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I. Eye Development

I. Eye Development

Sara Thomasy DVM, PhD, DACVO Mouse Day 8 Dog Day 11 Fields

Mouse Day 7 Dog Day 10 Prosencephalon

https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm Mouse Day 8 Dog Day 12

Cyclopia  Cyclopia - Formation of a single median  Synophthalmia – Two incompletely separated or fused globes  Concurrent severe craniofacial defects  Veratrum californicum . Day 14 of gestation in sheep  Steroidal alkaloids . Cyclopamine and jervine . Inhibit signal transduction during  Affects midline

Corn Lily or False Hellebore Day 15

Optic vesicle

Mouse Day 9.5

https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm Mouse Day 9.5 Dog Day 15

Optic vesicle

Microphthalmia

Optic stalk

https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm  Optic vesicle deficiency  Corresponding small palpebral fissure  Failure of normal growth . Failure of fusion of the fissure → colobomas . Failure to establish normal IOP

 Associated with a myriad of ocular defects  ASD  PHPV Neural plate deficiency  Cataract  Retinal dysplasia  Colobomatous malformations  Merle ocular dysgenesis

Intraretinal space

Mouse Day 11 Dog Day 18

https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm Mouse Day 11 coloboma Dog Day 18 https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm  “Defect”  Failure of fusion of the choroid fissure  “Typical colobomas” at the 6 o’clock position  Abnormal differentiation of the outer optic cup  “Atypical colobomas” at other locations

Charlois Collie Collie Day 25

Mouse Day 11 https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm

 Persistent keratolenticular attachment  Classic example: Peter’s anomaly  Corneal opacity with stromal & DM defects (B)  Persistent pupillary membrane (A) . Iris hypoplasia (C) . Anterior polar cataract (D)

B A D C Pupillary Provides nourishment membrane to the developing  Failure of the pupillary membrane to regress  Strands arise from iris collarette  DDx: Synechiae arise from pupillary margin

 Classified by location: Iris-to- . Iris-to-iris . Iris-to-lens

 Predisposed breeds:  Basenji  Mastiff  Pembroke Welsh Corgi  Chow Chow Week 8 Postnatal  ↑ IOP in animals <6 months of age . Marked buphthalmos → scleral elasticity  Arrest in normal development of AC . Concurrent ocular anomalies (eg. ASD)

 ↑ IOP in animals <6 months of age . Marked buphthalmos → scleral elasticity  Arrest in normal development of AC . Concurrent ocular anomalies (eg. ASD)

 Failure of the PL to rarify during development  “Primary” . Many predisposed breeds

http://www.eyedvm.com/eyeinfo.html Day 25

Hyaloid artery Lens Mouse Day 11.5 vesicle

 Failure of the hyaloid artery to regress

Rat  Concurrent cataract  Challenging surgery!  Ultrasound all surgical candidates

 Failure of vascular regression  Normal vitreous - antiangiogenic  Concurrent anomalies  Microphthalmia  Microphakia  Cataract  Retinal dysplasia  Inherited trait  Doberman  Staffordshire Bull Terrier

Rat

Day 29

Mouse Day 13 https://syllabus.med.unc.edu/courseware/embryo_images/unit-eye/eye_htms/eyetoc.htm  Abnormal formation of 1º 0r 2º lens fibers  Nuclear  Nonprogressive  Abnormal lens vesicle , separation or defects in lens epithelium/capsule  Peripheral

Rat  Miniature Schnauzer  Autosomal recessive  Bilateral  Posterior cortex → rapid progression  Microphthalmia

Shastry BS & Reddy VN. Biochem & Biophys Res Commun. 1994 ;203: 1663-7. Zhang et al. IOVS. 1991;32: 2662-5. Gelatt et al. JAVMA. 1983;183:99-102. Gelatt et al. AJVR. 1983;44:1130-2. Rat Microphakia Immature Cataract Microphakia Hypermature Cataract Elongated CB processes  Small optic vesicle → small lens vesicle  Concurrent microphthalmia  Abnormal optic vesicle orientation → small lens vesicle  ± Cataract  ↑ risk of lens luxation

Multifocal retinal dysplasia

Dog  “Difficult formation”  Incomplete contact between inner & outer optic cup  Classified by severity:  Focal/multifocal → retinal folds → inequity in growth of inner and outer optic cup

Dog Dog  “Difficult formation”  Incomplete contact between inner & outer optic cup  Classified by severity:  Focal/multifocal → retinal folds → inequity in growth of inner and outer optic cup  Geographic  Diffuse with retinal detachment

Dog Dog Optic nerve hypoplasia

Dog  RGC axon guidance defect  Abnormal retinal/ON development  ↓/Absent vision (2/8 cases visual)  Histologic features:  Vestigial ectopic ON elements (no axons) – 6/8 cases  Vitreous extension of retinal vessels – 5/8 cases  Predisposed breeds: . Poodle . Shih Tzu

da Silva EG, et al. Vet Ophthalmol. 2008 ;11:23-29.  Primary failure of RGC development  Failure of RGC axon initiation &/or guidance  Failure of RGC axons to reach  Concurrent ASD (3/5 cases)  Lack of:  Retinal vessels  NFL  RGCs

da Silva EG, et al. Vet Ophthalmol. 2008 ;11:23-29. Day 32

Mouse Day 17

 Abnormal differentiation of an isolated group of cells (early)  Abnormal invagination of ectodermal tissue (late)  Common locations (surface derived):  Cornea (at the lateral limbus)   Choristoma – Normal tissue in an abnormal location  Corneal dermoid  Hamartoma – Tissue normal to that location but in an abnormal configuration  Eyelid dermoid

 Predisposed breeds:  Dachshund  Dalmation  Doberman  German Shepherd  St. Bernard

Eyelid Agenesis  Abnormal orientation of the optic vesicle as it contacts  Temporal aspect of superior eyelid  Common sequelae: Exposure keratitis  Common concurrent abnormalities:  Anterior segment dysgenesis  Coloboma  Choroid  Optic nerve Photo courtesy of Dr. Daniel Dorbandt, University of Illinois

 Roberts & Bistner procedure . Dziezyc & Millichamp modification  Z-plasty  Cutler-Beard technique  Mustarde cross lid technique  Sliding skin grafts  Cryotherapy  Collagen injection  Lip to lid transposition