Cornea and Lens Histopathology Refractive Surgery Cataracts High Myopia
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Cornea and Lens Histopathology Refractive Surgery Cataracts High Myopia

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Chi-Chao Chan, M.D.

Chi-Chao Chan, M.D.
Immunopathology Section
Laboratory of Immunology
National Eye Institute
National Institutes of Health

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  • The cornea is the transparent anterior part of the eye’s tough fibrous outer coat and is the eye’s principal refractive element. The bulk of the cornea is comprised of interweaving lamellae of type I collagen fibers, which are spaced in an exquisitely regular fashion. Artifactitious clefts separate the stromal lamella in routine histologic sections. Cornea is composed of a nonkeratinized epithelium which usually five cells in thickness corvers the anterior surface of the cornea, , Bowman layer is a hyaline band of modified stroma, stroma Descemet’s membrane and a delicate monolayer of flattened endothelium. The stroma contains flattened dendritiform fibroblastlike cells called keratocytes. <br />
  • Molecular analyses revealed 10 fold lower IP-10/CXCL10 mRNA and two fold higher CCL5 mRNA in the fibrous tissue surrounding the Intacs channels, as compared to the central corneal stroma. IP-10/CXCL10 is a fibrotic and angiostatic chemokine produced by macrophages, endothelial cells and fibroblasts. IP-10/CXCL10, a CXC chemokine, which promotes chemoattraction but inhibits angiogenesis, is secreted by monocytes, endothelial cells, fibroblasts and keratinocytes. IP-10/CXCL10 regulates wound healing and inhibits fibrosis in the lung. IP-10/CXCL10 also induces apoptosis in several cell types. Therefore, it is not surprising that only occasional apoptotic cells are detected in the collagen scar tissue. <br />
  • Patient: Thomas McDonough <br />
  • Left: Thomas McDonough <br /> Right: Jacqueline Tran <br />
  • Lattice degeneration: occurs more frequently in myopic than non-myopic eyes, however its incidence is greater in moderate than severe myopia <br />
  • Lattice degeneration: occurs more frequently in myopic than non-myopic eyes, however its incidence is greater in moderate than severe myopia <br />
  • Lattice degeneration: occurs more frequently in myopic than non-myopic eyes, however its incidence is greater in moderate than severe myopia <br />
  • Margaret Bon <br /> Study by Benhamou and colleagues and Fujimotoe et al.structure of macular retinoschisis inner and outer schisis, need for ILM detachment (21 eyes, 10 had foveal detachment, 9/10 had ILM detachment) <br /> ILM detachment <br /> ELM to OPL detachment <br />
  • Margaret Bon <br /> Study by Benhamou and colleagues and Fujimotoe et al.structure of macular retinoschisis inner and outer schisis, need for ILM detachment (21 eyes, 10 had foveal detachment, 9/10 had ILM detachment) <br /> ILM detachment <br /> ELM to OPL detachment <br />
  • 30-50% of eyes will go on to develop CNV over the next 10 years <br />

Cornea and Lens Histopathology Refractive Surgery Cataracts High Myopia Cornea and Lens Histopathology Refractive Surgery Cataracts High Myopia Presentation Transcript

  • Cornea and Lens Histopathology Refractive Surgery Cataracts High Myopia Chi-Chao Chan, M.D. Immunopathology Section Laboratory of Immunology National Eye Institute National Institutes of Health
  • Classification Ocular Tissue (a z) cornea Trabecular meshwork Conjunctiva conjunctiva Cornea sclera Lens Optic Nerve retina Orbit/Extraocular Muscles Retina vitreous Sclera Trabecular meshwork Uvea (Iris, Ciliary body, Choroid) Vitreous iris Ciliary body lens retina choroid sclera optic nerve  The average size of a normal adult eye: 25 mm (h) x 24.5 mm (v) x 24 mm (AP)
  • Conjunctiva Gross (Macroscopic structure): » Palpebral (Tarsal) Conjunctiva » Fornical Conjunctiva » Bulbar Conjunctiva epithelium Microscopic Structure: » Epithelium (two or more layers) – Stratified epithelia, goblet cells » Substantia propria (fibrovascular tissue including nerves and lymphatics) Substantia propria
  • Cornea Cornea Epithelium Bowman layer Stroma Keratocyte Descement membrane Endothelium
  • Cornea Diameter: 11.5 x 10.5 mm (adult) Layers (520-540 mm centrally): » Epithelium (5-6 layers) » Bowman’s Layer (8 -14 nm) » Stroma (90% thickness) » Descemet’s Membrane (10-12 mm) » Endothelium (single layer) Nerve: unmyelinated nerves Avascular tissue
  • Refractive Surgery An eye surgery used to improve the refractive state of the eye and decrease or eliminate dependency on glasses or contact lenses Remodeling of the cornea The most common methods today use excimer lasers to reshape curvature of the cornea Successful refractive eye surgery can reduce or cure common vision disorders such as myopia (near sight), hyperopia (far sight) and astigmatism (non-perfected spherical cornea).
  • Refractive Surgery Radial Keratotomy (RK) Astigmatic Keratotomy (AK) Automated Lamellar Keratoplasty (ALK) Laser Refractive Surgery – Phototherapeutic Keratotomy (PTK) – Photorefractive Keratectomy (PRK) – Laser In Situ Keratomileusis (LASIK) – EPI-LASIK – Customized Transepithelial No-touch (C-TEN) Intrastromal Corneal Ring (Intacs)
  • LASIK Photorefractive Keratectomy (PRK) LASIK LASIK: Laser Assisted In Situ Keratomileusis A type of refractive surgery Wound healing only at the periphery of micotome incision Stromal reaction less after LASIK than PRK Requires a long time for wound healing Perz-Santonja, et al. Refract Surg 1998;14:601-9. Park, et al. Cataract Refract Surg 1999;25:842-50. Wachtlin, et al. Refract Surg 1999;15:451-8. Kato. Br J Ophthalmol 1999;83:1302-5.
  • LASIK
  • LASIK Intralamellar scar • Origin of lamellar binding: • Binding of collagen fibrils • Interweaving of lamellae • Stabilization by ground substance (extracellular matrix) Maurice & Monroe. Exp Eye Res 1990;50:59-63.
  • LASIK Microkeratome Courtesy of J. Douglas Cameron, MD
  • LASIK Microkeratome Courtesy of J. Douglas Cameron, MD
  • LASIK Femtosecond Microkeratome: Flap Hinge Courtesy of J. Douglas Cameron, MD
  • LASIK Microkeratome: Flap hinge Courtesy of J. Douglas Cameron, MD
  • LASIK Microkeratome: Flap hinge Courtesy of J. Douglas Cameron, MD
  • INTACS • A 47-yr-old man with a history of keratoconus and failure of using a Rigid Gas Permeable (RGP) contact lens, O.S. • Implantation of Intacs, O.U. • 10 mons later: Multiple, whitish, small crystalline deposits around the edges and the border of the superior Intacs segment nasally • Penetrating keratoplasty, O.S. Cao, et al. J Med Case Rep 2011, 5:398.
  • INTACS A. A space containing residue plastic (Intacs) material is surrounded by a dense acellular/ hypocellular collagen scar. The channel haze is observed at the inner edge of Intacs. B. The severely attenuated corneal endothelial cells. C. The acidophilic densification and mild inflammatory cell infiltration at the inner edge of Intacs. D. Immunochemistry of CD68 shows macrophage (CD68+) infiltration at the inner edge of Intacs. Cao, et al. J Med Case Rep 2011, 5:398.
  • Neovascularization • Corneal neovascularization is an unwanted vascular growth into the avascular cornea. Contact lens causing » Soft contact lens wearers - micropannus Inflammation » » Vascularized pannus Stromal keratitis – e.g., Cogan syndrome Stem cell deficiency Poor wound healing » Corneal transplantation under 2 yr.
  • Neovascularization Stem cell deficiency due to graft vs host disease
  • Neovascularization Cogan Keratopathy Courtesy of. David G. Cogan, MD
  • Lens Cornea Lens Cornea Lens
  • Lens Gross (Macroscopic structure): - Soft, elastic, avascular, transparent, highly refractile, biconvex structure composed of mainly crystallins - Anterioposterior: 3.5 - 5 mm (birth-adult) Equatorial: 6.4-9.0 mm (birth-adult) Microscopic Structure: - Capsule - Zonules - Lens Cells: Epithelium - Anterior - Equatorial - Cortex and Nucleus capsule epithelium cortex nucleus
  • Lens Microscopic Structure: capsule Capsule Zonules Lens Cells: Epithelium - epithelium cortex Anterior Equatorial nucleus Cortex and Nucleus Zonules C.B. Posterior lens
  • Transparent tissues: • Cornea • Lens Photographs using a fish-eye lens
  • Lens Lens Equator: • Capsule • Epithelia • Lens fiber Bow region Lens epithelial cell
  • Lens
  • Lens: Congenital Cataracts • Congenital cataract: opacity present at birth • Infantile cataract: opacity during 1st year life • Spherophakic • Lamellar, Polar, Sutural, Coronary, Cerulean, Nuclear, Capsular; Complete, Membranous • Rubella
  • Lens: Congenital Cataracts Trisomy 13 Pierre Robin Trisomy 18 PHPV *
  • Lens: Adult Cataracts Aging – Nuclear, Cortical, Posterior Subcapsular – In theory, everyone would get cataract if one lives long enough Drug-induced – Corticosteroids, Phenothiazines, Miotics, Aminodarone, etc. Trauma – Contusion, Injury: mechanical, chemical, radiation, etc. Metabolic – Diabetes Mellitus, Galactosemia, Wilson Disease, etc. Nutritional
  • Lens: Adult Cataracts Exfoliation Syndrome – – True Exfoliation Exfoliation Syndrome (Pseudoexfoliation) Cataract Associated with Uveitis Cataract & Skin Diseases – Atopic Dermatitis Glaukomflecken Cataract Associated with Degenerative Disorders – Retinitis Pigmentosa, Essential Iris Atrophy, etc.
  • Cataract: Anterior
  • Cataract: Equator
  • Cataract: Nucleus
  • Cataract: Posterior
  • Cataract: Soemmering’s Ring • Dumbbell shape • Congenital • IOL
  • Cataract: Periphery
  • Cataract: IOL • Cortical cleanup • IOL material • Optic edge design • Anterior capsule
  • Cataract: Exfoliation • • • • Age related disease Accumulation of abnormal fibrillar extracellular material Anterior segment involvement Cause cataract and glaucoma SEM a. SEM: lens capsule b. TEM: lens capsule c. TEM: lens epithelium Z: zonular fiber/lamella Ritch, Schlotzer-Schrehardt. Surv Ophthalmol 2001;45:265315.
  • Axial Myopia Average axial length of normal eye is 23.5-24.0 mm
  • Fundus Manifestations Tilted optic nerve Peripapillary chorioretinal atrophy Peripheral retinal changes Myopic Maculopathy Posterior staphyloma Macular schisis Atrophic changes in the RPE and choroid Lacquer cracks Choroidal neovascularization Macular atrophy
  • Tilted Optic Nerve Head • • • Because of the elongated eye, the nerve inserts obliquely Most commonly, the nerve head is tilted toward the temporal side This can make the assessment of the cup:disc ratio difficult and OCT nerve may be unreliable
  • Peripapillary Chorioretinal Atrophy • Due to tangential tractional forces of the elongating globe, the RPE, Bruch’s membrane, and choroid fall short of reaching the entrance of the nerve into the eye, and bare sclera is seen
  • Peripheral Retinal Changes         Lattice degeneration Paving-stone degeneration Pigmentary degeneration Chorioretinal atrophy White without pressure Retinal holes Retinal tears Retinal detachments
  • Lattice Degeneration • • Can develop retinal tear, breaks/holes May progress to retinal detachment
  • Paving-stone Degeneration Cobblestone degeneration
  • Posterior Staphyloma • Abnormal elongation of the globe and the attenuation of the sclera are accompanied by a localized ectasia involving the sclera, choroid, and RPE (outward bowing) • Histologically, staphylomas contain decreased amounts of scleral collagen bundles and decrease in caliber • Axial length elongation and/or posterior staphyloma may generate inward tractional force which is opposed by the residual posterior vitreous cortex, ILM, and/or retinal vessels • Detected in 9-35% of highly myopic eyes with posterior staphylomas • Majority remain stable • Can lead to foveal detachment and/or macular hole
  • Posterior Staphyloma • The prevalence and severity of staphylomas are found to increase with greater age, eye length, and myopic refraction • Most commonly involves the posterior pole, extending from 2 to 5 disc diameters nasal to the optic nerve to an area involving the macula • Best seen on B-scan ultrasound
  • Macular Foveoschisis Detected in 9-35% of highly myopic eyes with posterior staphylomas • Majority remain stable • Can lead to foveal detachment and/or macular hole •
  • Macular Foveoschisis Tnag, et al. J Ophthalmol 2010, 2010:1-4. • interbridging strands in the outer plexiform layer of the macular region • located mainly in the outer plexiform layer
  • Atrophic Changes in the RPE and Choroid Early degenerative changes affect the choriocapillaris and RPE – Loss of choroidal melanocytes and RPE atrophy  'tessellated/tigroid' fundus
  • Atrophic Changes in the RPE and Choroid In later stages, the neuroretina also becomes atrophic leading to generalized and/or patchy atrophy – Vision may begin to be affected at this stage
  • Lacquer Cracks • Yellow-white linear or stellate lesions that are typically horizontal oriented and branched • Represent mechanical breaks of the RPE, Bruch’s membrane, and choriocapillaris from elongation of the globe • Usually occur in eyes >26.5 mm in length and more common in males • Macular hemorrhages can sometime occur in the crack in the absence of CNV • Number usually increase over time and can be associated with the development of atrophy • Important prognostic factor for the development of CNV
  • Thank you!