We appreciate a response to our study from Dr Landers et al. They
reported that five out of ten eyes with abnormal result of Frequency
Doubling Perimetry (FDP) and normal result of Achromatic Automated
Perimetry (AAP) showed abnormal result on AAP four years later.[1] It
was
our mistake that we referred their study as a cross-sectional study in
our
paper. We apologize to them that we should have referr...
We appreciate a response to our study from Dr Landers et al. They
reported that five out of ten eyes with abnormal result of Frequency
Doubling Perimetry (FDP) and normal result of Achromatic Automated
Perimetry (AAP) showed abnormal result on AAP four years later.[1] It
was
our mistake that we referred their study as a cross-sectional study in
our
paper. We apologize to them that we should have referred it as one of
longitudinal studies along with another two papers.
Reference
1. Landers J, Goldberg I, Graham S. Detection of Early Visual Field. Loss in Glaucoma Using Frequency Doubling Perimetry and Short Wavelength. Automated Perimetry. Arch. Ophthalmol. 2003;121:1705-10.
Lutein and Zeaxanthin
dietary intake and age related macular degeneration
We read with interest the letter published by Vu et al (1)
which investigated the risk of age related macular degeneration (AMD) and its
association with the dietary carotenoids, lutein and zeaxanthin (LZ),
stratified by linoleic acid intake. Vu et al reported
a marked increase in the risk of both early and late AMD among people who
consumed greater than the median intake of linoleic
acid and higher dietary intakes of LZ.
We have a number of concerns in relation to the authors’
letter and their conclusions. The letter used cross-sectional data based on
photographic macular assessments of 71.9% of their sample of 2448 persons, who
attended follow-up examinations. The authors also included 212 persons who did
not have photographic macular assessment (10.8% of those with dietary
assessments). This is one area of concern. The dietary assessment method (food
frequency questionnaire FFQ) was not conducted at baseline, which only allows measurements
of association from the follow-up examination. Due to the cross-sectional
nature of the data, it is plausible and even likely that participants with
known signs of early macular degeneration or associated visual changes may have
increased their dietary antioxidant intakes (indication bias); for example,
after being told about their signs at the first examination, or at other times.
This bias may have occurred in particular amongst those consuming higher linoleic acid diets as higher intakes of linoleic acid have been reported to increase the risk of
AMD (2). An excellent example of this indication bias can be found in the
finding of a significantly increased risk of poor night vision associated with
increased consumption of carrots (3).
The letter also states that a possible protection existed
with high LZ intake on AMD among those with low levels of linoleic
acid intake. We could, however, not see any data in the results or tables to
support this statement.
We thought that these findings needed to be confirmed in
other study populations. Given our concerns about the cross-sectional data
design we explored this association with the incidence of AMD in the Blue
Mountains Eye Study cohort.Baseline
data were collected in 1992-94 from 3654 residents of the Blue
Mountains aged 49 years and over. Eye examinations were conducted
on residents at baseline and at follow-up using retinal photographs and the
Wisconsin AMD grading system (4). Dietary data were assessed at baseline
(n=2900) and follow-up examinations using a 145-item Food Frequency
Questionnaire (FFQ) (5). Of the participants examined at either or both the 5-
and 10-year examinations, 2454 had retinal photographs available for the
assessment of ARM lesions. Of the 2454 participants 2083 had complete FFQ data,
including 818 supplement users. We used the Willett method (6) to energy adjust
the linoleic and LZ data and investigated those with
less than and greater than median intake for linoleic
acid (median=6.6g) and 1 standard deviation increases of LZ (mean intake of
energy adjusted LZ intake was 819mg, with a SD of 475mg), using a
multivariate-adjusted discrete logistic model to assess factors associated with
10-year incident AMD.
We found no association with energy adjusted LZ intake and
the incidence of early, late or any AMD, whether or not this was stratified by linoleic acid intake (Table 1). Given that our median linoleic acid intake was less than the median used by Vu et
al (1) (6.6g verses 7.2g) we also stratified the data by the highest tertile of linoleic acid intakes
(cut-point 8.5g) and also found no association between LZ and incident AMD
(data not shown).
While the examination of cross-sectional data to investigate
associations with disease may be useful, conclusions drawn from such data need
to be made with care, in the light of other known literature. Other data have
demonstrated a potential protective effect from foods containing LZ (7) and
foods and supplements rich in LZ are known to increase (protective) macular
pigment density (8). In addition, Dietary Guidelines (9) include
recommendations to increase vegetables and fruit that are rich in LZ (e.g.
broccoli, green beans, silverbeet, brussel sprouts, oranges) (10).
The authors conclusions, based on their very limited data, are non-intuitive
and we are concerned that they are potentially misleading. Care needs to be
taken to continue to encourage the vegetable and fruit intakes of populations.
Victoria Flood, Elena
Rochtchina, Jie Jin Wang,
Paul Mitchell
Centre for Vision Research, University
of Sydney, Australia
Wayne Smith
Centre for Clinical Epidemiology and Biostatistics, University
of Newcastle, Australia
Correspondence to: Professor Paul Mitchell, Centre for
Vision Research, Westmead
Hospital, New South Wales,
2145.
References:
Vu
HTV, Robman L, McCarty
CA, Taylor HR, Hodge A. Does dietary lutein and zeaxanthin
increase the risk of age related macular degeneration? The Melbourne
Visual Impairment Project. Br J Ophthalmol 2006; 90: 389-390.
Seddon JM, Cote J, Bernard R. Progression of
age-related macular degeneration: association with dietary fat, transunsaturated fat, nuts, and fish intake. Arch Ophthalmol.
2003; 121: 1728-37.
Smith W,
Mitchell P, Lazarus R.Carrots,
carotene and seeing in the dark.Australian
& New Zealand Journal of Ophthalmology 1999; 27:200-203.
Mitchell
P, Smith W, Attebo K, Wang JJ. Prevalence of
age-related maculopathy in Australia.
The Blue Mountains Eye Study. Ophthalmology. 1995; 102: 1450-1460.
Smith
W, Mitchell P, Reay EM, Webb K, Harvey PW.
Validity and reproducibility of a self-administered food frequency
questionnaire in older people. Australian
New
Zealand Journal of Public Health. 1998; 22: 456-463.
Willett
W, Stampfer MJ. Total energy intake:
implications for epidemiologic analyses. Amer J Epidemiol. 1986; 124: 17-27.
Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, Burton TC, Farber MD, Gragoudas ES, HallerJ,
Miller DT et al. Dietary carotenoids, vitamins
A, C and E, and advanced age-related macular degeneration. Eye Disease Case-Control
Study Group. JAMA. 1994; 272:
1413-20.
Hammond
BR Jr, Johnson EJ, Russell RM, Krinsky NI, Yeum KJ, Edwards
RB, Snodderly DM. Dietary modification of human
macular pigment density. Invest OphthalmolVisSci. 1997; 38(9): 1795-1801.
National
Health and Medical Research Council. 2003. Dietary Guidelines for
Australian Adults.
Manzi F, Flood V, Webb K, Mitchell P. The intake of carotenoids in an older Australian population: The
Blue Mountains Eye Study. Pub Health
Nut. 2002; 5(2): 347-352.
Table 1: The odds ratio between baseline dietary lutein and zexanthin (LZ) intake,
stratified by linoleic acid (LA) intake (less than
and greater than median intake), and
10 year incident AMD in the Blue Mountains Eye Study
We read with great interest the article by Bernauer et al [1] on the
use hyaluronate artificial tear formulation �Hylo-Comod� favours the
formation of corneal calcification related to the phosphate content of eye
medications and frequent instillation. We agree with their conclusion and
would like to highlight that in the setting of dry chronically inflamed
eyes phosphate containing topical preparati...
We read with great interest the article by Bernauer et al [1] on the
use hyaluronate artificial tear formulation �Hylo-Comod� favours the
formation of corneal calcification related to the phosphate content of eye
medications and frequent instillation. We agree with their conclusion and
would like to highlight that in the setting of dry chronically inflamed
eyes phosphate containing topical preparations should be used with
caution. Even less frequent instillation of phosphate containing topical
preparation [prednisolone phosphate (0.5%) four times a day] in our
experience has resulted in calcium deposits within 48 hours in an eye with
secondary Sjogren�s syndrome (following Graft versus Host disease) in a 23
year old Caucasian lady following penetrating keratoplasty. This lady
underwent a total of three penetrating keratoplasties. The first was due
to a perforating corneal ulcer (unassociated with any calcification), the
second and third were due to infection of graft via epithelial defect over
calcium plaques leading on to perforation. Interestingly, she had
intensive topical �Hylo-prompt� preoperatively prior to her first graft.
In retrospect, we believe topical phosphate use following the first and
second corneal transplant in this setting along with an epithelial defect
resulted in the formation of a band keratopathy. Histopathological
analysis of the both corneal button specimen showed extensive
mineralisation 2 mm from the margin extending through the entire thickness
of corneal stroma with associated nuclear debris gram positive cocci and
inflammatory cells. The role of phosphate being the offending agent in our
case was amply demonstrated by the maintenance of clear cornea on
switching to prednisolone acetate preparation following the third
transplant.
As mentioned by Bernauer et al, Huige et al in 1991[2] first
described an association of band keratopathy in his series of eight
patients to a combination of steroid (with and without preservatives) and
beta blocker use and suggested an interaction between simultaneously given
steroid and beta-blocking agents, giving rise to calcium phosphate
precipitates in cornea. Taravella et al in 1994 [3] first reported five
case of topical steroid-phosphate induced band keratopathy. Scholtzer-
Schrehardt et al implicated topical steroid-phosphate preparation to the
formation of calcareous degeneration instead [4] and Lavid and co authors
described two cases with spontaneous calcific band keratopathy and
calcareous degeneration coexisting and occurring in eyes with severe dry
eyes secondary to GVH disease and Sjogren�s syndrome [5]. In a double-
masked experimental animal model Schrage et al [6] induced corneal
calcification following topical phosphate buffer irrigation of eyes after
alkali burn. Common to most reported cases including by Bernauer et al [1]
of either band keratopathy or calcareous degeneration are inflamed and dry
eyes due to variety of reasons with epithelial defect and normal serum
biochemistry. We feel that chronically inflamed and dry eyes are at risk
of developing calcium deposition when exposed to phosphate containing
topical preparations. We recommend that in this setting such preparation
should be used with caution especially in cases with epithelial defect.
Should such medication be unavoidable they should be withdrawn at the
first hint of mineralisation. We commend and support Bernauer et al�s
recommendation that declaration of the amount of phosphate buffers on drop
bottles and in the inserted leaflets should be introduced.
References
1. Bernauer, W., et al., Corneal calcification following intensified
treatment with sodium hyaluronate artificial tears. Br J Ophthalmol, 2006.
90(3): p. 285-8.
2. Huige, W.M., et al., Unusual deposits in the superficial corneal stroma
following combined use of topical corticosteroid and beta-blocking
medication. Doc Ophthalmol, 1991. 78(3-4): p. 169-75.
3. Taravella, M.J., et al., Calcific band keratopathy associated with the
use of topical steroid-phosphate preparations. Arch Ophthalmol, 1994.
112(5): p. 608-13.
4. Schlotzer-Schrehardt, U., et al., Corneal stromal calcification after
topical steroid-phosphate therapy. Arch Ophthalmol, 1999. 117(10): p. 1414
-8.
5. Lavid, F.J., et al., Calcareous corneal degeneration: report of two
cases. Cornea, 1995. 14(1): p. 97-102.
6. Schrage, N.F., et al., Phosphate buffer in alkali eye burns as an
inducer of experimental corneal calcification. Burns, 2001. 27(5): p. 459-
64.
We thank Barnes et al for their interest in our study and for
affording us the opportunity to correct some misinterpretations that
others may also have made regarding our paper.
We agree entirely that histological examination of the complete
excision surface as suggested by Mohs would be the ideal one should aim
at
and that it would be superior to conventional bread loaf histological
sect...
We thank Barnes et al for their interest in our study and for
affording us the opportunity to correct some misinterpretations that
others may also have made regarding our paper.
We agree entirely that histological examination of the complete
excision surface as suggested by Mohs would be the ideal one should aim
at
and that it would be superior to conventional bread loaf histological
sectioning. We dispute that this is realistically possible in
inhomogeneous and exceedingly mobile eyelid tissues unless they are
fixed
prior to excision as in the chemosurgery that Mohs originally described.
Trying to cut a complete 2mm thick saucer of tissue through fresh skin,
orbicularis, tarsal plate, orbital septum and fat and then transferring
it
without distorting the relative tissue orientation is a challenge that
few
are equal to. It might have been helpful if Barnes et al had shared
their practical experience of the technique with us in their letter.
That the risk of BCC recurrence relates to the tumour type is not
in
dispute and is indeed born out in our results. But it is helpful of
Barnes
et al to remind other readers of this fact. Histological subtype was not
specified in the greater portion of our series as our histopathologists
only pass comment when BCCs are infiltrative or unusual in other
respects.
We apologise for not stating this explicitly as it has clearly led to
some
misunderstanding.
However there is no justification for Barnes et al's assumption
that
the 'non-specified' tumours were small because 72% were managed by
direct
closure. We have clearly failed to get over a most important point.
Direct
closure under tension is not only possible in much larger lid defects
than conventionally taught but also gives far superior functional and
cosmetic results. As such we urge others to use this method of repair
more
widely.
That 76% of our tumours occurred on the lower lid should not come
as
a surprise to anyone as it is a well recognised fact. It does not
suggest
that our series is in any way biased.
That our series differs from the selected series in the Australian
Mohs database is self evident. We described our experience with an
unselected consecutive series of 223 secondary and tertiary periocular
Basal Cell Carcinomas (BCC) referrals to a UK regional Oculoplastic
service. Our case mix should therefore be representative of that in
other
similar UK units and our results are therefore more relevant to them
than
those of the high risk biased Australian Mohs series and our results can
be used as an audit benchmark. Although we have used conventional
non-Mohs
treatment, we achieved a very low recurrence rate.
We fully support that full histological margin control, as in Mohs
micrographic surgery, is the best treatment option in recurrent, high
risk
cases. Our study shows that careful non-Mohs BBC excision remains a
valuable, safe and cost effective option. Our technique offered the
patients with primary non-infiltrative BCC excellent cure rates and
functional and cosmetic outcomes with no recurrence over 5 years follow
up.
Correspondence to:
V T Thaller, FRCOphth
The Royal Eye Infirmary
Apsley Road
Plymouth
PL4 6PL
UK
vladimir.thaller@phnt.swest.nhs.uk
Thank you for writing and giving us the opportunity to further
comment on our case series and investigations. We wish to put several
misquotations right, respond to the accusation of inappropriate dosage,
comment on the declaration of ingredients, explain our case description
and substantiate the necessity to publish this case series.
Please note that we described five and not six cases. The...
Thank you for writing and giving us the opportunity to further
comment on our case series and investigations. We wish to put several
misquotations right, respond to the accusation of inappropriate dosage,
comment on the declaration of ingredients, explain our case description
and substantiate the necessity to publish this case series.
Please note that we described five and not six cases. The patient
described as case 1 used at some stage the Hylo-Comod drops every ten to
fifteen minutes, summarised in Table 1 as "up to 100x/day". This is not
the same as "more than 100 times" as you quote. Ofloxacin (Floxal) was
used and not norfloxacin. Dexamytrex eye drops were only used in a small
dosage in case 3 and 4. Several measures were taken when corneal
calcification occurred: EDTA drops were introduced, phosphate-buffered
Hylo-Comod stopped, dexamethasone phosphate replaced by prednisolone
acetate, superficial keratectomy attempted and finally penetrating
keratoplasties carried out. In contrast to what you indicate, we did not
warn that phosphate containing drops may lead to corneal epithelial
defects, but we stated: "that topical preparations, high in phosphate, may
cause severe adverse effects when used very frequently and on a damaged
corneal surface".
Frequent application of artificial tear products is an important
measure in the treatment of ocular surface disease with
keratoconjunctivitis sicca. In severe cases, artificial tears are
typically applied hourly or more frequently. The Swiss data sheet for Hylo
-Comod suggests a dosage individualised to the patient's needs [1]: "In
general, Hylo-Comod is instilled three times per day in both eyes. With
more severe symptoms Hylo-Comod can be applied without reservations more
frequently". This recommendation was followed. We do not share your view
that we used the artificial tear preparation Hylo-Comod off label.
The ingredients of Hylo-Comod are declared on the data sheet and the
inserted information leaflet. Unfortunately, European legislation does
intend a quantitative declaration of the pharmaceutically active agent
only, but no quantification of the adjuvants. The lack of such information
on the buffering system led to the described severe corneal complications
[2]. We did not expect that the phosphate concentration in Hylo-Comod
exceeds the concentration of alternative artificial tear products or of
the physiological tear film more than fifty times [3]. Such concentrations
put the time interval between applications into perspective.
Full-thickness corneal calcification following phosphate-rich eye
drops may develop as rapidly as within 48 hours. Table 1 gives an overview
on the time course of corneal calcification, and highlights the difference
to the well-known (post-)inflammatory superficial band keratopathies that
form over months and years. Please note that this table summarises the
process of corneal calcification, whereas the text section describes the
time course of ocular disease.
There are indeed several clues in the ophthalmic literature that
point to the hazard of high phosphate concentrations on a damaged corneal
surface. Whereas the role of phosphate buffers in irrigating solutions has
been studied systematically by your group [4], the investigation of
topical medications has only started. To our knowledge, our papers are the
first that provide information on the phosphate concentrations in
ophthalmic drop preparations [2,3]. This does not only help in the
interpretation of our case series, but also in the selection of eye
medication and in the clarification of previous studies. The combination
of amniotic membrane transplantation and phosphate-rich lubrication bears
a particular risk for corneal calcification: Anderson et al. described
fifteen patients (12.8%) that developed calcification on phosphate-rich
lubrication (Hylo-Comod among others) [5], whereas other groups have not
encountered such problems (J.K.G. Dart, personal communication).
The aim of our publication is the prevention of sight threatening
corneal complications. Ethical considerations prompted us
to inform also the Head of Ursapharm Arzneimittel well ahead of
publishing, hoping that the company would consider our advice to
reformulate their products which contain phosphate concentrations as high
as 160 mmol/l [6].
Good pharmaceutical practice would mean that the product information
gives a quantitative declaration of the phosphate buffers, particularly
so, if their concentration allows restricted use only.
References
1. Arzneimittelkompendium der Schweiz 2006. Documed, Basel, Switzerland
2006; 1538-1539.
2. Bernauer W, Thiel MA, Kurrer M, Heiligenhaus A, Rentsch KM, Schmitt A,
Heinz C, Yanar A. Corneal calcification following intensified treatment
with sodium hyaluronate artificial tears. Br J Ophthalmol 2006; 90: 285-
288
4. Schrage NF, SchloÃmacher B, Aschenberner W, et al. Phosphate buffer in
alkali eye burns as an inducer of experimental corneal calcification.
Burns. 2001;27:459-464.
5. Anderson SB, de Souza RF, Hofmann-Rummelt C, Seitz B. Corneal
calcification after amniotic membrane transplantation. Br J Ophthalmol
2003; 87: 587-591.
6. Bernauer W, Thiel MA, Rentsch KM. Phosphate in ophthalmologischen
Präparaten. Ophthalmologe (in press).
W. Bernauer1, M. A. Thiel1, A. Heiligenhaus2,
A. Yanar1 , K. M. Rentsch3
1 Department of Ophthalmology, University of Zürich, Switzerland
2 Department of Ophthalmology at St. Franziskus Hospital, Münster,
Germany
3 Institute of Clinical Chemistry, University of Zürich, Switzerland
Correspondence Prof. Dr. Wolfgang Bernauer
OMMA Eye Center and University of Zürich
Theaterstrasse 2
CH-8001 Zürich
SWITZERLAND
In a recent issue of the Journal Steven et al. describe secondary
retinal holes after removal of the inner limiting membrane (ILM) [1]. We
consider this a key retinal publication and therefore wish to strengthen
the importance of the authors' findings for modern surgery of the
vitreoretinal interface.
Interestingly, the paper included only patients with macular
puckers and cystoid macular oed...
In a recent issue of the Journal Steven et al. describe secondary
retinal holes after removal of the inner limiting membrane (ILM) [1]. We
consider this a key retinal publication and therefore wish to strengthen
the importance of the authors' findings for modern surgery of the
vitreoretinal interface.
Interestingly, the paper included only patients with macular
puckers and cystoid macular oedema, but not macular holes. In cases of
macular holes only a small-sized central part of the ILM will usually be
peeled. In contrast, macular puckers and cystoid oedemas will typically
affect a larger region of the posterior pole. Thus a more extensive
fraction of the ILM will be stripped if surgery is performed in such
cases.
More than thirty years ago Foos [2] described two anatomical
features of the ILM that might explain why current peeling of the
peripheral ILM may be unsafe. Firstly, the ILM is thickest at the posterior
pole and will become continuously thinner in the periphery. In the
initiation of the ILM removal this may increase the risk for direct retinal
trauma. Secondly, the Müller glia are more strongly attached to the ILM away from the macula. This may lead to indirect surgical trauma of the non-neuronal parts of the retina during the peeling process.
In conclusion, the more eccentric from the macula, the thinner and
the more adherent to the retina is the ILM. As described by Steven et al.,
removal of these peripheral ILM fractions may lead to retinal hole
formation. [1] Direct and/or indirect surgical trauma may be responsible
for such injury, which may not be related to toxic effect of dyes used.
One should therefore avoid stripping the peripheral ILM outside macular
region to prevent inadvertent retinal damage.
References
1. Steven P, Laqua H, Wong D, Hoerauf H. Secondary paracentral
retinal holes following internal limiting membrane removal. Br J
Ophthalmol. 2006;90:293-95.
2. Foos RY. Vitreoretinal juncture; topographical variations. Invest
Ophthalmol. 1972;11:801-8.
We read with interest the article by Wong T.Y. et al[1], which
studied a non-diabetic population consisting of 7992 people aged 49-73
years. Non-mydriatic retinal photographs of one eye were taken and graded
for retinopathy lesions using to standardised protocols. Surprisingly, the
presence of typical retinopathy lesions (microaneurysms or retinal
haemorrhages) in persons without diabetes did not signi...
We read with interest the article by Wong T.Y. et al[1], which
studied a non-diabetic population consisting of 7992 people aged 49-73
years. Non-mydriatic retinal photographs of one eye were taken and graded
for retinopathy lesions using to standardised protocols. Surprisingly, the
presence of typical retinopathy lesions (microaneurysms or retinal
haemorrhages) in persons without diabetes did not significantly predict
subsequent development of diabetes over a period of 3.5 years. Incident
diabetes developed in 4.7% and 3.6% of persons with and without
retinopathy lesions at baseline, respectively, with a multivariate
adjusted odds ratio, OR, 1.1, 95% confidence interval, CI, 0.7-1.9.
However, in persons with a family history of diabetes, presence of
retinopathy lesions at baseline predicted a doubling of the risk of
incident diabetes (OR 2.0, CI 1.1-3.8).
We previously reported findings from the Blue Mountains Eye Study
cohort (BMES, n=3654) that the 5-year risk of developing diabetes in
persons without diabetes but with retinopathy lesions at baseline was 3.5%
(7/202).[2] The BMES examined 3654 participants at baseline (1992-94) and
re-examined 2335 participants (75% of survivors) 5 years later (1997-99).
Dilated 6-field retinal photographs of all participants were taken at the
baseline and follow up examinations. Diabetes was diagnosed either from
medical history or fasting blood glucose >=7.0 mmol/L at examination.
Of the baseline participants without diabetes, 202 had retinopathy lesions
(haemorrhages, microaneurysms, soft and hard exudates). Our 3.5% diabetes
incidence over 5 years in this group is relatively similar to the 4.7%
diabetes incidence over 3.5 years reported by Wong T.Y. et al[1] in
persons with retinopathy lesions at baseline. These consistent findings
suggest that retinopathy lesions occurring in persons without diabetes are
likely to have multiple aetiologies. In persons with a family history of
diabetes, retinopathy lesions may indicate a pre-clinical stage of
diabetes. In the great majority of persons without diabetes, however,
retinopathy lesions are not necessarily linked to blood glucose. Reports
from the BMES[3] and Hoorn Study[4] showed that baseline impaired fasting
glucose or impaired glucose metabolism did not predict incident
retinopathy lesions in persons without diabetes. Older age and blood
pressure, however, were strongly related.[2,5] It is possible that the
same phenotype can result from different pathogenic conditions (such as
hypertension[6]) that damage the microvasculature. Given that retinopathy
lesions predict systemic vascular outcomes,[7] further research to clarify
the causes of these lesions is warranted.
References
1. Wong TY, Mohamed Q, Klein R, Couper DJ. Do retinopathy signs in
non-diabetic individuals predict the subsequent risk of diabetes? Br J
Ophthalmol 2006;90:301-3.
2. Cugati S, Cikamatana L, Wang JJ, Kifley A, Liew G, Mitchell P.
Five-year incidence and progression of vascular retinopathy in persons
without diabetes: the Blue Mountains Eye Study. Eye 2005 Sep 16; [Epub
ahead of print].
3. Babisch W, Beule B, Schust M, Kersten N, Ising H. Traffic noise
and risk of myocardial infarction. Epidemiology 2005;16:33-40.
4. van Leiden HA, Dekker JM, Moll AC, Nijpels G, Heine RJ, Bouter LM
et al. Risk factors for incident retinopathy in a diabetic and nondiabetic
population: the Hoorn study. Arch Ophthalmol 2003;121:245-51.
5. Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older
persons without diabetes and its relationship to hypertension.
Arch.Ophthalmol. 1998;116:83-9.
6. Wong TY, Klein R, Sharrett AR, Manolio TA, Hubbard LD, Marino EK
et al. The prevalence and risk factors of retinal microvascular
abnormalities in older persons: The Cardiovascular Health Study.
Ophthalmology 2003;110:658-66.
7. Wong TY, Mitchell P. Hypertensive retinopathy. N.Engl.J.Med.
2004;351:2310-7.
We read with great interest, Singh et. al.’s[1] perspective on
impression cytology and its uses in diagnosing ocular surface pathology.
The known higher exposure to UV radiation in both Australia and New
Zealand, and the increased incidence of ocular surface squamous neoplasia
(OSSN) in Australia,[2][3] recently led us to audit the incidence of OSSN
in conjunctival biopsies in New Zealand over a 6...
We read with great interest, Singh et. al.’s[1] perspective on
impression cytology and its uses in diagnosing ocular surface pathology.
The known higher exposure to UV radiation in both Australia and New
Zealand, and the increased incidence of ocular surface squamous neoplasia
(OSSN) in Australia,[2][3] recently led us to audit the incidence of OSSN
in conjunctival biopsies in New Zealand over a 6 year period.
We identified 132 invasive conjunctival and/or corneal biopsies
performed on 115 patients at Auckland City Hospital. Among the many
histopathological diagnoses, 6% of patients had no histological
abnormality, questioning the need for an invasive diagnostic procedure.
However, 62 (47%) biopsies were diagnosed with OSSN and 84% of those
affected were men, with an average age of 72 years. Published recurrence
rates are generally higher for more severe grades of OSSN[4] and four
subjects in our audit eventually required an exenteration. Furthermore, of
all biopsies on patients with OSSN, 27 biopsies had involvement of the
margins and 12 patients required more than one surgical procedure. Two
patients had recurrences even after clear margins at excisional biopsy and
one patient had repeat biopsy, as there was clinical suspicion of
recurrence but there was no histological evidence of further OSSN.
Although this disease is often regarded as a low grade malignancy
affecting elderly men,[4] it is not without significant morbidity and
occasionally mortality. However, these patients may not always be
medically fit, have sufficiently healthy ocular surface for a large
excision biopsy, or wish/consent to a biopsy.[5] Impression cytology may
therefore offer an inexpensive, non-invasive tool that can be used in the
outpatient clinic setting to help provide an objective evaluation of
suspicious conjunctival/corneal lesions that enables patients to make more
informed decisions about the need for surgery. Results of impression
cytology may also help the ophthalmologist in forming the decision to
perform an incisional or excisional biopsy and the necessity for any other
associated procedures, such as freeze-thaw cryotherapy of the
sclera/limbus and/or ethanol application to the cornea. Of course, the
size of the lesion, macroscopic appearance and overall clinical opinion
may still guide clinical decisions but impression cytology offers an
additional confirmatory tool to aid the process. In addition, impression
cytology can be used to monitor for recurrences in patients with
previously treated OSSN in the outpatient setting.
Although impression cytology only allows sampling of the superficial
cell layers,[1] the sensitivity of this technique has been documented at
70% when the lesion is found to be invasive by histology.[2] Consequently,
some invasive lesions may still be missed. We anticipate that there are
likely to be further improvements to the technique of impression cytology
to make it more logistically simple and less time consuming, with perhaps
an increase in sensitivity. In the meantime we agree that is a useful,
often underused, complimentary investigation in the management of OSSN.
References
1 Singh R, Joseph A, Umapathy T, Tint NL, Dua HS. Impression cytology
of the ocular surface. Br J Ophthalmol 2005;89:1655-9.
2 Nolan GR, Hirst LW, Bancroft BJ. The cytomorphology of ocular
surface squamous neoplasia by using impression cytology. Cancer 2001;93:60-7.
3 Lee GA, Hirst LW. Retrospective study of ocular surface squamous
neoplasia. Aust N Z J Ophthalmol 1997;25:269-76.
4 McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD.
Squamous cell carcinoma of the conjunctiva: a series of 26 cases. Br J
Ophthalmol 2002;86:168-73.
5 Tole DM, McKelvie PA, Daniell M. Reliability of impression cytology
for the diagnosis of ocular surface squamous neoplasia employing the
Biopore membrane. Br J Ophthalmol 2001;85:154-8.
We congratulate Kogure et al,[1] on a well designed longitudinal
study, which confirms the suspicions of many earlier investigators, who
conjectured that Frequency Doubling Perimetry (FDP) may be able to detect
visual field loss earlier than Achromatic Automated Perimetry (AAP) based
on cross-sectional data. In their text they refer to our longitudinal
study[2] as a cross-sectional one and go on to s...
We congratulate Kogure et al,[1] on a well designed longitudinal
study, which confirms the suspicions of many earlier investigators, who
conjectured that Frequency Doubling Perimetry (FDP) may be able to detect
visual field loss earlier than Achromatic Automated Perimetry (AAP) based
on cross-sectional data. In their text they refer to our longitudinal
study[2] as a cross-sectional one and go on to say that there have only
been two other papers, which have demonstrated that FDP predicts future
AAP visual field loss in a longitudinal fashion. Our paper was conducted
over a four-year period, with the first-year data presented as a cross-
sectional study[3] and the final data showing the relationship between FDP
and AAP longitudinally.[2]
In addition, Kogure et al. have shown quantitatively that the
location of FDP field loss can predict the location of future AAP field
loss. We also noted qualitatively a topographical relationship between the
two perimeters, however our original methodology had not included this
premise. Their topographical analysis adds credence to the principle that
these early FDP changes are the same visual field loss seen several years
later on AAP.
References
1. Kogure S, Toda Y, Tsukahara S. Prediction of future scotoma on
conventional automated static perimetry using frequency doubling
technology perimetry. Br J Ophthalmol. 2006;90:347â52.
2. Landers J, Goldberg I, Graham S. Detection of Early Visual Field
Loss in Glaucoma Using Frequency Doubling Perimetry and Short Wavelength
Automated Perimetry. Arch. Ophthalmol. 2003;121:1705-10.
3. Landers J, Goldberg I, Graham S. A Comparison of Short Wavelength
Automated Perimetry with Frequency Doubling Perimetry for the Early
Detection of Visual Field Loss in Ocular Hypertension. Clin. Exp.
Ophthalmol. 2000;28:248-52.
RE: Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction.
McGwin et al.[1] suggest that treatment of erectile dysfunction with sildenafil (Viagra®) or tadalafil (Cialis®), two phosphodiesterase
inhibitors (PDE5-I), may increase the odds of non-arteritic anterior
ischaemic optic neuropathy (NAION) in men with a history of myocardial
infarction (MI...
RE: Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction.
McGwin et al.[1] suggest that treatment of erectile dysfunction with sildenafil (Viagra®) or tadalafil (Cialis®), two phosphodiesterase
inhibitors (PDE5-I), may increase the odds of non-arteritic anterior
ischaemic optic neuropathy (NAION) in men with a history of myocardial
infarction (MI) or hypertension (HTN). We believe, however, that this
study is fraught with significant limitations (as the authors acknowledge)
that preclude drawing any conclusions about this relationship.
Case-control studies are susceptible to several biases that must be
carefully considered and controlled for in the study design,
implementation, and analysis.[2] For example, accurate and complete
ascertainment of exposure is critical in a retrospective case-control
study because both disease and exposure occur prior to study initiation.
The authors note that the interviewers were not blinded to the case or
control status of the patient, making it possible that the interviewer
may, even unconsciously, probe cases differently from controls for
exposure to a PDE5-I (interviewer bias). Another obstacle is that
patients were not consistently interviewed at the time of NAION event (or
index date for controls) about their PDE5-I usage. Hence, NAION patients
may have been more likely to remember drug usage (recall bias).
Furthermore, exposure misclassification may have occurred as timing, dose,
and duration of drug use relative to event onset were not captured
(exposure bias). This information is crucial for drugs used as needed
such as PDE5-I and particularly for short half-life drugs like sildenafil.
Perhaps, the most troublesome weakness of the study was the limited
sample size and differential participation rates of cases and controls,
likely resulting in selection bias that distorts the conclusion. The
authors note that almost one-fifth of the cases and one-third of the
controls refused to participate. The baseline cardiovascular
characteristics, while not significantly different (with the exception of
MI) between cases and controls, were consistently more prevalent in the
NAION group. This finding is not surprising given that these
cardiovascular conditions, especially in combination, are also risk
factors for NAION.[3] Thus, the MI and HTN subgroup analyses presented in Table 3 should be interpreted with skepticism.
Exacerbating the inherent problems are subgroup analyses that had no
a priori hypothesis. The dangers of unplanned subgroup analyses in
research are well documented.[4] Compounding matters is the sparse number
of patients, reflected in the exceptionally wide confidence intervals
(Table 3). The robustness of such extremely small cell numbers must also
be questioned, as the observed statistical significance for patients with
MI can be eliminated if only one or two patients are switched to an
alternative category. The authors also did not provide individual
patient totals by exposure group with and without MI, rendering it
impossible to replicate their results. Furthermore, there appear to be
errors in the numbers/percentages and crude odds ratios presented in Table 2.
In summary, the methodological limitations call into serious question
the authors’ conclusions. For men with a history of MI or HTN, therefore,
this study does not provide any valid evidence that the use of Viagra or
Cialis may increase the risk of NAION.
Rachel E. Sobel, MPH,
Pfizer Inc,
150 E 42nd St., MS#150-3-72,
New York, NY 10017.
Rachel.Sobel@pfizer.com
Joseph C. Cappelleri, PhD, MPH,
Pfizer Inc,
Global Research and Development,
Groton, CT.
References
1 McGwin G, Vaphiades MS, Hall TA, Owsley C. Non-arteritic anterior
ischaemic optic neuropathy and the treatment of erectile dysfunction. Br
J Ophthalmol 2006; 90:154-157.
2 Rothman KJ, Greenland S. Modern Epidemiology. Philadelphia, PA:
Lippincott-Raven Publishers, 1998.
3 Hatzichristou, D. Phosphodiesterase 5 Inhibitors and Nonarteritic
Anterior Ischemic Optic Neuropathy (NAION): Coincidence or Causality? J
Sex Med 2005; 2:751–758.
4 Assman SF, Pocock SJ, Enos LE, Kasten LE. Subgroup analysis and
other (mis)uses of baseline data in clinical trials. Lancet 2000; 35:1064-
1069.
Dear Editor,
We appreciate a response to our study from Dr Landers et al. They reported that five out of ten eyes with abnormal result of Frequency Doubling Perimetry (FDP) and normal result of Achromatic Automated Perimetry (AAP) showed abnormal result on AAP four years later.[1] It was our mistake that we referred their study as a cross-sectional study in our paper. We apologize to them that we should have referr...
Lutein and Zeaxanthin dietary intake and age related macular degeneration
We read with interest the letter published by Vu et al (1) whic...
Dear Editor,
We read with great interest the article by Bernauer et al [1] on the use hyaluronate artificial tear formulation �Hylo-Comod� favours the formation of corneal calcification related to the phosphate content of eye medications and frequent instillation. We agree with their conclusion and would like to highlight that in the setting of dry chronically inflamed eyes phosphate containing topical preparati...
Dear Editor,
We thank Barnes et al for their interest in our study and for affording us the opportunity to correct some misinterpretations that others may also have made regarding our paper.
We agree entirely that histological examination of the complete excision surface as suggested by Mohs would be the ideal one should aim at and that it would be superior to conventional bread loaf histological sect...
Dear Editor,
Thank you for writing and giving us the opportunity to further comment on our case series and investigations. We wish to put several misquotations right, respond to the accusation of inappropriate dosage, comment on the declaration of ingredients, explain our case description and substantiate the necessity to publish this case series.
Please note that we described five and not six cases. The...
Dear Editor,
In a recent issue of the Journal Steven et al. describe secondary retinal holes after removal of the inner limiting membrane (ILM) [1]. We consider this a key retinal publication and therefore wish to strengthen the importance of the authors' findings for modern surgery of the vitreoretinal interface.
Interestingly, the paper included only patients with macular puckers and cystoid macular oed...
Dear Editor,
We read with interest the article by Wong T.Y. et al[1], which studied a non-diabetic population consisting of 7992 people aged 49-73 years. Non-mydriatic retinal photographs of one eye were taken and graded for retinopathy lesions using to standardised protocols. Surprisingly, the presence of typical retinopathy lesions (microaneurysms or retinal haemorrhages) in persons without diabetes did not signi...
Dear Editor,
We read with great interest, Singh et. al.’s[1] perspective on impression cytology and its uses in diagnosing ocular surface pathology. The known higher exposure to UV radiation in both Australia and New Zealand, and the increased incidence of ocular surface squamous neoplasia (OSSN) in Australia,[2][3] recently led us to audit the incidence of OSSN in conjunctival biopsies in New Zealand over a 6...
Dear Editor,
We congratulate Kogure et al,[1] on a well designed longitudinal study, which confirms the suspicions of many earlier investigators, who conjectured that Frequency Doubling Perimetry (FDP) may be able to detect visual field loss earlier than Achromatic Automated Perimetry (AAP) based on cross-sectional data. In their text they refer to our longitudinal study[2] as a cross-sectional one and go on to s...
Dear Editor,
RE: Non-arteritic anterior ischaemic optic neuropathy and the treatment of erectile dysfunction.
McGwin et al.[1] suggest that treatment of erectile dysfunction with sildenafil (Viagra®) or tadalafil (Cialis®), two phosphodiesterase inhibitors (PDE5-I), may increase the odds of non-arteritic anterior ischaemic optic neuropathy (NAION) in men with a history of myocardial infarction (MI...
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