Uveal Tract Review

ANATOMY OF THE UVEAL TRACT The purpose of this document is to provide a general understanding of eye anatomy as it relates to the Uveal Tract. We will begin with a macro-view of the eye by reviewing the walls of the eye and then discuss the layers of the iris starting from the anterior border layer working our way back to the Iris Pigmented Epithelium (IPE).

Document Flow Walls of the eye 1. The Choroid 2. The Ciliary Body 3. The Iris a. Anterior Border Layer b. Stroma (Containing the Sphincter Muscle, Vessels & Nerves) c. Anterior Epithelium & Dilator Muscle d. Posterior Pigmented Epithelium

The globe of the eye is composed of a wall enclosing a cavity filled with fluid with three coats: 1. Fibrous (outer): sclera, cornea 2. Uveal Tract or Uvea (middle): choroid, ciliary body and iris 3. Nervous (inner): retina UVEAL TRACT or Uvea: The Uveal Tract function is the regulation of light to the retina (performed by the Iris), accommodation & production of aqueous (performed by the Ciliary Body) and nutrition to the outer layers of the retina (Choroid).

The Uveal Tract is the middle vascular/pigmented coat of the eye ball and has three parts (as shown above): 1. The Choroid: Contained in the posterior segment of the eye.

2. The Ciliary Body: Positioned between the Choroid and the Iris.

3. The Iris: The visible colored and anterior portion of the Uveal Tract/Uvea.

The Uveal Tract is firmly attached to the sclera at (3 locations as shown above): 1) The scleral spur 2) The exit points of vortex veins 3) The optic nerve UVEAL TRACT ANATOMY 1. THE CHOROID: The Choroid is filled with blood vessels and functions to supply oxygen and nutrients to the eye (particularly the photoreceptors). It is thickest at the far extreme rear of the eye (at 0.2 mm), while in the outlying areas it narrows to 0.1 mm.

There are two sources of blood supply to the retina: 1. The central retinal artery: 20-30% of the blood flows to the retina from the optic nerve head to nourish the inner retinal layers (photoreceptors) 2. The choroidal blood vessels: receives the greatest blood flow (65-85%)

2. THE CILIARY BODY: The ciliary body is a circular band of muscle that is connected and sits immediately behind the iris. The Ciliary Body allows for visual accommodation by pulling or relaxing the zonules resulting in changes in the lens shape (See image below). It also produces aqueous humor which fills the posterior and anterior chambers and provides nutrition for avascular tissues in the eye such as the cornea.

Aqueous humor flow

3. THE IRIS: The function of the Iris is to regulate light entry on to the fovea/retina, anchor the lens and absorb reflections of light. The Iris is the most anterior and colored part of the Uveal Tract. It is a thin and circular structure which forms a diaphragm like structure in front of the crystalline lens. The iris is attached to the middle of anterior surface of ciliary body and divides the space in front of the lens into anterior chamber and posterior chamber. Stroma of the iris is continuous with the stroma of the ciliary body. The iris is thickest at the collarette (1-2mm) and thinnest at the iris root (where it attaches to the Ciliary Body).

The average iris diameter is 12 mm with the pupil opening varying from 8mm down to 1.5mm with an average of 3-4mm. The diaphragm formed by the iris contains a central aperture known as the pupil which is not exactly central. It is a little nasal to the center.

Fun Fact: The word “iris� has originated from a Greek word. In Greek mythology the iris is the name of the Greek goddess of rainbow.

The Iris continued …

Anterior markings of the iris: The iris is divided into two areas: 1. Pupillary Zone (in blue): Extends from pupillary margin to the collarette and is relatively flat.  Pupillary margin is marked by a dark border, known as pupillary ruff. (See image below)  Pupillary ruff is the anterior termination of the iris pigmented epithelium (IPE) layer.  Iris is thickest (1-2 mm) at the collarette and located 2 mm away from pupillary margin.

2. Ciliary Zone (in blown): Of the iris extends from the collarette to iris root. The iris root is the thinnest part of the iris (.5mm thick). During blunt trauma, damage to iris occurs most commonly at the iris root, where the iris rips away from the ciliary body.  There are some depressions or pit arranged in rows present in the Ciliary Zone known as crypts.

The crypts are the location used for laser iridotomy as it needs less energy to form an opening.

1. Crypts are found in two locations.  Those present near the collarette are relatively larger and known as Fuchs’s crypt.  A few are seen in the periphery of the iris.

Pigment Ruff/Frill (False colorized image) Image on the right (using scanning electron microscopy) is of a normal pigmented frill or ruff.

If the iris pigment epithelium extends around the pupil margin anteriorly to an excessive degree; it is called ectropion uvae and can be an important sign of abnormal traction on the iris tissues, induced by tumor or other significant pathologic processes.

LAYERS OF THE IRIS: The iris is made up for following four layers…

1. Anterior Border Layer 2. Stroma, Sphincter Muscle, Vessels & Nerves 3. Anterior Epithelium & Dilator Muscle 4. Posterior Epithelium

Anterior Border Layer

1. ANTERIOR BORDER LAYER (ABL): The ABL lines the iris and is anterior to the iris stroma (See image above). The layer consists of mainly fibroblasts (on the surface) and melanocytes (beneath the fibroblasts) which are arranged in a meshwork. The color of the iris is determined by three variables: The pigment content (granule quantity, packaging and quality) within the melanocytes (typically 7 μm in length) of the anterior border layer & stroma.  Melanocytes synthesize and store melanin pigment within membrane-enclosed lysosome-related organelles (LROs) called melanosomes.  There are two types of melanin: 1. Eumelanin: dark pigment 2. Pheomelanin: Lighter color similar to yellow-red color 1. The density and structure of the iris stroma 2. The pigment epithelium

Image above showing the Anterior Border Layer sing scanning electron microscopy

Image above showing the Anterior Border Layer sing scanning electron microscopy

Above: The Anterior Border Layer of a brown iris is shown in cross section revealing the brown melanocytes on top of the stroma. (Image on right is a false colorized image).

Upper Right & Left: Pigment/freckles can be seen laying on top of the collagen fibers in the Anterior Border Layer.

Lower Left: Looking through a transparent layer of non-pigmented melanocytes to see this deep anatomy. The radiating wiggly white lines are iris vessels which are clad with collagen and are located in the mid-stroma. The brown spots of pigment are starting to obscure the collagen vessels of the blue iris (See the red circle).

Lower Right: Looking at a very thick collagen clad vessels using scanning electron microscopy.

Upper Left: In dark irides, pigment in the melanocytes opacifies the anterior border layer and obscures structures in the deeper stroma.

Upper Right: Transparency in a blue eye shows the collagen clad vessels in the mid stroma.

Bottom Left: (False colorized image) Melanocytes in a brown iris produce melanin in increased quantity, packaging and quality. The melanin is stored in the melanosomes where the cellular process gets fat and the cells and cytoplasm become large.

Bottom Right: (False colorized image) Under high magnification the fibroblasts are seen on top of the melanocytes.

Here the melanocytes are concentrated in the anterior border layer of the iris. The stroma of the iris has fibroblasts, some melanocytes and connective tissue. At the bottom of the iris the circumferential ridges of the Iris Pigmented Epithelium (IPE) can be seen. The dilator muscle highlighted in pink extends from the iris root to a point in the stroma below the midpoint of the sphincter.

Upper Left: (False colored image) The blue iris is absence of stromal pigmentation - the anterior border layer is transparent allowing one to see the mid stroma.

Upper Right: In a blue eye there are few melanin granules resulting in transparency of the anterior border layer.

Bottom Left: The anterior border layer of a brown eye is opaque with heavy pigment preventing transparency.

Bottom Right: Cells in the anterior border layer of a brown iris are full of larger melanin granules. Darker irides have more melanin granules, larger melanin granules and larger melanosomes.

Blue Eye Color In a transparent blue eye only the shorter wavelengths (blue wavelengths) have the energy to return to the observer’s eye. This is called “The Tyndall effect”. The longer, less energetic wavelengths of light are absorbed by the iris stroma and IPE.

ANTERIOR BORDER LAYER (ABL) continued ‌ Below: Different color irises are shown using scanning electron microscopy and transmission electron microscopy. As the size and frequency of the granules increase the darker the iris becomes.  The color of the iris is largely determined by three main variables: 1. The pigment content (granule quantity, packaging and quality) within the melanocytes of the iris Anterior Border Layer.

2. The density and structure of the iris stroma 3. The pigment epithelium

Above: The melanin granule size is a function of color. The darker the irises color the larger and more frequent the granule. (Note: Ota is Nevus of Ota which is a benign tumor located on the anterior border layer) Fun Fact: Prostaglandin cause darkening of the iris. When these cases have been examined pathologically the size of the granule has increased. There is NOT an increase in melanocytes.

Fun Fact: When counting cells in a standard field there appears to be the same number for cells in brown and blue eyes. Or in other words, a relatively similar number of melanocytes are found in all irides irrespective of their color.

IRIS DEFECTS/DISCOLORATION Iris Nevus of Ota: Is a benign tumor that arises in the melanocytes in the iris stroma. It is composed of low-grade spindle-type cells and is asymptomatic pigmented, wellcircumscribed lesions in the iris stroma. The nevus is flay or minimally elected and the melanin graduals are much larger in a Nevus than found in a typical brown iris.

Age-Related Iris Stromal Atrophy: The pigment epithelium is clearly visible through the centrally attenuated iris stroma as a chocolate brown color, with the pupillary sphincter standing out as a tan ring.

The peripheral iris stroma was minimally attenuated and appears light blue. There was no iris transillumination defects found in this 63 year old man’s healthy eyes.

Heterochromia: (Greek: heteros 'different' + chroma 'color') In complete heterochromia, one iris is a different color from the other. In partial heterochromia or sectoral heterochromia (as shown on the right), part of one iris is a different color from its remainder.

Layers of the iris ‌.continued

2.

IRIS STROMA, SPHINCTER MUSCLE, VESSELS & NERVES – The iris stroma forms the main bulk of iris tissue and contains the sphincter pupillae, dilator pupillae muscles, vessels and nerves.

A. STROMA: The stroma is a loosely, pigmented (melanocytes & clump cells), non-pigmented (fibroblast, lymphocyte, macrophage, mast cells) and highly vascular connective tissue that makes up the majority of the iris.

B. SPHINCTER PUPILLAE: Sphincter muscle is composed of spindle-shaped cells that are oriented parallel to the pupillary margin so contraction of the sphincter causes the pupil to constrict (a process known as Miosis). The muscle is circular, 0.75 to 1 mm wide, composed of smooth-muscle cells and 0.1 to 1.7 mm thick and is considerably thicker than the dilator papillae. The sphincter muscle is firmly adherent to the surrounding stroma of the iris.

Note: The Sphincter Pupillae…  Causes pupil constriction known as Miosis  Proper name is Sphincter pupillae m.  Is circularly arranged  Is parasympathetic innervation  Constriction is caused by: o Bright illumination o Sleeping o Convergence o Miotic drugs like Pilocarpine

C. VESSELS: The vessels provide oxygen and nutrients to the iris. The iris vessels usually follow a radial course from the iris root to the pupil margin and are surrounded by a dense network of collagenous fibrils which are embedded in to the collagen network of the stroma. The arrangement of collagen network prevents the iris vessels from kinking and compression during the extensive iris movement during constriction and dilatation of the pupil. Iris veins have very thin walls consisting of endothelium surrounded by a thin layer of collagen. Monocytes pass through the endothelium, enter into the iris tissue and develop into macrophage.

Macrophages & Cytokines As mentioned above, macrophages develop from white blood cells called monocytes. These cells exit blood vessels by passing through blood vessel endothelium to enter into the iris tissues. Once reaching their destination, monocytes develop into macrophages. Macrophages that differentiate from monocytes are specific to the iris tissue in which they reside. When the need for more macrophages arises in a particular tissue, the residing macrophages produce proteins called cytokines t hat cause responding monocytes to develop into the type of macrophage needed. Macrophages that specialize in removing iris tissue develop from cytokines produced in response to tissue injury. The process by which macrophages engulf and digest cells and pathogens is called phagocytosis.

Regarding cell death, apoptosis occurs in response to cell damage (the rapid raising and lowering of tissue temperature). The apoptotic process is very ordered: pigment cells perish in an organized genetically controlled series of events. Furthermore neighboring cells generally remain completely unaffected.

How does apoptosis occur in such a precise fashion? Cellular self-destruction occurs in a series of steps dictated by DNA transcription and translation. Upon receiving a ‘signal’ to die the cell begins to express proteins that promote the death process eventually resulting in the increased activity of a group of enzymes that cleave other proteins. These enzymes digest components of the cell cytoskeleton to cause the cell to round up and shrink. Within the nucleus the DNA condenses eventually breaking into small fragments. Eventually the cell breaks into smaller ‘blebs’ that remain entirely encased by a cell membrane. This design prevents the leaking of inflammatory chemicals and proteins within the cells into the extracellular fluid. The apoptotic blebs are eventually engulfed and destroyed by scavenger cells called macrophages.

Fun Fact: Programmed cell death also ensures an organism’s homeostasis. Normally 50-70 billion cells die each day due to apoptosis in the average human adult in an effort to balance a similar number of cells that are born each day in the cell cycle.

Colored scanning electron micrograph of a macrophage white blood cell. Macrophages are cells of the body's immune system. They are found in the tissues rather than in the circulating blood. Macrophages recognize apoptotic cells, foreign particles to include bacteria, pollen, dust, and phagocytose (engulf) and digest them. Magnification: x4000 when printed at 10 centimeters wide.

Layers of the iris ….continued

3.

ANTERIOR EPITHELIUM & DILATOR MUSCLE A. Dilator Pupillae: The dilator pupillae muscle extends from the iris root to a point in the stroma below the midpoint of the sphincter. A dense band of connective tissue separates the sphincter and dilator muscles from each other. Because of the radial arrangement of the fibres of the muscle, contraction of the dilator pupillae muscle pulls the pupillary portion toward the root, thereby enlarging the size of pupil (mydriasis).

Note: The Dilator Pupillae…  Causes pupil dilation known as Mydriasis  Proper name is “Dilator pupillae m.”  Is radially arranged  Is sympathetic innervation  Dilation is caused by: o The dark o Fear o Excitement o Drugs like Cyclogyl which is a Mydriatic

Layers of the iris ‌.continued

4.

POSTERIOR EPITHELIUM (IPE): Is a single layer of heavily pigmented simple columnar cells located at the posterior of the iris and is continuous with inner non-pigmented epithelial layer of ciliary body. The IPE is curled anterior at the pupil margin or pupillary ruff. All eyes have a maximum pigment of the IPE.

Upper Left: High magnification photo of the iris pigmented epithelium (IPE) shows the circumferential ridges on the posterior surface of the IPE. The circumferential ridges extent about a clock hour or so and interdigitate.

Upper Right: Radial macro ridges which are peritubular to the circumferential ridges are shown.

Pigment dispersion syndrome: Is a bilateral condition characterized by the liberation of pigment from the iris pigment epithelium. It is caused by the mechanical rubbing of the posterior pigment layer of the iris against lens zonules because of excessive posterior bowing of the mid-peripheral portion of the iris. Sometimes pigment epithelium itself may be abnormally susceptible to pigment shedding.

Upper Left: Pigment dispersion results in mid-peripheral iris transillumination defects.

Upper Right: Pigmentary glaucoma (PG) is glaucoma in the setting of pigmentary dispersion syndrome (PDS).

An indication of PDS is the Trabecular Meshwork being darkly-pigmented.

Note: Additional findings for PDS are corneal endothelial pigment (Krukenberg spindle), prominent backbowing of the iris, and a Scheie stripe (pigment deposition on the junction of the posterior lens capsule and vitreous face.