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Chasing the suspect:
keratoconus
Stephen D Klyce
The detection of keratoconus is a major
concern in the screening of refractive
surgical patients, since it is known that
its presence weakens the corneal stroma
and can lead to iatrogenic ectasia. While
clinical keratoconus is reliably detected
with corneal topography and slit-lamp
examination, means to detect the possi-
bility of keratoconus in its earliest stages
prior to the presence of slit-lamp findings
have been extensively explored, and it is
generally agreed that the first detectable
sign of keratoconus is a localised steepen-
ing seen with Placido corneal topography.
Several terms have been put forward to
describe this condition including preclini-
cal keratoconus, keratoconus suspect and
forme fruste keratoconus. While these
designations have been used interchange-
ably, doing so has led to problems in
understanding the natural history of
keratoconus.
Despite this short-coming, excellent
longitudinal studies are being conducted
and are slowly emerging in the literature.
In the June issue, Shirayama-Suzuki and
colleagues1 examined keratoconus pro-
gression in the fellow eye in unilateral
keratoconus patients over the course of
6 years. The fellow eyes were included if
they had no slit-lamp signs of keratoconus
or deterioration of spectacle-corrected
visual acuity. The authors found that just
over 20% of the fellow eyes progressed to
clinical keratoconus with evidence of
increased asymmetry, spherical equivalent
and higher-order irregularities, which they
documented with topographic indices and
Fourier analysis. As they note, keratoco-
nus is a slowly progressing disease, and
therefore it is likely that a longer follow-
up would result in more of their cohort
progressing to clinical keratoconus.
This study provides a better under-
standing of the natural history of this
progressive disease, for which expression
varies between patients as well as
between the eyes of the same patient.
Fortunately, only a minority of eyes of
keratoconus patients progress to the point
that requires corneal transplantation. And
Correspondence to: Dr Stephen D Klyce, Department
of Ophthalmology, Mt Sinai School of Medicine, New
York, NY 10029, USA; sklyce@klyce.com
Br J Ophthalmol July 2009 Vol 93 No 7
even these eyes may be arrested in their
ectasia progression before functional
vision is lost with UV-activated collagen
crosslinking after riboflavin treatment;
this exciting development2 is under
intense clinical investigation worldwide.
The Shirayama-Suzuki paper under-
scores the fact that keratoconus, with its
genetic underpinnings, expresses itself in a
variable fashion. The progressive thinning
and ectasia can be exacerbated by factors
such as eye rubbing and corneal refractive
surgery. The authors assembled their
group of eyes for their longitudinal study
following a literature definition of kera-
toconus suspect:3 the fellow eyes of
unilateral keratoconus that had no slit-
lamp findings.
The work of Shirayama-Suzuki et al
aimed to track the progression of kerato-
conus rather than its detection. However,
there are many other studies under way
that seek to create keratoconus detection
methods, for which the unilateral kerato-
conus eye model is not appropriate.
Inclusion of eyes from patients with
keratoconus biases the sample. Early
screening schemes need to discriminate
between normal variations in corneal
topography and variations in corneas that
might have keratoconus. Both eyes of
unilateral keratoconics have the same
genetic makeup, and therefore the less
affected eye already is known to have
keratoconus. The fellow eye that has no
clinical findings of any sort except for
certain topographical changes (vide infra)
should carry the diagnosis of forme fruste
keratoconus. The dictionary definition of
forme fruste is ‘‘an incomplete, abortive,
or unusual form of a syndrome or
disease,’’ and this fits the situation.
Preclinical keratoconus also seems appro-
priate here as well, but dual labels are
confusing and unnecessary.
However, ‘‘keratoconus suspect’’
should be a term reserved for corneas
with very specific topographic changes
and for patients who do not have
keratoconus in the fellow eye. In general
terms, a topographic keratoconus suspect
will have a localised area of abnormal
steepening which is often inferior, but can
be central, or, rarely, superior, and may
Editorial
present as an asymmetrical, truncated or
skewed-axis bowtie. The different config-
urations seen with keratoconus are shown
in fig 1. Since corneal topography nor-
mally presents with many variations in
the healthy eye,4 the challenge is to
determine the threshold between normal
variations and a qualified keratoconus
suspect. The seminal works of
Rabinowitz and colleagues5 6 have helped
differentiate between normal topography
and the keratoconus suspect. One of the
most useful criteria they have developed
to detect the common sign of inferior
steepening is the I-S value which calcu-
lates the vertical gradient in corneal
power across a 6 mm region. A useful
rule is that a 1.4–1.9 D gradient is
consistent with keratoconus suspect,
while a value greater than this would be
consistent with clinical keratoconus.
Values lower than this range would be
considered a normal variation in corneal
topography. Maguire and Bourne7 pre-
sented a subtle case they labelled a
keratoconus suspect based on their clin-
ical experience. In response to criticism
that their case was merely a normal
variation and that they were overdiagnos-
ing keratoconus, Maguire8 triumphed by
publishing the topography of the same
eye some 2 years later showing obvious
keratoconus progression.
These early experiences have taught us
how to recognise keratoconus suspect and
have led to the development of a number
of literature-validated keratoconus detec-
tion schemes.9 10 These, along with the
prior Rabinowitz work, have found their
way onto commercial corneal topogra-
phers. An example of a recent implemen-
tation is shown in fig 2. Several of these
corneal topographer software programs
are currently being used to screen patient
candidates for refractive surgery.
If these methods are to be properly
developed, they need to be able to
discriminate among several classifications
of corneal topography designations.
Unilateral keratoconus is a contraindica-
tion for refractive surgery, and such
patients are not in the group needing
sensitive screening. The patients whose
corneal topography can be classified as
keratoconus suspect are the patients that
need identification with sensitive detec-
tion schemes. Developing a method for
detecting suspect keratoconus using a
cohort of forme fruste keratoconus biases
the training sample. The sensitivity,
specificity and accuracy of such methods
more appropriately test for forme fruste
keratoconus and not keratoconus suspect.
845
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Editorial

Figure 1 Examples of keratoconus. (A) Forme fruste keratoconus (fellow eye, B, diagnosed as having clinical keratoconus). Note that the axial map
display scale has 1.5 D intervals; the vertical I-S power gradient in this cornea is in the 1.4–1.9 D range (see text for details). (B) Clinical keratoconus
with classical inferior steepening. (C, D) Both eyes of clinical keratoconus illustrating the skewed radial axis pattern. (E, F) Both eyes of unilateral
keratoconus. The right eye has the characteristic truncated bow tie pattern.

In summary, the term ‘‘keratoconus

suspect’’ should properly be reserved for
corneas with subtle signs of keratoconus
but without evidence of clinical keratoco-
nus in either eye. When studying new
methods for detecting keratoconus suspect,
researchers must not include in their cohort
those cases that lie outside the established
criteria. Fortunately, the work of
Shirayama-Suzuki et al is not affected by
these considerations. Rather, their further
studies on the natural history of keratoco-
nus are heartily encouraged. We now have
over two decades of corneal topography
records on our keratoconus patients.
Eventually we will have a fuller under-
standing of the variations in the course of
this disease for better prognosis and treat-
ment. Can we identify those patients who
will progress rapidly and treat them with
collagen crosslinking to stabilise their
corneas before they suffer visual loss? Can
we mould the moderately advanced cases
and lock in better topography with this
same technique? Time will tell, but we
have gone from guarded optimism to
unbridled enthusiasm that collagen cross-
linking may provide a very effective new
Figure 2 Example of a screening programme that detects keratoconus in this cornea and reports a method to manage ectasia thanks to the
severity of 45.4%. pioneering work from Dresden.2

846 Br J Ophthalmol July 2009 Vol 93 No 7

 Downloaded from bjo.bmj.com on April 5, 2014 - Published by group.bmj.com

Editorial

Competing interests: SDK is a consultant to Nidek.
Accepted 13 December 2008
Br J Ophthalmol 2009;93:845–847.
doi:10.1136/bjo.2008.147371
REFERENCES
1. Shirayama-Suzuki M, Amano S, Honda N, et al.
Longitudinal analysis of corneal topography in
suspect keratoconus. Br J Ophthalmol
2009;93:815–19.
2. Spörl E, Huhle M, Kasper M, et al. Artificial stiffening
of the cornea by induction of intrastromal cross-links.
Ophthalmologe 1997;94:902–6.
3. Waring GO III. Nomenclature for keratoconus
suspects. Refract Corneal Surg 1993;9:219–22.
4. Dingeldein SA, Klyce SD. The topography of normal
corneas. Arch Ophthalmol 1989;107:512–18.
5. Rabinowitz YS, McDonnell PJ. Computer-assisted
corneal topography in keratoconus. Refract Corneal
Surg 1989;5:400–8.
6. Szczotka LB, Rabinowitz YS, Yang H. Influence of
contact lens wear on the corneal topography of
keratoconus. CLAO J 1996;22:270–3.
7. Maguire LJ, Bourne WM. Corneal topography of
early keratoconus. Am J Ophthalmol
1989;108:107–12.
8. Maguire LJ, Lowry JC. Identifying progression of
subclinical keratoconus by serial topography analysis.
Am J Ophthalmol 1991;112:41–5.
9. Maeda N, Klyce SD, Smolek MK, et al.
Automated keratoconus screening with corneal
topography analysis. Invest Ophthalmol Vis Sci
1994;35:2749–57.
10. Klyce SD, Karon MD, Smolek MK. Screening patients
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Cover illustration

Carving the cornea: the von Hippel

Trephine
Illustrations courtesy of Mr Richard Keeler, Curator, Museum of the
Royal College of Ophthalmologists. Photos: Mark Thomas.
The von Hippel trephine was invented around 1888 by Arthur
von Hippel, a distinguished German ophthalmologist (1841–
1916). Arthur von Hippel graduated as a doctor of medicine and
surgery in 1865 and went on to study in Prague, Paris and
Vienna. It was here that he came under the influence of Hugo
von Arlt who persuaded him to specialise in ophthalmology, an
under-recognised subject at the time. He served as Professor of
Ophthalmology at the University of Giessen and in 1890
succeeded his mentor, Professor Jacobson at Konigsberg. He
worked in Konigsberg until 1901 when he moved to Gottingen
where he built the new eye clinic.
The main feature of the von Hippel Trephine was a clockwork
mechanism, which activated the rotation of a circular blade cornea transplantation) describing his technique of lamellar
allowing the surgeon to hold the instrument firmly in a inlay grafts. This paper opened the way for the first
perpendicular position to the cornea. To use the instrument the successful full thickness corneal transplant some years later
surgeon held it by the column with the forefinger placed on the but von Hippel is credited with being the first to transplant
small knob at the top. Depression of this knob released the corneal tissue in a human whilst retaining transparency of
clockwork coil inside the cylinder thereby rotating the blade. the graft.
The ornate key had two functions, one to wind up the The first full thickness graft from donor material was
mechanism and secondly to secure the adjustable depth of the performed by Eduard Zirm using a von Hippel trephine. The
cut by tightening the screw on the blade holding column. patient, Alois Glogar, had been blinded in both eyes by an
Corneal trephine blades of different diameters, 4, 5 and 6 mm accident with unslaked lime. The eye was operated on in 1905
were provided on the early models and later scleral trephines using a 5 mm trephine blade which was used on both the
were included. enucleated donor eye and the patient’s recipient eye.
In 1888 von Hippel published a paper titled ‘‘Eine neue
Methode der Hornhauttransplantation’’ (A new method for Richard Keeler, Arun D Singh, Harminder S Dua

Br J Ophthalmol July 2009 Vol 93 No 7 847

 Downloaded from bjo.bmj.com on April 5, 2014 - Published by group.bmj.com

Chasing the suspect: keratoconus

Stephen D Klyce

Br J Ophthalmol 2009 93: 845-847

doi: 10.1136/bjo.2008.147371

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