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Dr Cho and colleagues present data on a very small cohort of patients
with wet AMD that have switched treatment from either bevacizumab or
ranibizumab to aflibercept. Of note, this subgroup comprised approximately
8% of the total number of patients switched to aflibercept.
Any retrospective review is likely to be heavily biased by the
anticipated 'treatment benefit' of a new therapy particularly if, as in
this ca...
Dr Cho and colleagues present data on a very small cohort of patients
with wet AMD that have switched treatment from either bevacizumab or
ranibizumab to aflibercept. Of note, this subgroup comprised approximately
8% of the total number of patients switched to aflibercept.
Any retrospective review is likely to be heavily biased by the
anticipated 'treatment benefit' of a new therapy particularly if, as in
this case, the readers of retinal optical coherence tomography (OCT) scans
have the ability to manually correct and alter data that were originally
generated by semi-automated methods. In this study, the magnitude of
change observed in central foveal thickness was of marginal clinical
relevance (7.8% reduction from Baseline) after 1 injection and was further
attenuated by 6 months; these results suggest that the retinal OCT scan
reader was an important source of bias. This view is further supported by
the observation that visual acuity, which may be less liable to
investigator related bias, remained unchanged throughout.
Retrospective reviews are of scientific value when conducted in a
rigourous and independent manner. Selective reporting of data from this
study inevitably undermines any clinical conclusions regarding the
relevance of switching patients from anti-VEGF therapies to aflibercept.
Conflict of Interest:
I have consulted for a number of pharmaceutical companies including Novartis, the MAH of ranibizumab in the EU.
We read with interest Jackson and Morris's response to our letter.
The author's indicated that it was not possible to conduct a repeated
measures ANOVA using SPSS. However, SPSS provides several ways to analyze
repeated measures ANOVA through the general linear model command. There
are several excellent texts that illustrate how to conduct an ANOVA using
a repeated measures design in the SPSS environment....
We read with interest Jackson and Morris's response to our letter.
The author's indicated that it was not possible to conduct a repeated
measures ANOVA using SPSS. However, SPSS provides several ways to analyze
repeated measures ANOVA through the general linear model command. There
are several excellent texts that illustrate how to conduct an ANOVA using
a repeated measures design in the SPSS environment.
Second, they posed a question about whether it was reasonable to
assume that the data collected 18 months post surgically was specifically
related to data collected previously. To answer, yes, any time several
measurements are collected over time on the same subject, the data points
within each subject are related. Therefore the use of statistical
procedures that account for this clustering must be used. The fact that
the study was exploratory in nature does not preclude the application of
basic statistical principles. On the other hand, the authors correctly
noted that they had also analyzed the data using a 2x3 design. This
approach is reasonable. Unfortunately, the actual p-values were not
provided for the readers in the original article or in their response to
our editorial.
We would like to thank Dr. Geitzenauer for his comments and concerns
regarding our study.
As he has pointed out, in a non-inferiority study there is potential
for bias which may narrow down the difference in efficacy. Therefore,
conducting a superiority study simultaneously would be difficult, unless
sufficient quality is ensured during study planning, conduct as well as
data analysis.
We would like to thank Dr. Geitzenauer for his comments and concerns
regarding our study.
As he has pointed out, in a non-inferiority study there is potential
for bias which may narrow down the difference in efficacy. Therefore,
conducting a superiority study simultaneously would be difficult, unless
sufficient quality is ensured during study planning, conduct as well as
data analysis.
However, our study in question was a well-controlled study, with a
reasonable non-inferiority margin specified in advance, and conducted in
accordance with applicable Guidelines. Therefore we believe our study
method is acceptable.
The study plan was sufficiently evaluated as a double-masked
comparison study, and the study itself was conducted according to the
study protocol and in compliance with GCP (Good Clinical Practice).
Further, non-inferiority and superiority were verified for different
endpoints, Fluorescein staining score and Rose Bengal staining score,
respectively, and the methods were specified beforehand in the protocol.
In consideration of multiplicity, significance level was maintained by
adopting a closed testing method, by which superiority would be verified
only if inferiority has already been verified.
EU regulatory authorities have also accepted the simultaneous data
analysis for non-inferiority and superiority if it is a well-controlled
study, using previously specified analytical methods 1).
Therefore, we believe that the verification methods used in our study
are acceptable.
1) Committee For Proprietary Medicinal Products (CPMP) , Point to
consider on switching between superiority and non-inferiority, EMEA 2000;
July.
Takamura et al. report in a recent edition of the BJO about a "multi-
center, randomised, double-masked, parallel study" which leads to both a
non-inferiority and a superiority claim of the ophthalmic solution being
tested (diquafosol ophthalmic solution).(Reference 1) From a
methodological standpoint, the conclusions reached by the authors are not
in agreement with current accepted standards in th...
Takamura et al. report in a recent edition of the BJO about a "multi-
center, randomised, double-masked, parallel study" which leads to both a
non-inferiority and a superiority claim of the ophthalmic solution being
tested (diquafosol ophthalmic solution).(Reference 1) From a
methodological standpoint, the conclusions reached by the authors are not
in agreement with current accepted standards in the field of randomised
controlled trials.
It is methodologically unacceptable to draw conclusions about superiority
and non-inferiority at the same time using the same set of data. Already
at the design stage a decision has to be made whether a non-inferiority or
a superiority trial is to be conducted. Hence, claiming both non-
inferiority and superiority at the end of such a trial, as tempting as it
may be, violates fundamentals of clinical trials methodology.
Non-inferiority trials have specific characteristics which make emphasis
on rigorous methods even more important than in superiority
trials.(Reference 2) In a superiority trial, the objective is to detect a
difference, whereas in a non-inferiority trial, the objective is to fail
to detect a difference. These different objectives, among others, have
important implications with regard to the analysis and conclusion of a
trial. It is flawed to analyse and present data mixing up both approaches.
Recommendations for improving the quality of reporting of parallel-group
randomised trials, noninferiority and equivalence trials are published and
freely accessible on the internet. (References 3 and 4) Adoption of the
CONSORT statement in the editorial policy is likely to be beneficial to
the high standards of the BJO and would certainly be welcomed by this
reader.
Wolfgang Geitzenauer MD MSc FEBO
1 Takamura E, Tsubota K, Watanabe H, Ohashi Y. A randomised, double-
masked comparison study of diquafosol versus sodium hyaluronate ophthalmic
solutions in dry eye patients. BJO; 96(10):1310-5.
2 Fleming TR. Current issues in non-inferiority trials. Stat Med;
27(3):317-32.
I read the paper entitled "Risk of selected eye diseases in people
admitted to hospital for hypertension or diabetes mellitus: record linkage
studies" with interest. It elucidated that diabetes mellitus has a risk of
several ocular diseases with significance using two big epidemiological
data. However, I have two queries on their outcome by selecting the
association between cataract and diabetes mellitus.
I read the paper entitled "Risk of selected eye diseases in people
admitted to hospital for hypertension or diabetes mellitus: record linkage
studies" with interest. It elucidated that diabetes mellitus has a risk of
several ocular diseases with significance using two big epidemiological
data. However, I have two queries on their outcome by selecting the
association between cataract and diabetes mellitus.
First, Goldacre et al. described rate ratios concerning several eye
diseases caused by hypertension or diabetes mellitus. For example, risk of
cataract in diabetes was high presenting rate ratio (95% confidence
interval) of 2.95 (2.75 to 3.16) and 2.30 (2.24 to 2.35) in their two
epidemiological datasets (1). Although sex, age, year of admission and
patients' area of residence was adjusted by matching procedure, their
outcome is a hospital-based case control study with no specification on
the type of cataract. Mukesh et al. conducted a follow-up study, and
diabetes mellitus and having taken calcium channel blockers for longer
than 5 years were independent risk factors for posterior subcapsular
cataract (2), presenting hazard ratio (95% confidence interval) of 2.9
(1.7-5.1) and 2.9 (1.2-6.9), respectively. In addition, hazard ratio (95%
confidence interval) of age by one year increase for posterior subcapsular
cataract was 1.09 (1.07-1.1) (2). Effect of confounding variables on the
association between cataract and diabetes mellitus are more understandable
in cohort study compared with case-control study as mentioned above.
Second, Goldacre et al. described the study limitation for the lack
of information on the clinical state of diabetes mellitus including
treatment (1). The information on the clinical state of diabetes mellitus
is useful in combination with diabetic retinopathy.
The hospital-based case control study has a merit of satisfactory
statistical power, and further study on the association between cataract
and diabetes mellitus should be conducted including the above mentioned
information.
References
1. Goldacre MJ, Wotton CJ, Keenan TD. Risk of selected eye diseases
in people admitted to hospital for hypertension or diabetes mellitus:
record linkage studies. Br J Ophthalmol 2012;96:872-6.
2. Mukesh BN, Le A, Dimitrov PN, et al. Development of cataract and
associated risk factors: the Visual Impairment Project. Arch Ophthalmol
2006;124:79-85.
Using a chart review, Nyamori and colleagues estimated the incidence
of retinoblastoma in Kenya to be 1:17,000 live births, similar to global
estimates.1 They observed that late presentation was common, often
attributed to poor awareness or socioeconomic barriers which hinder access
to care. We describe a recent project to improve access to eye care for
people living in Western Kenya.
Using a chart review, Nyamori and colleagues estimated the incidence
of retinoblastoma in Kenya to be 1:17,000 live births, similar to global
estimates.1 They observed that late presentation was common, often
attributed to poor awareness or socioeconomic barriers which hinder access
to care. We describe a recent project to improve access to eye care for
people living in Western Kenya.
IcFEM Dreamland Mission Hospital in Kimilili achieved hospital status
in February 20122. With the support of Sabatia Eye Hospital and the
Provincial eye surgeon we then began offering affordable eye surgery once
a month. Demand for eye screening was high with people travelling long
distances to obtain services. In order to reach as many people as
possible, IcFEM engages local stakeholders by setting up community
leadership structures called Local Transformation Units2. These helped us
to obtain the agreement of local Chiefs, Councillors and Public Health
Officers to set up outreach clinics in isolated villages and at local
markets. Before each clinic, posters were put up in shops, pharmacies,
market places and read at public meetings. A team of two nurses and our
resident clinical officer then set up a stall where people could have
their visual acuity tested (using a chart which did not require literacy),
obtain reading glasses or medication, have simple foreign bodies removed
or be booked for surgery at the Mission Hospital.
Between January and July 2012, 751 people aged 2 to 100 years were
screened: 154 at outreach clinics in the villages, 198 at markets in
Kimilili, Kamukuywa and Chwele, and 399 at the hospital. Those being
considered for surgery were booked for assessment at the hospital before
the monthly operating list conducted by a specialist eye surgeon. Overall
115 patients, mean age 68 years, (15% of those screened) underwent
surgery: cataract extraction 106, foreign body removal 5, excision biopsy
2, tarsorrhaphy 1, peritomy 1. In spite of electricity cuts and use of the
emergency generator, only one patient had a complication (dislocated lens)
requiring further surgery. Following an overnight stay, operated patients
were given a talk including use of eye drops and booked for follow up
after two weeks. Complex cases, including children requiring a general
anaesthetic, could be referred to a specialist hospital.
Nyamori and colleagues recommend increasing public awareness of eye
problems and availability of treatment. We hope that the return to remote
villages of mainly elderly patients, some of whom were previously blind
and are now able to see, help in the fields or care for their
grandchildren, will contribute to this.
Rebecca Nightingale BSc, Consultant Physiotherapist
Jane Dobbs FRCP, Medical Superintendent
Clement Kiprop Dip-CMS, Head Clinical Officer
IcFEM Dreamland Mission Hospital
PO Private Bag, Kimilili 50204
Kenya
References
1. Nyamori JM, Kimani K, Njuguna MW, Dimaras H. The incidence and
distribution of retinoblastoma in Kenya. Br J Ophthalmol 2012; 96: 141-143
2. IcFEM www.icfem-mission.org
Acknowledgements
We thank the staff of Sabatia Eye Hospital for their assistance in setting
up the eye department and Dr Simon Daniell for installing the hospital eye
equipment. We acknowledge the dedicated team of specialist eye surgeons
and theatre sisters who with our colleagues at IcFEM Dreamland Mission
Hospital run the eye service. Our thanks also go to Dr Pippa Oakeshott for
her helpful advice.
Conflict of Interest:
Funders:
ROPE (Relief for Oppressed People Everywhere) www.rope.org.uk.
IcFEM ( Interchristian Fellowships' Evangelical Mission) www.icfem-mission.org
We read your paper entitled `Clinical factors associated with
malignancy and HIV status in patients with ocular surface squamous
neoplasia at Kililmanjaro Christian Medical Centre, Tanzania' with much
interest. It was an interesting insight into the characteristics of OSSN
patients in sub-saharan Africa. However, we had some queries and we hope
you can share your thoughts on them.
We read your paper entitled `Clinical factors associated with
malignancy and HIV status in patients with ocular surface squamous
neoplasia at Kililmanjaro Christian Medical Centre, Tanzania' with much
interest. It was an interesting insight into the characteristics of OSSN
patients in sub-saharan Africa. However, we had some queries and we hope
you can share your thoughts on them.
Firstly, we note that patients were selected based on external
appearance of lesions and we feel that this creates a selection bias as
patients with clinically less prominent lesions are less likely to be
recruited into the study. Your groupings of malignant lesions have
included mild to moderate dysplasia, many of which may be clinically less
prominent than more dysplastic lesions. This creates a bias where patients
selected are more likely to be of a higher dysplastic grade. However, we
do agree that selecting a large random group of patients from the general
population and testing them histologically may not be feasible.
Our second point is that the p value for independent association with
HIV status in the text (p = 0.035) is different from that in the table (p
= 0.01)
Thirdly, we note that you have concluded that HIV positive patients tend
to have a higher malignancy grade based on a regression model. However, we
were wondering if there was any explanation for the fact that CD4 counts
did not show a similar association. Furthermore, you concluded that
positive HIV status was associated with longer lesion duration, larger
lesion size, leukoplakia and the presence of feeder vessels. However, this
raises a few questions. Firstly, most would agree that a lesion of longer
duration is more likely to be of a larger size with corresponding feeder
vessels and show leukoplakic changes than one present for a shorter
duration. If it possible then that, HIV status was associated with the
above risk factors(large size, feeder vessels, leukoplakia) as HIV
patients themselves were more likely to have a lesion present for a longer
duration of time? Also, it is mentioned that women comprised of 69% of HIV
patients. We were wondering if in your experience, women in sub-Saharan
Africa may have lesser access to medical care which could have contributed
to the longer duration of lesions seen in HIV patients.
Lastly, it is stated that HIV patients are more likely to suffer a
recurrence. However, if HIV patients are more likely to have a larger
lesion for a longer duration, would this contribute to a higher recurrence
rate? Also, if HIV status is a postulated risk factor for the development
of dysplasia, it is highly conceivable that there are multiple dysplastic
foci. It is then possible that a `recurrent lesion' is in fact the
progression of a dysplastic lesion of another focus? As such, were all the
recurrences in the same spot of excision?
Thank you for your time and we hope to hear your thoughts on the
above queries!
References:
1. Clinical factors associated with malignancy and HIV status in
patients with ocular surface squamous neoplasia at Kilimanjaro Christian
Medical Centre, Tanzania. Makupa II, Swai B, Makupa WU, White VA, Lewallen
S. Br J Ophthalmol. 2012 Apr;96(4):482-4. Epub 2011 Nov PMID: 22075543
The authors thank the respondent for the observations and comments.
Most of our patients were referred to us by other ophthalmologists.
Unfortunately, as tertiary referral practitioners to the wider ophthalmic
community (uveitis: JCR, glaucoma: WHM and DD) we have no way of knowing
how many patients in our community are on brimonidine or how many cases of
brimonidine induced uveitis may be seen by other consultants. We ag...
The authors thank the respondent for the observations and comments.
Most of our patients were referred to us by other ophthalmologists.
Unfortunately, as tertiary referral practitioners to the wider ophthalmic
community (uveitis: JCR, glaucoma: WHM and DD) we have no way of knowing
how many patients in our community are on brimonidine or how many cases of
brimonidine induced uveitis may be seen by other consultants. We agree
with the respondent that brimonidine rechallenge testing adds to the
evidence for causality. This has previously been performed, in case
reports by Byles [1] (four patients), Goyal [2] (one patient), Cates [3] (one
patient) and Becker [4] (one patient). In all of these cases, uveitis
recurred on re-exposure. In our case series, all of the patients had field
threatening glaucoma, in one case in an only eye. Given the severity of
their alphagan side effects we could not ethically request that any
patient voluntarily trial re-exposure to the drug when its implication in
uveitis (sometimes hypertensive) is already so well documented.
1. Byles DB, Frith P, Salmon JF. Anterior uveitis as a side effect of
topical brimonidine. Am J Ophthalmol. 2000 Sep;130(3):287-91.
2. Goyal R, Ram AR. Brimonidine tartarate 0.2% (Alphagan) associated
granulomatous anterior uveitis. Eye (Lond). 2000 Dec;14(Pt 6):908-10.
3. Cates CA, Jeffrey MN. Granulomatous anterior uveitis associated with
0.2% topical brimonidine. Eye (Lond). 2003 Jul;17(5):670-1.
4. Becker HI, Walton RC, Diamant JI, Zegans ME. Anterior uveitis and
concurrent allergic conjunctivitis associated with long-term use of
topical 0.2% brimonidine tartrate. Arch Ophthalmol. 2004 Jul;122(7):1063-
6.
Article "Brimonidine (Alphagan) associated anterior uveitis" by
McKnight CM et al1 is informative. Cessation of brimonidine eye drops
resulted in improvement of uveitis in five cases. This case series has
produced further evidence that brimonidine may be responsible for uveitis/
raised IOP in some cases. However a critic may still argue the two events
to be coincidental. Unfortunately we have only a few anti glaucoma drug...
Article "Brimonidine (Alphagan) associated anterior uveitis" by
McKnight CM et al1 is informative. Cessation of brimonidine eye drops
resulted in improvement of uveitis in five cases. This case series has
produced further evidence that brimonidine may be responsible for uveitis/
raised IOP in some cases. However a critic may still argue the two events
to be coincidental. Unfortunately we have only a few anti glaucoma drugs
that can be used in uveitis. For the sake of the rest of glaucoma
patients, a few of these patients can be motivated to be volunteers.
Restarting the brimonidine in any of these patients and documenting the
reappearance of uveitis would produce stronger evidence. Moreover, their 5
patients1 presented with uveitis after using brimonidine for 13, 17, 6, 12
months and 5 years. Earlier reports also suggested that when brimonidine
is used, anterior uveitis can occur after approximately 1 year2/ 2 years3
of treatment. Keeping in view the common use of brimonidine, these case
reports reflect a very low incidence of uveitis and that too after use for
many months. Had authors stated their total number of patients on
brimonidine, we would have gained an idea of the frequency/ prevalence of
the problem.
References:
1. McKnight CM, Richards JC, Daniels D, Morgan WH. Brimonidine (Alphagan)
associated anterior uveitis. Br J Ophthalmol. 2012 Jan 18. [Epub ahead of
print]
2. Velasque L, Ducousso F, Pernod L, Vignal R, Deral V. [Anterior uveitis
and topical brimonidine: a case report]. J Fr Ophtalmol. 2004
Dec;27(10):1150-2. [Article in French]
3. Nguyen EV, Azar D, Papalkar D, McCluskey P. Brimonidine-induced
anterior uveitis and conjunctivitis: clinical and histologic features. J
Glaucoma. 2008 Jan-Feb;17(1):40-2.
We thank Dr Shoaib for his comments.
In the results we clearly state 'The indication for insertion was based on
the presence of ocular surface changes and poor tear film meniscus, with a
previous unsuc- cessful management by lubrication and topical medication
alone. Overall, 18 of the 25 patients had a concurrent systemic disorder
(table 1).'
Schirmer's test is , we believe , a poor test for dry eye in children. It
often r...
We thank Dr Shoaib for his comments.
In the results we clearly state 'The indication for insertion was based on
the presence of ocular surface changes and poor tear film meniscus, with a
previous unsuc- cessful management by lubrication and topical medication
alone. Overall, 18 of the 25 patients had a concurrent systemic disorder
(table 1).'
Schirmer's test is , we believe , a poor test for dry eye in children. It
often results in reflex tearing and is of little clinical value in
children. Tear break up time is only of value if we know what the normal
value is in CHILDREN. This is in fact the subject of our next manuscript
which is in review as I write this. In children under 12 years of age and
over 4 years of age , the non-invasive tear break up time using the
Tearscope ( Keeler , Windsor ,UK) is over 25 seconds ( unpublished data as
yet). So in children we looked at tear meniscus and ocular surface changes
such as PEE. We not only relied on subjective improvement but also
objective signs of improvement of ocular surface changes.
As for the comparison of cases of BKC, we can only comment on our own
paper which Dr Shoaib cites(1) . Please note that the majority of the
children in the 'Punctal Plug' manuscript had a systemic disorder which
led to secondary lid and corneal changes. In the article cited regarding
BKC (1) many of the children had neovascularisation of the cornea and
lubrication is clearly mentioned but not punctual plugs. We clearly state
here in the 'Punctal Plug' article that children who failed lubrication
were offered plugs. None of the cohort from the 2007 manuscript were in
this manuscript.
Finally, it is precisely because children can be so difficult to assess
that there has been no previous manuscript, to the best of our knowledge,
discussing punctual plugs exclusively in children.
1 Jones SM, Weinstein JM, Cumberland P, Klein N, Nischal KK. Visual
Outcome and Corneal Changes in Children with Chronic
Blepharokeratoconjunctivitis. Ophthalmology 2007;114:2271-2280
Dr Cho and colleagues present data on a very small cohort of patients with wet AMD that have switched treatment from either bevacizumab or ranibizumab to aflibercept. Of note, this subgroup comprised approximately 8% of the total number of patients switched to aflibercept.
Any retrospective review is likely to be heavily biased by the anticipated 'treatment benefit' of a new therapy particularly if, as in this ca...
We read with interest Jackson and Morris's response to our letter.
The author's indicated that it was not possible to conduct a repeated measures ANOVA using SPSS. However, SPSS provides several ways to analyze repeated measures ANOVA through the general linear model command. There are several excellent texts that illustrate how to conduct an ANOVA using a repeated measures design in the SPSS environment....
We would like to thank Dr. Geitzenauer for his comments and concerns regarding our study.
As he has pointed out, in a non-inferiority study there is potential for bias which may narrow down the difference in efficacy. Therefore, conducting a superiority study simultaneously would be difficult, unless sufficient quality is ensured during study planning, conduct as well as data analysis.
However, our st...
Dear editors,
Takamura et al. report in a recent edition of the BJO about a "multi- center, randomised, double-masked, parallel study" which leads to both a non-inferiority and a superiority claim of the ophthalmic solution being tested (diquafosol ophthalmic solution).(Reference 1) From a methodological standpoint, the conclusions reached by the authors are not in agreement with current accepted standards in th...
I read the paper entitled "Risk of selected eye diseases in people admitted to hospital for hypertension or diabetes mellitus: record linkage studies" with interest. It elucidated that diabetes mellitus has a risk of several ocular diseases with significance using two big epidemiological data. However, I have two queries on their outcome by selecting the association between cataract and diabetes mellitus.
First,...
Using a chart review, Nyamori and colleagues estimated the incidence of retinoblastoma in Kenya to be 1:17,000 live births, similar to global estimates.1 They observed that late presentation was common, often attributed to poor awareness or socioeconomic barriers which hinder access to care. We describe a recent project to improve access to eye care for people living in Western Kenya.
IcFEM Dreamland Mission Hos...
Dear Author,
We read your paper entitled `Clinical factors associated with malignancy and HIV status in patients with ocular surface squamous neoplasia at Kililmanjaro Christian Medical Centre, Tanzania' with much interest. It was an interesting insight into the characteristics of OSSN patients in sub-saharan Africa. However, we had some queries and we hope you can share your thoughts on them.
Firstly...
The authors thank the respondent for the observations and comments. Most of our patients were referred to us by other ophthalmologists. Unfortunately, as tertiary referral practitioners to the wider ophthalmic community (uveitis: JCR, glaucoma: WHM and DD) we have no way of knowing how many patients in our community are on brimonidine or how many cases of brimonidine induced uveitis may be seen by other consultants. We ag...
Article "Brimonidine (Alphagan) associated anterior uveitis" by McKnight CM et al1 is informative. Cessation of brimonidine eye drops resulted in improvement of uveitis in five cases. This case series has produced further evidence that brimonidine may be responsible for uveitis/ raised IOP in some cases. However a critic may still argue the two events to be coincidental. Unfortunately we have only a few anti glaucoma drug...
We thank Dr Shoaib for his comments. In the results we clearly state 'The indication for insertion was based on the presence of ocular surface changes and poor tear film meniscus, with a previous unsuc- cessful management by lubrication and topical medication alone. Overall, 18 of the 25 patients had a concurrent systemic disorder (table 1).' Schirmer's test is , we believe , a poor test for dry eye in children. It often r...
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