what-when-how
In Depth Tutorials and Information
OI type II, a transition from blue sclera at birth that pro-
gressively becomes normal with age in OI type III and
normal to gray sclerae in OI type IV. More recent other
genetic mutations leading to OI have included normal
sclerae in OI types V, VIII, XII and XIV; normal to blue or
gray sclerae in OI type VI; normal to light blue sclerae in
OI types VII, XI and XIII; and blue sclerae in OI types IX
and X. Sillence et al. also reported on the natural history
of blue sclerae in OI.
39
Blue sclerae in OI does have correlations with other
features of the eye that may be important for assessing
risk for other problems that may occur. For instance,
Evereklioglu et al. reported that blue sclera correlated
with corneal thinning in OI eyes.
15
As thin corneas have
been identified as a risk factor in glaucoma and its pro-
gression, OI patients are thought by many glaucoma
specialists in ophthalmology to be at increased risk for
glaucoma progression. Kaiser-Kupfer et al. have reported
that blue sclerae correlated with decreased ocular rigid-
ity.
40,41
Decreased ocular rigidity in OI eyes may put such
eyes at higher risk for retinal detachment or scleral rup-
ture if exposed to trauma.
population-based studies worldwide, and there is a
much higher prevalence in the Hispanic population and
those of West African ancestry (Baltimore Eye Survey,
Lales, Proyecto VER).
There is some evidence that suggests thinner corneas
increase risk of open angle glaucoma,
43,44
and therefore
persons with OI may be at higher risk of glaucoma dam-
age than those with corneal thicknesses that are in the
normal range. Similarly, structural abnormalities of the
lamina cribosa in persons with OI may increase risk for
glaucoma in some cases. An altered uveoscleral outflow
pathway in OI may also put OI eyes at risk for glaucoma.
Smolinska et al. described an OI patient with bilateral
glaucoma along with a central retinal vein occlusion in
one eye.
45
Superti-Furga et al. described a family with OI
(likely type IV) due to a defect in
COL1A2
in which one
affected family member had glaucoma in one eye, but no
further details of the ocular history, optic nerve examina-
tion or visual field were provided.
30
Rosbach described
another patient with OI and glaucoma who required sur-
gical intervention with trabeculectomy and drew atten-
tion to surgical issues for OI eyes.
46
There is also evidence that some genetic mutations in
OI may be more strongly associated with glaucoma and
its progression. In 2012, the Duke University Eye Center
glaucoma department identified families with mem-
bers affected by OI and primary open angle glaucoma
(POAG). One multiplex family had multiple members
with both POAG and OI type I while other members
were free of either disease. The pedigree of this family
is shown in
Figure 31.2
. Two sisters demonstrated sig-
nificant features of POAG including glaucomatous optic
nerve head cupping and peripheral visual field loss, with
representative photos shown in
Figure 31.3
. One was
controlled on eye drops alone but the other required tra-
becular meshwork laser treatment due to intolerance of
eye drops. Genomic DNA sequencing of
COL1A1
and
COL1A2
revealed a single nucleotide insertion in exon 6
of
COL1A1
(c.540_541insC). This mutation caused a shift
in the reading frame that would produce a premature ter-
mination codon in exon 8. This mutation was predicted to
cause mRNA instability and was present in both sisters.
Another sporadic patient had both OI type I and
POAG affecting both eyes. This patient had advanced
glaucomatous optic nerve cupping in one eye that
required surgical intervention. Genomic DNA sequenc-
ing of
COL1A1
and
COL1A2
identified a
COL1A1
accep-
tor splice site mutation (c.2452-2A>T or IVS36-2A>T)
in intron 36. Analysis of the effect of the mutation on
splice outcome in cultured dermal fibroblasts identified
three splicing products, two of which were very unstable
and resulted in a very small amount of stable mRNA.
The first transcript used a cryptic acceptor 58-56nt
upstream from the constitutive site. This caused inclu-
sion of the last 55nt of intron 36 in the mRNA, producing
Scleral Rupture
Pirouzian reported three cases of OI patients between
4 and 15 years old with traumatic and spontaneous
scleral rupture and uveal prolapse, all thought due to
scleral fragility in OI, with none of the patients aware of
the need for eyewear protection.
42
This case series high-
lighted the potential increased risk that OI eyes may
have for scleral openings and severe loss of vision with
trauma and advocated safety eye protection as a precau-
tion for OI patients.
Glaucoma and OI
Some OI eyes may be at increased risk for glaucoma.
In glaucoma, eyes develop progressive decline in the
visual field that results from progressive loss of retinal
ganglion cells and their axons within the optic nerve.
Elevated intraocular pressure (IOP) is a major risk fac-
tor for glaucoma, although many patients with the dis-
ease have no documented elevation in IOP. Reducing
IOP is the only currently available effective treatment
for glaucoma. There are many types and causes for
glaucoma. Glaucoma is often specified as either open or
closed angle form and then subdivided into primary or
secondary types. Treatment is focused on reducing IOP.
Treatment options include topical or oral medications,
laser therapy (various types) and surgical approaches
such as trabeculectomy or glaucoma implant therapy
that reduce IOP by diverting aqueous humor around
the trabecular meshwork to locations outside of the eye.
The prevalence of glaucoma among Caucasian popu-
lations over 40 years of age is between 1.1 and 2.1% in
