380::
1369::
1350::
1347:10
1265:.
1189:.
1181:.
1173:.
1161:.
1157:.
1084:.
1074:.
1064:11
1062:.
1058:.
982:.
952:^
938:.
928:.
918:30
916:.
912:.
861:.
835:.
827:.
819:.
809:23
807:.
803:.
754:.
744:.
730:.
726:.
712:^
698:.
688:.
676:.
672:.
624:.
614:27
612:.
575:^
563:.
507:A
477:.
308:,
291:.
267:,
119:,
115:.
1364:-
1354:-
1345:-
1335:D
1277:.
1250:.
1225:.
1200:.
1169::
1142:.
1117:.
1092:.
1070::
1043:.
1018:.
993:.
978::
946:.
924::
897:.
872:.
846:.
815::
787:.
762:.
738::
732:2
706:.
684::
657:.
632:.
620::
597:.
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
