Embryology, Anatomy and Physiology
Aging of the lens
Coloboma of the lens
Lens displacement (luxation and subluxation; ectopia lentis
After the optic vesicle forms, the ectoderm overlying it thickens to form the lens placode.
The lens placode then invaginates into the optic vesicle and becomes the lens vesicle after which it separates from the surface ectoderm.
The cells of the anterior wall of the lens vesicle persist as the anterior epithelium of the fully developed lens. Cells from the posterior and equatorial wall of the lens vesicle differentiate into lens fibers, lose their nuclei, and elongate to fill the vesicle. These cells are the primary lens fibers and represent the embryonic nucleus of the fully developed lens. After this stage lens epithelium is present only anteriorly.
At this stage, a clear, hyaline basement membrane is secreted by the lens cells and forms the lens capsule. The capsule then acts as an effective barrier between the lens material within and the rest of the body. Because this occurs prior to immunologic development, the embryo fails to 'learn' that lens protein is 'self.' Later in life, if lens protein escapes the confines of the capsule, a foreign body reaction will occur and result in a variable degree of ocular inflammation.
Lens fibers continue to form from the cells at the equator so that several layers are produced. The new fibers extend anteriorly and posteriorly to join with other fibers in a linear fashion forming suture lines which take on an upright 'Y' appearance anteriorly and an inverted 'Y' appearance posteriorly. This is the appearance of the lens at birth.
Although the 'Y' suture pattern produced at this stage remains throughout life, as the lens becomes larger, the next suture patterns to form become irregular and more difficult to see. Also, this 'Y' pattern is not present at all in many non-mammalian vertebrates.
Blood supply to the developing lens is provided in part by the hyaloid system (primary vitreous). When it has served its purpose, the vessels undergo resorption which mostly is complete at birth or soon after; however, it is not uncommon to take several weeks postnatally. In ruminants, especially cattle, hyaloid remnants are a common finding for many months after birth.
Anteriorly the lens nourishment is supplied by the tunica vasculosa lentis which is a mesodermal vascular network arising from the iris near the future pupillary space. These vessels also resorb prior to or shortly after birth.
The mature lens is transparent and biconvex. There is greater curvature to the posterior surface than to the anterior surface. The centers of these surfaces are referred to as the posterior and anterior poles, respectively. The circumference is the equator to which the zonular fibers attach.
The lens can be divided into several regions :
Transparent, amorphous, elastic membrane that envelopes the entire structure - thicker anteriorly than posteriorly. If the capsule is ruptured, it retracts due to its elasticity.
The capsule is semipermeable to allow passage of metabolites.
Layer of cuboidal cells; present beneath the anterior capsule only. It is the only lens tissue capable of regeneration; throughout life, epithelial cells divide, move to the equator, elongate, denucleate and become new lens fibers.
These are the bulk of the lens, divided into cortex and nucleus. Because new fibers are produced continuously, a particular fiber appears to be displaced deeper into the lens. This is helpful in determining when an insult may have occurred because, e.g., a non-progressive cataract which occurred during gestation would remain in the nuclear area; one that is more recent would be in the more superficial cortical areas.
The lens fibers are held together by an amorphous cement substance.
In at least some altricial birds such as pigeons, the nuclear region is opaque during the first few weeks after hatching (Lo, et al.). This apparently is due to aggregates of glycogen which eventually dissociate to form a homogeneous distribution, at which time the nucleus becomes clear. Although this technically is cataract (when opaque), it seems to be a normal phenomenon and is of no consequence to the individual because they do not need clear vision at this time.
Zonular or suspensory ligaments: These are termed zonules of Zinn and arise from the ciliary body to insert into and around the equatorial capsule. They provide major support for the lens and mediate accommodation.These zonules are strong in most domestic animals and are somewhat resistant to enzymatic lysis. In humans, enzymes such as alpha chymotrypsin are used to lyse the zonules prior to lens extraction for cataract.Anterior vitreous face: This is important clinically for our patients in that the posterior capsule of the lens and vitreous face are tightly adherent. This poses major difficulties when cataract extraction is attempted unless one accepts the fact that the posterior capsule must usually be left behind. This is not the case in humans and other primates: after zonulolysis lens extraction is relatively uncomplicated.
Contraction of the ciliary muscles relieves tension on the zonules which in turn allows the elastic capsule to retract. This causes the lens to become more convex therefore shortening the focal length so that the image of an object close to the eye will now fall on the retina. Accommodation is poor in most domestic animals largely due to poor development of the ciliary muscle.
The lens has a low metabolic rate with mostly anaerobic glycolysis. Oxygen is used by the epithelium and outer cortex. Interference with the normal metabolic pathways results in cataract formation often due to osmotic imbibition of fluid through the capsule due to build up of various metabolites within.
Lenticular or nuclear sclerosis is the gradual, age-related hardening of the nuclear and perinuclear areas of the lens . This occurs almost universally in all species after middle-age. Sclerosis appears to be related to an increase in the ratio of insoluble to soluble crystallins. Gamma-crystallin is the principle lens protein affected. Gamma-crystallin is restricted to the nucleus which may explain why the nuclear region predominantly is affected. There is no gamma-crystallin in the chicken lens which also does not appear to develop nuclear sclerosis even in old age.
With nuclear sclerosis, the central region of the lens starts to develop a gray-blue haze which becomes more pronounced with age (part of the reason for the color change is that yellow light is filtered out). Many people mistakenly term this cataract. Nuclear sclerosis is not cataract! A cataract is opacification of the lens through which useful vision cannot occur or through which the ocular fundus cannot clearly be seen; there is a degenerative change in the lens.
With nuclear sclerosis, vision (in domestic animals) is normal and the ocular fundus can clearly be seen. In patients in whom subjective analysis can be done, i.e., humans, dense nuclear sclerosis can be shown to interfere with visual acuity. However, in domestic animals there is no objective evidence of decreased visual acuity.
The most common congenital disease of the lens is cataract. However, because many forms of cataract are heritable (therefore congenitally predisposed), but do not appear until some time after birth, cataract in general will be covered under acquired diseases rather than here. Most of the congenital diseases described here are interesting findings, but are non-treatable and insignificant.
Aphakia is the lack of a lens. True aphakia is extremely rare and usually is associated with severe arrest in ocular development so that severe microphthalmia or congenital cystic eye is the result.
This is a rare condition which often is accompanied by coloboma of the uveal tract. Clinically the lens will appear notched or may be abnormal in shape, theoretically due to uneven tension on the lens capsule in the area of the uveal coloboma during development.
The lens is smaller than normal. It may be an isolated lesion or occur as part of a syndrome of multiple ocular anomalies. If not already cataractous at birth, it often will opacify later in life. Accompanying ocular defects usually preclude removal of these lenses for therapeutic purposes.
In this condition, the surface of the lens protrudes at the anterior or posterior pole in conical form (Aguirre and Bistner; Narfström and Dubielzig). Although uncommon, it is seen in many species. The defect in the lens capsule often appears as a circular defect of the lens and the protruding material may be opaque. The lens capsule in these defective areas often is weak and may spontaneously rupture.
Posterior lenticonus may be associated with persistent hyperplastic primary vitreous.
Lenticonus internum describes an abnormally shaped lens nucleus which extends into the posterior cortex.
Cataract is an opacity of the lens (including the capsule) which results in loss of transparency of the lens and, therefore, interferes with vision (or visualization of the ocular fundus) . It can be focal, thus not preventing vision through clear portions of the lens , or diffuse, thus severely diminishing visual capability or even blinding . On a cellular level, it is associated with intra- and extracellular vacuolation and local precipitation of protein, loss of epithelial cells, aberrant epithelial cell differentiation or epithelial cell metaplasia. Cataract is the most common disease of the lens, simply because the lens reacts to most insults by opacifying. Although it can be an isolated condition, it often is seen associated with ocular abnormalities (van der Woerdt, et al.).
The pathogenesis of cataract development is not fully understood (Kinoshita). Lens fiber transparency is affected by swelling and coagulation of protein. Opacification due to the imbibition of water may be reversible if the pathologic process is corrected (Fraunfelder and Burns). Opacification due to chemical changes in the proteins is irreversible. These biochemical changes often are specific for the type of cataract. Generally, water, percent of ash, sodium and calcium are increased, and oxygen consumption, glutathione, ascorbic acid, potassium, soluble protein and riboflavin are decreased.
Cataracts are classified in various ways and this multiplicity of classification schemes leads to confusion. An understanding of the disease process may be much more meaningful than any classification scheme. However, classification on the basis of stage of formation may be meaningful because this describes the progression of most cataracts regardless of cause (Playter).
Classification by stage of formation:Incipient - when first evidence of opacification is seen. Vision is not affected. The opacity may or may not progress.Classification on basis of age:
Incomplete (also called immature) - lens is largely, but not completely, opaque. The patient may have some vision; a tapetal reflex is visible. The lens may be slightly enlarged due to imbibition of water.
Complete (also called mature) - lens is totally opaque preventing vision in that eye. The lens may be intumescent (enlarged due to imbibition of water).
Complete with shrinkage (also called hypermature) - remaining lens fibers are opaque, but there is a reduction in this material as well as water, causing a decrease in the size of the lens, usually through flattening. If the capsule is clear, the patient may be able to see through portions where little to no cortical material remains or around the lens if shrinkage results in a smaller diameter.
Morgagnian - cortex is liquefied, but nucleus is not and floats in the cortex (settles with gravity).Congenital - present at birth.
Developmental - develops sometime after birth, but generally before adulthood - many of the heritable and nutritional cataracts fall into this category.These sometimes are referred to as 'juvenile' cataracts. This is unfortunate because others have taken this to mean a specific entity; 'juvenile' only describes the age at which the cataract was manifest.Degenerative - cataract formation after normal development. This includes cataracts which occur as a result of senescence (called 'senile' cataracts, but only as a descriptive term).
These apply regardless of type, cause, or other features.
Pupillary responses to light are normal unless there are other problems. Light can penetrate the cataract and stimulate the retina; if the cataract is unusually dense, the pupillary response may be somewhat sluggish or less pronounced, but will nevertheless be present.
Although most cataracts are progressive to some degree, you should never predict the onset of blindness.
Always examine the entire eye at the first sign of cataract so that the status of the retina and optic nerve can be established. This is for future reference when cataract extraction may be anticipated. It would be unfortunate, to say the least, to remove the cataract and then learn the patient had optic nerve hypoplasia or retinal degeneration.
Always use a mydriatic for examination of the lens and use a system like the otoscope part of a diagnostic set, not the ophthalmoscope.
Treatment of cataract is primarily surgical. It should be obvious, however, that poor vision due to an opacity of the nuclear or perinuclear area could be alleviated by pharmacologically dilating the pupil so that vision can occur around the opacity. Long lasting mydriatics, such as atropine drops, may be used to keep the pupil dilated with minimum effort on the part of the client. If the cataract is non-progressive, this may be all that is needed. If it progresses, surgery may be considered when the mydriatic no longer is helpful.
Intraocular surgery involves the use of specialized instruments and techniques, and is beyond the scope of this set of notes. Cataract extraction in the dog generally is reported to be about 70-75% successful if there is careful selection of patients and if procedures such as phacoemulsification are used. Prognosis in other species is as follows: cat - good; horse - poor in adult, good in foal less than 9 months old (Gelatt, et al.); primates - very good (easier than in others); cattle - good.
Intraocular surgery requires much practice and it is not recommended that the general practitioner attempt this type of surgery unless it is to be done routinely, and only after special training.
Cataract extraction is generally classified into two types:Intracapsular - removal of the lens without rupturing the capsule. Difficult in most nonhuman animals due to firm attachment of zonules and adherence to the anterior vitreous face.After cataract describes the production of opaque lens material by lens epithelial cells left behind during an extracapsular extraction.
Extracapsular - removal of the lens after removing the anterior capsule. The posterior capsule usually is left in place.
In young animals (particularly dogs less than 4 years old), there may be resorption of the cataractous lens (Rubin and Gelatt), sometimes to a degree sufficient to restore vision ; return of vision is rare and usually takes 8-12 months if it is going to occur. Clinically you will see a wrinkling of the lens capsule and less protrusion of the lens through the pupil (as viewed from the side). This finding indicates that the lens is undergoing resorption. The lens proteins (which are 'foreign') being lost through the capsule initiate an iridocyclitis which is variable in degree, but usually is mild. In most situations, the resorptive process and accompanying inflammation does not last for more than several months and the inflammation usually is easily controlled with topical corticosteroids and iridocycloplegics.
In this section are listed some of the specific types of cataracts that you might expect to see. Most are due to specific causes, but some represent distinct entities for which a cause has not been determined (Barnett).
Hyaloid cataract : Opacity is posterior subcapsular and capsular, and ranges in size from pinpoint to a large, white plaque containing blood vessels. It is caused by a defect in the resorptive process of the hyaloid vessels and is congenital. Usually not progressive; mydriatics may be helpful if vision is affected. Small hyaloid remnants (without lens opacity) commonly are found in all animals and are of no concern.
Y-suture cataract : Granular clumping along the arms of the Y-sutures. Not uncommon. It is important in that it progresses in some animals and it may represent a variable expression of a heritable cataract seen in golden retrievers.
Persistent pupillary membrane cataract : These are anterior capsular and usually non-progressive. May range in size from pinpoint to large plaque. Relatively few patients with persistent pupillary membrane will have cataract. Try mydriatics if vision is affected. Surgical therapy should not be attempted.
Metabolic cataract: Many metabolic diseases, diabetes mellitus being the best example , result in defective lens nourishment which in turn leads to cataract. Lesions first begin in the equatorial cortical or posterior subcapsular regions and often progress rapidly. Once they begin, they may advance to completeness regardless of treatment. Cataract extraction can be successful if the patient is being well-controlled for the systemic disease.In the case of diabetes mellitus, abnormally elevated blood glucose concentration leads to an increase in glucose within the lens. This overloads the normal glucose pathways and leads to increased sorbitol which cannot escape the lens and results in imbibition of fluid by the lens (opacification results).Rodents undergoing anesthesia also have been known to develop transient cataracts if the eyelids are not kept closed (Fraunfelder and Burns).
Toxic cataract: Numerous drugs will cause lenticular opacities (Sanford and Dukes). Fortunately, most of the common therapeutic agents do not appear to be cataractogenic in the normally used doses. Disophenol, used in treating hookworm infection, can cause lenticular opacities at doses not much higher than used clinically, but these opacities usually are reversible after the drug is discontinued.
Heritable: A wide variety of species and breeds have predisposition for cataractogenesis. In some breeds of dogs, for example, cataract formation is heritable. In others, the heritable nature of the disease is suspected, but not yet proven.Heritable cataracts generally are manifest within the first few years of life, but can be congenital. Each breed appears to have a pattern peculiar to itself.Complicated or secondary cataracts: Ocular injury, uveitis or other intraocular inflammation and some systemic illnesses may result in cataract (Ashton, et al.). If there is minor damage to the lens and the cause is ameliorated, the opacity formed probably will be stationary. If there is recurrent uveitis or if the original injury severely damaged the lens, the opacity may enlarge and eventually involve the entire lens.
Patients with heritable cataracts should not be used for breeding. If congenital or early onset cataracts occur in a breed which is not thought to have heritable cataracts, several things can be done to determine if the cataract is heritable. First, the sire and dam can be examined carefully for evidence of cataract; if the mode of inheritance is recessive, both parents could be phenotypically normal. The next step would be careful evaluation of the pedigree and, if possible, examination of related individuals. If the parents are normal and there is no evidence of cataract in the pedigree, then a second mating could be done and all the offspring examined. This is unacceptable from my point of view because there is a serious dog overpopulation problem and test breeding only contributes to the problem. In addition, if the condition is heritable, the puppies may be affected or carriers and may develop vision difficulty or pass on the trait. It would be better simply not to use dogs of questionable status for breeding.
The following is a partial list of breeds known to have or suspected of having heritable cataract, along with the age of onset, type of opacity initially and mode of inheritance, if known. Most eventually progress to complete opacification.Afghan - 4 months to 2 years - equatorial vacuoles - possibly autosomal recessive (Roberts and Helper).
American cocker spaniel - congenital or within first 4 years - posterior subcapsular or various cortical regions - at least one form is autosomal recessive (Yakely).
Golden retriever - congenital or within first year - posterior, triangular either along suture or subcapsular - thought to be dominant with variable penetrance (Rubin).
Miniature schnauzer - congenital or within first year - posterior subcapsular or complete - autosomal recessive (Barnett).
Old English sheepdog - congenital or within first year - nuclear or cortical - possibly autosomal recessive (Koch).
Poodles (miniature and toy) - within first 3 years - posterior subcapsular - autosomal recessive.
Other canine breeds - there is considerable literature on this subject; see cited references for more information (Bjerkås and Bergsjo; Gelatt, et al.; Narfström; Rubin and Flowers).
Cats - not much is known about heritable cataracts.
Horses - any foal with congenital or early onset cataract should be considered suspicious of having heritable disease, but specifics are not known. Morgan horses have been shown to have congenital nuclear cataracts which may be heritable in nature (Beech, et al.).
Other species - cataracts are commonly seen in other species and in some cases their heritability has been elucidated; cataracts considered to be heritable or for which other causes have not been demonstrated can be found in birds, degus, mice, pigs, rabbits, rats, sheep and others (Barr, et al.; Brooks, et al.; Gelatt; Slatter, et al.; Tsai, et al.).Treatment is aimed at eliminating the cause. Mydriatics may be helpful for incomplete cataracts, as described previously.
Partial or complete breakdown of the zonular attachments results in displacement of the lens. If the lens remains in the patellar fossa it is considered subluxated; if the lens moves into the anterior chamber or vitreous, it is luxated.
Congenital - rare, seen with other congenital problems.
Traumatic - usually there is severe concurrent intraocular damage because the trauma must be great in order to break down normal zonules.
Spontaneous - seen most frequently in terriers (wire-haired fox terrier, Sealyham, Welsh and Manchester); occasionally in Boston terriers, basset hounds and cocker spaniels. The disease is heritable and is the result of poorly developed zonules (Curtis and Barnett). The lens usually does not displace, however, until the individual is 2 to 5 years old. Seen occasionally in horses and cats (Olivero, et al.).
Secondary to other diseases, especially those leading to increased globe size, such as glaucoma. In the latter case, the zonules rupture due to stretching caused by enlargement of the globe.
The iris will show vibration or fluttering; this is termed iridodonesis and is essentially pathognomonic for ectopia lentis. Although usually easily seen, its visualization can be facilitated by doing gonioscopy. The anterior chamber may be more shallow than normal; the effect may be irregular because the lens may be tilted causing only one zone of iris to be displaced anteriorly. Evaluate the anterior chamber by observing the eye from the side.
In cases of spontaneous displacement in breeds having heritable predisposition, it is important to evaluate the opposite eye for signs of impending displacement because both eyes usually are affected. This should also be taken into consideration when giving a prognosis to the client.
Subluxation: The lens remains in the patellar fossa. In many instances, the lens will be shifted down or to one side so that there will be an aphakic crescent (the area of the pupil where there is no lens) ; if the lens has not yet shifted, an aphakic crescent will not be present. Subdue the room illumination and use a dim light source to facilitate seeing an aphakic crescent. An ultraviolet light source may be helpful in determining the position of the lens.
Luxation:Anterior luxation - The lens may go through the pupil and lie in the anterior chamber, where it may rub against the cornea and cause corneal edema. Usually, the equatorial border of the lens can be seen directly, or can be accentuated by shining a light from the side while viewing from the front: the border opposite to where the light is directed will shine. Ultraviolet light can also be used. If the cornea is too opaque, you will not be able to make the diagnosis.The lens may simply push the iris forward, causing an extremely shallow anterior chamber.Posterior luxation - The movement of the lens may cause vitreous liquefaction; this is called syneresis. The lens then may luxate into the vitreous cavity. This usually results in a deeper than normal anterior chamber, with a flattened iris profile. The lens usually settles down to the ventral aspect of the vitreous cavity.
In many cases, the lens may be mobile while still attached to the anterior vitreous face.
Lens displacement usually causes moderate iridocyclitis and, in most cases, it also causes glaucoma (presumably by impedance of aqueous flow by angle or pupillary block) with enlargement of the globe. An eye enlarged due to glaucoma from other causes also may have lens luxation. It is important to differentiate primary from secondary lens displacement in the enlarged eye. The breed of the dog is helpful, terriers probably being affected by primary lens displacement. If the glaucoma is affecting only one eye in a non-terrier breed, the other eye can be examined carefully: if this eye is normal, the luxation in the other eye probably is secondary. Sometimes the position of the lens may provide a clue. In primary luxation, gravity would displace the lens ventrally; when the lens is dislodged because the zonules have broken secondary to eye enlargement, some zonules may be more resistant so that the lens will be attached at that point; thus, if the lens is attached dorsally, the displacement may be secondary to eye enlargement.
Anterior lens displacement likely will cause glaucoma. Posterior luxation may be better tolerated by the eye, but it also can be associated with glaucoma; the reason for glaucoma in the case of a posteriorly luxated lens is not clear. These lenses have the potential of luxating anteriorly at any time.
Lens removal is the only rational treatment for spontaneous luxation or subluxation. The earlier the disease is diagnosed and treated, the greater the chance of saving vision. If glaucoma is present along with the displacement, or if there is vitreous degeneration, the prognosis is more guarded. If the glaucoma is chronic, it may persist after lens removal.
Other types of lens luxations must be handled according to their cause. For example, luxation secondary to glaucoma should not be treated surgically because the displacement is secondary. Traumatic lens displacements usually have a poor prognosis due to the severity of ocular damage.
This is an uncommon condition usually associated with severe trauma to the eye. Although any pointed object or missile can cause rupture in any species, a severe blow to the horse's head may result in rupture.
A traumatic cause is obvious in most cases. In the horse with rupture from non-penetrating trauma, the lens cortex may simulate fibrin in the anterior chamber.
Treatment involves removal of the lens in cases where removal may result in saving the eye. In other cases, the eye should be removed.
Medical treatment of cataract: Various compounds have been recommended for ocular or other application in the treatment of cataract, none of which has been found to be effective to date (MacMillan, et al.; Playter, et al.).