Introduction

Background
Ectopia lentis is defined as displacement or malposition of the crystalline lens of the eye.1,2,3 Berryat described the first reported case of lens dislocation in 1749, and Stellwag subsequently coined the term ectopia lentis in 1856 (describing a patient with congenital lens dislocation). The lens is considered dislocated or luxated when it lies completely outside the lens patellar fossa, in the anterior chamber, free-floating in the vitreous, or directly on the retina. The lens is described as subluxed when it is partially displaced but contained within the lens space. In the absence of trauma, ectopia lentis should evoke suspicion for concomitant hereditary systemic disease or associated ocular disorders.4,5

Ectopia lentis. Dislocated traumatic lens (cataract).

Ectopia lentis. Dislocated lens into the vitreous secondary to trauma.

Pathophysiology

Disruption or dysfunction of the zonular fibers of the lens, regardless of cause (trauma or heritable condition), is the underlying pathophysiology of ectopia lentis. The degree of zonular impairment determines the degree of lens displacement.

Frequency
United States Ectopia lentis is a rare condition. Incidence in the general population is unknown. The most common cause of ectopia lentis is trauma, which accounts for nearly one half of all cases of lens dislocation.

Mortality/Morbidity
Ectopia lentis may cause marked visual disturbance, which varies with the degree of lens displacement and the underlying etiologic abnormality.

Sex
Males appear more prone to ocular trauma than females; therefore, a male preponderance has been reported. Male and female frequency varies with the etiology of the lens displacement.

Age
Ectopia lentis can occur at any age.6 It may be present at birth, or it may manifest late in life.

Clinical
History

Common presenting symptoms (visual disturbance) include the following: o Red painful eye (secondary to trauma) o Decreased distance visual acuity (secondary to astigmatism or myopia) o Poor near vision (loss of accommodative power) o Monocular diplopia Determine if there is a history of ocular trauma. Obtain a detailed history investigating possible systemic disease associations. o Cardiovascular disease (eg, Marfan syndrome) o Skeletal problems -Marfan syndrome, Weil-Marchesani syndrome, or homocystinuria o Pertinent family history - Consanguinity, mental retardation, or unexplained deaths at young age (eg, autosomal recessive conditions, including homocystinuria, hyperlysinemia, ectopia lentis et pupillae,7 or sulfite oxidase deficiency)

Physical
A pediatrician or an internal medicine physician should perform a comprehensive physical examination of patients with ectopia lentis of undetermined etiology because of the commonly associated hereditary systemic disorders. The ocular examination should include the following:

Vision Ectopia lentis is potentially visually debilitating. Visual acuity varies with the degree of malpositioning of the lens. Amblyopia is a common cause of decreased vision in congenital ectopia lentis and is preventable and treatable. External ocular examination o Attention to orbital anatomy is important to evaluate for hereditary malformations (eg, enophthalmos with facial myopathic appearance seen in patients with Marfan syndrome).8 o Measure corneal diameter (megalocornea is associated with Marfan syndrome). o Strabismus is not uncommon (secondary to amblyopia). Retinoscopy and refraction o Careful retinoscopy and refraction is essential, often revealing myopia with astigmatism. o Keratometry may help ascertain degree of corneal astigmatism. Slit lamp examination o Evaluate lens position, and identify phacodonesis or cataract. o Measure intraocular pressure. Elevation may indicate secondary glaucoma. Causes of glaucoma in ectopia lentis include the following: (1) pupillary block, (2) phacoanaphylaxis or phacolytic, (3) posttraumatic angle recession, (4) poorly developed angle structures, and (5) lens in the anterior chamber. Dilated fundus examination: Retinal detachment is one of the most serious consequences of a dislocated lens.
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Causes
The numerous causes of ectopia lentis can be classified as follows:

Traumatic dislocation (most common cause) Hereditary ectopia lentis without systemic manifestations o Single (isolated) ectopia lentis is characterized by autosomal dominant inheritance with the genetic defect located on chromosome 15, causing a dysfunctional zonular apparatus. Microspherophakia is common. Although most often present at birth, late onset has been described. Typically, the lens is displaced supertemporally. o Ectopia lentis et pupillae is characterized by asymmetric eccentric pupils that are displaced in the opposite direction of the lens dislocation (toward the most dysfunctional zonular fibers). The condition usually is bilateral and typically

autosomal recessive. The irides often appear atrophic with transillumination defects on slit lamp examination.7 Cataracts commonly are seen.9 Systemic conditions commonly associated with ectopia lentis o Marfan syndrome is the most frequent cause of heritable ectopia lentis. The syndrome is transmitted as an autosomal dominant trait with variable expressivity and has a prevalence of approximately 5 per 100,000. Several point mutations involving the fibrillin gene on chromosomes 15 and 21 have been described and may relate to incompetent zonular fibers. Salient features of Marfan syndrome include tall stature, arachnodactyly, joint laxity, mitral valve prolapse, aortic dilatation, axial myopia, and increased incidence of retinal detachment. Lens dislocation occurs in about 75% of patients with Marfan syndrome and usually is bilateral, symmetrical, and supertemporal.10
o

Ectopia lentis. Supertemporal dislocation of a lens in the right eye of a patient with Marfan syndrome. Note the attached zonular fibers.
o

Homocystinuria is the second most common cause of hereditary ectopia lentis. It is an inborn error of metabolism most often caused by a near absence of cystathionine b-synthetase (the enzyme that converts homocysteine to cystathionine). Patients typically have fair skin with coarse hair, osteoporosis, mental retardation (nearly 50%), seizure disorder, marfanoid habitus, and poor circulation. Thromboembolic events constitute the major threat to survival, especially following general anesthesia. Lens luxation usually is bilateral, symmetrical, and inferonasal, and presents in nearly 90% of patients. Deficient zonular integrity secondary to the enzymatic defect has been implicated as the primary cause of lens displacement. Weil-Marchesani is a rare syndrome characterized by skeletal malformations (eg, short stature, brachycephaly, limited joint mobility, well-developed muscular appearance) and ocular abnormalities (eg, ectopia lentis, microspherophakia, lenticular myopia). The inheritance pattern is not well understood. Microspherophakia is the most prominent feature of this syndrome. High incidence of lens subluxation occurs inferiorly, often progressing to complete dislocation. Pupillary block glaucoma is common; therefore, prophylactic laser peripheral iridotomies are recommended.11

Ectopia lentis. Microspherophakia and spontaneous inferior dislocation of a lens in a patient with Weil-Marchesani syndrome. Sulfite oxidase deficiency is an extremely rare disorder caused by a defect in sulfur metabolism. Salient features include progressive CNS abnormalities that develop within the first year of life in concert with ectopia lentis. o Hyperlysinemia is an extremely rare autosomal recessive enzymatic defect of amino acid metabolism that is characterized by mental retardation and lens dislocation. Diagnosis is made by demonstration of increased plasma levels of lysine. Primary ocular disorders associated with ectopia lentis o Congenital glaucoma/buphthalmos o Pseudoexfoliation syndrome o Syphilis/chronic uveitis o Retinitis pigmentosa o Megalocornea o Aniridia o Hypermature cataract o Intraocular tumor o High myopia Systemic diseases rarely associated with ectopia lentis o Ehlers-Danlos syndrome o Crouzon disease o Refsum syndrome o Kniest syndrome o Mandibulofacial dysostosis o Sturge-Weber syndrome o Conradi syndrome o Pfaundler syndrome o Pierre Robin syndrome o Wildervanck syndrome o Sprengel deformity
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Differential Diagnoses
Cataract, Traumatic Glaucoma, Pseudoexfoliation Intraocular Lens Dislocation

Workup
Laboratory Studies
Perform appropriate diagnostic and laboratory evaluation, if a hereditary condition is suspected (eg, cardiac evaluation for Marfan syndrome, check serum and urine levels of homocysteine or methionine for homocystinuria).

Imaging Studies
Echography: Axial length measurement may be of benefit (patients with Marfan syndrome have large globes).

Treatment
Medical Care
Without an antecedent history of trauma, patients with ectopia lentis may possess a systemic disease with potentially deleterious effects; therefore, comanagement with the patient's pediatrician or internist is essential. Dietary restriction may be partially effective in patients with homocystinuria. Repair of an impending dissecting aortic aneurysm in Marfan syndrome may be life saving. If a hereditary condition is discovered, appropriate genetic counseling should be given. Moreover, all relatives with potential risk should be examined. Treatment of glaucoma is dependent on the etiologic mechanism.

In pupillary block (eg, patients who have Weil-Marchesani with microspherophakia), laser peripheral iridotomy or iridectomy should be performed, and intraocular pressure elevation should be treated medically. Prophylactic laser iridotomy in patients with microspherophakia is beneficial. Treatment of a lens dislodged into the anterior chamber is initially pharmacological with mydriasis/cycloplegia (to permit posterior migration of the lens behind the iris) in conjunction with ocular massage through a closed lid to promote this posterior migration. Surgical treatment will then be needed to prevent further complications. Treatment of a dislocated lens in the vitreous is surgical; however, many vitreoretinal surgeons may advocate observation if no visual disturbance or impending retinal complication is apparent.

Surgical Care
Lens surgery in ectopia lentis is technically challenging, and the numerous techniques and strategies are beyond the scope of this article.12

Indication for lensectomy o Lens in the anterior chamber

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Lens-induced uveitis Lens-induced glaucoma Lenticular opacity with poor visual function Anisometropia or refractive error not amenable to optical correction (eg, in a child to prevent amblyopia) Impending dislocation of the lens

References
1. Jarrett WH II. Dislocation of the lens. A study of 166 hospitalized cases. Arch Ophthalmol. Sep 1967;78(3):289-96. [Medline]. 2. Nirankari MS, Chaddah MR. Displaced lens. Am J Ophthalmol. Jun 1967;63(6):171923. [Medline]. 3. Nelson LB, Maumenee IH. Ectopia lentis. Surv Ophthalmol. Nov-Dec 1982;27(3):14360. [Medline]. 4. Clark CC. Ectopia lentis: a pathologic and clinical study. Arch Ophthalmol. 1939;21:124153. 5. Albert DM, Jakobiec FA. Pathology of the lens. In: Principles and Practice of Ophthalmology. 2000:2225-2239. 6. Nelson L. Ectopia lentis in childhood. J Pediatr Ophthalmol Strabismus. JanFeb 2008;45(1):12. [Medline]. 7. Omulecki W, Wilczynski M, Gerkowicz M. Management of bilateral ectopia lentis et pupillae syndrome. Ophthalmic Surg Lasers Imaging. Jan-Feb 2006;37(1):6871. [Medline]. 8. Parrish RK II. Anatomy, physiology, and pathology of the crystalline lens. In: Bascom Palmer Eye Institute's Atlas of Ophthalmology. 1999:241. 9. Duane T. Cataracts and systemic disease. In: Duane's Clinical Ophthalmology. 5. 1999:13-14. 10. Ganesh A, Smith C, Chan W, et al. Immunohistochemical evaluation of conjunctival fibrillin-1 in Marfan syndrome. Arch Ophthalmol. Feb 2006;124(2):205-9. [Medline]. 11. Wentzloff JN, Kaldawy RM, Chen TC. Weill-Marchesani syndrome. J Pediatr Ophthalmol Strabismus. May-Jun 2006;43(3):192. [Medline]. 12. Konradsen T, Kugelberg M, Zetterstrm C. Visual outcomes and complications in surgery for ectopia lentis in children. J Cataract Refract Surg. May 2007;33(5):81924. [Medline].