Selective wavelength pupillometry in Leber hereditary optic neuropathy.

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This case shows an unusual systemic cause for a
common ophthalmic presentation of apparently localized
orbital disease which was initially diagnosed as orbital
cellulitis.
Acknowledgements
The authors would like to acknowledge the Medical
Imaging Department, Wellington School of Medicine, for
their contribution.
Anne-Marie E Yardley MBChB, Nisha Sachdev
MBBS PhD and Neil S Aburn FRANZCO
Wellington Eye Department, Wellington Hospital,
Wellington, New Zealand
Received 21 July 2009; accepted 4 December 2009.
References
1. Otten TR, Stein PD, Patel KC, Mustafa S, Silbergleit A.
Thromboembolic disease involving the superior vena
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3. Altman SD. A practical approach for diagnosis and
treatment of central venous stenosis and occlusion.
Semin Vasc Surg 2007; 20: 189–94.
4. Sharafuddin MJ, Sun S, Hoballah JJ. Endovascular
management of venous thrombotic diseases of the upper
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90.
Selective wavelength pupillometry
in Leber hereditary optic
neuropathy
Leber hereditary optic neuropathy (LHON) is a maternally
inherited disorder related to a point mutation in mitochon-
drial DNA. It is characterized by subacute, sequential
visual loss due to optic nerve dysfunction. An unusual
feature of LHON is preservation of the pupillary light
reflex to a broad spectrum (white) light despite significant
visual loss.1,2The pathophysiologic basis of this visual-
pupillary dissociation is not understood and has led some
to question its existence.3The bilateral and fairly symmet-
ric nature of the visual loss in this disorder and the need for
specialized instrumentation to quantify the pupil deficit
have made it difficult to obtain enough data to resolve this
controversy. Pathologic specimens of the optic nerve and
retina are scant because affected patients are relatively
young.
New insight may be gained on the issue of visual-
pupillary dissociation in LHON because of the recent
identification of a subset of retinal ganglion cells that
subserve non-visual functions.4These non-visual gan-
glion cells contain a photopigment, melanopsin, and thus
can be intrinsically activated by high intensity, short
wavelength light. Furthermore, these cells are the main,
if not exclusive, source of light signal driving the pupil
light reflex.
Figure 3.
angioplasty balloon across the central venous occlusion.
Venographic image with arrow indicating inflated
Figure 4.
cular stent in place with venous flow restored.
Venographic image with arrow indicating endovas-
322 Letters to the Editor
© 2010 The Authors
Journal compilation © 2010 Royal Australian and New Zealand College of Ophthalmologists

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Herein we record pupil responses to short and long
wavelength light in a patient with unilateral visual loss
due to LHON in order to evaluate the function of the
melanopsin-expressing retinal ganglion cells.
A 28-year-old female experienced subacute painless
visual loss in her right eye. Investigations were unreveal-
ing except for the presence of a primary genetic mutation
ND6 (14484)associated
revealed visual acuity of count fingers right eye (OD) and
6/6 left eye (OS). Threshold automated perimetry showed
diffuse depression of sensitivity with a central scotoma
inferonasally OD and was normal OS. Funduscopy
revealed optic atrophy OD but was otherwise normal.
Pupils were briskly reactive to a bright, focal white light. A
minimal relative afferent pupil defect OD was noted.
Pupillographic testing with equiluminant, high inten-
sity monochromatic coloured light was performed using a
customized pupillometer (IdeaMedical, Denmark). The
light stimulus was an array of long (660 nm, red) or short
withLHON.Examination
(470 nm, blue) wavelength light emitting diodes cali-
brated to an intensity of 100 and 300 cd/m2. The light
stimulus, first red then blue, was presented to each eye for
20 s under mesopic conditions. Pupillary movements were
recorded continuously in real-time using an infrared
camera (Sony nightvision). The digital signal was exported
for processing using a customized analysis program.
In both eyes of the patient, the pupil contraction ampli-
tude to blue light was greater than that to red light,
a finding recently reported (Fig. 1a,b).5In addition,
the pupils maintained a steadily contracted state during
20 s of blue light stimulation, suggesting activation of
melanopsin-mediated (intrinsic) phototransduction.4The
difference in mean contraction amplitude between the
healthy and affected eye was small, 5% and 6% using blue
and red light stimulation, respectively (Fig. 1c).
It has been reported that the pupil response to high
intensity, short wavelength light (100 cd/m2, <480 nm) is
predominantly driven by melanopsin, as S cones are small
120
100
80
60
40
20
0
Pupil size (%)
(a)
Light: 100 cd/m2 for 20 s
Mean pupil size during light stimulation:
59% of baseline
46% of baseline
Pupil recording in healthy eye of patient
to blue light stimulus (470 nm)
to red light stimulus (660 nm)
020406080
Time (s)
120
100
80
60
40
20
0
Pupil size (%)
(b)
Light: 100 cd/m2 for 20 s
Mean pupil size during light stimulation:
65% of baseline
51% of baseline
Pupil recording in affected eye of patient
to blue light stimulus (470 nm)
to red light stimulus (660 nm)
0 204060 80
Time (s)
120
100
80
60
40
20
0
Pupil size (%)
(c)
Light: 100 cd/m2 for 20 s
Pupil recording to blue (470 nm) light
affected eye
healthy eye
0 2040 6080
Time (s)
Pupil recording to blue (470 nm) light
affected eye
healthy eye
120
100
80
60
40
20
0
Pupil size (%)
(d)
Light: 300 cd/m2 for 20 s
0 20 4060 80
Time (s)
Figure 1.
wavelength light stimulus. Blue line = pupil recording using a short wavelength light stimulus. (a) Pupil responses in healthy eye. (b) Pupil
responses in affected eye. (c) Interocular comparison of pupil responses to short wavelength light at 100 cd/m2. (d) Same as C but at
300 cd/m2.
Graphic representation of pupil response to monochromatic coloured light stimulation. Red line = pupil recording using long
Letters to the Editor323
© 2010 The Authors
Journal compilation © 2010 Royal Australian and New Zealand College of Ophthalmologists

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in number.5In our patient, the absence of a further increase
in contraction amplitude with increasing intensity sug-
gests that maximal activation of melanopsin-mediated
phototransduction was obtained at 100 cd/m2(Fig. 1c,d).
Assuming that the maximal pupil contraction ampli-
tude represents the maximal number of functioning
melanopsin ganglion cells, we found only 5% loss of
functionalpupillomotor capacity
poor vision. The pupil response to red light, mediated
mostly by M/L cones, showed an expected similar
percentage loss because cone contribution to the pupil
light reflex is transmitted via functioning melanopsin
ganglion cells.
One hypothesis to explain the visual-pupillary disso-
ciation described in patients with LHON is that, com-
paredwith visualganglion
ganglion cells are relatively resistant to the intracellular
metabolic derangement induced by the gene defect. His-
topathologic studies of eyes from patients with LHON
have shown relative sparing of melanopsin ganglion cells
compared with more diffuse, severe loss of visual
ganglon cells (A Sadun, Doheny Eye Institute, pers.
comm., 2009). Our pupillometric results provide the
first functional data supporting this hypothesis, but a
single case study does not permit any firm conclusions
tobemade.Futurestudies
length pupillometry are anticipated in order to examine
whether patients with unilateral LHON show relative
preservation of their pupil responses as compared with
other types of optic neuropathy such as traumatic or
ischemic.
intheeyewith
cells,themelanopsin
usingselectivewave-
Aki Kawasaki MD,1Kristina Herbst MD,2Birgit
Sander PhD2and Dan Milea MD PhD2
1Hôpital Ophtalmique Jules Gonin, Neuro-ophthalmology
Unit, Lausanne, Switzerland; and2Glostrup Hospital,
Department of Ophthalmology, Copenhagen, Denmark
Received 13 September 2009; accepted 9 November 2009.
REFERENCES
1. Wakakura M, Yokoe J. Evidence for preserved direct
pupillary light response in Leber’s hereditary optic
neuropathy. Br J Ophthalmol 1995; 79: 442–6.
2. Bremner FD, Shallo-Hoffmann J, Riordan-Eva P, Smith
SE. Comparing pupil function with visual function in
patients with Leber’s hereditary optic neuropathy. Invest
Ophthalmol Vis Sci 1999; 40: 2528–34.
3. Jacobson DM, Stone EM, Miller NR et al. Relative affer-
ent pupillary defects in patients with Leber’s hereditary
optic neuropathy and unilateral visual loss. Am J Oph-
thalmol 1998; 126: 291–5.
4. Hankins MW, Peirson SN, Foster RG. Melanopsin: an
exciting photopigment. Trends Neurosci 2008; 31: 27–
36.
5. Kardon R, Anderson SC, Damarjian TG, Grace EM,
Stone E, Kawasaki A. Chromatic pupil responses pref-
erential activation of the Melanopsin-mediated versus
outer Photoreceptor-mediated pupil light reflex. Oph-
thalmology 2009; 116: 1564–73.
Intraocular lens outcomes:
a concern
I read the recent publication by Statham et al.1Statham et al.
concluded that ‘The AcrySof Toric IOL provides a signifi-
cant improvement in postoperative astigmatism and UCVA
when compared statistically with its spherical counterpart
for patients with low degrees of corneal astigmatism’.1I
have concerns regarding this report. First, the number of
subjects is very few hence the result is only a preliminary
result. Larger studies on various groups of subjects
(gender, age and race) might be useful. Second, Statham
et al. did not assess all clinical parameters of the cases
during the operations, as well as complications after the
procedures. These data are helpful for judging whether
the technique is actually better. In addition, the cost-
effectiveness and cost utility comparison between the two
techniques should also be assessed. Without these data, it
cannot reach the conclusion that one option is better than
the other.
Viroj Wiwanitkit MD
Wiwanitkit House, Bangkhae, Bangkok, Thailand
Received 3 November 2009; accepted 9 November 2009.
REFERENCES
1. Statham M, Apel A, Stephensen D. Comparison of the
AcrySof SA60 spherical intraocular lens and the
AcrySof Toric SN60T3 intraocular lens outcomes in
patients with low amounts of corneal astigmatism. Clin
Experiment Opthalmol 2009; 37: 775–9.
Intraocular lens outcomes:
a concern – response
We thank Professor Viroj Wiwanitkit for his comments1
and interest in our article.2Our aim was to examine
whether the AcrySof Toric IOL (SN60T3) was useful for
reducing postoperative refractive astigmatism and improv-
ing uncorrected visual acuity (UCVA) when compared
with its spherical counterpart, the AcrySof IOL (SA60),
in a group of patients with low degrees of corneal
astigmatism.2We chose to look at patients with low
degrees of corneal astigmatism because they are the most
commonly encountered group in clinical practice with the
majority (64.4%) of patients having between 0.25 and 1.25
DC of corneal astigmatism.3We chose patient-centred
outcome measures in postoperative refractive astigmatism
and UCVA, given that postoperative spectacle indepen-
dence was the most commonly cited reason for undergoing
cataract surgery in a recent study.4Our study was large
enough to show a statistically significant improvement in
these outcome measures using a method that makes the
324Letters to the Editor
© 2010 The Authors
Journal compilation © 2010 Royal Australian and New Zealand College of Ophthalmologists