Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
The Eye: Anatomy, Histology & Histopathology Gillian Shaw, DVM, MS Jefferson Doyle, MD MHS MA (Oxon) (in absentia) September 9, 2013 [email protected] [email protected] Overview • Abnormal • Macroscopic Anatomy • Some clinical presentations of eye disease • Microscopic Anatomy – Normal – Abnormal • Methods of eye evaluation – Inflammation • Terminology • Examples – Neoplasia • Examples – Degenerative conditions • Glaucoma • Macular Degeneration • Cataract Anatomy Uvea = pigmented parts of the eye = iris, ciliary body, choroid Eye Embryology • Surface Ectoderm: Corneal epithelium; Lens • Neural Tube: Retina; Iris epithelium & muscles, Ciliary body epithelium • Mesoderm: everything else Ways to evaluate the eye structures • External exam – orbit, eyelids, eyelashes, corneal surface • Slit lamp exam – for examining the anterior part of the eye (cornea, sclera, iris, anterior aspect of lens) • Fluorescein dye – Corneal surface – diagnoses corneal surface disease (ulcers) • Ultrasound – interior structures (lens, vitreous cavity, fundus) • Indirect ophthalmoscopy – interior structures including fundus (back of the eye, also includes macula and optic nerve head) • Optical Coherence Tomography (OCT) – mostly used for examining retinal layers Ways to evaluate eye function • Schirmer tear test – measures tear production • Fluorescein Dye • Intravascular – evaluates vascular integrity when fundus is examined concurrently • Visual evoked potentials – evaluates retina and whether the signal gets to the brain • Electroretinogram – evaluates the cells that make up the retina (retinal degeneration) • Perimetry – visual field testing (glaucoma) Clinical Eye Lesions • Buphthalmos – enlarged globe • Exophthalmos – protrusion of the globe • Phthisis bulbi – shrinkage of the globe after injury or inflammation • Anisocoria – having pupils of different size • Hyphema – blood in anterior chamber • Hypopyon – inflammatory cells in anterior chamber • Synechia – Anterior = iris adhered to cornea – Posterior = iris adhered to lens http://www.vlsstore.com/ME2/Audiences/dirmod.asp? sid=&nm=&type=Abstract&mod=Publications%3A%3AA rticle&mid=8 Buphthalmos http://www.moorevet.com/Feline/FeLV.html http://webeye.ophth.uiowa.edu/eyeforum/atlas/p ages/asymmetrical-bilateral-exophthalmus.html Exophthalmos Anisocoria Synechia Hyphema Phthisis Bulbi Hypopyon http://emedicine.medscape.com/art icle/1207755-media http://www.answers.com/topic/synechia http://pics.nypetrescue.org/London/lo ndon2sm.jpg http://www.medrounds.org/ophthalmologypearls/2006/12/clinical-case-report-mycobacterium.html Slit Lamp Examination Indirect Ophthalmoscopy -requires dilated pupils Ultrasound Inflammation : Terminology Select examples: • • • • • • • Conjunctivitis – conjunctiva Keratitis – cornea Iritis – iris Cyclitis – ciliary body Iridocyclitis – iris & ciliary body Hyalitis/Vitritis – vitreous body Uveitis – Anterior – iris & ciliary body – Posterior – ciliary body and choroid • Retinitis – retina • Chorioretinitis – retina & choroid • Endophthalmitis – uvea, retina and ocular cavities • Panophthalmitis – all ocular structures including sclera • Optic Neuritis – optic nerve Conjunctivitis In this case, accompanied by chemosis – edema of conjunctiva http://www.cat-health-guide.org/cateyeinfection.html The Source of (all) this info • UC Davis’s Ophthalmic Pathology Primer • http://www.vetmed.ucdavis.edu/courses/vet_ eyes/eye_path/epath_overview_index.html http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology Normal Dog Eye http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology - Cornea Normal Dog Eye Cornea • Epithelium (Ep) – stratified squamous cells • Stroma (S) – dense collagen • Descemet’s membrane – basement layer of endothelium • Endothelium – single layer of cuboidal cells http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Corneal Edema http://www.infovets.com/healthycatsinfo/F218.htm Occurs when the endothelium’s ability to keep the corneal stroma relatively dehydrated is overwhelmed (endothelial specific damage or epithelial damage). Edema appears histologically as white space between tissue components. http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_pa th/epath_overview_index.html Keratitis Corneal neovascularization Ulcerative keratitis with accompanying corneal edema and neovascularization http://www.merckveterinarymanual.com/mv m/index.jsp?cfile=htm/bc/30109.htm http://www.acvs.org/AnimalOwners/HealthConditions/LargeAnimalEquineTopic s/OphthalmologySurgicalEmergencies/ Keratitis http://www.aafp.org/afp/2004/0701/p123.html http://www.alnorthumbriavets.co.uk/index.php?pa ge=equine-client-meetings Corneal ulcers stain with fluorescein dye, which fluoresces green in UV light. The dye adheres to the exposed negatively charged corneal stroma. Keratitis Normal cornea Ulcerative keratitis with acute inflammation within the stroma http://eulep.pdn.cam.ac.uk/images/3307.0_TMB.jpg http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology – Anterior & Posterior Chambers Normal Dog Eye Drainage of Aqueous Humor Ciliary body (blue & spongy in this figure) produces aqueous humor, which flows into posterior chamber, then thru the pupil into the anterior chamber and exits the eye via the drainage angle. http://http://www.gcot.net/images/aqueous.jpg http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Anterior & Posterior Chambers • Anterior chamber is between the cornea and the front surfaces of the iris and lens – Contains aqueous humor, which exits through the filtration angle (where the iris meets the cornea) • Posterior chamber is between the posterior surface of the iris and the sides of the lens – Contains aqueous humor which is produced by the ciliary body http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology – Iris Normal Dog Eye Iris • Anterior border layer • Stroma – loose spongy connective tissue • Dilator muscle layer – smooth muscle in mammals, striated muscle in birds • Posterior epithelium • Color determined by number of pigmented cells http://www.missionforvisionusa.org/anatomy/2005/10/iris-histology.html Uvea Beginning of choroid Anterior & Posterior Uveitis Inflammatory cells (purple/blue) expanding the choroid and iris. This case is due to a viral infection in a cat. http://www.vspo.us/vspo/nextSaf.php?cid=8719&parentID=8697 http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology – Filtration Angle Normal Dog Eye http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Drainage/Filtration Angle • Pectinate ligament (PL) • Trabecular meshwork (TM) • Collecting channel (CC) (canal of Schlemm) • Problems with the filtration angle can lead to glaucoma – Congenital = goniodysgenesis http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology – Lens Normal Dog Eye http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Lens • Capsule (C) – Anterior is thicker than posterior • Lens Fibers (LF) (cells) • Lens bow is where the nuclei of elongating lens fiber cells line up towards the posterior part of lens • Lens is prone to artifact in processing and sectioning Cataract •Any opacity in the lens •Many different causes •Metabolic •Inflammatory •Degenerative http://www.i4vision.co.uk/#/cataract/4516520406 http://www.dog-health-guide.org/cataractindog.html http://users.jyu.fi/~anskarv/research.html Lens Pathology Cataracts Vacuolation Bladder cells and epithelial proliferation Fiber degeneration Fibrous metaplasia of epithelium http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Histology – Retina Normal Dog Eye Retina • Retinal Pigmented Epithelium • Photoreceptors (PRs) = rods and cones (contain photosensitive pigments), Outer Nuclear Layer • Outer Plexiform Layer Back of the Eye – Where PRs talk to Horizontal (HCs) and Bipolar cells (BCs) • Inner Nuclear Layer & Plexiform Layer (HC and BC nuclei) • Inner Plexiform Layer – Where HCs and BCs talk to Ganglion and Amacrine cells • Ganglion Cell (GC) Layer • Nerve Fiber Layer (axons of GCs – becomes optic nerve) Front of the Eye http://webvision.med.utah.edu/imageswv/schem.jpeg Retina • Photoreceptors = rods and cones (contain photosensitive pigments), Outer Nuclear Layer • Ganglion Cell Layer • Nerve Fiber Layer (axons of GCs – becomes optic nerve) http://webvision.med.utah.edu/imageswv/3dlabel.jpeg Retina Tapetum lucidum • Photoreceptors = rods and cones (contain photosensitive pigments), Outer Nuclear Layer • Ganglion Cell Layer • Nerve Fiber Layer (axons of GCs – becomes optic nerve) http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Tapetum Lucidum http://www.4to40.com/qa/index.asp?id=3743 http://fr.academic.ru/dic.nsf/frwiki/1604972 Macula Macula – the area of the retina in primates (including humans) that is rich in cone photoreceptors and is responsible for fine, sharp, straight-ahead vision (entire retina in this photo is the macula) Fovea – the area where there is a depression formed by thinning of the inner retinal layers to allow light to directly shine on the photoreceptor layer http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Retinal Structure: Optical Coherence Tomography (OCT) Optical Coherence Tomography (OCT) R-4300 for Greatest Depth, R-2200 for Greatest Resolution R4300 Whole Eye R2200 Posterior R2200 Anterior R2200 Periphery Histology Mouse SD-OCT 43 Retinal Function: Electroretinogram (ERG) b-wave Bipolar cells Rod Cone a-wave Photoreceptors ON ON OFF 3rd order neurons Bipolar cells ERG Intensity Series -2.4 -2.0 -1.42 -1.19 -0.79 -0.39 -0.002 0.39 0.85 1.4 og cdS/m2) 2.3 2.8 100 µV A 0 50 100 150 200 250 Electroretinographic features of the retinopathy, globe enlarged (rge) chick phenotype. Montiani-Ferreira F, Shaw GC, Geller AM, Petersen-Jones SM. Mol Vis. 2007 Apr 4;13:553-65. B 0 50 100 150 Abnormal Electroretinogram GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. Peachey NS, Ray TA, Florijn R, Rowe LB, Sjoerdsma T, Contreras-Alcantara S, Baba K, Tosini G, Pozdeyev N, Iuvone PM, Bojang P Jr, Pearring JN, Simonsz HJ, van Genderen M, Birch DG, Traboulsi EI, Dorfman A, Lopez I, Ren H, Goldberg AF, Nishina PM, Lachapelle P, McCall MA, Koenekoop RK, Bergen AA, Kamermans M, Gregg RG. Am J Hum Genet. 2012 Feb 10;90(2):331-9. Visual function: Optokinetic Device Cell transplantation as a treatment for retinal disease. Lund RD, Kwan AS, Keegan DJ, Sauvé Y, Coffey PJ, Lawrence JM. Prog Retin Eye Res. 2001 Jul;20(4):415-49. Eye – Species Differences Normal mouse eye – rodents have shallow anterior chambers and relatively large lenses that take up a large portion of the vitreous cavity http://www.aomf.ca/appl6.html Eye – Species Differences Normal rabbit retina. They have large retinal blood vessels on the surface of the retina, with capillary extensions down into retinal tissue. This would be considered a pathological lesion in other species. http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Murine Retinal Degeneration Models Retinal degeneration mutants in the mouse. Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR. Vision Res. 2002 Feb;42(4):517-25. Ocular Neoplasia • Neoplasia can arise from any part of the eye • Some common examples: – Melanoma (iris, choroid, conjunctiva) – Ciliary body adenoma / carcinoma – Glioma (optic nerve) – Squamous cell carcinoma (cornea) Melanoma http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoints/200 9GrossCond.pdf http://www.merckvetmanual.com/mvm/htm/bc/eene909.htm Melanoma http://www.merckvetmanual.com/mvm/htm/bc/eene05.htm • Can arise from the iris, ciliary body epithelium or the choroid. • Well differentiated tumors are composed of heavily pigmented cells that can be round to spindle shaped. Poorly differentiated tumors can be composed of poorly pigmented cells. http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/Pow erPoints/Japan09/NeoplasiaFelJap2009.pdf http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoints/J apan09/NeoplasiaK9Japan2009.pdf Ciliary Body Adenoma / Carcinoma http://www.merckvetmanual.com/mvm/htm/bc/eene910.htm http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoints/Jap an09/NeoplasiaFelJap2009.pdf Ciliary Body Adenoma / Carcinoma Cuboidal to polygonal shaped cells arranged in papillary to tubular patterns. One prominent characteristic is the thick basement membranes (stained with PAS stain in upper right photo). http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoints/Japan09/NeoplasiaFelJap2009.pdf Optic Nerve Glioma Spindle shaped cells arranged in bundles and streams http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoin ts/Japan09/NeoplasiaK9Japan2009.pdf Corneal Squamous Cell Carcinoma http://www.vetmed.wisc.edu/pbs/dubielzig/pages/coplow/PowerPoints/Neoplasia08.pdf Veterinary Ophthalmology Vol. 11, 4 Pages: 269-272 Glaucoma • Historically thought to be vision loss due solely to increased intraocular pressure – Can happen in some people despite normal intraocular pressure – Now considered to be an “optic neuropathy” leading to death of retinal ganglion cells and thus blindness • Hallmarks: – – – – Loss and/or death of retinal ganglion cells Optic nerve degeneration (causes optic disk cupping) Closure of filtration angle Breaks in Descemet’s membrane (corneal endothelium basement membrane) Glaucoma Closed filtration angle Retinal ganglion cells missing http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Glaucoma Break in Descemet’s membrane Cupping of optic disc http://www.vetmed.ucdavis.edu/courses/vet_eyes/eye_path/epath_overview_index.html Vascular eye disease models • Age-related macular degeneration – Dry = drusen deposition between choroid & RPE – Wet = vascular problem caused by unhappy (hypoxic) cell signalling • Diabetic retinopathy & Retinopathy of prematurity – Pathogenesis similar to wet AMD http://jirehdesign.com/eye-illustrations/eye-conditions-illustrations/co0069.html Fluorescein Angiography Macular Degeneration • Affects older adults • The macula is affected primarily, so central vision is lost • Two types: – Wet form – new blood vessels invade the subretinal space from the choroid and leak fluid thus separating the retina from the RPE, which leads to photoreceptor degeneration – Dry form – cellular debris (drusen) builds up between the RPE and the retina leading to photoreceptor degeneration Macular Degeneration http://www.ahaf.org/macular/about/understanding/normal-macula-compared.html Macular Degeneration •Dry AMD – drusen under RPE •Wet AMD – retinal neovascularization Oxygen-induced Retinopathy (OIR) Retinopathy of Prematurity P7 mice are exposed to 75% oxygen, which induces loss of immature retinal vessels and slows development of the normal retinal vasculature, leading to a central zone of vasoobliteration (VO). After returning mice to room air at P12, the central avascular retina becomes hypoxic, triggering both normal vessel regrowth and a pathologic formation of extraretinal neovascularization (NV). Questions?