During the first 9 to 10 months of a monkey’s life, a period that
is equivalent to the rapid infantile phase of ocular growth in human
infants,
25 choroidal thickness increases at a slow but
steady rate. Early during this period, the eyes of most normal monkeys
also reach and then maintain the ideal refractive state, a low degree
of hyperopia.
17 18 25 The absence of a clear
relationship between choroidal thickness and
refractiveerror in normal/control monkeys suggests that these
ideal ametropias have relatively little influence on choroidal
thickness. The slow increase in choroidal thickness throughout early
development presumably reflects normal maturation. Obviously, the
increase cannot be accounted for by stretching as a result of normal
ocular elongation. Measures of choroidal thickness in adult subjects
(Hung L-F, unpublished data, 1999) suggest that the monkey
choroid continues to increase in thickness until approximately 1.5
years, approximately the age at which axial growth normally begins to
asymptote.
The main result of this study is that during this early period of
monkey ocular development, choroidal thickness is highly sensitive to
abnormal refractive errors and optical defocus. Our most compelling
evidence comes from the observation that an abrupt change in the eye’s
effective refractive status causes rapid alterations in choroidal
thickness, which, under a variety of rearing conditions, are
consistently in the appropriate direction to reduce the eye’s
ametropia. Experimental manipulations that impose myopic defocus (e.g.,
putting on a positive lens or removing a diffuser from an eye with
form-deprivation myopia) produce a rapid and in some cases a dramatic
increase in choroidal thickness. In contrast, manipulations that cause
the eye to suddenly experience hyperopic defocus decrease choroidal
thickness and reduce the normal rate of choroidal thickening. These
observations arguably provide the strongest evidence to date that the
primate eye, like the chicken eye,
26 can identify the sign
of optical defocus or at the least discriminate between hyperopic and
myopic refractive states.
The interocular and intersubject differences in choroidal thickness
measured at the end of the treatment period also demonstrate that the
nature of the retinal image influences choroidal thickness. It could be
argued that these alterations in choroidal thickness represent passive
changes associated with overall changes in eye size. For example, at
the end of the form deprivation period, the choroids in eyes with axial
myopia were thinner than those in their fellow nontreated eyes, but the
eyes were larger. Similarly, at the end of a period of negative lens
wear, axially myopic eyes had thinner choroids than hyperopic eyes that
had been viewing through positive lenses. If the volume of the choroid
remained constant, an increase in eye size, specifically in retinal
area, would lead to a reduction in choroidal thickness and vice versa.
Although a contribution from such passive factors cannot be ruled out,
the rapid compensating choroidal changes after lens removal argues for
vision-dependent modulation of choroidal thickness. It should also be
kept in mind that for almost every monkey, the stimulus for altered
ocular growth existed throughout the treatment period.
If the eye’s refractive state influences choroidal thickness, it would
be expected that a chronic refractive error would maintain the choroid
in an altered state. In the case of the lens-reared monkeys, our most
common treatment strategy involved sequential increases in lens power
that were intended to maintain a relatively constant stimulus to the
eye’s emmetropization mechanism. Observations from such monkeys and
from those that did not fully recover from induced anisometropia
indicate that the eye’s effective focus can influence choroidal
thickness for a long time. For example, eyes that do not fully recover
from induced myopia exhibit persistently thicker choroids, a result
that is in the direction opposite that which would be predicted on the
basis of eye size alone.
The vision-dependent choroidal thickness changes that occur in young
monkeys are qualitatively similar to those observed previously in young
chicks.
11 12 In both chicks and monkeys, form deprivation
and hyperopic defocus promote choroidal thinning, myopic defocus
promotes an increase in choroidal thickening, and anisometropia
produces interocular differences in choroidal thickness. These
compensating changes in thickness occur very quickly. In young chicks,
significant choroidal changes can be observed within
hours
15 27 of the onset of form deprivation, with the
maximal effects occurring within 7 days.
12 We found
evidence of thickness changes in monkeys at the first measurement
session after an abrupt anisometropic change in refractive error (after
4–7 days). As in the chick, changes in the monkey’s choroid can
persist for an extended period if the stimulus for a compensating
refractive change is maintained.
12 And finally, in both
chicks and monkeys, the changes in choroidal thickness precede any
significant vision-dependent changes in overall eye
size.
11 12 15
There are, however, substantial quantitative differences in the
vision-dependent changes in choroidal thickness between chicks and
monkeys. The largest choroidal thickness changes in the monkey were on
the order of 40 to 50 μm, which for a typical infant would produce
less than a 0.50-D change in refractive error. These thickness changes
are comparable in magnitude with those observed in tree
shrews
13 and marmosets
20 but are much smaller
than in the chick, in which the choroidal thickness changes encompass a
range of approximately 400 μm and can alter the eye’s refractive
error by almost 10 D.
12 Although the lower dioptric
contribution of the choroid in monkeys can be attributed in small part
to the fact that infant monkeys have larger eyes than young chicks,
this interspecies difference appears primarily to reflect differences
in the anatomy of the choroid. In the chick, vision-dependent changes
in choroidal thickness reflect size changes in the conspicuous lacunae
that are concentrated in the suprachoroidal space.
11 27 These lacunae and smaller vessels in the choriocapillaris, which appear
to be lymphatic vessels,
28 29 30 dilate in response to
myopic defocus, presumably as a result of fluid accumulation. Choroidal
thinning is associated with compression of these vessels. The monkey
choroid also contains lymphatic capillaries, and the suprachoroid is
organized into flat sinuslike spaces that appear to be analogous to the
large lymphatic lacunae in the chicken’s eye.
31 32 33 However, these lymphatic structures occupy a smaller proportion of the
choroid in the monkey and may cause the choroid to be thinner in
monkeys (approximately 170 μm at age 3 months) than in chicks
(approximately 250 μm at age 5 days).
12 Moreover, the
suprachoroid of monkeys is organized into a reticulum by
interdigitating laminae that stain positively for smooth muscleα
-actin.
33 This regular architecture and its likely
contractile nature could limit the degree to which the choroid in
monkeys can thicken.
The way in which the eye’s refractive state influences choroidal
thickness is not understood. That local choroidal expansion occurs in
the chick during the recovery from form deprivation that is restricted
to only a portion of the retina
11 suggests that visual
information is communicated to the adjacent choroid from localized
retinal mechanisms.
34 These choroidal changes could be
mediated through local molecular and/or neural actions. Changes in
choroidal retinoic acid synthesis,
35 ion
36 and protein concentrations,
37 proteoglycan
synthesis,
11 15 and/or blood flow
38 39 during
and after form deprivation may provide the osmotic drive for fluid
accumulation. Histologic observations suggest that during the recovery
from form-deprivation myopia there is a massive movement of fluid
across the retina into the choroid
27 and an increase in
active fluid transfer within the choroidal lymphatic
system.
40 In addition, both the chick and primate choroids
contain nonvascular contractile cells,
33 41 42 and it has
been suggested recently that in primates intrinsic choroidal ganglia
could mediate some local choroidal responses through innervation to
smooth muscle cells.
33 However, because disrupting
information flow through the optic nerve prevents choroidal thinning in
response to hyperopic defocus,
12 extraocular factors may
also influence vision-dependent changes in choroidal
thickness.
11 12 The central nervous system is known to
innervate the choroid from a variety of sources.
43
Regardless of how visual experience influences choroidal thickness, it
appears that as in the chick, changes in choroidal thickness are
intimately involved in the visual regulation of refractive development
in monkeys. That choroidal thickness is modulated by visual experience
in such diverse species as the chicken,
11 12 tree
shrew,
13 marmoset,
20 and monkey suggests that
the same phenomenon may occur in humans. We propose that, at least
early in life, choroidal thickness in humans is also influenced by
factors associated with the eye’s effective refractive state. If this
proves to be the case, the choroid may participate in the regulation of
the refractive state of the human eye.