Pathology of eye i-2013-final

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Pathology of eye i-2013-final

  1. 1. Today’s Quranic verse ‘Turn not your cheek away from people in scorn and pride, and not on earth haughtily; for God does not love anyone who acts proudly and boastfully. Be modest in your bearing and lower yo voice; for the ugliest sound is the donkey’s braying.’ (Luqman 31: 18-19
  2. 2. Pathology of the Eye - I Dr. Khurshid Anwar https://www.facebook.com/pages/Interactive-Neuroscience/160305064167505
  3. 3. Outline and Introduction SECTIONS 1. Orbit 2. Eyelid 3. Conjunctiva 4. Cornea 5. Uvea 6. Lens 7. Retina/Vitreous 8. Optic Nerve/Glaucoma
  4. 4. Intro - Basic Anatomy
  5. 5. EYE PATHOLOGY-1
  6. 6. Orbit • Functional Anatomy and Proptosis – The orbit is a compartment that is closed medially, laterally, and posteriorly. Any disease process that increases orbital contents results in the forward displacement of the eye, proptosis. – Proptosis may be axial (directly forward) or positional. • Axial proptosis – Glioma and meningioma • Positional (inferior and medial proptosis) – Sarcoid or neoplasm (lymphoma or epithelial neoplasm such as pleomorphic adenoma or adenoid cystic carcinoma)
  7. 7. Thyroid-Related Orbitopathy (Graves’ Disease) • Autoimmune condition, triggered by TSH-R Antibodies, with lymphocytic infiltration, fibrosis and enlargement of extra-ocular muscles. • Proptosis, strabismus/muscle-restriction, exposure problems (dryeye), and compressive optic neuropathy. • Treated with steroids, radiation therapy, or surgical decompression (opening the orbital walls into the sinuses)
  8. 8. THYROID EYE DISEASE Soft tissue involvement • Periorbital and lid swelling • Conjunctival hyperaemia • Chemosis • Superior limbic keratoconjunctivitis Eyelid retraction Proptosis Optic neuropathy Restrictive myopathy
  9. 9. Orbit – Thyroid-Related Orbitopathy
  10. 10. Orbit - Trauma • “Blow–out” fractures occur when blunt trauma to the eye causes the orbit to rupture • Orbital Floor fractures can cause restricted upgaze if there is muscle entrapment
  11. 11. Orbit - Inflammation • Orbital Cellulits frequently extends from adjacent sinus infections, or periocular trauma. • A life and sight threatening emergency! Can extend into the cavernous sinus, and brain. • “Pre-Septal” vs. “Post-Septal” can be distinguished by involvement of intraorbital structures
  12. 12. Orbit - Inflammation
  13. 13. Orbit • Other Orbital Inflammatory Conditions – Orbital cellulitis • Caused by fungal infection (Mucormycosis) • Appears in systemic conditions such as Wegener granulomatosis – Idiopathic orbital inflammation (orbital inflammatory pseudotumor) • • • • • May be unilateral or bilateral May be confined to the lacrimal gland (sclerosing dacryoadenitis) Extraocular muscles (orbital myositis) Tenon’s capsule (posterior scleritis) In the long-term, patients may show evidence of systemic vasculitis or other forms of connective tissue diseases
  14. 14. Orbital Neoplasms – Most frequent primary neoplasms are vascular in origin • capillary hemangioma (infancy and early childhood) • lymphangioma • encapsulated cavernous hemangioma (adults) – Only a handful of orbital masses are encapsulated • pleomorphic adenoma • dermoid cyst • neurilemmoma – Malignant lymphoma – In Children • rhabdomyosarcoma is the most common primary malignancy of orbit. • neuroblastomaa is the most common metastatic tumor. – Metástasis: may produce characteristic periocular echymoses • prostatic carcinoma • metastatic neuroblastoma • Wilms tumor
  15. 15. LIDS - Anatomy LAYERS: • • • • • Skin Orbicularis Tarsal plate Meibomian glands Palpebral conjunctiva
  16. 16. Anatomy of the conjunctiva and the eyelids
  17. 17. Eyelid • Functional Anatomy – The eyelid covers and protects the eye, and generates critical components of the tear film – The eyelid is a composite of skin externally and a mucosa (the conjunctiva) on the surface apposed to the eye – Eccrine and apocrine glands (glands of Moll) populate the eyelid. – Blepharitis: • Obstruction of the drainage system of the sebaceous glands by chronic inflammation or by neoplasm – Lipid extravasating into surrounding tissue and provoking a granulomatose response is called a lipogranuloma or chalazion
  18. 18. LIDS - Histology
  19. 19. LIDS - Tumors • Benign – – – – Chalazion vs. Hordeolum Papillomas/Verrucae Epidermal inclusion cysts Many others • Malignant – Basal cell carcinoma (most common, located in lower eyelid & medial canthus) – – – – Sebaceous cell carcinoma (D/D chalazion, belephritis) Squamous cell carcinoma Melanoma (rare) Kaposi sarcoma in AIDS
  20. 20. LIDS - Tumors • Chalazion – a cyst of the meibomian gland • Hordeolum – an inflammed cyst of the MG (foreign body granuloma)
  21. 21. Conjunctiva • Thin (transparent), non-keratinized skin covering the sclera (bulbar) or the inner surface of the lid (palpebral) • Rich in goblet cells, which secret the mucinous components of the tear film The palpebral layer is continous with bulbar layer at fornix
  22. 22. Conjunctiva • Functional Anatomy The conjunctiva is divided into topologic zones, each with distinctive histologic features and responses to disease: • Palpebral conjunctiva – The conjunctiva lining the interior of the eyelid (palpebral conjunctiva) is trown into minute papillary folds in allergic conjunctivitis and bacterial infectious conjunctivitis • Fornix – In viral conjunctivitis, lymphoid follicles may enlarge sufficiently to be visualized clinically – Granulomas (sarcoid) – Primary lymphoma • Bulbar conjunctiva
  23. 23. Conjunctivitis (pink eye) It is an inflammation of the conjunctiva due to a viral (Adenovirus), bacterial, or allergic cause Most cases of conjunctivitis run a predictable course, and the inflammation usually clears up in a few days. Conjunctivitis is a common disease, especially in children. Although conjunctivitis can be highly contagious (known to spread rapidly in schools or daycare settings), it is rarely serious and will not damage vision if detected and treated promptly.
  24. 24. Trachoma Trachoma is the world’s leading cause of preventable blindness of infectious origin. Caused by the bacterium Chlamydia trachomatis. It spreads through direct personal contact, shared towels and cloths, and flies that have come in contact with the eyes or nose of an infected person. If left untreated, repeated trachoma infections can cause severe scarring of the inside of the eyelid and can cause the eyelashes to scratch the cornea (trichiasis). In addition to causing pain, trichiasis permanently damages the cornea and can lead to irreversible blindness. It spreads in areas that lack adequate access to water and sanitation, affects the most marginalized communities in the world. Globally, almost 8 million people are visually impaired by trachoma; 500 million are at risk of blindness from the disease throughout 57 endemic countries http://www.cdc.gov/healthywater/hygiene/disease/trachoma.html
  25. 25. Conjunctivitis A rare granulomatous variety… Cat-scratch Fever! (Bartonella henselae)
  26. 26. Conjunctiva • Conjunctival Scarring – Caused by: • • • • Chlamydia trachomatis (trachoma) Caustic alkalis A sequela to ocular cicatricial pemphigoid Iatrogenically through reaction to drugs or as a concequence of surgery – Painful, dry eye
  27. 27. Conjunctiva Degenerative conditions • Pinguecula – on the conjunctiva only • Pterygium – encroaching onto cornea • Histologically identical • Both involve “elastotic degeneration” of the conjunctiva, usually due to chronic ultraviolet exposure.
  28. 28. Conjunctiva • Pterygium and Pinguecula – Appear as submucosal elevations on the conjunctiva – Result from actinic damage Pterygium • • • • • In the conjunctiva astride the limbus Formed by fibrovascular connective tissue that migrates onto the cornea May possibly induce mild astigmatism Commonly excised Occasionally precursors of actinic-induced neoplasms (SCC, Melanoma) Pinguecula • Does not invade the cornea as pterygium does • Focal dehydration (dellen: a saucer-like depression in the corneal tissue) • Solar elastosis: sun-damaged collagen with elastic-like properties, that are the reason why the pinguecula is yellow in color • Actinic granuloma may develop secondary to a foreign body granulomatous reaction against the elastotic collagen
  29. 29. Conjunctiva – Degenerative conditions • Small pinguecula • Pterygium
  30. 30. Conjunctival Neoplasm – Squamous neoplasms (CIN – Conjunctival intraepithelial neoplasia & SCC) • May be associated with the presence of human papillomavirus types 16 & 18 – Mucoepidermoid carcinoma (more aggressive course) – Conjunctival nevi – Conjunctival melanoma • Tend to develop in the limbus • Most cases develop through a phase of intraepithelial growth termed primary acquired melanosis with atypia, which is analogous to melanoma in situ • Spread first to the parotid or submandibular lymph nodes • Mortality rate: 25% – Lymphoma; Spread first to the parotid or submandibular lymph nodes
  31. 31. Conjunctiva Neoplasm CIN (squamous cell), HPV 16/18
  32. 32. Sclera • May appear “blue” in a variety of conditions: – high intraocular pressure (staphyloma) – osteogenesis imperfecta – congenital melanosis oculi • Heavily pigmented congenital nevus of the underlying uvea • Together with periocular cutaneous pigmentation – Nevus of Ota
  33. 33. Cornea • Functional Anatomy – The cornea and its overlying tear film – and not the lens – make up the major refractive surface of the eye – Corneal stroma lacks blood vessels and lymphatics (is very transparent; corneal transplantation is usually successful) – Scars can exist due to inflammation or trauma
  34. 34. Cornea - Histology 5 Layers: 1. Epithelium – Continuous with conj, richly innervated by CN-V1 2. Bowman’s Membrane 3. Stroma – The thickest central portion (90%). This is where LASIK/Refractive surgery happens! Primarily made up of Type 1 Collagen in uniformlyspaced lamellar bundles. 4. Descemet’s membrane 5. Endothelium – pumps the water out of the cornea and keeps it clear
  35. 35. Cornea The uniform spacing of the stromal collagen bundles at a distance of approx ¼ wavelength light allows transparency .
  36. 36. Normal corneal microarchitecture
  37. 37. Cornea - Refractive Surgery • • Excimer Laser is applied to the stromal bed, underneath a reflected corneal flap (LASIK= Laser-Assisted Stromal In-situ Keratomileusis). The tissue is ablated precisely to counteract the refractive error of the eye.
  38. 38. LASIK – Traumatic Flap Dislocation
  39. 39. Cornea-Pathology • Functional Anatomy – Descemet membrane increases in thickness with age • It is the site of copper deposition in the Kayser-Fleischer ring of Wilson disease • Keratitis (inflammation of cornea) and Ulcers – Bacterial (frequent in contact lens users, pseudomonas most common) – Fungal – Viral (especially herpes simplex and herpes zoster) • Chronic herpes simplex keratitis may be associated with a granulomatous reaction to Descemet’s membrane – Protozoal (Acanthoamoeba) – Autoimmune, Syphilis etc
  40. 40. Cornea - Bacterial Ulcer Epithelial defect, infiltrate of white cells into the cornea, and a layered leukocyte collection in the AC (Hypopyon)
  41. 41. Cornea - HSV Keratitis Epithelial “dendritic” Keratitis Stromal Keratits (note the vessels and clouding) chronic herpes simplex keratitis may be associated with a granulomatous reaction involving the Descemet membrane
  42. 42. Corneal degenerations May be either unilateral or bilateral & typically non-familial. Calcific band keratopathy is characterized by deposition of calcium in the Bowman layer. This condition may complicate chronic uveitis, especially in individuals with chronic juvenile rheumatoid arthritis. Actinic band keratopathy develops in individuals who are exposed chronically to high levels of ultraviolet light. In this condition, extensive solar elastosis develops in the superficial layers of corneal collagen in the sun-exposed interpalpebral fissure, hence the horizontally distributed band of pathology. ("oil-droplet keratopathy.“) Keratoconus is fairly common disorder characterized by progressive thinning and ectasia of the cornea without evidence of inflammation or vascularization and leads to irregular astigmatism that is difficult to correct with spectacles. Activation of collagenases, gelatinases, and matrix metalloproteinases has been implicated in the pathogenesis of this condition
  43. 43. Cornea - Ectasia Progressive deformation of cornea is an ectasia. Keratoconus is the most common ectatic degenerative change. Ectasia can also be a complication of refractive surgery.
  44. 44. Cornea – Dystrophy Group of progressive, usually bilateral mostly genetically determined, noninflammatory opacifying disorders characterized by abnormal tissue morphology, function, or abnormal depositions of material into the cornea. MANY types, affecting each specific layer (epithelial, Bowmans membrane, stroma or endothelium). Fuchs Dystrophy Affecting the endothelium, is one of the principal indications for corneal transplantation in the United States. The two major clinical manifestations of Fuchs endothelial dystrophy-stromal edema and bullous keratopathy-are both related to a primary loss of endothelial cells. Macular Dystrophy Least common, autosomal recessive, most severe, characterized by multiple, gray-white opacities that are present in the corneal stroma and that extend out into the peripheral cornea) Crystalline Dystrophy Granular Dystrophy Lattice Dystrophy Map-Dot-Fingerprint Dystrophy
  45. 45. Cornea – Stromal Dystrophy Granular Dystrophy Hyaline material deposited in stroma Diverse mutations in TGFB1 disrupt the folding of keratoepithelin, and depending on the exact mutation, lead to the deposition of various types of proteinaceous deposits in the cornea.
  46. 46. Cornea – Stromal Dystrophy Lattice Dystrophy Amyloid deposition with “applegreen” birefringence. Stains with Congo Red
  47. 47. Cornea Transplant
  48. 48. The Uvea “The uvea” is: 1. 2. 3. The Iris The Ciliary body The Choroid Each has a function 1. 2. 3. Iris is a diaphragm for light Ciliary body suspends & flexes the lens, & makes the aqueous humor The choroid helps nourish the outer retina The choroid is among the most richly vascularized sites in the body As in the retina, there are no lymphatics within the uvea
  49. 49. The Uvea - Angle • The “angle” is a special region of the uvea where the iris meets the cornea – Regulates the outflow of Aqueous humor through the Canal of Schlem – Determines the Intraocular pressure (Important in Glaucoma)
  50. 50. The Uvea - Inflammation • “Uveitis” is inflamation of any combination of the iris, ciliary body, or choroid. • Many etiologies (autoimmune, syphilis, sacrcoid, TB, HLA-B27, infectious, idiopathic, etc…) • Many names (iritis, anterior uveitis, iridocylitis, choroiditis, posterior uveitis etc.) depending on the location • Sometimes associated with SERIOUS systemic inflamatory diseases (eg. arthritic diseases), inflamatory bowel disease, and vasculitis.
  51. 51. Uveitis Causes: • Infectious agents – e.g.: pneumocystis carinii • Idiopathic – e.g.: sarcoidosis • Autoimmune Sympathetic ophthalmia Sympathetic ophthalmia, an example of noninfectious autoimmune uveitis Characterized by bilateral granulomatous inflammation typically affecting all components of the uvea: a panuveitis. May complicate a penetrating injury of the eye. In the injured eye, retinal antigens sequestered from the immune system may gain access to lymphatics in the conjunctiva and thus set up a delayed hypersensitivity reaction that affects not only the injured eye but also the contralateral, noninjured eye. Condition may develop from 2 weeks to many years after injury. Enucleation of a blind eye (which can be the sympathizing eye rather than the directly injured eye) may yield diagnostic findings. Treated by the administration of systemic immunosuppressive agents.
  52. 52. The Uvea – Anterior Uveitis • Anterior uveitis/iritis • WBCs floating in the aqueous
  53. 53. Uvea – Posterior Uveitis • Active Toxoplasmosis Choroiditis, and old scar (above)
  54. 54. The cherry-red spot in Tay-Sachs disease. A, Fundus photograph of the cherry-red spot in Tay-Sachs disease. B, Photomicrograph of the macula in a patient with TaySachs disease, stained with periodic acid-Schiff to highlight the accumulation of ganglioside material in the retinal ganglion cells. The presence of ganglion cells filled with gangliosides outside the fovea blocks the transmission of the normal orange-red color of the choroid, but absence of ganglion cells within the fovea (to the right of the vertical bar) permits the normal orange-red color to be visualized, accounting for the so-called cherry-red spot.
  55. 55. Uveal Neoplasm – Most common intraocular malignancy of adults: metastasis, typically to the choroid from breast and lung • Suggestive of extremely short survival – Nevi and Melanomas • Uveal melanoma – – – – – Most common primary intraocular malignancy of adults (7-20/million) Histologically spindle & epitheloid type SIZE OF TUMOR/CELL TYPE/PROLIFERATIVE INDEX Melanomas of the ciliary body and choroid are more aggressive Most spread first to the liver; metastases appear many years after treatment (dormancy). – Mortality: 40% at ten years • Uveal nevi – Especially choroidal nevi, are common, affecting 10% of the Caucasian population.
  56. 56. The Uvea - Tumors • The uvea (especially choroid) is also richly pigmented, and primary melanocytic tumors are common. • Nevi and malignant melanomas are both relatively common, and can be difficult to distinguish, clinically. • Tumors with “spindle-B” or epithelioid histologic patterns are malignant
  57. 57. Anterior Segment Functional Anatomy The anterior chamber is bounded anteriorly by the cornea, laterally by the trabecular meshwork, and posteriorly by the iris. Aqueous humor, formed by the pars plicata of the ciliary body, enters the posterior chamber, bathes the lens, and circulates through the pupil to gain access to the anterior chamber. The lens is a closed epithelial system; the basement membrane of the lens epitheliuim (known as the lens capsule) totally envelops the lens. With aging, the size of the lens increases. Neoplasms of the lens have not been described.
  58. 58. The Lens • A transparent, avascular structure consisting of concentric cellular fibers • Highest protein content of the body (Crystallins), which account for a high refractive index • Interaction of the ciliary body muscle, through the zonular fibers, cause dynamic shape changes. • In concert with the cornea, helps to focus light on the retina.
  59. 59. CATARACT – The term cataract describes lenticular opacities that may be congenital or acquired. – Causes: • Systemic diseases: – – – – Galactosemia Diabetes mellitus Wilson disease Atopic dermatitis • Drugs: – Corticosteroids • • • • • Radiation Trauma Many intraocular disorders Age-related cataract (nuclear sclerosis) Smoking
  60. 60. The Lens • • • • • The deepest fibers are the oldest ones The lens continues to fatten throughout life Central fibers become sclerotic and opaque with time Entire structure encapsulated Lens cells migrate and elongate into fibers
  61. 61. The Lens - Cataract Opacities of the lens develop with time, or insult • UV light, steroids, and inflammation are pathogenic factors
  62. 62. The Lens – Cataract surgery • A opening into the lens capsule is made • The cataract is emulsified with ultrasound energy, and aspirated out of the eye
  63. 63. The Lens – Cataract surgery The dense, cloudy crystalline lens is removed, and replaced with an optical implant. Inflammatory reactions to lens material may develop following exposure of the intact lens cortex caused by rupture of the capsule due to trauma or as a result of cataract extraction. It has been suggested that antigen-antibody complexes containing lens cortical material develop especially in the presence of Propionibacterium acnes (which acts as an adjuvant), generating a lens-induced uveitis
  64. 64. Rubella syndrome, or congenital rubella, is a group of physical abnormalities that have developed in an infant as a result of maternal infection and subsequent fetal infection with rubella virus. It is characterized by rash at birth, low birth weight, small head size, heart abnormalities, visual problems and bulging fontanelle.
  65. 65. Hypermature Cataract & Glaucoma Occasionally, the lens cortex may liquefy nearly entirely, a condition known as hypermature or morgagnian cataract. High-molecular-weight proteins from liquefied lens cortex may leak through the lens capsule(phacolysis). This phacolytic protein-either free or contained within macrophages-may clog the trabecular meshwork and contribute to elevation in intra-ocular pressure and optic nerve damage; phacolytic glaucoma is an example of secondary open-angle glaucoma.
  66. 66. GLAUCOMA • The Anterior Segment and Glaucoma The term glaucoma refers to a collection of diseases characterized by distinctive changes in the visual field and in the cup of the optic nerve. Most of the glaucomas are associated with elevated intraocular pressure, although some patients with normal intraocular pressure may develop characteristic optic nerve and visual field changes (normal or low-tension glaucoma). It is the third most common cause of blindness in world Risk Factors Diagnosis of Glaucoma Intraocular pressure ( IOP ) and its measurement. (tonometry) Optic disc examination. Visual Field examination ( perimetry ) Age Race Family Diabetese Eye injuries Drugs
  67. 67. Classification of Glaucoma – Glaucoma may be classified as: • Open angle glaucoma – Increased resistance to aqueous outflow in the open angle – Primary – Secondary • Angle closure glaucoma – The peripheral zone of the iris adheres to the trabecular meshwork and impedes the egress of aqueous from the eye. – Primary – Secondary
  68. 68. Open angle glaucoma • Primary – The most common form of glaucoma – Few changes are apparent – Mutations in the GLC1A gene which encodes the protein myocilin located on chromosome 1 have been associated with a subset of individuals with juvenile and adult primary open-angle glaucoma. • Secondary – – – – – – Phacolysis (liquefied lens cortex, leaking through the lens capsule) Senescent red blood cells after trauma (ghost cell glaucoma) iris epithelial pigment granules (pigmentary glaucoma), fragments of oxytalan fibers (exfoliation glaucoma), and necrotic tumors (melanomalytic glaucoma) . Anything that contributes to elevate the pressure on the surface of the eye (episcleral venous pressure) in the presence of an open angle can contribute to other types of secondary open angle glaucoma
  69. 69. Angle closure glaucoma Primary – Typically develops in eyes with shallow anterior chambers – Often found in patients with hyperopia (hypermetropia) – Consequences: » Pupillary block » Iris bombé apposing it to the trabecular mesh work » Corneal edema » Bullous keratopathy Secondary (causes) – Contraction of various types of pathologic membranes that form over the surface of the iris (chronic retinal ischemia is associated with the up-regulation of VEGF) – Necrotic tumors – Iridocorneal endothelial syndrome – Following intraocular surgery or penetrating trauma – Tumors in the ciliary body
  70. 70. ENDOPHTHALAMITIS & PANOPHTHALAMITIS Causes: • Blunt trauma • Corneal infections • Uveitis The term endophthalmitis is not applied clinically unless there is suppurative inflammation within the vitreous humor is poorly tolerated by the retina; after only a few hours of exposure to acute inflammation, the retina may be irreversibly damaged Exogenous (originating in the environment and gaining access to the interior of the eye through a wound) Endogenous (delivered to the eye hematogenously). Panophthalmitis: inflammation within the eye that involves the retina, choroid, and sclera and extends into the orbit may produce proptosis
  71. 71. Acknowledgements •Books: Robbins and Cortran, Pathologic Basis of Disease •Images: RC-PBD, Elsevier Various public internet sources

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