Cornea and LensCornea and Lens

Chi-Chao Chan, M.D.

Immunopathology Section

Laboratory of Immunology

National Eye Institute

National Institutes of Health

HistopathologyRefractive Surgery

CataractsHigh Myopia

ClassificationClassificationClassificationClassification

Conjunctiva Cornea Lens Optic Nerve Orbit/Extraocular Muscles Retina Sclera Trabecular meshwork Uvea (Iris, Ciliary body, Choroid) Vitreous

corneacornea

conjunctivaconjunctiva

sclerasclera

irisirisCiliary bodyCiliary body

lenslens

retinaretina

choroidchoroid

sclerasclera

optic nerveoptic nerve

vitreousvitreous

Ocular Tissue (a z)

Trabecular meshworkTrabecular meshwork

retinaretina

The average size of a normal adult eye: 25 mm (h) x 24.5 mm (v) x 24 mm (AP) The average size of a normal adult eye: 25 mm (h) x 24.5 mm (v) x 24 mm (AP)

ConjunctivaConjunctivaConjunctivaConjunctivaGross (Macroscopic structure):

» Palpebral (Tarsal) Conjunctiva » Fornical Conjunctiva» Bulbar Conjunctiva

Microscopic Structure:» Epithelium (two or more layers)

– Stratified epithelia, goblet cells

» Substantia propria (fibrovascular tissue including nerves and lymphatics)

epitheliumepithelium Substantia propriaSubstantia propria

CorneaCorneaCornea

Epithelium

Bowmanlayer

Stroma

Keratocyte

Descement membrane

Endothelium

CorneaCorneaCorneaCornea

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

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. Wachtlin, et al. Refract Surg 1999;15:451-8.Park, et al. Cataract Refract Surg 1999;25:842-50. Kato. Br J Ophthalmol 1999;83:1302-5.

Photorefractive Keratectomy (PRK) LASIK

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.

LASIKMicrokeratome

Courtesy of J. Douglas Cameron, MD

LASIKMicrokeratome

Courtesy of J. Douglas Cameron, MD

LASIKFemtosecond 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.

INTACSA. 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

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.

• Corneal neovascularization is an unwanted vascular growth into the avascular cornea.

Neovascularization

Stem cell deficiency due to graft vs host disease

Neovascularization

Cogan Keratopathy

Courtesy of. David G. Cogan, MD

LensLensLensLens

Lens

Cornea

Cornea

Lens

LensLensLensLensGross (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

capsulecapsule

epitheliumepithelium

cortexcortex

nucleusnucleus

LensLensLensLensMicroscopic Structure: Capsule Zonules Lens Cells: Epithelium

- Anterior - Equatorial

Cortex and Nucleus

capsulecapsule

epitheliumepithelium

cortexcortex

nucleusnucleus

Posterior lens

C.B.

Zonules

Photographs using a fish-eye lens

Transparent tissues:• Cornea• Lens

LensLensLensLens

Lens epithelial cellLens epithelial cell

Lens Equator:Lens Equator:• CapsuleCapsule• EpitheliaEpithelia• Lens fiberLens fiber

Bow regionBow region

LensLensLensLens

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

Pierre Robin Trisomy 18 PHPV

*

Trisomy 13

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

a. SEM: lens capsuleb. TEM: lens capsulec. TEM: lens epithelium

Z: zonular fiber/lamella

Ritch, Schlotzer-Schrehardt. Surv Ophthalmol 2001;45:265-315.

SEM

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

• 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

Posterior Staphyloma

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

• interbridging strands in the outer plexiform layer of the macular region

• located mainly in the outer plexiform layer

Tnag, et al. J Ophthalmol 2010, 2010:1-4.

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!