SURVEY OF OPHTHALMOLOGY VOLUME 27 - NUMBER 3.

NOVEMBER-DECEMBER 1982

REVIEW

Ectopia Lentis
LEONARD B. NELSON, M.D., AND IRENE H. MAUMENEE, M.D.

Department of Pediatric Ophthalmology, Wills Eye Hospital, Philadelphia, Pennsylvania, and Wilmer Oph-
thalmological Institute, The Johns Hopkins Hospital, Baltimore, Maryland

Abstract. Ectopia lentis was lirst described more than 200 years ago, but its value as a significant
diagnostic clue to the presence of other ocular and systemic disorders has only recently been
appreciated. Ectopia lentis may cause a marked reduction in visual acuity, which varies with the
type and degree ofdislocation and the presence ofother ocular abnormalities. An approach to the
diagnostic evaluation of the patient with ectopia lentis is outlined. The differential diagnosis is
reviewed in detail both clinically and histologically, The complications of ectopia lentis and the
;;;;priate management of affected patients are discussed. (Sure Ophtbalmol 27:143-160,

Key words. dislocated lens lectopia lentis heredity l l

metabolic disorder l microspherophakia myopia

l zonular abnormality
l

T
he dislocated lens was probably first described I. Diagnostic Evaluation
by Berryat in 1749. W A century later the term
The diagnosis of ectopia lentis usually requires a
ectopia lentis was introduced by Stellwag to de-
thorough evaluation with wide dilatation of the pu-
scribe congenital dislocationsW But it was many
pil. The lens may be minimally dislocated, bisecting
years before ectopia lentis became recognized as an
the pupil, totally dislocated into the anterior cham-
important diagnostic clue to the possible presence of
ber, or free-floating in the vitreous. An accurate
other ocular or systemic disorders.
evaluation of the patient with ectopia lentis can usu-
The most significant ocular manifestation of ec-
ally be made by following a sequential approach, as
topia lentis is a reduction in visual acuity. The
described in the following paragraphs and outlined
amount of visual disturbance varies with the type
in Table 1.
and degree of dislocation and the presence of associ-
ated ocular abnormalities. Minimal subluxation of
a lens may cause no visual symptoms. But when the A. FAMILY HISTORY
zonules are disrupted, causing increased curvature A complete and detailed history from either the
of the lens, the result may be lenticular myopia and patient or the parents should be obtained prior to
astigmatism. If an eye with a dislocated lens has the ocular evaluation. Specific inquiry should be
glaucoma, cataract, or retinal detachment, then the made as to the possibility of cardiovascular disease
visual consequences are more serious, including and complications, skeletal abnormalities, and visu-
permanent loss of vision. al disturbances. A history of consanguinity, early
Ectopia lentis continues to be a diagnostic and family deaths, and mental retardation should also
therapeutic challenge for most ophthalmologists. A be obtained.
thorough systemic and ocular evaluation is neces-
sary to establish the etiology and to initiate the ap-
B. PHYSICAL EXAMINATION
propriate therapeutic and prophylactic measures.
This article will review the approach to the patient A detailed physical examination of patients with
with ectopia lentis, the differential diagnosis, the ectopia lentis should be performed by a pediatric or
possible complications and overall management. medical consultant. However, there are certain
143
144 Surv Ophthalmol 27(3) November-December 1982 NELSON, MAUMENEE

Fig. 1. Extension ofthumb beyond the ulnar surface of the Fig. 2. Overlap of the thumb and fifth linger when clasped
hand. around the opposite wrist.

physical signs that may help the ophthalmologist in vation of a lens that is either, (1) out of place, or (2)
the diagnostic evaluation. On inspection of the ocu- loose. Thus, attention to these two matters is of
lar adnexae, a clinical appearance of enophthalmos utmost importance. Phakokinesis is frequently over-
caused by reduced subcutaneous fat, combined with looked unless it is specifically sought out as a possi-
flat malar areas and hypoplastic facial muscles, ble finding. The cornea1 diameter in the Marfan
gives a characteristic facial “myopathic” appear- syndrome is classically increased, giving the ap-
ance. This appearance is often found in patients pearance of megalocornea.“’ The high incidence of
with the Marfan syndrome. In homocystinuria, the strabismus in patients with ectopia lentis may be
hair is often coarse and lightly colored. A high nar- explained on the basis of amblyopia.
row palate similar to that found in the Marfan syn-
drome is frequently present. E. SLIT LAMP EXAMINATION
One should examine the extremities, looking for
The slit lamp examination should include an
the particularly short hands and feet of the Weill-
evaluation of the depth of the anterior chamber and
Marchesani syndrome or the excessively long and
the appearance of the iris and pupil; it should also
distal limbs (arachnodactyly) of the Marfan syn-
determine whether transillumination, iridodonesis,
drome. In the thumb sign, a combination of a nar-
or both exist. An evaluation of the lens position and
row hand, long digits, and loose-jointedness allows
shape before and after dilatation, as well as of the
the thumb to extend well beyond the ulnar surface
zonular complement, should be performed. It is im-
of the hand (Fig. 1). ‘79In the wrist sign, the combi-
portant to assess the adequacy of the pupillary space
nation of a thin wrist and long digits results in over-
for a possible aphakic correction. Phakokinesis can
lap of the thumb and fifth finger when they clasp the
be best observed by having the patient change gaze
opposite wrist (Fig. 2).‘“’ Both of these signs are
from one objective of the slit lamp to the other while
found quite frequently in the Marfan syndrome.
the examiner views the eye through the lowest pow-
er of the slit lamp. Because anomalies of the irido-
C. VISUAL ACUITY
cornea1 angle may be present in association with
Since ectopia lentis is potentially disastrous to ectopia lentis, a careful gonioscopy is indicated as
visual function, it is important to establish a visual well.
acuity early. It has been our experience that am-
blyopia is the most common cause for decreased F. RETINOSCOPY AND REFRACTION
vision in ectopia lentis, and should be treated with
Retinoscopy (or examination with a hand-held
occlusion therapy. A careful refraction is of para-
slit lamp) may be the only way the diagnosis of
mount importance. If anisometropia is present, it
ectopia lentis can be made in an infant without sub-
should be corrected optically. A close follow-up of
jetting the patient to general anesthesia. Using this
the visual acuity and/or the binocular fixation pat-
technique, the edge of the dislocated lens may be
tern is necessary.
identified in the pupillary space.
Retinoscopy may reveal a significant refractive
D. EXTERNAL OCULAR EXAMINATION
error, usuallv mvonia and astigmatism. Occasional-
The diagnosis of ectopia lentis rests on the obser- ly an’accurate refraction may”be extremely difficult
ECTOPIA LENTIS 145

TABLE 1 TABLE 2

LXagnostic Evaluation Ocular Disorders with Ectopia Lentis

Family history Retinoscopy and refraction T raumaU.l il

Physical examination Ophthalmoscopy Retinitis pigmentosa’.“.”
Visual acuity Keratometry readings Persistent pupillary memhraw”
External ocular examination Axial length measurements :\niridia’“.‘1.1
Slit lamp examination Rieger’s syndrome~~l~.~~~.~
178
Megalocor nea’l’
Dominantly inherited klepharoptosis and high myopia””
C:ongenital glaucoma*
because of tilting or dislocation of the lens. In these
cases an aphakic refraction may be performed. If an
aphakic refraction improves visual acuity, then ei- T:\BLE 3
ther aphakic contact lenses or spectacles should be
,$:ytternic. Disorders with Rare!)’ :lssociated Ectoj~ia Lent it
considered. We have not hesitated to give aphakic
spectacles to children as young as 4 years old in 121arf:nn-like syndrome with hyaloretinal drqeneraticm”’
Syphi]is”.“‘~‘.i”~~~
order to achieve development of good visual acuity.
Sturgr-\Vcher syndrome”‘,”
Mandihulofacial dysostosis”“’
G. OPHTHALMOSCOPY Ehlers-Danlos syndrome”“‘-‘“’
(Zrouzon’s disease””
Ophthalmoscopy is important in the evaluation Refsum’s syndrome””
of the patient with ectopia lentis. The most deleteri- Scleroderma”’
ous cause ofvisual reduction in these patients is a Kniest svndrome*
retinal detachment. Peripheral retinal findings may *Personal ohsrr\~ation
include prominent white without pressure, lattice
degeneration, and retinal holes. Other retinal ah-
normalities, such as retinoschisis, optic atrophy,
and central retinal arttar); occlusion, occur less
homocystinuria, Weill-Marchesani_syndrome, hy-
frequently.
perlysincmia, and sulfite oxidase deficiency. ;L\ num-
ber of ocular conditions have been associated with
H. KERATOMETRY
dislocation of the lens, and these are listed in Table
X krratometric reading prior to retinoscopy may 2. Systemic disorders that are associated rarely with
assist in determinina the refraction ofthese patients. ectopia lentis are listed in Table 3.
\C’r have found that astigmatism in many patients is
mainly rorneal. Kcratometric readings have been A. GENETIC ECTOPIA LENTIS WITHOUT
performed on 137 eves of patients with the Marfan SYSTEMIC MANIFESTATIONS
syndrome.“’ Thrse’important findings will be dis-
1. Simple Ectopia Lentis
cussed in the section on ocular manifestations of the
hlarfan svndromr. Simple ectopia lentis occurs either as a congenital
disorder or as a spontaneous disorder of late on-
I. AXIAL LENGTH MEASUREMENTS set.“” “” Both are inherited in the majority of cases as
autosomal dominant conditions without associated
The Grst histopathologic report on the eyes of a
systemic ahnormalities.” Recessive inheritance is
patient with the Marfan syndrome demonstrated
rare, usually occurring in families in which consan-
extreme size of the globe.” Further pathologic re-
guinity has been documented.” The ocular anomaly
ports have confirmed this observation.‘.‘“” Axial
in simple ectopia lentis is usually manifested as a
length measurements have been taken only in the
bilateral, symmetric, upward and temporal dis-
Marfan syndrome.“’ The important prognostic in-
placement of the lens. Occasionally. the degree of
dications of the measurements will be discussed be-
displacement varies considerably between the two
low in the section on the Marfan syndrome.
eyes.
Spontaneous late subluxation of the lens occurs
II. Differential Diagnosis
between the ages of 20 and 65 years.‘“” There is often
Genetic cctopia lentis has been described in marked irregularity and degeneration ofthe zonular
which no other ocular or systemic abnormalities fibers with subluxation of the lens inferiorly. Herni-
(simple ectopia lentis, either congenital or of de- ation of the vitreous associated with zonular degen-
layed onset, and ectopia lentis et pupillae). It may cration may occur through the zonular defect into
also occur as a common manifestation of systemic the anterior chamber. Both types of ectopia lentis
hereditary disorders, including Marfan syndrome, are associated with cataracts and retinal detach-
146 Surv Ophthalmol 27(3) November-December 1982 NELSON, MAUMENEE

ment.g2 Glaucoma usually occurs more frequently in One patient had a spontaneous unilateral retinal
spontaneous late subluxation of the lens than in the detachment at age 28. The author unfortunately did
congenital type.77.‘23 not include any pictures of the patients, which may
Seland described the changes in the zonular fibers explain why his description went largely unnoticed.
from a patient with congenital simple ectopia len- The eponym “Marfan syndrome” has been used
tis.“j4 Although the ultrastructure of the lens capsule instead of “Williams syndrome” after Matfan, in
was normal, it was completely devoid of zonular 1896, described a 5’/2-year-old who had long thin
fibers in most areas. The remaining capsular attach- extremities.“* Boerger, a pediatrician, was the first
ments were underdeveloped. Farnsworth and co- to point out that ectopia lentis is part of the clinical
workers examined the lens from a patient who had manifestation of this syndrome.‘*
presumably an identical diagnosis and found simi- The prevalence of the Marfan syndrome is from
lar zonular abnormalities.54 However, they also four to six per 100,000 people, without racial or
found a reduction of the lens fibers to 20% of their ethnic predilection. ‘43 It is an autosomal dominant
normal cross-sectional area. condition with variable expressivity and it is charac-
terized by skeletal, cardiovascular, and ocular
2. Ectopia Lentis et Pupillae anomalies. Approximately 15% of cases have no
family history and are presumably derived from a
Ectopia lentis et pupillae is a rare congenital dis-
new mutation.‘4J An elevated paternal age may be a
order in which there are combined anomalies of the
significant factor in the occurrence of these new mu-
lens with pupillary displacement. In two studies in
tations. In one study of 23 sporadic cases, there was
which ectopia lentis occurred without systemic ab-
an increased mean paternal age ofalmost 7 years.13”
normalities, 81% to 93% had simple ectopia lentis
The basic defect of the Marfan syndrome is still
and 7% to 19% had ectopia lentis et pupillae.34J09
unknown. Prockop and Sjoerdsma found an elevat-
The pupils are characteristically oval or slit
ed excretion in the urine of hydroxyproline in three
shaped and ectopic, and they frequently dilate poor-
patients with the Marfan syndrome.14* Because hy-
l~.~* The condition is usually bilateral, commonly
droxyproline is an amino acid unique to collagen,
not symmetrical but with the lenses and pupils dis-
these findings in the Marfan syndrome may be of
placed in the opposite direction from each other.
fundamental importance, suggesting a primary de-
Microspherophakia has been documented histo-
fect involving collagen. The increased hydroxypro-
pathologically. ‘OB
line excretion may indicate increased amounts and
Marked transillumination of the iris periphery
a rapid rate of breakdown of soluble collagen.
has been reported in six patients with ectopia lentis
Subsequently, a higher ratio of soluble to insolu-
et pupillae.‘08 We have seen well-documented cases
ble collagen in skin and fibroblast cultures from
with this condition which do not have iris transillu-
Marfan patients has been demonstrated.‘40 Krieg
mination. The Max-fan syndrome, in which ectopia
and Muller”” found a decrease of type-l collagen
lentis is commonly present, is another disorder in
synthesis in aortic explants obtained at surgery for
which iris transillumination has been documented
repair of a dissecting aneurysm. Biochemical evalu-
clinically. ‘I5 As with simple ectopia lentis, cataract
ation has provided evidence that the increase in
formation, glaucoma, and retinal detachment can
soluble collagen is due to a defect in the biosynthesis
occur.
of type-l collagen, resulting from a qualitative and
Ectopia of the lens and pupil follows a recessive
quantitative change of the a2 chain.‘5g The early
mode of inheritance. However, there has been one
cross-links of type-l collagen require that (~2 chain.
report suggesting dominant inheritance.lm Another
The alteration of this chain results in increased col-
description of a family showing dominant transmis-
lagen solubility, decreased collagen linking, and
sion was clinically atypical for this disorder.lg2 Con-
thus a reduction in its overall tensile strength. A low
sanguinity is frequently reported42*5g or suspected.‘6g
content of type-l collagen in the media and adventi-
tia of the aorta causes a reduction in its strength,
B. SYSTEMIC DISORDERS COMMONLY
which is necessary to withstand the pulsating blood
ASSOCIATED WITH ECTOPIA LENTIS
pressure from the heart. As a result, the aorta may
1. Ma&n Syndrome expand and dilate, leading to the gradual develop-
ment of an aneurysm.
a) General Comments
Recently, reduced tissue levels of dihydroxylysin-
The first description of a family with the Marfan onorleucine (skin) and 3-hydroxy-pyridinium (aor-
syndrome was probably made by an ophthalmol- ta) were demonstrated in Marfan patients.‘*” These
ogist, Elkanoh Williams, in 1895.‘- He described abnormalities may result in a malalignment of some
several members of a family as having upwardly of the collagen fibrils involving the a2 chain of Type
displaced lenses and generalized loose-jointedness. 1 collagen. The defect in the a2 chain may cause a
ECTOPIA LENTIS 147

disturbance in the specific intermolecular cross- tic disease process) ,‘33 new randomized prospective
linking during the organization of Type 1:lll protocols have begun. ‘43Finally, improved prosthe-
collagens. sis and surgical techniques for the cardiovascular
complications have lowered the morbidity and
b) Skeletal Manifestations mortality.45
Abnormalities of the skeletal system include ex- Patients with the Marfan syndrome are at in-
cessive height caused by increased length of the dis- creased risk of endocarditis and should receive anti-
tal limbs (arachnodactyly), loose-jointedness, scoli- biotic prophylaxis with dental or surgical proce-
osis and anterior chest deformities. The skeletal dures.‘3,203 It is recommended by some investigators
proportions demonstrate an increased arm span in that patients not participate in contact sports, iso-
relation to body height and an elongated lower seg- metric exercises, and weight lifting.‘43 Since there
ment (pubis to sole) as compared to the upper seg- apparently is an increased risk of vascular rupture
ment (pubis to vertex). ‘**J~~The absolute height is during and shortly after pregnancy, women with
not as important as the patient’s relative height giv- echocardiographic evidence of aortic dilatation are
en the family background. These patients tend to be advised against pregnancy.‘43
the tallest in their families.
Scoliosis is often severe and the most disabling d) Ocular Manifestations
skeletal complication. It generally worsens rapidly An appearance of enophthalmos, especially in se-
during the adolescent growth spurt. An attempt has verely affected children, may be caused by reduced
been made to shorten this rapid growth to prevent or absent retrobulbar fat. Many patients present
progression of scoliosis and to reduce body height. with a facial “myopathic” appearance as a result of
In female patients, this reduction requires the ad- reduced subcutaneous fat, flat malar areas, hypo-
ministration of estrogen on a daily basis with pro- plastic facial muscles, and some degree of frontal
gesterone for 5 days each month to prevent dysfunc- bossing.
tional bleeding. I70 No conclusive data are available In the young age group, reduced visual acuity
yet to show whether this therapy is effective. Other often results from delayed and inadequate refrac-
forms of therapy, all having varied success, include tion with the inevitable development of amblyopia,
mechanical bracing with physical therapy and spi- which is often bilateral. Among the Marfan patients
nal fusion.15’ there is a much wider distribution of refractive pow-
Corrections of the deformity of the anterior tho- er, as well as a higher proportion of extreme refrac-
rax should be performed only if there is cardiopul- tive errors, than is found in the normal popula-
monary compromise. The age when the pectus ex- tion.“” Moderate-to-high myopia, however, is most
cavatum can be repaired and the long-term results frequently seen.
have not been established. The cornea1 diameter may be increased, giving
the appearance of megalocornea.“’ The iris mor-
c) Cardiovascular Manifestations
phology is often striking. The anterior iris surface is
The major cardiovascular complications of aortic commonly homogeneous with a decreased number
dilatation, dissecting aortic aneurysm, and “floppy of circumferential ridges, furrows, and crypts; thus
mitral valve” were first described clearly in 1943.4,“2 it has a smooth, velvety appearance.’ Iris transillu-
The vascular tissues mainly involved are those un- mination, more marked at its base, occurs in ap-
der high vasodynamic stress, such as the ascending proximately 10% of patients.“’ Commonly the pu-
aorta and the mitral valves. The aortic dilatation pil is miotic and difficult to dilate; occasionally, it is
usually begins at the base and may be progressive. eccentric.
This simulates the course seen in syphilitic The presence of angle abnormalities - bridging
aortitis.“’ pectinate strands, inconspicuous Schwalbe’s line,
The average life expectancy is halved in the Mar- and irregularity and fraying of the iris root - has
fan syndrome. In over 95% of the cases in which a been described by several investigators.‘7,‘88 These
cause of death can be established, a cardiovascular angle changes, however, are not pathognomonic of
problem is at fault. ‘2gAn echocardiogram should be the Marfan syndrome because they have been found
obtained annually. ‘43 If aortic dilatation is demon- in a variety of connective-tissue disorders,lg as well
strated, prophylactic propranolol is recommended as in the normal population. Gonioscopy will help
to reduce myocardial contractility in an attempt to demonstrate iridodonesis even if it is not appreciat-
stay progression of aortic dilatation and to prevent ed on slit lamp examination.
acute dissection of the aorta.‘43 Although the initial Ectopia lentis occurs in 50% to 80% of patients
trials of propranolol treatment were disappointing with the Marfan syndrome. 43.82.‘lS.l22 It is almost al_
(partly because they were begun too late in the aor- ways bilateral and symmetrical. Usually the
 148 Surv Ophthalmol 27(3) November-December 198;2 NELSON, MAUMENEE

amount of dislocation is stable from early child-

hood. In 193 Marfan patient eyes with ectopia len-
tis, progression was personally observed in 7.5%.1’s
The direction of dislocation is most commonly
superotemporal (Fig. 3). The lens may be dislocated
slightly backwards, as well as vertically and hori-
zontally. This leaves a gap between the pupillary
border and the anterior lens surface. In patients
with even marked dislocation of the lens, a numeri-
cally good zonular complement can often be ob-
served in the area of dislocation. This finding corre-
sponds to the surgical observation that the zonular
fibers do not break readily if a subluxed lens in a
Fig. 3. Superotemporal dislocation of the lens in a Marfan
Marfan patient has to be removed. Chemical stud- patient. Note the parallel alignment of the zonular fibers.
ies to date have shown no evidence of collagen in the
zonules.‘8’” The deficiency in collagen cross linking
demonstrated in the aorta of Marfan patients does
not help to explain lens dislocation in this disorder. hypoplasia of the dilator muscle.‘47v’50 The sparsely
Myopic changes and retinal detachments are the developed dilator muscle seems to account for the
two main retinal findings in Marfan patients. The poor dilatation of the pupil.
choroid may be thin with various degrees of scleral The zonules and ciliary epithelium may appear
crescents. Posterior staphylomata are uncommon in normal by light microscopy.‘47 However, on scan-
the Marfan patient. One patient with an anterior ning electron microscopy, widespread separation of
intercalary staphyloma required a scleral graft.‘O the zonular fibers into a fan offilaments with attenu-
Th e peripheral retinal changes include lattice ation towards the lens capsule has been demonstrat-
degeneration and retinal holes. In eyes with dis- ed. A second scanning electron microscopic evalua-
located lenses, retinal detachments have occurred tion showed abnormally large and grossly granular
both spontaneously and following intraocular capsular fibers and zonular fibrils.“5 However, the
surgery.3’,“3,g’ zonular fibrils maintained the normal parallel
Keratometric readings in a large series of Marfan orientation.
patients demonstrated flatter corneas than nor- Abnormalities of the chamber angle include pec-
ma1.“3,“5 The steepest cornea1 curve often corre- tinate ligaments, interpreted as incomplete separa-
sponds to the direction of the dislocation of the lens. tion of iris and trabecular meshwork and scarcity of
Marfan patients with dislocated lenses had much the circular fibers of the ciliary body. Anomalies in
flatter corneas than those without ectopia lentis. the outflow channel consist of changes in the config-
Also, patients who developed retinal detachments uration, size, and position of Schlemm’s canal.‘8*“‘~‘“0
showed a trend towards more marked flattening of The most striking feature of the Marfan syn-
the cornea.‘15 drome on many pathologic evaluations is the ex-
The mean axial length measurements for Marfan treme size of the globe.‘J’JgO Although there may be
patients without ectopia lentis was 23.39 mm and an extremely thin choroid and sclera, a staphyloma
for those with dislocation, 25.96 mm. The mean has not been demonstrated histopathologically. The
axial length of patients with a retinal detachment common finding of ocular enlargement in histolo-
was 28.47 mm, versus a mean of 24.90 mm for all pathologic cases is consistent with the clinical find-
Marfan patients with or without dislocation of the ings obtained by axial length measurements.“5
lens but without a retinal detachment. Finally, no
patient with a normal axial length developed a 2. Homocystinuria
spontaneous retinal detachment.“5
a) General Comments
Few histopathologic studies of the eyes of Marfan
patients have been reported.5’J’0~‘47J50 Hypopigmen- Homocystinuria is an inborn error of metabolism
tation of the posterior iris pigment epithelial layer of the sulfur-containing amino acids. Carson and
was first observed by Dvorak-Theobald5’ and was Neil1 first detected homocystinuria using urine
confirmed by Ramsey and co-workers.‘47 This his- chromatography in patients with ectopia lentis
topathological finding helps explain the clinical ob- while systematically searching for metabolic abnor-
servation of iris transillumination in the Marfan malities in mentally retarded institutionalized indi-
patient. I” The iris has been demonstrated histologi- viduals in Northern Ireland.25,27 Simultaneously and
cally to lack the usual circumferential ridges, fur- independently, Gerritsen and associates64l65 in
rows, and crypts and to have widespread patchy Madison, Wisconsin, found the same metabolic de-
 TABLE 4
Causes of Homoqystinuria

Cystathionine-B-synthetase deficiencyQ6
Pyridoxine responsive5l63
Pyridoxine unresponsivessl’34J67
N-5-methyltetrahydrofolate-homocysteine methyltransfer-
ase deiiciency84,‘06
N-5-lo-methyltetrahydrofolate reductase deficiency61,i68
Secondarv to treatment with 6-azauridiness

feet in an infant thought to have cerebral palsy.

The frequency of the condition is about 0.02 1% in
the mentally retarded, 0.17% in the mentally re- Fig. 4. Biochemical reactions in homocysteine metabo-
tarded with ocular abnormalities, and about 5% of lism. Several of the involved enzymes are indicated by
all cases with non traumatic dislocated lenses.17’j numbers: (1) methionine adenosyltransferase; (2) be-
While screening 41,800 well babies, one case of ho- taine-homocysteine methyltransferase; (3) N-5-methylte-
mocystinuria was detected.lg7 trahydrofolate-homocysteine methyltransferase; (4) N-5,
Homocystinuria is an autosomal recessive condi- lo-methylene tetra-hydrofolate reductase; (5) cystation-
tion. Like the Marfan syndrome, it is characterized ine-fi-synthetase (6)cystathionase. (Modified from
by skeletal, cardiovascular, and ocular abnormali- Spaeth GL: The usefulness of pyridoxine in the treatment
of homocystinuria: A review of postulated mechanisms of
ties. Mental retardation occurs in approximately
action and a new hypothesis. Birth Defects 12:347-354,
50% of cases and may be progressive. Homocystin-
1976).
uria with recurrent episodes of pyridoxine- and fo-
lit-acid responsive, “schizophrenic-like” behavior
was documented in a mildly retarded adolescent lar to that found in the blood of patients with homo-
girl. 6’ It is one of three hereditary systemic disorders cystinuria. ‘I8 Since this study, several reports have
associated with ectopia lentis that can be diagnosed confirmed the abnormally increased adhesiveness of
biochemically. (Hyperlysinemia and sulfate oxidase the platelets,6s35 whereas others have indicated the
deficiency are the others.) platelets to be normally adhesive.33~H0
Homocysteine is not normally detected in either Platelet kinetics in patients with homocystinuria
urine or plasma. Cystathionine-P-synthase delicien- have demonstrated discrepant results. Harker and
cy is the most common cause of homocystinuria. colleagues’” noted a decrease in platelet survival and
However, homocystinuria may be a manifestation an increase in platelet consumption using “‘Cr-
of several other enzyme deficiencies in the same platelets in four homocystinuric patients. By experi-
metabolic pathways (Table 4). The important bio- mental induction of homocystinuria in baboons, the
chemical pathways are illustrated in Figure 4. authors showed the formation of platelet thrombi on
The sodium-nitroprusside test is used to screen altered nonendothelialized vascular surfaces. The
for homocysteine in the urine. In the test, 5 ml of chronic injury to endothelium by homocystine
urine is mixed with 2 ml of 5% sodium cyanide. seems to have created the conditions for early
After 10 minutes, two to four drops of 5% sodium atherosclerotic lesions. Two subsequent studies
nitroprusside are added, which causes a bright red have found the platelet survival to be within normal
color in the presence of homocysteine or cystine. limits in patients with homocystinuria.“‘,‘*” Apart
Because the test will be positive in many conditions from such factors as genetic heterogeneity or differ-
in which sulfur-containing metabolites are excreted, ences in plasma homocysteine levels, the discrep-
such as cystinuria, urine chromatography or high- ancy in platelet survival time may be due to differ-
voltage electrophoresis is necessary for a definitive ences in methods of investigation.
diagnosis. The silver nitroprusside test is more spe- Homocystine has been demonstrated to acceler-
cific for homocysteine or cystine. ate clotting in vitro. ‘4g This was shown to occur
Thrombotic vascular occlusions constitute the through the activation of the Hageman factor,
main threat to survival in patients with homocystin- which has the capacity to initiate clotting. It was
uria. However, the pathophysiologic mechanism of suggested that perhaps the strategically localized
homocystinuric thrombotic tendency remains un- deposition of homocysteine in the intima of blood
settled. The platelets may be involved in the patho- vessels may be responsible for the unusual frequen-
genesis of this disorder. Increased platelet adhesive- cy of thrombosis in the homocystinuric patient.
ness was produced by adding homocystine to Finally, homocysteine may produce changes in
normal whole blood in vitro in concentrations simi- the arteries and other connective tissues by altering
150 Surv Ophthalmol 27( 3) November-December 1982 NELSON, MAUMENEE

the state of aggregation and the normal fibrillar secondary to hyperinsulinemia.85 It is postulated
structure of proteoglycan molecules.“’ The effect of that the pancreatic islet cell is sensitive to the hyper-
homocysteine on proteoglycan synthesis has been methionemia associated with homocystinuria and
considered to be an important factor in the initiation causes hypoglycemia by inducing hyperinsuline-
of arteriosclerotic lesions, but little evidence has mia. Finally, it is probably best to avoid drugs that
been accumulated to support this hypothesis. may predispose to a hypercoagulable state, such as
One treatment of homocystinuria to correct the oral contraceptives.‘54
metabolic defect has involved a low-methionine and
high-cystine diet, which has not been uniformly suc- b) Skeletal Manifestations
cessfu1.‘4~24~26~50~‘34 This diet has not only failed to nor- Excessive height and low ratio of upper segment
malize completely the abnormal biochemical lind- to lower segment are common skeletal findings in
ings, but it is difficult to prescribe (all eggs, meat the homocystinuric patient.16’ These findings are
and cow’s milk are forbidden).6 When this diet is similar to those of the Marfan syndrome. General-
prescribed to infants, failure to gain weight may be a ized osteoporosis with vertebral collapse, scoliosis,
serious complication.‘35 deformities of the anterior chest, and a modest de-
Another approach to therapy is the supplementa- gree of limitation ofjoint mobility are other skeletal
tion with coenzymes. Pyridoxine (vitamin B,) is the anomalies in homocystinuria.‘22 Many of the pa-
coenzyme necessary to activate the enzyme cystath- tients have a toes-out “Charlie Chaplin” gait.
ionine-P-synthase, which is the most common enzy-
matic deficiency in homocystinuric patients.“” Bar- c) Cardiovascular Manifestations
ber and Spaeth were the first to demonstrate that
certain homocystinuric patients respond biochemi- The etiology of cardiovascular disease in homo-
cally to oral pyridoxine by lowering plasma homo- cystinuria involves intimal and endothelial changes,
disruption of the elastic lamillae, and partial or
cysteine and methionine concentrations.5 Some au-
thors have confirmed the beneficial effect of complete obstruction of all-size vessels in various
pyridoxine,‘j2@ while others have not.63,‘26 Approxi- organs.26,67,g8J6’ Cardiac murmurs 7 cardiomegaly,
mately half of the cases seem to respond biochemi- and hypertension are often present. Fatal coronary
cally to pyridoxine. ‘74 The effect of pyridoxine fol- occlusion has occurred in several adolescents, with
lows a dose-response curve; some cases which are one described in an 1 l-year-old.23 Thrombosis in the
unresponsive at low doses will respond when given arteries is manifested by arterial bruits, loss of
up to 500 mg daily.6 It may be that some of the pulses, and ischemic symptoms. Acute gangrene of
unresponsive cases would respond to doses larger the leg requiring amputation occurred in an 18-
than those presently employed. year-old homocystinuric patient.58 Dilatation of the
In one of our patients, homocystinuria was de- aorta, which is commonly found in the Marfan syn-
tected at birth by the sodium-nitroprusside test, drome, is not a characteristic cardiac abnormality
with later proof by chromatography. She had the in patients with homocystinuria.
test performed at that time because two older sib-
d) Ocular Manifestations
lings had confirmed homocystinuria, one with a dis-
located lens in the anterior chamber requiring ex- Ectopia lentis is the ocular hallmark of homocys-
traction. At age 3 days, our patient was started on tinuria and can be detected in approximately 90%
pyridoxine. She is now 23 years old with normal of patients. 43~‘75The dislocation is bilateral and sym-
intelligence (recent college graduate), moderate metrical, with the lens usually migrating either infe-
myopia, and mild generalized osteoporosis. There riorly or inferonasally (Fig. 5). The lens in homocys-
has been no evidence of ectopia lentis or a previous tinuria is much more mobile than in the Marfan
thromboembolic episode. syndrome. This may be related to the clinical obser-
Because elevated homocysteine may cause vascu- vation of progressive irregularity of the zonular li-
lar injury with secondary platelet thromboemboli, a bers and the appearance of a fringe of white zonular
rational approach to prevent this phenomenon is remnants at the equator of the lens and on the sur-
necessary. In the homocystinuric patient who is un- face of the ciliary body.‘45J46
responsive to pyridoxine, the use of a combination of Ectopia lentis is an acquired and progressive ab-
antiplatelet utilization drugs, dipyridamole, and normality in this disorder. The earliest detection of
acetylsalicylic acid may provide protection against ectopia lentis was in a 3-year-old.‘22 It was not rec-
thrombus formation.76 ognized in another patient until 28 years of age.35
Anesthesia may present significant risks to the Myopia is common and may precede the detection
homocystinuric patient. ‘5~3g~‘5’ Besides the phenom- of ectopia lentis by several years.‘” The develop-
enon of frequent episodes of thromboemboli, the ment of progressive lenticular myopia is often the
homocystinuric patient may develop hypoglycemia first sign of a lens dislocation.
ECTOPIA LENTIS
Fig. 5. Inferior dislocation of the lens in a homocystinuric
patient. Note the absence of most zonular fibers.
The concentration of cystine, an amino acid, may
be low in the urine and plasma of homocystinuric
patients.‘74” Zonular fibers normally have a high
content of cystine.“” In homocystinuria, a delicien-
cy of cystine may affect normal zonular develop-
ment and consequently predispose to lens
dislocation.‘,“”
Although microphthalmos has been reported in
homocystinuria, no axial length measurements were
taken.‘,“” Most patients have blue irides. Aniridia
was reported in one case, in which the mother and
brother of the patient also had aniridia.‘38,‘3g Albin-
ism was described in seven patients, although a de-
tailed description was not provided.3
Retinal detachment is usually a complication of
lens surgery, although it may occur spontaneously.43
Optic atrophy has been observed, usually on the
basis of glaucoma. ‘38~‘75Reports on the changes in
the retinal vasculature are limited. Wilson and
Ruiz*“” described a &year-old boy with homocystin-
uria who developed acute glaucoma and later re-
vealed bilateral central retinal artery occlusions
with optic disc pallor. Another homocystinuric pa-
tient demonstrated sclerotic changes of a retinal ar-
tery that may well have represented a branch arteri-
al occlusion.‘**
Henkind and Ashton7g first reported histopatho-
logically the ocular findings in four eyes of three
homocystinuric patients. They found the zonular
fibers deficient adjacent to the lens. There zonules
had recoiled to the surface of the ciliary body and
were matted and retracted into a feltwork that fused
with a greatly thickened basement membrane of the
nonpigmented epithelium.
The greatly thickened basement membrane over-
lying the ciliary body in homocystinuria has subse-
quently been shown by electron microscopy to be
composed of degenerate zonular material.14* In ad-
151
dition, Ramsey and coworkers noted that the degree
of zonular abnormality was related to age;14” the
younger the patient, the more normal appearing
zonular fragments composed of oriented filaments
could be identified.
3. Weill-Marchesani Syndrome
a) General Comments
In 1932, Weill found, among eight cases with pre-
sumed Marfan syndrome, a patient who was short
in stature and had “short swollen lingers” with
limited range of motion.‘“” Seven years later, Mar-
chesani recognized the combination of short lingers
(brachydactyly) and microspherophakia as a syn-
drome.“’ The Weill-Marchesani syndrome is rarer
than either the Marfan syndrome or homocystin-
uria. Mental retardation is not a characteristic of
this disorder and no metabolic defect has been
found (Table 5).
Although the Weill-Marchesani syndrome is un-
equivocally familial, the precise hereditary pattern
remains unclear. Among parents and relatives, var-
ious features such as brachydactyly and short stat-
ure have been described, suggesting an autosomal
dominant mode of inheritance.‘02~‘4’~‘77 One family
with successive generations of presumed Weill-
Marchesani syndrome was reinvestigated by
McKusick and shown to represent a generally
short-statured family with simple autosomal domi-
nant ectopia lentis. “y~‘20~‘22The syndrome has also
been considered to be a recessive disorder with par-
tial expression in the heterozygote. The high rate of
consanguinity in this syndrome supports the latter
pattern of inheritance.48.‘24.‘04
6) Skeletal Man$estations
The skeletal features of the Weill-Marchesani pa-
tient are the antithesis of those found in the Marfan
patient. Weill-Marchesani patients are short, with a
large thorax and stubby spade-like hands with in-
creased subcutaneous tissue. The head is often bra-
chycephalic with a depressed nasal bridge. Many of
the patients have marked limitation of mobility
upon both active and passive motion of their lingers
and wrists. Seeleman described the fingers and toes
of a S-year-old boy as capable of only minimal flex-
ion.‘63 Generalized joint stiffness and reduced
mobility are also commonly observed in these
patients.“’
c) Ocular Manifestations
Although lenticular abnormalities may be absent
in the Marfan syndrome and homocystinuria, the
presence of microspherophakia is considered a pre-
requisite to the diagnosis of the Weill-Marchesani
152 Surv Ophthalmol 27(3) November-December 1982 NELSON, MAUMENEE

TABLE 5
Systemic Features a/ tke Marfan Syndrome,
Homocystinuria, and the Weill-Marckesani Syndrome

Weill-Marchesani
Marfan Syndrome Homocystinuria Syndrome

Inheritance Autosomal dominant Autosomal recessive Unsettled but probably

autosomal recessive

Skeletal Arachnodactyly Occasional Stocky build

arachnodactyly
Joint laxity Osteoporosis Short digits
Sternal deformity Sternal deformity Tight joints
Brachycephaly

Vascular Dilatation and/or Dilatation with None

dissection of thrombosis in
aorta. Aortic medium-sized arteries
and mitral valve and veins
disease
Mental retardation Absent Frequent Absent

Skin Striae distensae Malar flush None

Livedo reticulosis
Gait Normal “Charlie Chaplin” Normal
gait

syndrome (Fig. 6). g4 Microspherophakia however,
may occur as an isolated familial anomaly in either
an autosomal dominant or a recessive pattern.% It
has also been described in a pedigree of primordial
dwarfism with features unlike those of the Weill-
Marchesani syndrome. ‘*’ Microspherophakia has
been reported in association with such systemic syn-
dromes as the Marfan syndrome and homocystin-
uria,43 Alport’s syndrome,‘72 and Klinefelter’s
syndrome. ‘O
Microspherophakia is commonly present prior to
dislocation of the lens. ” It may be progressive and
responsible for the significant myopia that develops
in these patients. Jones described two children
whose myopia progressed by 7 and 15 diopters with-
in one year as the lens of each gradually assumed a
more spherical shape.”
The lens may maintain a central position with
identification of its equator following dilatation.
With time, subluxation of the lens develops, usually
in an inferior direction. In one series, the frequency
of ectopia lentis was approximately 84%; 18.2 years
was the mean age at diagnosis.g4 The zonules, which
frequently appear abnormally elongated and lax,
may contribute to the development of spherophakia
and ectopia lentis. 3’ However, there is no histologic
evidence to confirm this clinical observation. The
overall lenticular mass itself has been shown to be
reduced by approximately 25% .g4
The elongated zonules do permit the lens to move
forward, increasing its area of contact with the
iris.18’ The sequence of progressive shallowing of the
anterior chamber eventually results in pupillary-
block glaucoma. The observation, in which miotics
increase the pupillary block whereas mydriatics re-
lieve it, was referred to as “inverse glaucoma” by
Urbanek18’j and has since been confirmed by
others Il.83,95,165,198
Parasympathomimetic agents cause contraction
of the ciliary muscle and further loosening of the
zonules support. Cycloplegic agents, on the other
hand, relax the ciliary muscle, which results in
tightening of the zonular support and posterior
movement of the lens. If a miotic does not cause a
rise in pressure in the microspherophakic eye, then
it may be assumed that the lens is dislocated, with a
poor zonular complement.”
Feiler-Ofry and co-workers described a family
with abnormalities of the anterior chamber angles,
one of which had the Weill-Marchesani syn-
drome with glaucoma. 56These chamber angle anom-
alies, which include bridging pectinate strands, nu-
merous iris processes, fraying of the iris root, and
anomalous angle vessels, have been described in
other disorders of connective tissue and, therefore,
are not specific for this disorder.lg Other ocular ab-
normalities rarely reported in the Weill-Marchesani
syndrome include megalocornea,g7 eccentric pu-
pil,‘@ nonspecific chorioretinal degeneration’& and
scleral staphyloma.“’
4. Hyperlysinemia
Hyperlysinemia is a rare disorder due to an in-
born error of metabolism of the essential amino acid
lysine.202 The diagnosis is made by demonstration of
elevated plasma levels of lysine using paper chroma-
ECTOPIA LENTIS
Fig. 6. Microspherophakic lens following dilatation in a
Weill-Marchesani patient. Note the central position with
identification of the lens edge. (Courtesy of the Scheie Eye
Institute Library).
tographyt6* and is confirmed by either ion ex-
change’73 or spectrophotometric methods.47 Lysine-
ketoglutamate reductase, which converts lysine to
saccharopine, was found to be reduced considerably
in patients with hyperlysinemia.44 The role of lysine
metabolism in the extraocular muscles, zonules and
nervous tissue is incomplete. Therefore, the patho-
genesis of the associated anomalies in hyperlysin-
emia is unkncwn.
There are seven recorded cases of this metabolic
disorder with some clinical findings in common.
Four of the patients had profound mental retarda-
tion 2,66.17’and three had hypotonic muscles.661’7’
Consanguinity was commonly reported, suggesting
a recessive mode of inheritance.‘j6zi7’
Ocular abnormalities have been found in two pa-
tients with hyperlysinemia. One patient had bilater-
al subluxated lenses and lateral rectus muscle pare-
sis and another had bilateral spherophakia.17’
Neither patient had any systemic abnormalities,
which casts doubt on the possibility of a single gene
defect. Although more patients are needed to prove
that these ocular findings may be the result of the
same gene that causes hyperlysinemia, they should
be considered in the differential diagnosis of ectopia
lentis.
5. Sulfite Oxidase Deficiency
Sulfite oxidase deficiency is an extremely rare
metabolic disorder in sulfur metabolism that leads
to increased urinary excretion of S-sulfocysteine,
taurine, sulfite, and thiosulfate.g~8g~‘66
A deficiency of
sulfite oxidase activity, resulting in an inability to
convert sulfite to sulfate, has been considered re-
sponsible for abnormal urinary metabolites and an
inability to excrete inorganic sulfate.lz7 The meta-
bolic defect responsible for loss of enzyme activity
may be due to low hepatic levels of the molybdeum
153
cofactor.g5” A diagnosis may be made by finding an
increased urinary thiosulfate through quantitative
determination and the presence of S-sulfocysteine
by means of two-dimensional separation of urinary
amino acids.8g
The main clinical features of the three reported
cases of sulfite oxidase deficiency are the involve-
ment of the central nervous system and the develop-
ment of ectopia lentis. One patient was born with
neurological abnormalities including severe mental
retardation and seizures. The patient deteriorated
to a virtually decorticate state by 9 months.Hg Bi-
lateral ectopia lentis was discovered when the pa-
tient was 1 year old. Another patient demonstrated
similar neurologic abnormalities at birth, except
that ectopia lentis was noted at 3 weeks of age.’ The
third patient was normal until 18 months of age,
when the neurologic symptoms developed; ectopia
lentis was not diagnosed until the patient was 4
years old. Sulfite oxidase deficiency was demon-
strated in cultured skin fibroblasts from one patient
whose parents both had intermediate levels of en-
zyme activity. I’6 This observation indicates a genet-
ic basis of the disorder and suggests an autosomal
recessive inheritance pattern.
The progressive neurologic abnormalities in sul-
fite oxidase deficiency have been investigated. The
neuropathology of one patient demonstrated corti-
cal atrophy, which was most severe in the parietal
area.‘5A Histologic changes showed severe and wide-
spread loss of neurons, myelin, and axons, with sur-
rounding glial proliferation. When S-sulfocysteine
was injected into rat brain, neuronal degeneration
and swelling of dendritic processes were induced.“’
Although the mechanism of brain damage and ec-
topia lentis remains unknown, the association of
these two findings should alert the opthalmologist to
the possibility of this rare syndrome.
C. OCULAR DISORDERS WITH ECTOPIA
LENTIS
There are various ocular disorders that have been
reported to occur with ectopia lentis. The most com-
mon is ocular trauma, which was the cause of ectop-
ia lentis in 53% of cases in one series.g’ In other
series, the incidence of trauma resulting in a dis-
placed lens ranges from 22% to 56% .13’ Most of the
other associated ocular disorders are cited in indi-
vidual case reports, some of which lack adequate
clinical and laboratory information. These ocular
disorders include retinitis pigmentosa,7,72,74 persis-
tent pupillary membrane,37 aniridia,22,44” Rieger’s
syndrome,i01~1n5~‘78megalocornea,g2 and dominantly
inherited blepharoptosis, high myopia, and ectopia
lentis. We have observed ectopia lentis in several
patients with congenital glaucoma.
154 Surv Ophthalmol 27(3) November-December 1982 NELSON, MAUMENEE

D. SYSTEMIC DISORDERS WITH RARELY to escape. ‘I6 If this occurs, a phacolytic uveitis with
ASSOCIATED ECTOPIA LENTIS or without a secondary glaucoma may result, re-
quiring a cataract extraction.30*g0
Ectopia lentis has been associated with other sys-
Glaucoma is a common and often serious compli-
temic disorders. It was described in a Marfan-like
cation of ectopia lentis. The mechanism of glauco-
syndrome with hyaloideoretinal degeneration.36
ma in these eyes varies greatly. In post-traumatic
Syphilitics have been found to have dislocated
cases, glaucoma is frequently caused by a post con-
lenses, often with a history of trauma.7’,‘57a,‘70a
cussion deformity characterized by degeneration
Whether the treponemal infection or the trauma
and sclerosis of the ciliary body and trabeculae and
directly affects the zonules is not clear. Other sys-
recession of the iris root.‘57s20’ These pathologic lind-
temic diseases in which ectopia lentis has rarely
ings indicate that glaucoma is not caused directly by
been reported include Sturge-Weber syndrome,46,57
the displaced lens and that it would have occurred
mandibulofacial dysostosis,loO Ehlers-Danlos syn-
in these traumatized eyes even if the lens had not
drome,‘83*‘84 Crouzon’s syndrome,13’j Refsum’s syn-
dislocated. Glaucoma may result from outflow ob-
drome,* and scleroderma.‘55 We have observed ec-
struction by chronic inflammatory cells from a lens-
topia lentis in a patient with the Kniest syndrome.
induced uveitis,78 macrophages from a phacolytic
It seems unlikely that ectopia lentis would escape
glaucoma,2g~30 pigment particles released by trau-
detection in a majority of these conditions. In our 55
ma,4g or vitreous forced into the anterior chamber
patients with Ehlers-Danlos syndrome, and the 22
angle.32 Finally, it may occur from pupillary block,
with Crouzon’s syndrome, not one had a dislocated
as described in the Weill-Marchesani syndrome, or
lens. However, it would be advantageous to obtain
by dislocation of the lens into the anterior chamber.
dilated slit lamp examinations on more of these pa-
Iridectomy is often the treatment of choice; it can
tients to document the presence of a displaced lens.
prevent or cure the pupillary block glaucoma and
III. Complications simultaneously provide a clear optical area.
Although the lens in ectopia lentis may remain
The patient with ectopia lentis may be followed clear for many years, the gradual development of a
for many years without significant ocular problems. cataract is frequent. The lens opacity may be partial
However, ocular complications associated with dis- or complete with eventual morgagnian changes if it
placement of the lens are unfortunately frequent becomes totally dislocated posteriorly in the vitre-
and often serious. The associated abnormalities in- ous. Besides causing a visual disturbance, a hyper-
clude amblyopia, uveitis, glaucoma, cataract forma- mature cataract may also be responsible for phaco-
tion, and retinal detachment. lytic glaucoma.‘16
Ectopia lentis may cause visual symptoms that Retinal detachments are common and often dis-
vary in severity, depending on the position of the astrous complications in the eye with ectopia lentis.
lens. The lens may remain in its normal central They have been reported spontaneously in cases of
position, dislocated slightly backwards, with mini- congenital dislocation of the lens regardless of sur-
mal refractive error. Lenticular myopia may result ‘6,28,205
Jensen and Cross described retinal de-
gery.
from increased curvature of the lens because of re- tachments in the Marfan syndrome and homocys-
laxation of or poor complement of the zonules. A tinuria only in eyes with aphakia or ectopia lentis.g3
displaced lens may be tilted, causing a significant However, they found no significant difference in the
myopia and astigmatism which are difficult to cor- frequency of retinal detachment before or after lens
rect optically. Finally, if the lens is sufficiently surgery. Treatment of retinal detachment is often
displaced so that it occupies only a portion of the difficult because the dislocated lens may interfere
pupillary aperture, an aphakic correction will be with visualization of areas of degeneration or tears
necessary. These refractive errors in ectopia lentis responsible for the condition. Jarrett found that of
may play a role in the development of amblyo- 38 retinal detachments in a series of 166 cases of
pia. 6g,87Therefore, early and careful refraction is ectopia lentis, only 14 were successfully repaired.g’
necessary to avoid the occurrence of amblyopia.
Uveitis may occur in ectopia lentis by two differ-
IV. Management
ent mechanisms. Iridocyclitis, the most common
complication in one series of displaced lenses, may Ectopia lentis continues to be a perplexing man-
be due to contact irritation of the ciliary body or agement problem for the ophthalmologist. Empha-
iris.13’ This type of uveitis is often acute, temporary, sis should be directed toward improvement of vision
and recurrent and is usually responsive to topical and the preservation of the globe through preven-
steroids. A posterior dislocation is usually well toler- tion or amelioration of complications. Trauma may
ated for years, provided the lens capsule does not precede the migration of a previously subluxated
become permeable or rupture, allowing lens protein lens into the anterior chamber or vitreous. These
ECTOPIA LENTIS 155

patients more commonly have retinal detachments may lead to both intraoperative and postoperative
following trauma. Therefore, they should be ad- complications. Some authors feel that the mere
vised against participation in contact sports.4’ presence of a subluxated lens is reason to remove it,R
The patient with ectopia lentis may have one of whereas others feel that specific indications are
the hereditary disorders with potentially serious necessary. 20~3’.75.88a,“5 These indications for lens sur-
systemic abnormalities. Hence it is mandatory for gery would include: (1) the presence of a lens in the
the ophthalmologist to refer all these patients to the anterior chamber, especially with lens touch of the
appropriate pediatric or medical consultant for cornea1 endothelium; (2) a lens opacity that is ma-
evaluation. If one of the hereditary disorders is dis- ture or hypermature; (3) evidence of lens-induced
covered, then the family must be counseled about uveitis; (4) an inadequate visual acuity that is un-
the risks ofhaving subsequent affected children. It is correctable by refraction and iris manipulation; (5)
important that all relatives at risk be identified and imminent complete luxation of the lens.
have a thorough examination. The surgical techniques for the removal of a dislo-
Early diagnosis of ectopia lentis, with the proper cated lens are numerous and there is much disagree-
optical correction either through a phakic or aphak- ment about which procedure is the most desirable.
ic zone of the pupillary area, may decrease the inci- In one method, a double-pronged needle is passed
dence of amblyopia. If the edge of the subluxated through the pars plana to trap and support the dis-
lens crosses the pupil, a patient may use the aphakic located lens.” The lens is then removed with cap-
part for distance and the phakic for near vision. sule forceps or an erysiphake. This procedure in-
Manipulation of the iris may be necessary to create volves much manipulation and may be traumatic to
a larger area for an aphakic correction. A mydriatic the eye; it can no longer be recommended.
instilled at regular intervals may improve the vision Open sky vitrectomy with successful cryoextrac-
and also test whether a surgical or laser manipula- tion of 22 dislocated lenses has been reported.‘” In-
tion of the iris is worthwhile. If chronic mydriasis is cluded in the series were patients with the Marfan
difficult, as in the Marfan patient with a hypoplastic syndrome, homocystinuria and simple ectopia len-
iris dilator muscle, then an optical iridectomy may tis. In 21 cases, the dislocated lenses were removed
increase the aphakic pupillary space adequately.‘% intracapsularly. In the other case, the lens nucleus
Straatsma and associates’*’ have used photocoag- had been dislocated in a previous operation and
ulation of the iris to provide a larger pupillary open- secondary glaucoma had developed. The authors
ing. We have also successfully used the argon laser. state that all patients had “useful vision” postopera-
However, a longterm follow-up of these patients is tively. A longterm follow-up of these patients is
necessary to determine whether this method of cre- needed.
ating a larger pupillary opening is satisfactory. Jensen and Cross reported the results of surgery
The treatment of glaucoma in ectopia lentis de- on 115 patients with the Marfan syndrome and 42
pends on the type of glaucoma present. In pupillary patients with homocystinuria.“3 Surgical techniques
block due to microspherophakia, peripheral iridec- included discission, aspiration and intra- or extra-
tomy has been suggested as the safest procedure.3’ capsular extraction. Vitreous loss occurred in 30%
However, surgical complications are common with of patients with either syndrome. In the Marfan
frequent vitreous loss because of the lack of protec- patients, 25% of the eyes subsequently developed
tion of the vitreous face by the lens periphery. Laser retinal detachment, while this complication oc-
iridectomy, preferably performed prior to the devel- curred in 11% of homocystinuric patients. Sixty-
opment of glaucoma, has been proposed as a safer eight percent of the Marfan patients and 54% of
treatment.‘“” This may be combined with thymoxa- the homocystinuric patients benefited from lens
mine,15” a specific alpha-adrenergic blocking surgery.
agent. lg4 Thymoxamine causes miosis with little or In a longterm studyla6” of 46 eyes with ectopia
no effect on ciliary muscle,73 depth of the anterior lentis that underwent surgery, intracapsular extrac-
chamber,lR2 or facility of outflow.‘g3 Finally, a lens in tion was performed in 3 1 cases (69.5%). The indica-
the anterior chamber should be vigorously treated tion for surgery was poor visual acuity with best
initially with cycloplegic and mydriatic agents that optical correction. Diagnoses in these patients in-
may relieve the pupillary block and allow the lens to cluded simple ectopia lentis, Marfan syndrome or
fall back behind the iris,5’a,77,206Massage on the cor- homocystinuria (one patient only). An improve-
nea through a closed lid may help the lens return to ment in visual acuity as tested five years postopera-
its original position. These maneuvers should be tively ranged from 38.6% in Marfan patients to
attempted prior to surgical intervention, especially 50% of the simple ectopia lentis patients. Complica-
in patients with homocystinuria who are at in- tions, including retinal detachment and glaucoma,
creased risk with general anesthesia. occurred in 64% of the Marfan patients and in 10%
Lens surgery in ectopia lentis can be difficult and of patients with simple ectopia lentis.
 156 Surv Ophthalmol 27(3) November-December 1982 NELSON, MAUMENEE

Discission and aspiration has been associated tis or even phacolytic glaucoma. Examination of the
with a low incidence of complications.“4J60 In one anterior chamber aqueous for macrophages can
series ofeight patients with ectopia lentis, the preop- help clarify the diagnosis where questionable. To-
erative visual acuities ranged from 20140 to 201 tally dislocated, leaking lenses should be removed
200.‘14 Postoperatively, the visual acuities ranged after the intraocular pressure is lowered and the eye
from 20125 to 20170. In three of the four eyes in is quieted with topical steroids. Using the open sky
which lens aspiration was performed because of ele- method, the lens can be extracted with a cryoprobe
vated pressure, the intraocular pressure was con- or with a vitreous cutting instrument after the ante-
trolled postoperatively without medication. Howev- rior vitreous has been removed with a vitreous cut-
er, two of the four eyes required repeated discission. ting device.
Three of the nine eyes operated for reduced visual
acuity required a subsequent single discission. No V. Summary
significant intraoperative or postoperative compli-
Ectopia lentis is an ocular disorder with diverse
cations occurred in this small series, but a longterm
etiologies. Each affected individual should have: (1)
follow-up is needed.
a thorough family history that includes whether car-
With the availability of automated vitrectomy in-
diovascular, skeletal, or ocular abnormalities exist
struments, vitreous loss and its sequelae can be
in other family members; (2) a complete ophthal-
avoided. Peyman and coworkers reported on 32 eyes
mologic evaluation of both eyes; (3) an ophthal-
with ectopia lentis surgically managed with the vi-
mologic evaluation of other family members; and
trophage. ‘37These patients were followed for a peri-
(4) a pediatric or medical consultation to determine
od ranging from 5 to 45 months. In 12 cases caused
whether ectopia lentis is an isolated finding or part
by trauma, good surgical results were obtained in 10
of a hereditary systemic disorder.
eyes. Except for minimal intraocular bleeding and
The prognosis for vision varies with the type and
transient cornea1 edema, there were no significant
degree of dislocation and the possible presence of
operative complications in the traumatic cases.
ocular complications. Therefore, emphasis needs to
Those eyes with phacolytic glaucoma returned to
be directed toward early diagnosis and appropriate
normal intraocular pressure following lensectomy
ocular rehabilitation.
and vitrectomy. In one case, a lens with a hard
nucleus and dislocation into the vitreous, was suc-
Acknowledgment
cessfully removed through a clear cornea1 incision
while the vitrophage tip was maintained in the vitre- Joseph H. Calhoun, M.D., reviewed the manuscript
ous through a sclerotomy. In this case, no signifi- and provided helpful suggestions.
cant adverse changes were noted in the late follow-
up period. References
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