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patients but are still included in this section to report
the range of eye alterations that have been found in OI.
Some of these findings are more common and benign,
such as refractive errors (myopia, hyperopia and astig-
matism) that may be corrected with glasses or contact
lenses. Other findings are more serious and may lead to
permanent visual loss if untreated, including glaucoma
and retinal detachment. More population-based studies
are required to fully understand how frequently these
findings occur among the OI population and the differ-
ent types of OI.
abnormalities - also had optic nerve hypoplasia. Using
light and electron microscopy, Kasner, Mietz and Green
observed agenesis of Bowman's layer in the cornea of
an autopsy eye for an 18-year-old patient with OI type
III;
12,13
this cornea had a thickened epithelial basement
membrane (55-60 nm), an anterior stroma with slightly
irregular and disorganized lamellae, more regular deep
lamellae and collagen fibers with uniform thickness
in the anterior and mid stroma. The Descemet's mem-
brane was mildly thickened and the collagen fibers were
reduced in diameter compared to controls. Blue sclera
was associated with moderate thinning, especially at the
globe equator. Corneal stromal fibers were 25% narrower
and scleral stromal fibers were 50% narrower than those
of controls for this OI type III patient. Prominent elastic
fibers (normally only small in number) were also present
in the sclera of this OI type III eye.
12,13
Historical Ocular Histology Studies in OI
Various histopathology studies of eyes from patients
with OI have demonstrated a range of impact that OI
can have on the eye. Ruedemann reported one of the first
clinicopathologic studies of OI congenita and blue sclera
in 1953, describing three cases of OI with thin fibrous
coats, a deficiency of collagen bundles and fewer fibers
in a looser framework than normal in light microscopic
studies of the cornea and sclera.
7
Manchot et al. found
profoundly blue sclera on a neonatal case of OI (likely
type II) along with (1) an approximately 50% reduction
in corneal thickness compared with an age-matched con-
trol; (2) an approximately 33% reduction in scleral thick-
ness compared with an age-matched control and (3) a
marked excavation of the optic nerve head cup believed
to be from abnormal development of the lamina cribosa.
8
Haebara et al. studied one OI eye with electron micros-
copy and found the corneal and scleral collagen fibers
were more uniform and slender with a reduced cross
striation periodicity and diameter compared to those
of controls. These investigators suggested the collagen
identified was pathologically immature.
9
Blümcke et al.
examined the cornea of an infant OI eye with electron
microscopy and found a 30% reduction in diameter of
collagen fibers in the corneal mid stroma with rare cross
striations and some more densely packed fibers; they
also determined by biochemistry that a disorder of tropo-
collagen synthesis or extracellular collagen aggregation
or both were present.
10
Chan et al. determined by elec-
tron and light microscopy in four cases of OI congenita
(likely OI type II) that there was about a 25% reduction
in corneal collagen fiber diameter and more than 50%
reduction in scleral collagen fiber diameter compared
with those of controls; in these eyes, the collagen fibers
were more characteristic of immature collagen fibers and
the episcleral fibers had more uniformity and a smaller
range of differences in diameter and periodicity com-
pared to those of controls.
11
They hypothesized that these
scleral features contributed to increased transparency of
the sclera and to the blue scleral hue seen in many OI
patients.
11
One of their cases - a stillborn male with blue
sclerae, numerous fractures and multiple other systemic
Major Cornea Findings in OI
Corneal Thinning
Corneal thinning is a common finding in OI patients.
Histopathology reports have found reduced corneal
thickness up to 50% of normal.
8
Pedersen and Bramsen
reported a 15% reduction in average corneal thickness
in OI patients compared to controls (OI mean corneal
thickness of 0.443 ± 0.003 (SEM) mm compared to a
normal mean corneal thickness of 0.522 ± 0.004 mm).
14
Evereklioglu et al. further reported that the lower central
corneal thickness (CCT) in OI correlated with the pres-
ence of blue sclera.
15
Dimasi et al. have isolated genetic
loci for CCT based on candidate gene analysis of OI
genes with implications for glaucoma because of the
potential for progression of glaucoma with thin CCT.
16
Keratoconus
Keratoconus is a bilateral ectatic disorder with central
or paracentral corneal thinning that results in protrusion
of the central cornea with a cone-like configuration. The
profound astigmatism and refractive error caused by this
condition leads to distorted vision. The condition may be
corrected by contact lenses if mild. When more severe,
more advanced corneal procedures are required to
improve the refractive properties of the cornea including
INTACS rings (intrastromal corneal rings) and partial or
full thickness corneal transplants. In some patients with
keratoconus, the Descemet's membrane may also spon-
taneously rupture, leading to abnormal hydration and
clouding of the cornea, a condition called hydrops, with
further loss of vision. Iron rings and corneal scarring
may develop. Beckh et al. reported one family was found
with OI tarda with five of six OI members having both
keratoconus and OI; one patient with blue sclera also
required cornea transplantation after corneal infection
