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Bilateral naevus of Ota with
choroidal melanoma and diffuse
retinal pigmentation in a dark
skinned person
Naevus of Ota (naevus fusculocoeruleus
ophthalmomaxillaris) was described by the
Japanese dermatologist, Ota, in 1939 as a
dermal melanocytic hamartoma that presents
as bluish hyperpigmentation along the
ophthalmic, maxillary, and mandibular
branches of the trigeminal nerve. It is
bilateral in less than 5% cases, occurring
frequently in Orientals (0.2%–1%) and darker
races and rarely in white people (0.04%).
Open angle glaucomas and choroidal mela-
noma are the rare ocular involvements. Ota’s
naevus is more common in Asians than white
people but uveal melanoma occurs predomi-
nantly in white populations.
12
Dark skinned
patients represent only 1% of all cases of
orbital melanomas.
3
The risk of developing
uveal melanoma in a patient with naevus of
Ota is one in 400 patients in their lifetime.
12
We report a rare case of bilateral naevus of
Ota with a right (RE) choroidal melanoma
and left (LE) diffuse pigmentation of retina.
Case report
A 73 year old Anglo-Indian woman was
referred with complaints of photopsia. She
had black hair and light brown skin.
Examination revealed a brownish-black pig-
mentation of the conjunctiva, episclera, and
periocular skin bilaterally (fig 1). Visual
acuity for distance and near was 6/6 and
N5, respectively, in each eye. Heterochromia
was present, the right iris being a darker
brown than the left, which had a sector of
light brown colour. Gonioscopy and intra-
ocular pressure were normal. The right
fundus revealed a pigmented, large, elevated
choroidal mass 10 disc diameter (DD) in size,
4 DD superonasal to the disc. Drusen were
overlying it. No subretinal fluid was seen. The
left eye showed a patchy dark pigmentation
3 DD in size, at the temporal edge of the
macula. A ridge-like pigmented elevation,
3 DD long, was also seen along the super-
onasal vessels. Both optic discs and maculas
were normal. Ultrasound in the right eye
showed a 10 mm tumour, 4.2 mm high.
Fluorescein angiography confirmed its inde-
pendent circulation. A systemic examination
found no signs of metastasis. A diagnosis of a
bilateral naevus of Ota with low grade,
choroidal melanoma in the right eye (fig 2)
and retinal pigmentation in the left eye was
made. The patient was reluctant to accept the
option of enucleation in view of the right
vision. A
125
I radioactive plaque was applied
(COMS study). A follow up examination
3 years postoperatively showed a flatter,
yellow 4 DD61.5 DD scarred tumour with
mottled pigmentation. The left melanosis
remained unchanged. The vision was 6/6 in
both eyes 6 years after
125
I treatment and
cataract surgery.
Comment
Ota’s naevus is commonly seen unilaterally
(90%). Bilateral involvement is rare. It
represents melanocytes that have not
migrated completely from the neural crest
to the epidermis during the embryonic stage.
Orientals and pigmented races have a high
prevalence with a predilection for women (1:
4.8). Variable prevalence among different
populations suggests genetic influences,
although familial cases are rare. Two peak
ages of onset in early infancy (50%) and in
early adolescence suggest hormonal influ-
ence.
1
In addition to the skin, pigmentation
may involve oral mucosa, tympanic mem-
brane, intranasal mucosa, leptomeninges and
ocular structures such as the sclera, retro-
bulbar fat, cornea, lens, trabeculum, disc, and
retina. Associated malignant melanomas of
the uvea, orbit, skin, and CNS have been
described.
2
Choroidal melanomas are known
to occur in less than 4% of cases and
glaucoma has been noticed in less than 10%
of cases.
4
Our case reports a rare occurrence of
bilateral naevus of Ota with choroidal malig-
nant melanoma in the right eye and retinal
pigmentation in the left eye in a pigmented
person. She was born to Anglo-Indian par-
ents but did not know how far back in time
the intermarriage had occurred.
Ophthalmological follow up care is necessary
for patients with increased melanosis. This
case illustrates the need for regular ophthal-
mic review of all pigmented lesions and the
recognition that patients with naevus of Ota
may also have the additional complication of
melanoma. There is need for close observa-
tion of all pigmented lesions of the eye.
Regardless of the patient’s race, there is a
greater than normal chance that a patient
with the naevus of Ota might have a
malignant melanoma develop within one of
the affected tissues.
S Sharan, J R Grigg, F A Billson
Save Sight Institute, University of Sydney, Department
of Ophthalmology, Sydney Eye Hospital, 8 Macquarie
Street, Sydney 2000, Australia
Correspondence to: Sapna Sharan, Save Sight
Institute, University of Sydney, Department of
Ophthalmology, Sydney Eye Hospital, 8 Macquarie
Street, Sydney 2000, Australia;
sapnasd@yahoo.co.uk
doi: 10.1136/bjo.2005.070839
References
1 Hidano A, Kajima H, Ikeda S, et al. Natural
history of nevus of Ota. Arch Dermatol
1967;95:187–95.
2 Gonder JR, Shields JA, Albert DM, et al. Uveal
malignant melanoma associated with ocular and
oculodermal melanocytosis. Opht halmology
1982;89:953–60.
3 Margo CE, McLean IW. Malignant melanoma of
the choroid and ciliary body in black patients.
Arch Ophthalmol 1984;102:77–9.
4 Roy PE, Schaeffer EM. Nevus of Ota and
choroidal melanoma. Surv Ophthalmol
1967;12:130–40.
Treatment of neurotrophic
keratopathy with nasal dilator
strips
Neurotrophic keratopathy, characterised by
poorly healing corneal epithelium, occurs in
eyes with decreased corneal sensory innerva-
tion. Clinical findings include chronic epithe-
lial defects and corneal ulceration. Numerous
conditions predispose to neurotrophic kerato-
pathy including diabetes mellitus, accidental
and surgical trauma, herpes simplex and
herpes zoster keratitis, leprosy, and topical
anaesthetic abuse.
Management of neurotrophic keratopathy
includes ocular lubrication, pressure patch-
ing, autologous serum eye drops,
1
fitting of a
bandage contact lens,
2
amniotic membrane
grafting,
34
and surgical tarsorrhaphy.
Surgical tarsorrhaphy can be very successful
in resolving neurotrophic corneal ulceration,
5
but many patients find this option cosmeti-
cally unacceptable.
We describe a novel method of non-
surgical tarsorrhaphy using over the counter
adhesive, non-medicated, nasal dilator strips
(NDS) (Breathe Right Nasal Strips,
Whippany, NJ, USA) applied vertically across
the eyelids (fig 1). The adhesive strip consists
of parallel bands of plastic imbedded in a
pad, and is available in different sizes.
The nasal strips were originally developed
to treat patients with snoring problems,
6
or to improve nasal congestion.
7
In rhino-
logical applications, the strip is typically used
Figure 1 Oculodermal pigmentation.
Figure 2 Choroidal melanoma.
LETTERS
PostScript
..............................................................................................
Accepted for publication 1 May 2005
Br J Ophthalmol 2005;89:1529–1545 1529
www.bjophthalmol.com
horizontally across the nose in order to open
the nasal airway. In the current study, we
applied the strip vertically over the closed
eyelid as shown in figure 1. The adhesive strip
creates a firm and effective eyelid closure,
and patients can control the application and
removal of the strip. The strips have the
advantage of being relatively inexpensive,
reusable, and reversible, and their use has
replaced standard eye patching in our clinical
practice. We have noted success with the use
of these strips for the management of
neurotrophic ulceration and describe two
representative cases.
Case reports
A 60 year old woman developed a neuro-
trophic corneal ulcer following a complicated
retinal detachment repair. After a year of
standard medical therapies, including lubri-
cation and frequent conventional patching,
she continued to have a 4 mm64mm
chronic non-healing epithelial defect.
Treatment with reversible NDS tarsorrhaphy
was initiated with instructions to apply the
strips at bedtime and as much as possible
during the day. Nine weeks later the corneal
epithelial defect had healed completely. Over
the next year she gradually decreased the
wearing time of the strips and is currently
stable without their use.
A 48 year old woman with a 6 mm62mm
neurotrophic corneal ulcer was referred for
management after failing numerous medical
and surgical therapies including lubrication,
autologous serum eye drops, patching, and
an amniotic membrane graft. The patient was
instructed to use NDS tarsorrhaphy according
to the schedule described in the previous
case. Within 2 weeks the corneal epithelial
defect healed completely. The patient con-
tinues to apply the tarsorrhaphy but with
decreasing frequency.
The novel use of nasal dilator strips to
perform a temporary tarsorrhaphy has aided
us greatly in our management of neuro-
trophic corneal ulceration. We believe it is an
attractive, cost effective, efficient alternative
to patching for any ocular condition. In
addition, nasal strip tarsorrhaphy allows for
immediate reversibility that facilitates patient
acceptance.
M T Magone, G D Seitzman, S Nehls,
T P Margolis
Francis I Proctor Foundation, University of California
San Francisco, 95 Kirkham Street, San Francisco, CA
94143, USA
Correspondence to: T P Margolis, MD, PhD, Francis I
Procter Foundation, 95 Kirkham Street, San Francisco,
CA 94143, USA; tpms@itsa.ucsf.edu
doi: 10.1136/bjo.2005.073114
References
1 Matsumoto Y, Dogru M, Goto E, et al. Autologous
serum application in the treatment of neurotrophic
keratopathy. Ophthalmology
2004;111:1115–20.
2 Montero J, Sparholt J, Mely R, et al. Retrospective
case series of therapeutic applications of
lotrafilcon a silicone hydrogel soft contact lenses.
Eye Contact Lens 2003;29:72–5.
3 Solomon A, Meller D, Prabhasawat P, et al.
Amniotic membrane grafts for nontraumatic
corneal perforations, descemetoceles, and deep
ulcers. Ophthalmology 2002;109:694–703.
4 Prabhasawat P, Tesavibul N. Preserved amniotic
membrane transplantation for conjunctival
surface reconstruction. Cell Tissue Bank
2001;2:31–9.
5 Cosar CB, Cohen EJ, Rapuano CJ, et al.
Tarsorrhaphy: clinical experience from a cornea
practice. Cornea 2001;20:787–91 .
6 Ufberg J. Fenton G. Effect of breathe right nasal
strip on decrease snoring. Rhinology
1997;35:50–2.
7 Ochi K, Mitsui M, Kaneko T, et al. The application
of Breathe Right for otorhinolaryngologic
disorders. Otorhinology 1997;90:597–601.
Confocal microscopy of the
cornea in nephropathic cystinosis
Cystinosis is an autosomal recessive inherited
disorder of amino acid metabolism charac-
terised by the deposition of cystine crystals in
the eye, kidney, reticuloendothelial system,
and various other tissues.
1
Childhood or
nephropathic cystinosis can present as an
infantile or a juvenile variant.
1
The infantile
variant tends to have a more devastating
course and is associated with growth retarda-
tion, rickets, and eventual renal failure which
requires transplantation within the first
decade.
1
The juvenile variant has later onset
and milder nephropathy.
1
In nephropathic cystinosis, crystal deposits
usually appear in the peripheral, anterior
cornea within the first year of life and
progress centrally and posteriorly until the
entire cornea is involved.
2–7
The diagnosis can
be confirmed histopathologically by demon-
stration of characteristic crystals by electron
microscopy in a conjunctival biopsy.
89
Stromal deposition of crystal deposits has
been demonstrated by confocal microscopy.
9
We provide the first demonstration, to the
best of our knowledge, of cystine crystals in
the corneal epithelium using in vivo confocal
microscopy.
Case report
A 9 year old boy presented to the King
Khaled Eye Specialist Hospital in Riyadh,
Saudi Arabia, with a complaint of recurrent
foreign body sensation, associated with
severe photophobia and blepharospasm. He
had been diagnosed with infantile nephro-
pathic cystinosis at age of 9 months and had
been treated with systemic cysteamine. On
examination, the visual acuity was 20/20 in
the right eye and 20/25 in the left eye. The
intraocular pressure was 12 mm Hg in both
eyes. Slit lamp examination showed crystal
deposits of 2.5 in Gahl density score
7
in both
corneas, predominantly involving the ante-
rior stroma and with limbus to limbus
distribution (fig 1). Dilated fundus examina-
tion was normal with no maculopathy or
peripheral retinal pigment abnormalities.
Topical treatment with cysteamine 0.5%
drops resulted in symptomatic relief.
Confocal microscopy (Confoscan 3, Nidek
Technologies, Vigonza, Italy) demonstrated
crystalline deposits in the corneal epithelium
(fig 2A, B) and stroma (fig 2C, D). Crystal
deposits in the corneal epithelium were
needle shaped and fusiform shaped and
oriented parallel to the plane of the epithelial
cells (fig 2A, B). In the basal cell layer, the
crystals were associated with dendritic cells
(fig 2B). The highest crystal density was in
the mid-stroma, where fusiform shaped
crystals were more predominant than needle
shaped crystals (fig 2C). The lowest crystal
density was in the posterior stroma, where
most of the deposits were needle shaped
(fig 2E). Within the stroma the crystals were
oriented parallel to the plane of the stromal
lamella. The needle shaped crystals were
highly variable in length with some as long
as 100 mm. The endothelial cell layer was
normal.
Comment
The current case clearly documents that
crystalline deposits may be found in the
epithelium of patients with nephropathic
cystinosis, unlike previous electron micro-
scopic
8
and confocal microscopic
9
studies that
suggest these deposits are localised to the
stroma. In addition, we found maximum
crystal density in the mid-stroma and mini-
mum density in the posterior stroma, in
contrast with a previous report in which
maximum crystal density was just anterior to
Descemet’s membrane.
9
We hypothesise the presence of these
abnormal deposits in the corneal epithelium
may contribute, in part, to the foreign body
sensation and photophobia that is invariably
associated with this disorder, as well as the
predisposition to recurrent epithelial ero-
sions. Chronic low grade inflammation of
the epithelium and epithelial basement
membrane zone associated with recurrent
epithelial erosions is the probable explana-
tion for the presence of dendritic cells in the
basal epithelium of the central cornea.
10
Successful reduction in the density of corneal
crystals and symptomatic relief was obtained
with the use of topical cysteamine 0.5%
drops, as in previous reports.
5–7
Figure 1 Applying a nasal dilator strip
vertically over the eyelid creates an easily
reversible tarsorrhaphy. It also provides an
effective and, for patients, cosmetically
acceptable way to treat chronic corneal
neurotrophic disorders.
Accepted for publication 10 May 2005
Figure 1 Crystal deposits in the right eye
predominantly involving the anterior and mid-
stroma, with limbus to limbus distribution.
1530 PostScript
www.bjophthalmol.com
A H Alsuhaibani, M D Wagoner
Anterior Segment Division, Department of
Ophthalmology, King Khaled Eye Specialist Hospital,
Riyadh, Kingdom of Saudi Arabia
A O Khan
Pediatric Ophthalmology and Strabismus Division,
Department of Ophthalmology, King Khaled Eye
Specialist Hospital, Riyadh, Kingdom of Saudi Arabia
Correspondence to: Michael D Wagoner, MD, King
Khaled Eye Specialist Hospital, PO Box 7191, Riyadh
11462, Kingdom of Saudi Arabia;
mwagoner@kkesh.med.sa
doi: 10.1136/bjo.2005.074468
References
1 Theone JG. Cystinosis. J Inherit Metab Dis
1995;18:380–6.
2 Wong VG, Schulman JD, Seegmiller JE.
Conjunctival biopsy for the biochemical diagnosis
of cystinosis. Am J Ophthalmol 1970;70:278–81.
3 Kaiser-Kupfer MI, Chan CC, Rodriques M, et al.
Nephropathic cystinosis: immunohistochemical
and histopathologic studies of cornea,
conjunctiva, and iris. Curr Eye Res
1987;66:17–22.
4 Cotran PR, Bajart AM. Congenital corneal
opacities. Int Ophthalmol Clin 1992;32:93–105.
5 Iwata F, Kuehl EM, Reed GF, et al. A randomized
clinical trial of topical cysteamine disulfide
(cystamine) versus free thiol (cysteamine) in the
treatment of corneal cystine crystals in cystinosis.
Mol Genet Metab 1998;64:237–42.
6 Gahl WA, Kuehl EM, Iwata F, et al. Corneal
crystals in nephropathic cystinosis: natural history
and treatment with cysteamine eyedrops. Mol
Genet Metab 2000;71:100–20.
7 Khan AO, Latimer B. Successful use of topical
cysteamine formulated from the oral preparation
in a child with keratopathy secondary to
cystinosis. Am J Ophthalmol 2004;138:674–5.
8 Kenyon KR, Sensenbrenner JA. Electron
microscopy of cornea and conjunctiva in
childhood cystinosis. Am J Ophthalmol
1974;78:68–76.
9 Grupcheva CN, Ormonde SE, McGhee C. In vivo
confocal microscopy of the cornea in
nephropathic cystinosis. Arch Ophthalmol
2002;120:1742–5.
10 Gillette TE, Chandler JW, Greiner JV. Langerhans
cells of the ocular surface. Ophthalmology
1982;89:700–11.
Total parenteral nutrition,
vitamin E, and reversible macular
dysfunction morphologically
mimicking age related macular
degeneration
A variety of nutrient deficiencies may predis-
pose to the development of age related
macular degeneration (AMD).
1
Patients
receiving parenteral nutrition (TPN) may be
at particular risk of early onset AMD, because
of inadequate or excess nutritional supple-
mentation.
1
Studies including the Eye
Disease Case-Control Study and Beaver Dam
Eye Study have evaluated the relation
between antioxidant and micronutrient
levels, and the risk of AMD.
2–4
A protective
effect of high plasma vitamin E levels was
convincingly demonstrated.
5
We describe a patient treated with parent-
eral fluid support who developed visual
symptoms and signs of AMD, in conjunction
with longstanding vitamin E deficiency.
Isolated cases of visual disturbance in
patients undergoing TPN have been reported
in the literature
67
; however, to our knowl-
edge, no case of visual disturbance attributed
to vitamin E deficiency has been reported in
this context.
Case report
A 57 year old man received parenteral fluid
five times a week at home because of short
bowel syndrome secondary to Crohn’s dis-
ease. It was thought he had undergone bowel
adaptation to meet macronutrient and micro-
nutrient needs in the 13 years since his
surgery. He presented with subacute visual
disturbance. He described altered colour
perception in situations analogous to macular
stress testing (moving from dark adapted
situations to bright lights) and enlarging
central scotomata. Visual acuity was 6/6 in
the right eye, 6/12 in the left. Visual fields,
intraocular pressures, and neurological
examination were normal. Funduscopy
revealed macular soft drusen, and extensive
subretinal basal laminar deposits in the
macular region, more marked in the right
than left eye (fig 1). Electroretinogram was
normal.
The patient was receiving electrolyte sup-
port 6 days a week at time of presentation.
Measured haematological parameters and
urea and electrolyte levels revealed a low
haemoglobin level (11.0 g/dl), and a mild
degree of macrocytosis (102.3 fl). Because
hypervitaminosis and/or deficiency in trace
minerals were suspected, serum values of
vitamins A, E, B1, B2, B6, plasma zinc,
copper, selenium, manganese, caeruloplas-
min, and red cell GSH activity were mea-
sured. Results revealed vitamin E deficiency
(12 mmol/l, normal range: 14–39 mmol/l). A
retrospective survey of previous serum vita-
min E levels suggested longstanding defi-
ciency, with levels of 10 mmol/l, and 13 mmol/
l, 6 months and 1 year respectively, before
onset of symptoms. Treatment with vitamin
supplementation lead to complete resolution
of symptoms in 3 weeks. Vitamin E levels
returned to normal; however, fundal appear-
ances remained unchanged.
Comment
The presence of bilateral hard and soft drusen
and pigmentary abnormalities in the macula
are the clinical hallmarks of AMD.
8
The early
onset of morphological changes at Bruch’s
membrane/retinal pigment epithelium (RPE)
interface may relate to vitamin or micronu-
trient deficiency, associated with parenteral
nutrition.
7
Cumulative oxidative damage may have an
important role in the pathogenesis of AMD,
since accumulation of lipofuscin pigments
may arise as a consequence of antioxidant
deficiency, or under pro-oxidant conditions.
5
Evidence exists for an association between
atrophic AMD and excessive lipofuscin accu-
mulation.
89
Compromised RPE in this con-
text is believed to be due to the amphiphilic
structure and photoreactivity of the di-retinal
conjugate A2E, the major constituent of
lipofuscin.
59
Antioxidant vitamins have been
shown to aid in the defence against AMD.
5
Vitamins E and C suppress A2E epoxidation,
suggesting one mechanism by which these
vitamins may protect the ageing macula.
9
Vitamin E deficiency was present consis-
tently over the 12 month period preceding
symptom onset, reinforcing the likelihood
that the clinical presentation had been
caused by vitamin E deficiency. Vitamin E
deficiency results in retinal degeneration,
excessive RPE lipofuscin, and decrease in
the polyunsaturated fatty acid content of rod
outer segments and the RPE.
5
Furthermore,
vitamin E deficiency may cause mild macro-
cytic anaemia and accumulation of ceroid
lipofuscin in nerves, affecting function of
central and peripheral nervous systems.
6
Patients with sufficient gut length for protein
calorie nutrition receiving parenteral fluids
may run the risk of micronutrient deficiency
despite a normal diet, and may present to the
ophthalmology department. We recommend
formal micronutrient screening in patients
with extensive small bowel resection.
Figure 2 Crystal deposits in the corneal epithelium and stroma. A mixture of needle shaped and fusiform shaped crystals are present in (A) the
superficial epithelial cell layer and (B) the wing cell layer. (C) Dendritic cells are present in the basal cell layer. (D) The greatest density of crystals is in
the mid-stroma, where fusiform shaped crystals are the predominant morphology. (E) The least density of crystals is in the posterior stroma, where
needle shaped crystals are the predominant morphology.
Accepted for publication 10 May 2005
Competing interests: none declared
Figure 1 Macular soft drusenosis,
characterised by subretinal basal laminar
deposits in the macular region.
PostScript 1531
www.bjophthalmol.com
L Porter
Dundee Medical School, Dundee, UK
N Reynolds
Department of Medicine, Dundee Medical School,
Dundee, UK
J D Ellis
Department of Ophthalmology Ninewells Hospital and
Medical School, Ninewells Road, Dundee DD1 9SY,
UK
Correspondence to: Dr John Ellis, Department of
Ophthalmology, Ninewells, Dundee DD1 9SY, UK;
john.ellis@tuht.scot.nhs.uk
doi: 10.1136/bjo.2005.074195
References
1 Vinton NE. Heckenlively JR, Laidlaw SA, et al.
Visual function in patients undergoing long-term
total parenteral nutrition. Am J Clin Nutr
1990;52:895–902.
2 The Eye Disease Case-Control Study Group.
Antioxidant status and neovascular age-related
macular degeneration. Arch Ophthalomol
1993;111:1366, 1499, and 104–9.
3 Lyle BJ, Mares-Perlman JA, Klein BEK, et al.
Antioxidant intake and risk of age-related nuclear
cataracts in the Beaver Dam Eye Study. Am J
Epidemiol 1999;149:801–9.
4 Seddon JM, Ajani UA, Sperduto RD, et al. Dietary
carotenoids, vitamins A, C and E, and advanced
age-related macular degeneration. JAMA
1994;272:1413–20.
5 Beatty S, Hui-Hang K, Henson D, et al. The role of
oxidative stress in pathogenesis of age-related
macular degeneration. Surv Ophthalmol
2000;45:115–34.
6 Kawakubo K, Matsumoto T, Mochizuki Y, et al.
Progressive encephalopathy in a Crohn’s disease
patient on long-term total parenteral nutrition:
possible relationship to selenium deficiency.
Postgrad Med J 1994;70:215–9.
7 Yassur Y, Snir M. Melamed S. Bilateral
maculopathy simulating ‘‘cherry-red spot’’ in a
patient with Crohn’s disease. Br J Ophthalmol
1981;65:184–8.
8 Zurdel J, Richard G. Clinical manifestations and
natural history and ARMD. ARMD Current
Treatment Concepts. Medical radiology. Londo n:
Springer, 2001.
9 Sparrow JR, Fishkin N, Zhou J, et al. A2E a by-
product of the visual cycle. Vis Res
2003;43:2983–90.
Spontaneous involution of
autologous lenses and
phacoanaphylaxis reaction i n
Stickler syndrome
Stickler syndrome is a ‘‘hereditary progres-
sive arthro-ophthalmopathy’’
1
caused in the
majority of cases by mutations of the COL2A1
gene encoding for type II collagen.
2
The
disease is transmitted as an autosomal
dominant trait with high penetrance but
variable expressivity.
3
Most common ocular
manifestations of the disease are myopia,
vitreous veils and degeneration, early catar-
act, retinal peripheral breaks and retinal
detachment.
34
Case report
This patient had typical ocular and extrao-
cular clinical manifestations of Stickler syn-
drome. She was fitted with contact lenses
(217.00 dioptres) at the age of 1 month.
Despite the relatively poor vision, hearing
impairment and skeletal problems, she devel-
oped well mentally and attended regular
school. With glasses (215.00) the visual
acuity (VA) was stable, around 6/21 (20/75)
for distance and J2 for near in both eyes.
A mild central opacity of the posterior lens
capsule was initially observed in both eyes
when she was 7 years old (fig 1A). The IOP
was 12 mm Hg, the corneas clear, anterior
chambers deep and devoid of any inflamma-
tory signs. Fundus examination disclosed no
changes from previous examinations (fig 1B).
Refraction and VA in both eyes remained
unchanged.
Accepted for publication 23 May 2005
Funding: none.
Conflict of interest: none.
Figure 1 (A) Mild opacity of the lens posterior capsule of the right eye initially observed at the age
of 7 years. (B) Appearance of the fundus demonstrating the retinal pigmentary changes in the
periphery and retinal degenerative changes within the posterior pole. (C) Marked opacification and
fusion of the lens capsules in the right eye observed at 9 years of age. (D) Mild capsule opacities
are still observed 2 years later, at 11 years of age. The refractive error at this stage is +1.25 and
the visual acuity for distance is 6/12 (20/40).
Figure 2 (A) Large cortical remnants are seen within the capsular bag remnant in the left eye with
an intense flare and many inflammatory cells. The cornea is still mildly hazy 2 weeks after the
phacoanaphylactic reaction. (B) The vitreous of the left eye is hazy with many cortical lens remnants
observed with transillumination at the slit lamp. (C) Right eye is quiet, the refractive error is +1.25,
and the uncorrected visual acuity 6/12 (20/40) despite the presence of mild lens capsule opacities.
(D) Left eye is also quiet showing the same characteristics as the right eye.
1532 PostScript
www.bjophthalmol.com
On 23 June 2002, at the age of 9 years, she
complained of blurred vision in the right eye.
Without glasses, VA for distance was 6/60
(20/200) and for near less than J16.
Involution of the lens material with marked
opacity of the fused capsules was detected
(fig 1C). Accurate retinoscopy was not
possible. No intraocular inflammatory signs
were observed.
On 23 May 2004, the right eye lens
opacities reabsorbed. Mild posterior capsule
opacity remains (fig 1D). VA without correc-
tion was 6/12 (20/40) and J10. Refraction
disclosed +1.25 D. The left eye VA and
myopia remained unchanged.
Six weeks later sudden pain, redness, and
loss of vision in the left eye occurred. A high
IOP of 60 mm Hg, hazy cornea, mutton fat
keratic precipitates with flare 3+ and cells 4+
were observed in the left eye anterior
chamber. She was treated with corticoster-
oids and antiglaucoma drops. Two weeks
later, a central tear of the posterior capsule
with large cortical remnants within the
capsular bag (fig 2A) and a multitude of
floating lens remnants with a granulomatous
inflammatory reaction were observed in the
vitreous (fig 2B). Following complete arrest
of the inflammatory processes and a return to
normal of the IOP, medical treatment was
discontinued 5 weeks after its initiation.
At her last visit on 21 November 2004, both
eyes were quiet. Only mild scattered lens
capsule opacities were detected in both eyes
(figs 2C and 2D). The VA without correction
was 6/12 (20/40) and J10 in both eyes. With
correction (+1.25) for distance and near
addition (+3.00), the VA in both eyes was 6/
9 (20/30) and J1 respectively. Multifocal
glasses were prescribed.
Comment
A quiet and uneventful involution of the
autologous lens occurred in the right eye
when the child was 9 years old. The mechan-
ism of this phenomenon is unclear and may
be associated with abnormalities of the lens
collagen and/or crystallines. The lens involu-
tion in the right eye was not associated with
any noticeable symptom but for a drop in
vision. Progressive clearing of the lens opacity
was followed by emmetropisation of the
initial refractive error and visual improve-
ment in the left eye. Two years later,
spontaneous involution of the lens in the
other eye was associated with a marked
intraocular granulomatous inflammatory
reaction (‘‘granulomatous uveitis’’) reminis-
cent of a phacoanaphylaxis reaction. This
acute reaction was, most probably, associated
with the ‘‘escape’’ of immune tolerance
towards the autologous lens antigens.
We are not aware of previous reports in the
literature describing similar ocular phenomena.
I Habil, E Cohen, I Karshai, D BenEzra
Pediatric Ophthalmology Unit, Hadass ah Hebrew
University, Jerusalem, Israel
F Behar-Cohen
Rothschild Ophthalmic Foundation, Paris, France
D BenEzra, F Behar-Cohen
U598, INSERM, Paris, France
Correspondence to: David BenEzra, MD, PhD,
Hadassah Hebrew University Hospital, POB 12000
Jerusalem, Israel; benezra@md.huji.ac.il
doi: 10.1136/bjo.2005.076935
References
1 Stickler GB, Belau PG, Farrell FJ, et al. Hereditary
progressive arthro-ophthalmopathy. Mayo Clin
Proc 1965;40:433–55.
2 Francomano CA, Liberfarb RM, Hirose T, et al.
The Stickler syndrome is closely linked to
COL2A1, the structural gene for type II collagen.
Pathol Immunopathol Res 1988;7:104–6.
3 Donoso LA, Edwards AO, Frost AT, et al.
Identification of a stop codon mutation in exon 2
of the collagen 2A1 gene in large stickler
syndrome family. Am J Ophthalmol
2002;134:720–7.
4 Spallone A. Stickler’s syndrome: a study of 12
families. Br J Ophthalmol 1987;71:504–9.
Temporal pterygium: benign or
not?
A true pterygium is a degenerative and
hyperplastic process in which the cornea is
invaded by a triangular fold of bulbar
conjunctiva. Duke-Elder states that the pter-
ygium when single is almost invariably found
on the nasal side.
1
The literature on pter-
ygium is abundant and almost from the
beginning the emphasis has been placed on
its location on the nasal side.
Squamous cell neoplasia of the conjunctiva
is relatively uncommon and can masquerade
as common, but less significant, ocular sur-
face conditions including pterygium or
chronic blepharoconjunctivitis. We present a
case of intraepithelial neoplasia, initially
diagnosed as inflamed pterygium.
Case report
A 77 year old man, who had worked on the
railways, presented with a 3 week history of
redness on the outer aspect of the left eye. No
history of associated pain, discharge, or
watering was elicited.
His medical history included hypertension
and hypercholesterolaemia under treatment.
Best corrected visual acuity in each eye was
6/5. On inspection of the anterior segment,
the left temporal conjunctiva showed a fleshy
tissue encroaching on the temporal periph-
eral cornea (fig 1). The peripheral cornea
showed an elevated ridge with punctate
staining. The overlying conjunctiva was
injected. The rest of the ocular examination
was within normal limits.
A provisional diagnosis of inflamed pter-
ygium of left eye was made and the patient
was commenced on prednisolone 0.5% eye
drops at this stage with advice to review in
2 weeks’ time.
On follow up no significant change was
noticed in the lesion. On further inquiry the
patient gave a history of injury to left eye
with hot ashes many years earlier. In view of
the atypical location and the appearance of
the lesion, we did an excision biopsy of
the conjunctival and corneal lesion.
Histopathology revealed an irregular epithe-
lial thickening associated with dyskeratosis
and full thickness dysplasia. Numerous mito-
tic figures, some atypical, were present
throughout the epithelium (fig 2). A diag-
nosis of conjunctival intraepithelial neoplasia
was made. Although no unequivocal evidence
of invasion was seen in the multiple sections
examined, fragmentation of the tissue during
processing precluded confirmation of com-
plete excision.
The patient was referred for further treat-
ment to an ocular oncologist and underwent
ruthenium plaque therapy followed by topical
5-fluorouracil treatment.
Comment
Temporal pterygium is reported, although
Dolezalova found only one case of unilateral
temporal pterygium out of 1388 Arab patients
with pterygia.
2
We would therefore consider
this case to be atypical.
The role of pterygium in the development
of ocular surface squamous neoplasia is
unclear.
3
Both conditions have a strong
association with exposure to ultraviolet-B
radiation. Sevel and Sealy’s study of 12
squamous cell carcinoma and 17 carcinoma
in situ arising in 100 pterygia found that it
can be difficult to distinguish a ‘‘reactive
pterygium’’ from carcinoma in situ and
malignant change should be considered in a
pterygium if there is unusual evidence of
invasion, extension, or if the lesion becomes
particularly vascular.
4
To our knowledge, the last reported case of
temporal pterygium was in the 1970s.
25
We
present this case to refresh the memory and
to highlight the importance of keeping an
index of suspicion for squamous cell neopla-
sia in any atypical presentation of the more
Accepted for publication 20 June 2005
Figure 1 Left eye showing presence of a soft
tissue lesion on the temporal conjunctiva
encroaching on the limbus before local excision
and radiotherapy.
Figure 2 Section through the conjunctiva
stained with haematoxylin and eosin. The main
figure demonstrates grossly and irregularly
thickened, dysplastic epithelium (Ep; scale bar,
100 mm). The inserts show an atypical mitosis
(above, arrow) and dyskeratosis (below,
arrowhead) within the epithelium.
PostScript 1533
www.bjophthalmol.com
common conjunctival lesions such as pter-
ygium.
B Ramasamy, S A Quah, M S Wishart
Department of Ophthalmology, North Cheshire
Hospitals NHS Trust, Lovely Lane, Warrington WA5
1QG, UK
P Hiscott
Unit of Ophthalmology, Department of Medicine,
University Clinical Departments, Duncan Building,
Daulby Street, Liverpool L69 3GA, UK
Correspondence to: Balasubramanian Ramasamy,
Department of Ophthalmology, Warrington Hospital
NHS Trust, Lovely Lane, Warrington WA5 1QG, UK;
anitharams@aol.com
doi: 10.1136/bjo.2005.071993
References
1 Duke-Elder S. System of ophthalmology, Vol III,
Part I. St Louis: Mosby, 1965:573–83.
2 Dolezalova V. Is the occurrence of a temporal
pterygium really so rare? Ophthalmologica
1977;174:88–91.
3 Lee GA, Hirst LW. Ocular surface squamous
neoplasia. Surv Ophthalmol 1995;39:429–50.
4 Sevel D, Sealy R. Pterygia and carcinoma of the
conjunctiva. Trans Ophthalmol Soc UK
1968;88:567–8.
5 Awan KJ. The clinical significance of a single
unilateral temporal pterygium. Can J Ophthalmol
1975;10:222–6.
Simultaneous intraosseous and
intradural capillary
haemangioma of orbit
Primary intraosseous haemangioma is an
uncommon tumour of bone which tends to
involve the vertebrae and skull.
12
Bony
orbital lesions are rare with very few case
reports in the literature.
134
Simultaneous
intradural involvement has never been
reported in association with an orbital com-
ponent. We report an unusual case of
capillary haemangioma of the orbital roof
with periorbital and dural involvement.
Case report
A 39 year old white male was seen with a
1 year history of painless right upper eyelid
swelling and reduced superior visual field. He
had marked downward (3 mm), outward
(2 mm), and axial (4 mm) displacement of
the right globe (fig 1A), with limitation of
elevation and 5 dioptres of hypotropia in
upgaze. The remaining ocular and systemic
evaluation were normal.
Contrast enhanced CT and gadolinium
enhanced magnetic resonance imaging
(MRI) (fig 1B) demonstrated a well circum-
scribed faintly calcified mass centred within
the bony roof of the right orbit. It was
homogeneously isointense to grey matter on
T1WI, slightly hyperintense on T2WI, and
demonstrated marked homogeneous contrast
enhancement. Transosseous extension
intraorbitally was noted, with displacement
of the superior rectus muscle, optic nerve,
and globe inferiorly without evidence of
invasion or encasement. Transosseous exten-
sion of the mass intracranially was comple-
tely extra-axial in location, with involvement
of the adjacent dura. Provisional diagnosis in
the absence of a known primary tumour, was
intraosseous meningioma.
The patient underwent right sided frontal
craniotomy and orbital osteotomy with piece-
meal gross total resection of the right orbital
roof, the involved adjacent periorbita, dura
and bone.
Grossly, pathological samples including
dura (fig 2A) were soft and reddish-light
tan coloured in appearance. Microscopic
examination (fig 2B) revealed a cellular
capillary haemangioma of bone, with peri-
orbital and dural involvement (fig 2D), con-
sisting of thin walled blood vessels with some
osteoblastic activity and new bone formation.
Tumour immunohistochemistry stains for
CD34 (fig 2C), CD31, vimentin, and O13
were positive, confirming a vascular origin.
Comment
Intraosseous haemangiomas are benign
tumours arising from the intrinsic blood
vessels of bone and are two to three times
more common in females than males.
135
They are slow growing, accounting for only
0.7–1% of bone tumours, with the most
common site being the vertebrae and skull
(frontal and parietal).
134
They are typically
seen in the adult population, with a peak in
the fourth decade, although any age can be
affected.
1 3–6
Haemangiomas are histopatho-
logically classified as either cavernous (com-
mon in the skull and orbit) or capillary
(found mainly in vertebrae).
1
The pathogen-
esis of these tumours is unknown.
1
The clinical presentation of orbital
intraosseous haemangioma is usually a pro-
gressive asymptomatic mass which may lead
to proptosis, diplopia, optic neuropathy, and
ptosis. To date, the largest series
3
contained
21 cases, of which four were of the capillary
type.
3
Though intracranial extension has been
noted in the past, intradural lesion is reported
only once with calvarial capillary haeman-
gioma (sphenoid)
5
but never with orbital
invasion.
Plain films typically show bony erosion
with scalloped bone giving a ‘‘sunburst’’
appearance.
14 5
Cavernous and capillary hae-
mangiomas usually have similar imaging
findings with differentiation made on histo-
pathological analysis.
1
The differential diagnosis for a localised lytic
bone lesion with calcifications is wide, includ-
ing primary bone tumours such as osteosar-
coma, chondrosarcoma, meningioma,
haemangioma, brown tumour, or infection.
Reactive lesions, such as xanthoma of bone,
aneurysmal bone cyst, and reparative granu-
loma are also in the differential. Careful
radiological evaluation in combination with
clinical history and findings usually allows for
differentiation among these different lesions.
With respect to our case, the characteristic
high signal intensity on T1 imaging usually
seen in vertebral haemangiomas was absent,
probably the result of a relatively low fat
content.
12
Accepted for publication 22 June 2005
Competing interests: none declared
Figure 1 (A) A 39 year old patient showing proptosis and ptosis in the right eye. (B) Gadolinium
enhanced coronal T1 fat saturated image through the orbits demonstrates an intraosseous mass in
the right orbital roof, with intraorbital and intracranial extension. The intracranial portion was
completely extra-axial, with associated dural involvement, as indicated by the thickened and
enhancing dura adjacent to the dominant intracranial component. (C) Contrast enhanced coronal
computed tomography (CT) image through the orbits demonstrates an intraosseous mass in the
right orbital roof, with intraorbital and intracranial extension. Its heterogeneous appearance is the
result, in part, of scattered calcifications throughout the mass. Mass effect upon the superior
extraocular muscle group is evident.
1534 PostScript
www.bjophthalmol.com
In our case, atypical dural enhancement on
imaging was noted with associated erosion of
overlying frontal bone.
Preferred treatment for symptomatic hae-
mangiomas is surgical resection of the entire
lesion, with preoperative embolisation.
13–6
Radiation has been advocated for large and/
or unresectable lesions.
147
N B Shah
Aravind Eye Hospital, Madurai, India
V A White
Department of Pathology, and Ophthalmology and
Visual Sciences, VGH, UBC, Canada
M Heran
Department of Radiology, VGH, UBC, Canada
C Haw
Department of Neurosurgery, VGH, UBC, Canada
J Rootman
Departments of Ophthalmology and Visual Sciences,
and Pathology, VGH, UBC, Canada
Correspondence to: Dr Jack Rootman, Department of
Ophthalmology and Visual Sciences, University of
British Columbia, 2550 Willow Street, Vancouver, BC,
Canada V5Z 3N9; jrootman@interchange.ubc.ca
doi: 10.1136/bjo.2005.074427
References
1 Sweet C, Richard S, Bharat Mehta. Primary
intraosseous hemangioma of the orbit: CT and MR
appearance. AJNR 1997;18:379–84.
2 Ross JS, Masaryk TJ, Modic MT, et al. Vertebral
hemangioma: MR imaging. Radiology
1987;165:165–9.
3 Relf SJ, Bartley GB, Unni KK. Primary orbital
intraosseous hemangioma. Ophthalmology
1991;98:541–7.
4 Hook SR, Font RL, Mc Cary JA, et al. Intraosseous
capillary hemangioma of the frontal bone.
Am J Ophthalmol 1987;103:824–7.
5 Khanam H, Maurice HL, Charles LW, et al.
Calvarial hemangiomas: report of 2 cases and
review of the literature. Surg Neurol
2001;55:67–72.
6 Hornblass A, Zaidman GW. Intraosseous orbital
cavernous hemangioma. Ophthalmology
1981;88:1351–5.
7 Pandey SS, Pandey AK. Osseous hemangiomas.
Arch Orthop Trauma Surg 1981;99:23–8.
Two novel mutations of connexin
genes in Chinese families with
autosomal dominant congenital
nuclear cataract
Congenital or childhood cataract is a clini-
cally and genetically highly heterogeneous
lens disorder, with autosomal dominant
inheritance being most common. Non-syn-
dromic congenital cataracts have an esti-
mated frequency of 1–6 per 10 000 live
births,
1
with one third of cases familial.
Underlying mutations have identified 14
genes involved in the pathogenesis of isolated
inherited cataract, including seven genes
coding for crystallins (CRYAA, CRYAB,
CRYBA1/A3, CRYBB1, CRYBB2, CRYGC,
CRYGD), two for gap junctional channel
protein (GJA3 and GJA8), two for lens
membrane protein (LIM2 and MIP), one for
beaded filament structural protein 2 (BFSP2),
and one for glucosaminyl (N-acetyl) transfer-
ase 2 (GCNT2), one for heat shock transcrip-
tion factor (HSF4). Here we report two novel
heterozygous mutations in the GJA8 and
GJA3 genes, in two Chinese families affected
by autosomal dominant congenital nuclear
cataracts.
Figure 2 (A) Gross tumour mass showing involved resected dura. (B) HPE: 864 magnification
showing thin walled blood vessels and osteoblastic activity of intraosseous cellular capillary
haemangioma. (C) 6640 magnification with CD 34 positivity confirming vascular origin. (D) 6640
dural involvement by capillary haemangioma.
Accepted for publication 6 June 2005
Competing interests: none declared
Table 1 Two point LOD scores for linkage between the cataract locus and 1q
markers in family A
Marker
order
Map
location
LOD scores at h =
0.00 0.10 0.20 0.30 0.40 0.50
D1S2651 142.24 24.49 0.23 0.25 0.14 0.01 0.00
D1S2746 147.60 24.39 0.53 0.60 0.46 0.22 0.00
D1S252 150.27 23.90 0.40 0.25 0.10 0.02 0.00
D1S2344 153.59 1.44 1.29 1.03 0.70 0.32 0.00
D1S442 154.74 0.43 0.04 0.25 0.10 0.02 0.00
D1S498 155.89 2.40 1.95 1.46 0.94 0.42 0.00
D1S2346 158.75 1.20 0.93 0.65 0.36 0.11 0.00
D1S305 159.32 2.40 1.95 1.46 0.94 0.42 0.00
D1S1595 161.05 0.49 0.50 0.41 0.25 0.08 0.00
D1S2635 165.62 0.61 0.56 0.43 0.27 0.09 0.00
D1S1167 168.52 2.44 1.95 1.46 0.94 0.43 0.00
D1S2844 175.03 2.40 1.95 1.46 0.94 0.42 0.00
D1S2878 177.86 24.75 0.09 0.23 0.22 0.14 0.00
Table 2 Two point LOD scores for linkage between the cataract locus and 13q
markers in family B
Marker
order
Map
location
LOD scores at h =
0.0 0.1 0.2 0.3 0.4 0.5
D13S1316 0.00 21.13 1.34 1.08 0.66 0.25 0.00
D13S1236 2.77 1.63 1.34 0.99 0.61 0.23 0.00
D13S175 6.03 1.04 0.88 0.66 0.40 0.16 0.00
D13S232 6.99 25.25 20.56 20.15 0.01 0.05 0.00
D13S1243 9.79 26.19 20.76 20.32 20.12 20.03 0.00
Pedigree and haplotype construction were undertaken using Cyrillic v.2.1 software (figs 1A and 2A).
PostScript 1535
www.bjophthalmol.com
Case report
We studied two Chinese three generation
nuclear cataract families with a dominant
pattern of inheritance. Clinical information
and blood specimens were obtained from 16
members of family A (seven affected and
nine unaffected), and 13 members of family
B (nine affected and four unaffected). All
participants had a full ocular assessment to
document the phenotype. The phenotype of
two families was characterised by bilateral
nuclear cataract that was present at birth or
developed during infancy. There was no
evidence of other systemic or ocular defects.
After obtaining informed consent, we used
a panel of 46 microsatellite markers to study
13 loci for known candidate genes of auto-
somal dominant congenital cataract suscept-
ibility. The markers’ order and position were
obtained from the Marshfield Genetic
Database (www.marshfield.org/genetics/
maps). Genotyping and data collection were
conducted by ABI Prism GeneMapper v 3.0
software. We carried out two point linkage
analysis using the MLINK program from the
Linkage v.5.10 software package. It suggested
positive linkage on chromosome 1q21.1 (lod
score was 2.44 for marker D1S1167) in family
A and chromosome 13q11–12 (lod score was
1.63 for marker D13S1326) in family B
(tables 1 and 2).
There are two strong candidate genes in
these regions, GJA8 encoding connexin
50 (Cx50) and GJA3 encoding connexin
46 (Cx46). We screened the mutation of
candidate genes by bidirectional sequencing
polymerase chain reaction products (300–
700 bp). Sequence analysis of the entire
coding region and immediate flanking
regions detected a heterozygous 191 T R G
(AF217524) transition in exon 2 of GJA8,
resulting in a Val R Gly substitution at codon
64 (fig 1B). Sequence analysis of GJA3
detected a heterozygous 134 G R C
(AF075290) transition, resulting in a
Trp(TGG) RSer (TCG ) substitution at codon
45 (fig 2B). We examined all unaffected
members of two families and 200 unrelated
normal controls for GJA3 and GJA8 gene
mutations but failed to detect these sequence
variations.
Comment
Three connexins are expressed in the lens:
connexin 43, connexin 46, and connexin 50.
Gap junction intercellular communication is
an essential part of the cell–cell communica-
tion system, which facilitates the exchange of
ions, metabolites, signalling molecules, and
other molecules with a molecular weight up
to 1 kDa.
2
Each gap junction channel is composed of
two hemi-channels, or connexons, which
dock in the extracellular space between
adjacent cells, and each connexon comprised
six integral transmembrane protein subunits
known as connexins. All connexins have four
transmembrane domains and two extracel-
lular loops with cytoplasmic N and C termini.
To date, four heterozygous missense Cx50
mutations (P88S, E48K, R23T, and I247M)
have been described, causing a nuclear or
zonular nuclear pulverulent cataract.
3–6
Six
mutations of Cx46 have been associated with
ADCC, including five missense mutations
(F32L, P59L, N63S, P187L, and N188T) and
one insertion mutation (1137 insC), which
resulted in a frame shift at codon 380
(S380fs).
7–12
Currently, two mutations occurred: Cx50
(G22R and D47A) results in cataracts in the
mouse,
13 14
but no dominant spontaneous or
mutagen induced cataracts have been asso-
ciated with the murine gene for GJA3 (Gja3).
V64G and W45S substitutions in two
Chinese families occurred within evolutiona-
rily conserved residues across species for
Cx50 and Cx46 (figs 1E and 2E). These two
mutant amino acid residue locate at the
phylogenetically conserved extracellular loop
1 (E1). The two extracellular loops mediate
docking between connexons and the E1 loop
has also been shown to be important for
determinant of the transjunctional voltage
required for closure of gap junction pores.
15
The mutant proteins may disrupt normal
interactions between the two connexons,
which may reduce resistance of the inter-
cellular channel to the leakage of small ions.
In conclusion, two novel heterozygous
mutations, V64G in Cx50 and W45S in
Cx46, were identified in two Chinese
families. These further expand the genetic
and phenotypic heterogeneity of cataract.
Z Ma, J Zheng, F Yang, J Ji, X Li, X Tang,
X Yuan, X Zhang, H Sun
Eye Center of Tianjin Medical University, Tianjin,
China
ZMa
National Center of Human Genome Research
(Beijing), Beijing, China
Correspondence to: Huimin Sun, Eye Center of Tianjin
Medical University, Tianjin, China;
doctorsunhm@eyou.com
doi: 10.1136/bjo.2005.075184
References
1 Lambert SL, Drack AV. Infantile cataracts. Surv
Ophthalmol 1996;40:427–58.
2 White TW. Unique and redundant connexin
contributions to lens development. Science
2002;295:319–20.
3 Shiels A, Mackay D, Ionides A, et al. A missense
mutation in the human connexin 50 gene (GJA8)
underlies autosomal dominant ‘‘zonular
pulverulent’’ cataract on chromosome 1q.
Am J Hum Genet 1998;62:526–32.
4 Berry V, Mackay D, Khaliq S, et al. Connexin 50
mutation in a family with congenital ‘‘zonular
nuclear’’ pulverulent cataract of Pakistani origin.
Hum Genet 1999;105:168–70.
5 Polyakov AV, Shagina IA, Khlebnikova OV, et al.
Mutation in the connexin 50 gene (GJA8) in a
Russian family with zonular pulverulent cataract.
Clin Genet 2001;60:476–8.
6 lloughby CE, Arab S, Gandhi R, et al. A novel
GJA8 mutation in an Iranian family with
progressive autosomal dominant congenital
nuclear cataract. J Med Genet 2003;40:e124.
7 Mackay D, Ionides A, Kibar Z, et al. Connexin46
mutations in autosomal dominant congenital
cataract. Am J Hum Genet 1999;64:1357–64.
8 Gerido DA, White TW. Connexin disorders of the
ear, skin, and lens. Biochim Biophys Acta
2004;1662:159–70.
Figure 1 (A) Pedigree and haplotype analysis of family A showing segregating nine microsatellite
markers on chromosome 1, listed in descending order from the centromere. Squares and circles
symbolise males and females, respectively. Solid and open symbols denote affected and unaffected
individuals, respectively. IV:2 is the proband. (B) Sequence chromatograms showing the
heterozygous 191 T R G transition that converts a Val residue (GTC) to a Gly residue (GGC) at
codon 64. (C) Sequence chromatograms of wild type allele. (D) Schematic diagram of the predicted
Cx50 polypeptide and location of V64G and known mutations. M1–M4, transmembrane domains
1–4; E1 and E2, extracellular domains 1 and 2, respectively. (E) Cx50 multiple protein sequence
alignment in different specices. Reference sequence numbers of protein are human (NP_005258),
mouse (NP_032149), and chicken (NP_990328). The arrow directed the mutant amino acid
residue.
Accepted for publication 1 June 2005
Competing interests: none declared
1536 PostScript
www.bjophthalmol.com
9 Rees MI, Watts P, Fenton I, et al. Further evidence
of autosomal dominant congenital zonular
pulverulent cataracts linked to 13q11 (CZP3) and
a novel mutation in connexin 46 (GJA3). Hum
Genet 2000;106:206–9.
10 Jiang H, Jin Y, Bu L, et al. A novel mutation in
GJA3 (connexin46) for autosomal dominant
congenital nuclear pulverulent cataract. Mol Vis
2003;9:579–83.
11 Bennett TM, Mackay DS, Knopf HL, et al. A
novel missense mutation in the gene for gap-
junction protein alpha3 (GJA3) associated with
autosomal dominant ‘‘nuclear punctate’’
cataracts linked to chromosome 13q. Mol Vis
2004;10:376–82.
12 Li Y, Wang J, Dong B, et al. A novel connexin46
(GJA3) mutation in autosomal dominant
congenital nuclear pulverulent cataract. Mol Vis
2004;10:668–71.
13 Tusnady GE, Simon I. The HMMTOP
transmembrane topology prediction server.
Bioinformatics 2001;17:849–50.
14 Rong P, Wang X, Niesman I, et al. Disruption of
Gja8 (a8 connexin) in mice leads to
microphthalmia associated with retardation of
lens growth and lens fiber maturation.
Development 2002;129:167–74.
15 Rubin JB, Verselis V, Bennett MVL, et al. domain
substitution procedure and its use to analyze
voltage dependence of homotypic gap junctions
formed by connexins 26 and 32. Proc Natl Acad
Sci USA 1992;89:3820–4.
Pneumosinus dilatans in a
13 year old female
Pneumosinus dilatans (PSD) is abnormal
dilatation of paranasal sinuses that may
occasionally present with visual symptoms.
We present a case of PSD associated with
sickle cell trait which occurred with visual
deterioration.
Case report
A 13 year old female presented with gradual
painless decrease of vision in both eyes for
1.5 years. Over this period her visual acuity
dropped from 20/30 (RE) and 20/160 (LE) to
hand motion in both eyes. Except for optic
atrophy in both eyes, other ocular examina-
tions were normal. In the visual field there
was diffuse peripheral field loss and general-
ised depression. Past medical history was
insignificant except for an appendectomy
5 years earlier.
An increased level of sickle cell haemoglo-
bin which constituted 24.9% of her total
haemoglobin was documented. Her Hb
A2
and
HbF were in the normal range. She had
anaemia with haemoglobin level of 9 g/dl,
which we could not find any reason for.
Significant expansion of paranasal sinuses
including maxillary, frontal, ethmoidal, and
sphenoid sinus was visible on magnetic
resonance images (MRI) of the patient as
shown in figure 1. Based on the MRI of the
patient, the diagnosis of PSD would be
appropriate.
Bilateral consecutive frontal craniotomy
was performed in order to unroof the optic
canal with the hope to release stretching of
the optic nerve which we thought was the
reason for her visual deterioration. Figure 1
(bottom) is an image of the surgical proce-
dure. It is clear that the optic nerves have
been entrapped in the bony canal and
probably suffered from severe stretching
and/or compressive effects. Six months after
the procedure her visual acuity was 20/1200
in both eyes.
Comment
Pneumosinus dilatans is an abnormal dilata-
tion of one or more of the paranasal sinuses.
It has diverse manifestations including pro-
gressive visual loss if the sphenoid sinus is
involved and/or if it is associated with optic
nerve meningioma. If the ethmoidal sinus is
involved it may present with proptosis.
1
Although a valve mechanism raising the
pressure inside the sinus is thought to be
responsible for this condition,
2
the exact
etiology is unknown.
3
In case of optic nerve
damage the nerve is usually compressed in
long bony tubes.
4
Pneumosinus dilatans has
been associated with meningioma of the
intracanalicular optic nerve and anterior
chiasmal angle,
56
middle cranial fossa ara-
chnoid cyst,
7
cerebral hemiatrophy, and
prolonged cerebrospinal fluid shunting.
8
To our knowledge this is the first case of
PSD associated with sickle cell trait. PSD has
not been associated previously with haema-
tological disorders. Considering the fact that
sickle cell trait is generally an asymptomatic
condition and the patient’s mother was also
an asymptomatic carrier, an aetiological
relation is unproved. On the other hand,
both conditions are rare in our population,
therefore the probability of coincidence by
chance would seem to be extremely low. The
question remains whether our patient had an
unusual form of sickle cell trait associated
with gross bony involvement and deformity.
Different treatments have been proposed
for PSD. These include subtotal resection of
the medial wall of the maxillary sinus by an
endoscopic approach,
9
osteotomy of the
deformed fronto-orbital bossing, and oblit-
eration of the sinus with fat.
10
Because of
global and massive expansion of the sinuses
and severe optic nerve dysfunction in this
case, we preferred to decompress the optic
nerve by removing the roof of bony canal
which surrounded the intracranial optic
nerve. This resulted in mild visual improve-
ment.
M S Sanjari, M Modarreszadeh, K Tarassoly
Ophthalmology Department Eye Research Center,
Rasool Akram Hospital, Tehran, Iran
Correspondence to: Kia Tarassoly, MD,
Ophthalmology Department, Eye Research Center,
Rasool Akram Hospital, Tehran, Iran; kiatarassoly@
hotmail.com
doi: 10.1136/bjo.2005.069567
Figure 2 (A) Pedigree and haplotype analysis of family B showing segregation of four
microsatellite markers on chromosome 13q. Squares and circles symbolise males and females,
respectively. Solid and open symbols denote affected and unaffected individuals, respectively. IV:5
is the proband. (B) Sequence chromatograms showing the heterozygous 134 G RC transition
resulting in a Trp(TGG) RSer (TCG ) substitution at codon 45. (C) Sequence chromatograms of wild
type allele. (D) Exon organisation and mutation profile of GJA3. Cx46 has nine structural domains
including a cytoplasmic amino-terminus (NT), four transmembrane domains (M1–M4), two
extracellular loops (E1–E2), a cytoplasmic loop (CL), and a cytoplasmic carboxy-terminus (CT). The
relative locations of the W45S mutation and other mutations associated with dominant cataracts in
humans are indicated. (E) Cx50 multiple protein sequence alignment in different species. Reference
sequence numbers of protein are human (NP_068773), mouse (NP_058671), rat (Rattus
norvegicus) (NP_077352), and zebrafish (Donio rerio) (NP_997525). The arrow directed the
mutant amino acid residue.
Accepted for publication 1 March 2005
PostScript 1537
www.bjophthalmol.com
References
1 Skolnick CA, Mafee MF, Goodwin JA.
Pneumosinus dilatans of the sphenoid sinus
presenting with visual loss. J Neuro-ophthalmol
2000;20:259–63.
2 Wolfensberger M. Pathogenesis of pneumosinus
maxillaris dilatans. HNO 1984;32:518–20.
3 Walker JL, Jones NS. Pneumosinus dilatans of the
frontal sinuses: two cases and a discussion of its
aetiology. J Laryngol Otol 2002;116:382–5.
4 Stretch JR, Poole MD. Pneumosinus dilatans as the
aetiology of progressive bilateral blindness.
Br J Plast Surg 1992;45:469–73.
5 Hirst LW, Miller NR, Hodges FJ 3rd, et al.
phenoid pneumosinus dilatans. A sign of
meningioma originating in the optic canal.
Neuroradiology 1982;22:207–10.
6 Mai A, Karis J, Sivakumar K. Meningioma with
pneumosinus dilatans. Neurology
2003;60:1861.
7 Redla S, Husami Y, Colquhoun IR. Apparent
paradoxical vault changes with middle cranial
fossa arachnoid cysts—implication for aetiology.
Clin Radiol 2001;56:851–5.
8 Van Schayck R, Niedeggen A. Pneumosinus
dilatans after prolonged cerebrospinal fluid
shunting in young adults with cerebral
hemiatrophy. A report of two cases and review of
the literature. Neurosurg Rev 1992;15:217–23.
9 Juhl HJ, Buchwald C, Bollinger B. An extensive
maxillary pneumosinus dilatans. Rhinology
2001;39:236–8.
10 Tellado MG, Mendez R, Lopez-Cedrun JL, et al.
Pneumosinus dilatans of the frontal and ethmoidal
sinuses: case report. J Craniomaxillofac Surg
2002;30:62–4.
Pellucid marginal degeneration
coexistent with cornea plana in
one member of a family
exhibiting a novel KERA mutation
Characterised by flattening of the normally
convex corneal surface, small corneas, high
hyperopia, and arcus senilis, autosomal
recessive cornea plana is secondary to KERA
mutation.
1–3
KERA encodes keratocan, an
evolutionary conserved small leucine rich
proteoglycan. Keratocan, highly and uniquely
expressed in the cornea, is composed of core
proteins consisting mostly of leucine rich
repeats (LRRs).
1–3
All patients documented to
be homozygous for one of the four previously
reported KERA mutations have disruption of
LRR architecture and demonstrate similar
cornea plana phenotypes.
1–3
In contrast,
corneal pellucid marginal degeneration
(PMD) is an idiopathic progressive ectatic
corneal disorder that is clinically diagnosed
by characteristic thinning, resultant ‘‘against
the rule’’ astigmatism, and absence of opa-
city.
4
We report a case of superior PMD
coexistent with cornea plana in a family
exhibiting a novel KERA mutation and docu-
ment the ophthalmic findings of the family.
Case series
Twelve individuals from a Saudi nuclear
family were studied after institutional review
board approval and family informed consent
had been obtained from the family. Clinical
findings and diagnoses are summarised in
figures 1 and 2, and table 1. Only one family
member (patient 4) had a history of progres-
sive visual difficulty over the last several
years, and this was due to an increasing
astigmatic refractive error. Axial lengths and
keratometry readings were recorded using
the Zeiss IOL-Master (2001 model), and
corneal topography was performed using the
Bausch & Lomb Orbiscan 2Z (2002 model).
All family members underwent KERA DNA
sequencing using methods previously
described.
3
A novel mutation was detected
Figure 1 (Top) Magnetic resonance images show significant dilatation of paranasal sinuses.
(Bottom) Surgical field image. ‘‘O’’ is intracranial part of optic nerve, ‘‘+’’ is the bony canal after
partial removal; the metal instrument is a suction device tip.
Cornea plana
Pellucid marginal degeneration
and cornea plana
11
2
1
753 12109864
Figure 1 The family pedigree.
Figure 2 (A) The small flat corneas of a typical patient (No 3) are shown. (B) The slit lamp
appearance of patient 3 is shown. (C) In addition to small flat corneas and early arcus senilis,
patient 4 also demonstrated superior corneal thinning (arrow, LE) with associated corneal ectasia
characteristic of superior pellucid marginal corneal degeneration. (D) Topography, LE of patient 4
shows the characteristic high astigmatism of superior pellucid marginal corneal degeneration.
1538 PostScript
www.bjophthalmol.com
in exon 2, [1454 C.T, ENST00000266719],
changing an arginine amino acid at position
279 to a stop codon [R279X]. The resultant
truncated protein lacks the terminal 73
amino acids of normal keratocan. This muta-
tion was homozygous in the five siblings with
clinically evident cornea plana (Nos 3, 5, 7,
11, 12) and the sister with clinical findings of
PMD and cornea plana (No 4). All other
family members (Nos 1, 2, 6, 8, 9, 10) were
heterozygous for the mutation and clinically
unaffected.
Comment
All four previously reported KERA mutations
disrupt keratocan LRR architecture and are
associated with similar corneal phenotypes in
documented homozygotes.
1–3
The current
mutation [R279X] similarly disrupts LLR
function, as the prematurely truncated pro-
tein lacks two LRRs of normal keratocan and
is associated with the expected cornea plana
phenotype. Interestingly, one homozygous
individual (No 4) demonstrates corneal find-
ings compatible with both superior PMD
(corneal thinning with astigmatism) and
autosomal recessive cornea plana (small
corneas, arcus senilis)—the presence of arcus
senilis excludes classic PMD alone by defini-
tion.
45
It is unlikely that the KERA mutation
itself is responsible for the PMD findings in
this individual. The sectorial thinning and
progressive high astigmatism characteristic of
superior PMD have not been reported in
individuals documented to be homozygous
for KERA mutation or in other pedigrees
consistent with autosomal recessive cornea
plana.
1–3 6
The PMD findings of patient 4 are
most likely the result of coincidence—that is,
the occurrence of both cornea plana and PMD
in the same individual. However, a defect in a
poorly understood mechanism other than
KERA itself that is responsible for normal
keratocan function cannot be completely
excluded as an explanation for these find-
ings.
7
A O Khan
Division of Pediatric Ophthalmology, King Khaled Eye
Specialist Hospital, PO Box 7191, Riyadh 11462,
Saudi Arabia
M Aldahmesh, A Al-Saif, B Meyer
Aragene Project, King Faisal Specialist Hospital and
Research Center, MBC 03-8, PO Box 3354, Riyadh
11211, Saudi Arabia
Correspondence to: Arif O Khan, MD, Division of
Pediatric Ophthalmology, King Khaled Eye Specialist
Hospital, PO Box 7191, Riyadh 11462, Saudi Arabia;
arif.khan@mssm.edu
doi: 10.1136/bjo.2005.073510
References
1 Pellegata NS, Dieguez-Lucena JL, Joensuu T,
et al. Mutations in KERA, encoding keratocan,
cause cornea plana. Nat Genet 2000;25:91–5.
2 Lehmann OJ, El-Ashry MF, Ebenezer N, et al. A
novel keratocan mutation causing autosomal
recessive cornea plana. Invest Ophthalmol Vis Sci
2001;42:3118–22.
3 Khan AO, Al-Saif A, Kamburosis M. A novel
KERA mutation associated with autosomal
recessive cornea plana. Ophthal Genet
2004;25:147–52.
4 Sridhar MS, Mashesh S, Bansal AK, et al. Pellucid
marginal corneal degeneration. Ophthalmology
2004;111:1102–7.
Table 1 Pertinent biometric and clinical characteristics of the family are summarised
123 4 5 67 891011 12
Age (years) 50 43 26 24 23 19 18 17 12 10 8 6
Keratometry RE 43.32,
43.95@102
40.61,
41.06@017
26.49,
28.60@060
45.79,
52.73@085
29.74,
32.23@138
42.51,
42.78@076
28.77,
30.21@086
43.10,
43.49@077
41.01,
41.98@093
39.52,
40.37@087
23.94,
26.81@035
31.72,
33.19@180
Keratometry LE 43.44,
44.23@101
40.96,
41.98@082
26.66,
30.13@104
38.66,
47.14@149
29.76,
31.78@065
42.51,
42.94@105
29.27,
33.28@090
42.72,
43.66@093
41.11,
42.51@092
39.61,
40.27@087
24.83,
27.42@117
32.02,
33.48@158
Horizontal corneal diameter
(RE, LE in mm)
10, 10 11, 11 8, 8 8, 8 8, 8 10, 10 8, 8 10, 10 11, 11 11, 11 8, 8 8, 8
Axial length (RE, LE in mm) 22.89,
22.34
23.81,
23.78
21.55,
21.62
25.17,
24.88
21.97,
22.05
23.43,
23.68
22.91,
23.65
23.19,
22.98
24.13,
24.05
24.11,
24.22
24.13,
23.88
22.18,
22.61
Cycloplegic refraction,
vision with refraction RE
+0.50,
20/30
plano,
20/20
+8.50,
20/60
plano-10.00
6110, 20/60
+9.5023.006030,
20/30
21.25
20/25
+10.0021.006080,
20/30
20.75,
20/20
20.50,
20/20
20.25,
20/20
+8.5022.506107,
20/40
+8.00,
2/30
Cycloplegic refraction,
vision with refraction LE
+2.00,
20/60
20.50,
20/20
+1.0029.006060,
20/50
plano-10.00
6070, 20/50
+11.0022.506140,
20/60
21.50
20/25
+9.0021.006180,
20/50
20.50,
20/20
20.50,
20/20
plano,
20/20
+9.00, 20/125 +8.00,
12/30
Comments Amblyopia
LE, anterior
chamber
shallow
both eyes,
peripheral
stromal
haze both
eyes
Prominent
arcus senilis
both eyes,
otherwise
normal
ophthalmic
exam
Amblyopia LE,
16 prism dioptres
esotropia at near
with correction
Pellucid
marginal
degeneration
both eyes,
small cornea
both eyes,
arcus senilis
both eyes
Amblyopia LE.RE,
20 prism dioptres
esotropia at near with
correction
Normal
ophthalmic
exam with
deep
anterior
chamber
both eyes
Amblyopia LE Normal
ophthalmic
exam with
deep
anterior
chamber
both eyes
Normal
ophthalmic
exam with
deep
anterior
chamber
both eyes
Normal
ophthalmic
exam with
deep
anterior
chamber
both eyes
Amblyopia LE.RE,
40 prism dioptres
V-pattern esotropia
at near with
correction, iris
defect RE
Amblyopia
RE.LE,
poor
cooperation
Accepted for publication 1 May 2005
PostScript 1539
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5 Sridhar MS, Mahesh S, Bansak AK, et al.
Superior pellucid marginal corneal degeneration.
Eye 2004;18:393–9.
6 Forsius H, Damsten M, Eriksson AW, et al.
Autosmal recessive cornea plana. A clinical and
genetic study of 78 cases in Finland. Acta
Ophthalmol Scand 1998;76:196–203.
7 Dipple KM, McCabe ERB. Phenotypes of patient s
with ‘‘simple’’ Mendelian disorders are complex
traits: thresholds, modifiers, and systems
dynamics. Am J Hum Genet 2000;66:1729–35.
Alteration of cyclic frequency by
botulinum toxin injection in adult
onset cyclic esotropia
Cyclic strabismus is an uncommon disorder
in which strabismus comes and goes alter-
nately, consistently, and repetitively over a
period of time. In a 48 hour cycle, a 24 hour
period of orthotropia would be followed by a
24 hour period of constant strabismus. Cycles
of 24 hour
1
to 96 hour
2
patterns have been
reported. Most cases have been described in
children, and the aetiology of cyclic strabis-
mus is still speculative.
Case report
A 57 year old woman was referred to
Kaohsiung Medical University Hospital with
the complaint of a periodic visual fluctuation
of a ‘‘good day‘‘ and a ‘‘bad day’’ alternately
for about 6 months. She had diplopia on bad
days. She did not have diabetes or hyperten-
sion. There was no history of strabismus,
amblyopia, patching therapy, ocular trauma,
or oculomotor palsy. She had received trials
of Mestinon treatment by two neurologists.
Except for pterygium excision 4 years earlier,
other ocular and medical history were unre-
markable. There was no family history of
strabismus.
Her visual acuity was 20/25 with +1.25 lens
RE and 20/20 LE plano. Cycloplegic refraction
was +1.25 RE and +0.50 LE. The anterior
segments were normal except for recurrent
pterygia on the nasal limbus in both eyes.
Ophthalmoscopic examination, ocular align-
ment (fig 1A), and ocular motility were
normal. Since the initial examination was
on her ‘‘good day,’’ she was asked to come
back the next day—that is, on the ‘‘bad day.’’
The next day, there was a 25 prism dioptre,
commitant right esotropia (fig 1B) with full
ocular motility. The visual acuity was
unchanged. Brain and orbit magnetic reso-
nance imaging studies were unremarkable
except for a suspected small arachnoid cyst
on the right side of the falx.
She received 2.5 U botulinum toxin
(Botox) injection in her right medial rectus
muscle (MR). The alignment was orthotropia
1 week after the injection. She was asympto-
matic for about 2 months, but the cyclic
pattern returned with a 96 hour cycle by
patient history. A repeated 2.5 U Botox
injection in right MR, which was given
3 months after the first, produced another
asymptomatic period of 2 months. Two
months after the second injection, she
experienced constant strabismus without
cyclic pattern, which persisted for about
1 year. She received right MR recession by
4 mm and right lateral rectus muscle resec-
tion by 5 mm for constant esotropia of
25 prism dioptres. After the surgery, the
alignment was orthotropic and no recurrent
of the cyclic pattern during 1 month of follow
up. The stereopsis was 200 seconds of arc by
Titmus test.
Comment
Adult onset cyclic strabismus is rare,
2–8
and,
to the best of our knowledge, only 10 patients
have been reported. The reported cases of
adult onset cyclic strabismus are summarised
in table 1. The patients had various ages of
onset between 21 and 67 years. Most
reported cases demonstrated 48 hour cyclic
patterns. The persistence of the cycles, if not
interrupted by surgery, was as long as
7 years.
8
It is interesting that adult onset
cyclic strabismus occurs predominantly in
females and is frequently related to ocular or
orbital diseases, trauma, or surgery.
4–8
Botox injection has been used as treatment
of cyclic strabismus.
7
However, no change of
the cyclic pattern was mentioned. We noted
that the cyclic pattern in our patient changed
3 months after the first Botox injection, and
the cycles were eliminated 2 months after the
second injection.
The characteristics of cyclic strabismus in
children are an average age of onset between
3 and 4 years, moderate hyperopia, and
moderate angle.
3
However, a female prepon-
derance was not noted in childhood onset
cyclic esotropia. No pertinent explanation for
cyclic strabismus has been reported.
Although Botox only has a temporary effect,
both Botox injection
7
and eye muscle surgery
3
produce good ocular alignment results. More
evidence and further investigation are
required to elucidate the mystery.
Acknowledgements
The authors thank Professor William F Hoyt and
Professor Creig S Hoyt for their review and criticism
of this letter.
Y-H Lai
Department of Ophthalmology, Kaohsiun g Medical
University Hsiao-Kang Hospital, Kaohsiung Medical
University, Kaohsiung, Taiwan
D R Fredrick
Department of Ophthalmology, University of
California, San Francisco, San Francisco, CA, USA
Figure 1 (A) ‘‘Good day’’—orthotropia; (B)
‘‘Bad day’’—esotropia.
Table 1 Summary of the adult onset cyclic strabismus
Case
No
Age of
onset
(years) Sex
Cyclic
pattern
Duration
of
cycles Angle (D)
Related diseases
or coexistent conditions Outcome References
1 34 Male 4 days 3 years ET 35
Optic atrophy both eyes, alcohol
abuse
No treatment Frenkel
2
2 32 Female* 2 days NA ET 35 NA No treatment, CPP? Helveston
3
3 53 Female 2 days NA
XT 15,
RHT 30
Graves’ disease OT after muscle surgery Knapp
4
4 55 Female 2 days NA RHT 25 Graves’ disease OT after muscle surgery Knapp
4
5 67 Female 2 days 5 years
ET 25,
RHT 8
RD RE, 360
˚
encircling scleral
buckling procedure RE, cyclic
mydriasis and ptosis
No treatment, CPP Troost
5
6 34 Female 2 days 9 weeks
LHT 20,
XT 10
Craniofacial surgery for fronto-
orbital fibrous dysplasia, left side
OT after muscle surgery Metz
6
7 46 Female 2 days 1 year
ET 12 to
45
ECCE RE, high myopia RE
Botulinum toxin injection, ET
2D with cycle eliminated after
muscle surgery
Riordan-Eva
7
8 21 Female 5 days? 2 years ET 25
RD RE, vitreolensectomy and
silicone oil exchange RE
Botulinum toxin injection, CPP Riordan-Eva
7
9 49 Female 2 days 7 years
RHT 15,
ET 25
ECCE RE, RD and PVR RE, PVT
and scleral buckling RE, ECCE LE,
prophylactic encircling band
surgery LE
OT after muscle surgery Bagheri
8
10 57 Female 2 days 1year ET 30 Recurrent pterygia in both eyes,
Botulinum toxin injection,
cyclic pattern changed,
OT after muscle surgery
Present report
*Information provided by Dr Eugene Helveston (personal communication). NA, not available; CPP, cyclic pattern persisted; D, prism dioptre; ET, esotropia; XT,
exotropia; RHT, right hypertropia; LHT, left hypertropia; OT, orthotropia; RD, retinal detachment; PVR, proliferative vitreoretinopathy; ECCE, extracapsular
cataract extraction; PVT, posterior vitrectomy.
1540 PostScript
www.bjophthalmol.com
Correspondence to: Yu-Hung Lai, Department of
Ophthalmology, Kaohsiung Medical University Hsiao-
Kang Hospital, Kaohsiung Medical University, 100
Zihyou 1st Road, Kaohsiung, 807, Taiwan; yuhung.
lai@msa.hinet.net
doi: 10.1136/bjo.2005.069021
References
1 Windsor CE, Berg EF. Circadian heterotropia.
Am J Ophthalmol 1969;67:565–71.
2 Frenkel RE, Brodsky MC, Spoor TC. Adult-onset
cyclic esotropia and optic atrophy. J Clin Neuro-
ophthalmol 1986;6:27–30.
3 Helveston EM. Cyclic strabismus. Am Orthopt J
1973;23:48–51.
4 Knapp P. Special types of muscle anomalies
associated with Graves’ disease. Ophthalmology
1979;86:2081–4.
5 Troost BT, Abel L, Noreika J, et al. Acquire d cyclic
esotropia in an adult. Am J Ophthalmol
1981;91:8–13.
6 Metz HS, Searl SS. Cyclic vertical deviation. Trans
Am Ophthalmol Soc 1984;82:158–65.
7 Riordan-Eva P, Vickers SF, McCarry B, et al.
Cyclic strabismus without binocular function.
J Pediatr Ophthalmol Strabismus
1993;30:106–8.
8 Bagheri A, Ahmadieh H, Repka MX. Acquired
cyclic strabismus in an adult. J Pediatr Ophthalmol
Strabismus 2002;39:310–12.
Hand hygiene in routine
glaucoma clinics
Nosocomial infection occurs via the hands of
healthcare workers (HCWs).
1
Hand hygiene
reduces hospital infection rates; however,
HCWs seldom comply with this.
2
We determined how often ophthalmolo-
gists and allied professionals cleaned their
hands and whether intervention was effec-
tive.
Participants, methods, and results
We conducted the study in the daily glau-
coma clinics of Moorfields Eye Hospital
where policy states that all HCWs must clean
their hands between patients.
For 1 week, hand hygiene practice was
monitored covertly by two observers.
Potential hand cleaning opportunities were
before or during patient contact, before or
after manipulative procedures, and after
glove removal. Manipulative procedures were
defined as 5-fluorouracil subconjunctival
injection, taking an eye swab, suture, or
supramid removal, and bleb needling or
massage.
Without revealing how the study was
conducted, preliminary results were pre-
sented and also distributed by memo. Two
weeks after this intervention, hand hygiene
was re-monitored for 1 week.
Baseline hand hygiene episodes were 18%
but increased significantly to 28% (p = 0.005)
following intervention (table 1). Before inter-
vention two out of seven people performing
procedures cleaned their hands, but not for
the single episode that 5-fluorouracil was
used. However, after intervention six out of
seven HCWs cleaned their hands (p = 0.04),
including all three episodes in which 5-
fluorouracil was handled.
Before intervention, female HCWs cleaned
their hands significantly more than males
(30% v 9%, p,0.001). After intervention
hand hygiene increased further for females
(54%, p,0.001) with no change for males
(11%, p = 0.57).
Nurses had the highest frequency of hand
cleaning but with no change after interven-
tion (69% v 58%, p = 0.36). Increased hand
hygiene was significant for doctors following
intervention (11% v 20%, p = 0.01).
Comment
Recently, nosocomial infection has attracted
considerable media interest. While proble-
matic worldwide, the United Kingdom has
one of the highest rates of methicillin
resistant Staphylococcus aureus (MRSA).
3
The
hands of HCWs are a major route of
transmission. Hand hygiene frequencies
range from 3%,
2
increasing to more than
60% when HCWs are aware of being
observed.
4
In our study, hand hygiene was low (18%).
Although significant improvement followed
intervention (28%) this was far from the
hospital standard. Our new level of hand
cleaning is likely to be transient as all but one
study has demonstrated sustained improve-
ment.
5
Previous studies, including our own, have
shown that female HCWs clean their hands
more often than males.
6
In general, sex
differences in hand washing are explained
by the social role theory—that is, females are
communal whereas men are agentic.
7
Hence,
women are more likely than men to partici-
pate in socially acceptable behaviour such as
hand washing.
8
In our study, intervention
produced a significant improvement in hand
hygiene for females with no effect on males.
Behaviourally, men are less easily influenced
than women,
7
which may explain why inter-
vention had no effect on male HCWs.
As with previous studies
59
our nurses had
the highest frequency of hand hygiene (69%).
This could be because most nurses are female
or because of an emphasis on hand washing
in their undergraduate training. However,
with our nurses hand hygiene did not
increase following intervention. Possibly few
nurses were present at the lecture, hence,
they only received written information con-
cerning initial study results.
As observed by others,
569
we found hand
hygiene among doctors was low (11%).
However, intervention had its greatest effect
on the doctors (p = 0.01). Although numbers
are small, intervention had a positive effect
on manipulative procedures, especially when
using 5-fluorouracil.
Our study demonstrates that hospital
policy is not being practised. Getting HCWs
to clean their hands has been an ongoing
struggle since Semmelweis. It has been
suggested that patients should ask their
healthcare professional to hand wash.
10
Although controversial, this may help in the
eradication of hospital acquired infection.
E Mensah, I E Murdoch, K Binstead,
C Rotheram, W Franks
Moorfields Eye Hospital NHS Foundation Trust, City
Road, London EC1V 2PD, UK
Correspondence to: E Mensah, Moorfields Eye
Hospital NHS Foundation Trust, City Road, London
EC1V 2PD, UK; eveosh@aol.com
Accepted for publication 3 May 2005
Table 1 Effect of intervention on hand hygiene compliance
Hand hygiene before intervention
Hand hygiene after
intervention
p ValueNo (%) No (%)
Hand hygiene opportunities 249 291
Hand hygiene episodes before patient contact 36 (14) 73 (25) 0.002
Hand hygiene episodes during patient contact 8 (3) 8 (3) 1.00
Total hand hygiene episodes 44 (18) 81 (28) 0.005
Hand hygiene episodes for procedures 2/7 (0/1 for 5-FU) 6/7 (3/3 for 5-FU) 0.04
Sex of healthcare worker
Female 32/107 (30)* 62/115 (54** ,0.001
Male 12/133 (9)* 20/182 (11)** 0.57
Profession of healthcare worker
Doctor 21/191 (11) 44/220 (20) 0.01
Nurse 18/26 (69) 25/43 (58) 0.36
Optometrist 3/19 (16) 8/26 (31) 0.25
Other 2/8 (25) 1/7 (14) 0.62
Only three out of nine examination bays were observed for 1 hour at a time, in random order, during morning (from 09:30 to 12:30) and afternoon (from 14:00
to 17:00) clinics.
Data were analysed using x
2
contingency tests.
5-FU = 5-fluorouracil.
*p,0.001; **p,0.001.
Local ethics approval was obtained for this study.
doi: 10.1136/bjo.2005.072538
Accepted for publication 21 May 2005
PostScript 1541
www.bjophthalmol.com
References
1 Bauer TM, Ofner E, Just HM, et al. An
epidemiological study assessing the relative
importance of airborne and direct contact
transmission of microorganisms in a medical
intensive care unit. J Hosp Infect 1990;15:301–9.
2 Bischoff WE, Reynolds TM, Sessler CN, et al.
Handwashing compliance by health care workers.
The impact of introducing an accessible, alcohol-
based hand antiseptic. Arch Intern Med
2000;160:1017–21.
3 Tiemersma EW, Bronzwaer SLAM, Lyytikainen O,
et al. Methicillin-resistant Staphylococcus aureus
in Europe, 1999–2002. Emerg Infect Dis
2004;10:1627–34.
4 Pittet D, Simon A, Hugonnet S, et al. Hand
hygiene among physicians: performance, beliefs,
and perceptions. Ann Intern Med 2004;141:1–8.
5 Hugonnet S, Perneger TV, Pittet D. Alcohol-based
handrub improves compliance with hand hygiene
in intensive care units. Arch Intern Med
2002;162:1037–43.
6 van de Mortel T, Bourke R, McLoughlin J, et al.
Gender influences handwashing rates in the
critical care unit. Am J Infect Control
2001;29:395–9.
7 Eagly AH. Sex differences and social
behaviour: a social role interpretation. Hillsdale,
NJ: Erlbaum, 1987.
8 Johnson HD, Sholcosky D, Gabello K, et al. Sex
differences in public restroom handwashing
behaviour associated with visual behaviour
prompts. Percept Mot Skills 2003;97(3
Pt1):805–10.
9 Pittet D, Hugonnet S, Harbarth S, et al.
Effectiveness of a hospital-wide programme to
improve compliance with hand hygiene. Infection
control programme. Lancet 2000;356:1307–12.
10 Jarvis WR. Handwashing—the Semmelweis
lesson forgotten? Lancet 1994;344:1311–12.
Successful treatment of
Wegener’s granulomatosis
associated scleritis with
rituximab
Rituximab (Rituxan, Genentech, Inc, South
San Francisco, CA, USA) is a new anti-CD20
B cell monoclonal antibody that has been
used successfully to treat refractory cases of
Wegener’s granulomatosis (WG).
1–3
There has
been no published report of its effect in
Wegener’s associated eye disease. We
describe the successful treatment of
Wegener’s associated scleritis with rituximab.
Case report
A 21 year old man with WG, proved on renal
biopsy and by anti-neutrophil cytoplasm
antibody (ANCA) positivity 6 years earlier,
presented with bilateral, painful, red eyes. On
examination his visual acuities were 6/4 right
eye and 6/5 left eye. Anterior segment
examination showed subconjunctival hae-
morrhage, congested scleral vessels, scleral
oedema, peripheral corneal infiltrates, and
mild anterior chamber inflammation in each
eye. Funduscopy revealed bilateral swollen
optic discs with scattered retinal haemor-
rhages in the right eye. A diagnosis of scleritis
was made. Oral prednisolone was increased
from 5–40 mg daily and maintenance oral
mycophenolate mofetil 2 g daily was contin-
ued. Topical prednisolone acetate 1% hourly
was commenced to both eyes.
Over the next month the scleritis had not
improved and his systemic vasculitis had
become more active, causing arthralgia,
haemoptysis, and new vasculitic skin lesions.
His white cell count (WCC) had risen to
13.9610
9
compared to 9.6610
9
the previous
month. His ANCA had become positive by
indirect immunofluorescence (titre of 1 in
25), and by proteinase 3 specific ELISA (titre
22 units, normal range ,10). A new infiltrate
was present in the lower lobe of his right lung
on chest x ray.
Owing to concern over the total cumulative
dose of cyclophosphamide he had previously
received (.25 g), he was given an intrave-
nous infusion of rituximab 1 g. Intravenous
cyclophosphamide (12.5 mg/kg, adjusted for
renal function) was also given with the
rituximab infusion. These infusions were
repeated after 2 weeks.
This led to an immediate significant systemic
improvement accompanied by reduction of
WCC to 9.6610
9
and ANCA became undetect-
able. The pulmonary infiltrate resolved. The
scleritis also resolved promptly, evident from
completely white eyes, resolution of active
scleral vessels, corneal infiltrates, optic disc
swelling, and subjective resolution of ocular
pain. At 7 months after the infusion, the
patient remained in remission. His systemic
treatment was slowly reduced to prednisolone
15 mg daily and mycophenolate mofetil
750 mg twice daily.
Comment
Rituximab is a humanised monoclonal anti-
body against the CD20 antigen that is
expressed on the cell surface during early
pre-B cell development and persists through
all stages of B cell differentiation.
4
It results
in rapid depletion of CD20 positive B lym-
phocytes from the circulating blood and is
well tolerated. The precise role of B cells in
the pathogenesis of WG remains elusive at
present, but several possibilities exist. B cells
can act as antigen presenting cells to T cells or
provide additional co-stimulatory signals for
them. Another possibility is that self reactive
B cells, derived from unusual B cell subsets,
5
may follow an alternative maturation pro-
cess, including the continued expression of
CD20 during antibody production.
There has been no report on its effect on
WG associated scleritis. Our patient was
given rituximab primarily for his generalised
vasculitis, but his refractory scleritis also
responded promptly. Although he also
received cyclophosphamide at the same time,
the dose and course were limited to avoid
toxicity. Therefore, in this case the prompt
improvement was attributed to rituximab,
rather than cyclophosphamide.
This is the first case reporting rituximab as
an effective treatment for refractory WG
associated scleritis.
C M G Cheung, P I Murray
Ophthalmology, Division of Immunity and Infection,
University of Birmingham, Birmingham, UK
C O S Savage
Nephrology, Division of Immunity and Infection,
University of Birmingham, Birmingham, UK
Correspondence to: Professor P I Murray, Academic
Unit of Ophthalmology, Birmingham and Midland Eye
Centre, City Hospital, Dudley Road, Birmingham B18
7QU, UK; p.i.murray@bham.ac.uk
doi: 10.1136/bjo.2005.075689
References
1 Specks U, Fervenza FC, McDonald TJ, et al.
Response of Wegener’s granulomatosis to anti-
CD20 chimeric monoclonal antibody therapy.
Arthritis Rheum 2001;44:2836–40.
2 Keogh KA, Wylan ME, Stone JH, et al. Induction
of remission by B lymphocyte depletion in eleven
patients with refractory antineutrophil cytoplasmic
antibody-associated vasculitis. Arthritis Rheum
2005;52:262–8.
3 Ferraro AJ, Day CJ, Drayson MT, et al. Effective
therapeutic use of rituximab in refractory
Wegener’s granulomatosis. Nephrol Dial
Transplant 2005;20:622–5.
4 Stashenko P, Nadler LM, Hardy R, et al.
Characterization of a human B lymphocyte-
specific antigen. J Immunol 1980;125:1678–85.
5 Chumley MJ, Dal Porto JM, Cambier JC. The
unique Ag receptor signaling phenotype of B-1
cells is influenced by locale but induced by
antigen. J Immunol 2002;169:1735–43.
Retinopathy is not the only ocular
symptom: myasthenia gravis in
association with interferon
therapy
Interferons (IFNs) have antiviral and anti-
mitogenic effects and are often used in the
treatment of viral hepatitis or some neo-
plasms. However, they have various side
effects including fever, nausea, depression,
retinopathy, and autoimmune diseases.
Although myasthenia gravis (MG) is rarely
associated with IFN therapy, some cases
developing MG after IFN or IFN/ribavirin
combined therapy for chronic active hepatitis
C have been reported.
1–5
We report such a case
by reviewing the clinical data.
Case report
A 69 year old man with chronic hepatitis C
for 11 years had been treated with IFN-a
monotherapy (IFN 6610
6
IU three times a
week after 2 weeks of daily injections). The
first treatment started in April 2002. There
was no complication noted in that treatment.
After the therapy hepatitis C virus activity
settled for a while, but during the observation
his clinical data showed a rise in hepatitis C
virus RNA and aminotransferases. He under-
went IFN-a therapy conjugated with ribavirin
(IFN 6610
6
IU three times a week after
2 weeks of daily injections, ribavirin 800 mg
twice a day) again on 6 December 2002.
During the course his condition was checked
periodically, mainly in terms of retinopathy.
He had finished 7 months of treatment
without significant side effects.
Around December 2003 he began to notice
fluctuating diplopia. Examination revealed his
reduced right adduction, exotropia and left/
right hypertropia. Since his condition drifted
and there was no significant disorder on
magnetic resonance imaging, MG was sus-
pected and edrophonium chloride was tested.
With the medication, his diplopia prominently
improved and MG was diagnosed; however,
there was no elevation in his anti-acetylcholine
receptor antibody titre or other auto-antibo-
dies, and thymoma was not detected.
Comment
It is well known that IFN therapy induces
autoimmunity. Thyroid auto-antibodies are
the most frequent findings; autoimmune
hepatitis, rheumatoid symptoms, induction
of insulin dependent diabetes, etc, are also
seen. In relation to this autoimmune effect,
several cases concerning MG associated with
IFN therapy have been reported. Some cases
developed myasthenia newly or others exa-
cerbated pre-existing symptoms.
1–5
It is
reported that cases with pre-existing MG
have a tendency to present more severe
symptoms including myasthenic crisis.
4
The
pathogenesis is not completely understood
Accepted for publication 19 June 2005
1542 PostScript
www.bjophthalmol.com
because of the complex immunological
effects of IFNs, including enhanced lympho-
cyte cytotoxicity, inhibition of T suppressor
cell function, increased expression of major
histocompatibility complex (MHC) class I
antigens, production of proinflammatory
cytokines, and differentiation of antigen
presenting cell activation of T helper lympho-
cytes by autoantigens. Some or all of them
might contribute to the development of
autoimmune disease.
6
In this case the patient had no sign of MG
or other autoimmune disease before the IFN
treatment. His symptom is limited only to
extraocular muscles: the condition is rela-
tively mild. That is consistent with the
previous report referring to the relation
between the severity and the presence of a
history of autoimmune disease; but the fact
that anti-acetylcholine receptor antibody titre
was not elevated is contradictory.
4
We could
not establish the causality.
These days many patients with chronic active
hepatitis C virus receive IFN or IFN/ribavirin
combined therapy. We usually examine these
patients only in terms of retinopathy. Although
this case could be a coincidental sporadic
autoimmune disorder, we should take MG into
consideration. We should recognise the risk of
development or worsening of MG and be
careful in managing patients undergoing ther-
apy, especially when they already have MG or
compatible symptoms. It can be a serious
complication although it is very rare.
A Oishi, K Miyamoto, S Kashii, N Yoshimura
Department of Ophthalmology and Visual Sciences,
Kyoto University Graduate School of Medicine, Kyoto,
Japan
Correspondence to: Dr Akio Oishi, Department of
Ophthalmology and Visual Sciences, Kyoto University
Graduate School of Medicine, Kyoto, Japan; aquio@
kuhp.kyoto-u.ac.jp
doi: 10.1136/bjo.2005.077537
References
1 Gurtubay IG, Morales G, Arechaga O, et al.
Development of myasthenia gravis after interferon
alpha therapy. Electromyogr Clin Neurophysiol
1999;39:75–8.
2 Borgia G, Reynaud L, Gentile I, et al. Mya sthenia
gravis during low-dose IFN-alpha therapy for
chronic hepatitis C. J Interferon Cytokine Res
2001;21:469–70.
3 Weegink CJ, Chamuleau RA, Reesink HW, et al.
Development of myasthenia gravis during
treatment of chronic hepatitis C with interferon-
alpha and ribavirin. J Gastroenterol
2001;36:723–4.
4 Konishi T. A case of myasthenia gravis which
developed myasthenic crisis after alpha-interferon
therapy for chronic hepatitis C. Rinsho
Shinkeigaku 1996;36:980–5.
5 Harada H, Tamaoka A, Kohno Y, et al.
Exacerbation of myasthenia gravis in a patient
after interferon b treatment for chronic active
hepatitis C. J Neurol Sci 1999;165:182–3.
6 Dumoulin FL, Leifeld L, Sauerbruch T, et al.
Autoimmunity induced by interferon-a therapy for
chronic viral hepatitis. Biomed Pharmacother
1999;53:242–54.
Tobacco-alcohol amblyopia: a
maculopathy?
Tobacco-alcohol amblyopia or toxic-nutri-
tional optic neuropathy is a condition char-
acterised by papillomacular bundle damage,
central or caecocentral scotoma, and reduc-
tion of colour vision in a patient who abuses
tobacco and alcohol.
12
There is consensus
that nutritional deficiency has an important
role as well.
34
The appearance of the optic
nerve is usually normal, but peripapillary
dilated vessels and haemorrhages have been
described.
56
Testing with static perimetry
often reveals central scotomas. Although this
syndrome has been classified as optic neuro-
pathy, the primary lesion has not actually
been localised to the optic nerve and may
possibly originate in the retina, chiasm, or
even the optic tracts. We report two cases of
tobacco-alcohol amblyopia and their electro-
physiological findings after testing with
multifocal electroretinography (MERG).
Case reports
Case 1
A 47 year old woman presented with a gradual
decrease in vision over 4 months. Her medical
history showed that she has been in excellent
health. She smoked one pack of cigarettes per
week and had two to three beers daily. She
denied any use of any medications in the past
few months. She and her husband have been
on a diet which contained fewer vegetables
than their normal intake, for 4 months. Family
history was unremarkable.
Visual acuity was 20/50 right eye and
20/100 left eye. Colour vision using the
pseudoisochromatic plates was four of eight
in right eye and two of eight in left eye.
Intraocular pressure was 12 mm Hg right eye
and 15 mm Hg left eye. She had normal
anterior segment in both eyes. Her pupils were
sluggish to direct stimulation of light with no
afferent defect. Ocular motility was normal.
Funduscopy showed anomalous optic nerves
with no pallor, and normal maculas. Testing
with 24-2 static perimetry revealed an inferior
and nasal defect in the right eye; superonasal,
inferior, and central defect in the left eye
(fig 1A). Humphrey 10-2 static perimetry
showed bilateral caecocentral scotomas
(fig 1B). Magnetic resonance imaging (MRI)
of the brain and orbit with and without
contrast was normal. Serology tests for Lyme
and antinuclear antibodies (ANA) were nega-
tive. Complete blood count, serum vitamin B12,
and folate were within normal limits. MERG
testing showed severe reduction in amplitude
mostly centrally in both eyes (fig 2).
Case 2
A 55 year old woman presented with progres-
sive decrease in vision of both eyes over
1 month. She had a history of multiple
intracranial aneurysms that were clipped
15yearsearlier.Shewasnotusingany
medications. She smoked one pack of cigarette
a day for 25 years and has five to eight drinks
per week. Family history was positive for
glaucoma in her mother. Visual acuity was
counting fingers at 1 foot right eye and at
2 feet left eye. She could not identify any of the
pseudoisochromatic colour plates in both eyes.
She had normal anterior segment in both eyes.
Pupillary reactions were sluggish to light
stimulation with no afferent defect.
Funduscopy showed mildly swollen optic
nerves in both eyes (fig 3). Kinetic perimetry
Accepted for publication 1 July 2005
Figure 1 Static perimetry using (A) the 24-2 program shows an inferior arcuate defect in the right
eye; a superonasal and an inferior defect in the left eye. (B) The 10-2 program shows bilateral
central defects.
PostScript 1543
www.bjophthalmol.com
showed bilateral central scotomas. A CT scan
(withandwithoutcontrastagent)ofthebrain
and orbit was normal. Complete blood count,
serum vitamin B12, and folate were within
normal limits. Genetic testing of mitochondrial
DNA for Leber’s hereditary optic neuropathy
showed that the patient has the LHON 3460 G
mutation. Multifocal ERG was performed and
showed decreased amplitudes centrally with
normal latency (fig 4).
Comment
We describe two cases of ‘‘tobacco-alcohol
amblyopia in patients who had a history of
high alcohol intake (cases 1 and 2) and shortly
after dietary alteration (case 1). In both cases,
MERG testing showed decreased amplitudes in
the central region, suggesting retinal dysfunc-
tion in the macula. The condition of the patient
in case 2 may have been precipitated by a
metabolic injury (tobacco, alcohol) to geneti-
cally ‘‘compromised’’ mitochondria. This shows
the clinical overlap in conditions of inherited
mitochondrial dysfunction and acquired ones
such as tobacco-alcohol amblyopia.
7
The clinical findings seen in tobacco-
alcohol amblyopia can occur in any disease
of anterior visual pathway from the retina to
the optic tract and there is there is little
evidence to suggest that the locus of pathol-
ogy is restricted to the optic nerve.
Hhistopathological studies on animal models
of nutritional amblyopia showed lesions in
the retina, optic nerve and tract,
8
and the
maculopapillary bundle.
9
Electrophysiological
abnormalities in animal models of tobacco-
alcohol amblyopia showed reduced ampli-
tudes with normal latencies using visual
evoked potentials,
10 11
and increased a-wave
and b-wave implicit times and decreased b-
wave amplitudes using full field electroreti-
nograms.
12
MERG signals are believed to arise from
the outer retina (photoreceptor and bipolar
cell layer) with only minimal contribution
from the inner retina and optic nerve (gang-
lion cells and nerve fibre layer).
13
Therefore,
the severe reduction in amplitude in our
patients suggests that the outer retina,
particularly in the macula, is involved in this
condition.
R Behbehani, R C Sergott, P J Savino
Neuroophthalmology Service, Wills Eye Hospital,
Thomas Jefferson University, Philadelphi a, PA, USA
Correspondence to: Raed Behbehani, MD, PO Box
1262, 130013 Safat, Kuwait;
r_behbehani@hotmail.com
doi: 10.1136/bjo.2005.079137
References
1 Traquair HM. Toxic amblyopia, including
retrobulbar neuritis. Trans Ophthalmol Soc UK
1930;50:351.
2 Golnik KC, Schaible ER. Folate-responsive optic
neuropathy. J Neuro-ophthalmol 1994;14:163.
3 Victor M. Tobacco-alcohol amblyopia. A critique
of current concepts of this disorder, with special
reference to the role of nutritional deficiency in its
causation. Arch Ophthalmol 1963;70:313.
4 Victor M, Mancall EL, Dreyfus PM. Deficiency
amblyopia in the alcoholic patient: a
clinicopathologic study. Arch Ophthalmol
1960;64:1.
5 Carroll FD. Nutritional amblyopia. Arch
Ophthalmol 1966;76:406.
6 Frise´n L. Fundus changes in acute nutritional
amblyopia. Arch Ophthalmol 1983;101:577.
7 Cullom ME, Hayes KL, Miller NR, et al. Leber’s
hereditary optic neuropathy masquerading as
tobacco-alcohol amblyopia. Arch Ophthalmol
1993;111:1482.
8 Rodger FC. Degenerative changes in the rat visual
pathway when thiamine and riboflavin
deficiencies are combined. Br J Ophthalmol
1954;38:154.
9 Smiddy WE, Green WR. Nutritional amblyopia.
A histopathologic study with retrospective clinical
correlation. Graefes Arch Clin Exp Ophthalmol
1987;225:321–4.
10 Ikeda H, Tremain KE, Sanders MD.
Neurophysiological investigation in optic nerve
disease: Combined assessment of the visual
evoked response and electroretinogram.
Br J Ophthalmol 1978;62:227.
11 Kupersmith MJ, Weiss PA, Carr RE. The visual
evoked potential in tobacco-alcohol amblyopia
and nutritional amblyopia. Am J Ophthalmol
1983;95:307.
12 Pawlosky RJ, Bacher J, Salem N Jr. Ethanol
consumption alters electroretinogra ms and
depletes neural tissues of docosahexaenoic acid
in rhesus monkeys: nutritional consequences of a
low n-3 fatty acid diet. Alcohol Clin Exp Res
2001;25:1758–65.
13 Hood DC, Odel JG, Chen CS, et al. The multifocal
electroretinogram. J Neuro-ophthalmol
2003;23:225–35.
TTT: local light absorption and
heat convection versus heat
conduction
Miura and co-authors have contributed
valuable experimental data on transpupillary
thermotherapy (TTT) for choroidal neovascu-
larisation (CNV) in a rat model.
1
In their
scholarly discussion section, they speculate
that the variability in power settings they
encountered in heating experimental CNV
may be due to a ‘‘variation of heat conduction
in experimental CNV.’’
1
There are more prob-
able explanations for that variability. As
reported previously in the authors’ reference
7:‘‘lightabsorptioninpigmentclumpsfrom
Figure 2 Trace arrays of multifocal ERG showing decreased amplitudes in both the right eye (A)
and the left eye (B) with almost isoelectric responses centrally and improvement towards the
periphery.
Figure 3 Fundus photographs showing swollen discs with some telangiectatic vessels in both eyes.
(A) Right eye, (B) left eye.
Accepted for publication 18 July 2005
The authors have no proprietary interest in any of the
instruments used or any other aspect of this study.
Figure 4 Trace arrays of patient 2 showing reduced amplitude in the central region of both eyes.
MAILBOX
1544 PostScript
www.bjophthalmol.com
prior focal photocoagulation can cause local hot
spots in large TTT treatment fields.’’
2
Additionally, local choroidal blood flow
2
may
have been altered by vascular remodelling that
occurred in the 14 days between the intense
focal laser photocoagulation that the authors
used to produce CNV and their subsequent
liposomal monitored TTT at the site.
Chorioretinal temperature rise from a
lengthy 60 seconds TTT exposure is affected:
(1) by pigmentation at the treatment site,
which determines how effectively laser radiant
energy is converted locally into thermal energy,
and (2) to a lesser extent by choroidal blood
flow,
3
which transfers thermal energy by heat
convection away from the exposure site. It is
unlikely that local heat conduction is altered
significantly by the initial photocoagulation or
subsequent tissue remodelling because heat
conduction in most normal biological tissues is
essentially the same as that of water.
4–6
M A Mainster
Department of Ophthalmology, University of Kansas
Medical School, 3901 Rainbow Boulevard, Kansas
City, KS 66160-7379, USA
D H Silney
Laser/Optical Radiation Program, US Army
Environmental Hygiene Agency, Aberdeen Proving
Ground, MD 21010, USA
Correspondence to: Professor Martin A Mainster,
Department of Ophthalmology, M53009, University
of Kansas Medical School, 3901 Rainbow Boulevard,
Kansas City, KS 66160-7379, USA;
mmainster@kumc.edu
doi: 10.1136/bjo.2005.082453
References
1 Miura S, Nishiwaki H, Ieki Y, et al. Chorioretinal
temperature monitoring during transpupillary
thermotherapy for choroidal neovascularisation.
Br J Ophthalmol 2005;89:475–9.
2 Mainster MA, Reichel E. Transpupillary
thermotherapy for age- related macular
degeneration: long-pulse photocoagulation,
apoptosis, and heat shock proteins. Ophthalmic
Surg Lasers 2000;31:359–73.
3 Welch AJ, Wissler EH, Priebe LA. Significance of
blood flow in calculations of temperature in laser
irradiated tissue. IEEE Trans Biomed Eng
1980;27:164–6.
4 Mainster MA, White TJ, Tips JH, et al. Retinal-
temperature increases produced by intense light
sources. J Opt Soc Am 1970;60:264–70.
5 Welch AJ, van Gemert MJC. Optical-thermal
response of laser-irradiated tissue. New York:
Plenum Press, 1995.
6 Mainster MA. Decreasing retinal
photocoagulation damage: principles and
techniques. Sem Ophthalmol 1999;14:200–9.
Accepted for publication 6 September 2005
NOTICES
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th
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th
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at www.kcco.net/isgeo.
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The MCLOSA Winter Symposium will be held
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CORRECTIONS
doi: 10.1136/bjo.2005.75895corr1
In the letter titled, Patient satisfaction with
anaesthesia comparing sun-Tenon’s block
and topical anaesthesia (Br J Ophthalmol
2005;89:1228) the second author was
omitted. The second author for this letter
was R W D Bell, Sunderland Eye Infirmary,
Queen Alexandra Road, Sunderland SR2
9HP, UK. The author apologises for this
omission.
doi: 10.1136/bjo.2004.58941corr1
In the paper titled, En-face optical coherence
tomography (OCT): A new method to analyse
structural changes of the optic nerve head
in rat glaucoma (Br J Ophthalmol 2005;89:
1210–6) one of the author’s name has been
spelt incorrectly. The author Podolean AG,
should be spelt Podoleanu AG. The journal
apologises for this error.
PostScript 1545
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