Ocular Therapeutics Ashok Garg
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1Fundamentals and Preliminary Considerations in Ocular Therapeutics2

Ocular Defense System1

Ashok Garg
(India)
Eye like the other parts of the body has natural defence mechanism.
Eye is one of the highly specialized sensory organs of the body. Nature has provided eye with bony and anatomical protection and physiological reflexes. Eyes are protected from radiational hazards. Immunological process, Biochemical and enzymatic systems protect the eyes from ocular inflammation.
Ocular defence system is broadly classified in two categories:
  1. Physical protection.
  2. Physiological protection.
 
PHYSICAL PROTECTION
Eyeballs are well-protected in the bony orbit. The eye lies in the front half of the orbit surrounded by fat and connective tissue and is supported by a fascial hammock. The eyeball lies in a quadrilateral pyramid or pear-shaped bony cavity situated on the either side of the root of the nose called orbit. Orbit stalk is the optic canal. The orbit lies behind the orbital septum and has a roof, a floor; a medial wall and a lateral wall. The protective orbit is made up of seven bones namely maxilla, frontal, zygomatic, lacrimal, ethmoid, sphenoid and palatine. The bones of the anterior margin of the orbit are thick and strong but most of the walls are thin. Its two medial walls are parallel and two lateral walls form a 90° angle with each other. Each eyeball is suspended by extraocular muscles and their facial sheath. The anterior part of eyeball and center of cornea are just at the level of line joining the upper and lower bony orbital margins so that eyeball is protected from any kind of damage as a result of fall on the face side or when a large object hits the orbits. The eyeball is also protected by orbital fat to absorb any shock or vibrations specially in condition of concussion and free fall injury and provides a protective cushion. However, in counter coup injury the medial walls of the bony orbit give way as these are the weakest part of the orbits (Figs 1.1 and 1.2).
Lattice arrangement of collagen fibers adds to the strength of the cornea. Descemet membrane elasticity reduces the risk of corneal perforation. Criss-cross pattern of zonular fibers hold the lens in place.
Condensed part of the peripheral vitreous supports the retina.
The special physical protection in term of anatomical safeguards is provided by extra-length of the optic nerve between scleral entry and optic canal so that even if the eye is temporarily 4expulsed, the optic nerve cannot detach itself away from the eyeball.
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Fig. 1.1: Anatomy of the orbital cavity (Physical defense system of the eye).Courtesy: Kanski Clinical Ophthalmology, Butterworths International Edition
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Fig. 1.2: Walls of the orbit
The firm attachment of optic nerve to the bony optic canal through its dural covering also ensures that optic nerve cannot be pulled out of intracranial cavity. The intraorbital portion of optic nerve is much longer (25 mm) than the distance between the back of globe to the optic foramen (18 mm). This allows for significant forward displacement of globe without causing excessive stretching of the optic nerve.
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PHYSIOLOGICAL PROTECTION
A number of physiological factors provide protection to the eye.
The blinking reflex of the eye protects and helps to moisten and lubricate the exposed part of the eyeball. The eyelashes acts as antennae to warn against any foreign body coming near to eyeball and reflexly stimulate the closure of eyelids. Eyelashes also produce physical obstruction against flying particles, dust and dirt, etc. The Bell's phenomenon protects the cornea from exposure and injury. The pupil regulates the entry of light into the eyes. Iris diaphragm makes the posterior segment, a dark-room.
The pigment epithelium of the retina adsorbs the light after it passes through the anterior layers of retina. Cilioretinal arteries also acts as nutrition of the macula in CRA occlusion cases.
The cornea absorbs most of the infrared rays of the sunlight. The lens by its biochemical mechanism absorbs most of the UV rays of the sunlight so that retina is protected from the harmful effects of the sunrays. Intact corneal epithelium acts as a strong barrier against invasion by most of the microorganisms and also acts as selective permeable membrane. Micropolysaccharides in the corneal stroma prevent swelling of the cornea. Descemet membrane acts as a strong barrier against invading organisms. Due to absence of blood vessels in the cornea and lens, these two structures do not suffer from primary inflammation and also from neoplastic pathology. The optical integrity and normal function of the eye depend on an adequate supply of fluid covering its surface. The exposed part of the globe—the cornea and the bulbar conjunctiva—is covered by a thin fluid film referred to as preocular tear film. Tears refer to fluid film known as preocular tear film, and the conjunctival sac.
The volume of the tear fluid is about 5–10 microliter and about 95 percent of it, is produced by the goblet cells and the accessory lacrimal glands of the conjunctiva, in healthy individuals.
Tear film is a complete trilaminar structure which is directly in contact with the environment and is critically important for protecting the eye from external influences.
The precorneal tear film consists of three layers each of which has separate functions (Figs 1.3 and 1.4).
 
Outer Lipid Layer
It is secreted by meibomian glands and has three main functions:
  1. To retard the evaporation of the aqueous layer of the tear film.
  2. To increase surface tension and assist in the vertical stability of the tear film so that tears do not overflow the lower lid margin.
  3. To lubricate the eyelids as they pass over the surface of the globe.
 
Middle Aqueous Layer
This is secreted by main lacrimal gland and the accessory lacrimal glands and has four main functions:
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Fig. 1.3: Tear film layers (Physiological protection of the eye).Courtesy: Allergan India Limited
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Fig. 1.4: Three layers of precorneal tear film.Courtesy: Kanski Clinical Ophthalmology, Butterworths International Edition
  1. It supplies atmospheric oxygen to the corneal epithelium.
  2. It has antibacterial substances like lactoferrin and lysozyme.
  3. It provides a smooth optical surface by abolishing any minute irregularities of the cornea.
  4. It washes away debris from the conjunctiva and cornea.
 
Inner Mucin Layer
This is very thin and is secreted by the goblet cells in the conjunctiva and also by the crypts of Henle and glands of Manz. The main function of this layer is to convert the corneal epithelium from a hydrophobic to the hydrophilic surface. An aqueous solution form a smooth and even layer when dropped on to a hydrophilic surface. This layer enables the corneal epithelium to be adequately wetted.
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In addition to adequate amounts of aqueous tears and mucin, three other factors are necessary for effective resurfacing of the cornea by the precorneal tear film.
  1. A normal blink reflex which ensures that the mucin is brought from the inferior conjunctiva and rubbed into the corneal epithelium.
  2. Congruity between the external ocular surface and the eyelids ensures that the precorneal tear film spread evenly over the entire cornea.
  3. Normal epithelium is necessary for the adsorption of mucin on to its surface cells.
The chemical composition of human tear is quite complex containing proteins, lipids, metabolites, enzymes, electrolytes and other elements which play an important role in the defence of the outer eye.
The tear protein fraction forms the first line of defence against external influences.
In normal human tears, three types of immunoglobulins, namely IgA, IgG and IgM are present.
In normal tears secretory IgA and IgG form the first line of ocular defence and may act to modulate the normal flora of ocular adnexa allowing saprophytic growth which prevents pathological flora colonizing the ocular surface.
These globulins also prevent adherence of bacteria to the mucosal surface and neutralize viruses and toxins.
Tears transport metabolic products and provide a pathway for WBC in cases of injury.
Avascularity of the cornea is an important factor for antigenicity.
HDA in the peripheral cornea allows tissue immune reaction only when the blood vessels invade the corneal tissue.
In short, the eye is physically well-protected and the physiological mechanisms retain the transparency of media and visuosensory character of the retina. Cornea and lens are immunologically well- protected.
The ocular defence system during physical or pathological attacks is too strong to break the defence barrier.
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