Familial corneal patterns in pellucid
marginal degeneration: uncovering
a possible etiology
Hajirah N. Saeed, MD
• Last year: a case report of a possible hereditary
component in PMD
• Since then, we developed a protocol to
prospectively study the clinical signs, disease
progression, and possible hereditary patterns of
PMD in patients and their family members.
– The purpose of this study is to assess tomographic and
topographic signs of PMD in patients with an
established diagnosis of PMD as well as their family
members, and to investigate the possible genetic
origins of PMD via whole exome sequencing (WES).
• Five patients with a diagnosis of PMD as well as
their first-degree relatives underwent Pentacam
imaging.
• A total of 16 participants were included in this
study.
• Pentacam imaging was evaluated for
abnormalities using the Belin-Ambrosio
enhanced ectasia display.
• Blood was analyzed via WES.
• Other variables that were assessed included
history of allergies and eye rubbing
• Two of the five families had members other than the proband who
demonstrated abnormal imaging.
• One family had members that demonstrated clinical signs of disease
requiring surgical or other intervention.
• Four of the five probands had a history of vigorous eye rubbing.
• Three out of five had environmental allergies.
• Four of the five families that participated had a member with a
developmental disability.
• WES revealed genetic variations including insertions, deletions, and
single nucleotides polymorphisms in between those who
phenotypically displayed symptoms of PMD and those who did not.
– In our autosomal recessive family, a candidate gene was C1orf116,
which encodes a putative androgen-specific receptor and found to be
involved in keratoconus phenotype in mice
Pentacam scans of a normal participant utilizing the Belin-Ambrosio ectasia
display. Maps on the top of the figure for either eye are baseline elevation maps,
middle maps are exclusion maps, and the bottom maps are difference maps
depicting the change in elevation between the baseline and exclusion maps. This
scan shows no significant change in elevation (green). Pachymetric maps are not
shown.
A and B depict abnormal Pentacam imaging in the right and left eyes, respectively, in a
participant with known, clinically manifest PMD. The bottom difference maps show
significant elevation difference (ED) on the posterior corneal (K) surface of the right eye
(red and yellow) and both anterior and posterior K surfaces in the left eye.
C and D depict abnormal Pentacam imaging in a 1st degree relative of participant
A/B, suggesting subclinical disease. Difference maps show borderline ED on the
anterior K surface of the right eye (yellow only) and significant ED on the anterior
corneal surface of the left eye (red and yellow) along with borderline changes on
the posterior K surface of the left eye (yellow only). Participant C/D is
asymptomatic
Example of PMD on topography with
crab claw pattern and inferior thinning
Family pedigrees. Arrows indicate probands; red indicates clinical
signs of disease and abnormal Pentacam imaging; yellow indicates
no clinical signs of disease but abnormal Pentacam imaging.
Questions marks indicate that that family member was unable to
be tested with the Pentacam.
• This study illustrates a possible hereditary component
to PMD and warrants further investigation.
Environmental influences as allergies and eye rubbing
may be significant variables in PMD. WES of DNA from
probands and their family members suggests a genetic
component to PMD.
• The incidence of developmental disabilities in the
family members of patients with PMD is a new finding.
In continuing to sequence DNA we hope to determine
what link, if any, exists between PMD and certain
developmental abnormalities.