We thank Dr. John Sloper for his comments regarding this clinical
pathological case of advanced human glaucoma, visual field loss, and
central visual system degeneration. [1]
Dr. Sloper states "Gupta et al. state that both magnocellular and
parvocellular cells from the lateral geniculate nucleus of a patient with
glaucoma are significantly smaller than those in three control subjects."
We respectf...
We thank Dr. John Sloper for his comments regarding this clinical
pathological case of advanced human glaucoma, visual field loss, and
central visual system degeneration. [1]
Dr. Sloper states "Gupta et al. state that both magnocellular and
parvocellular cells from the lateral geniculate nucleus of a patient with
glaucoma are significantly smaller than those in three control subjects."
We respectfully disagree with his statement.
In the present article, randomized stereological methodology was used
to measure cross-sectional areas of neurons in the glaucoma case and each
of the 3 control cases. We show that radii of the magnocellular neurons
in the glaucoma index case are smaller than those in each of the controls
(boxplots in Figure 4C). However, radii of the parvocellular neurons in
the glaucoma index are smaller than only one of the three controls
(boxplots, Figure 5C).
Dr. Sloper's concern that the multiple t-tests showing these
differences are "statistically invalid" is a valid concern, as the
measurements compared in the t-tests are not independent. While the
boxplots clearly show the results as described in the text, another valid
way to show these results statistically is to use Confidence Intervals.
Using the means in Table 2, we calculate a 95% Confidence Interval (with 2
degrees of freedom) for the mean of the magnocellular control averages.
This interval is (347.54 μm2, 575.79 μm2), and this interval does not include
the glaucoma mean value of 273 μm2 in magnocellular neurons. For the
parvocellular means, the 95% Confidence Interval for the mean value for the
control averages is (132.13 μm2, 357.87 μm2), which does include
the glaucoma average. These findings suggest that neuron shrinkage in
magnocellular layers of the lateral geniculate nucleus occurs in this case
of human glaucoma. This is consistent with neuron shrinkage described in
the lateral geniculate nucleus in experimental primate glaucoma. [2,3,4]
Dr. Sloper reminds us that tissue processing and obliquity of
sectioning are important factors to consider when interpreting the finding
of reduced cortical ribbon thickness in visual cortex. Great care was
taken to process the brain tissue under similar conditions, and to avoid
areas where the sectioning may have been oblique when examining coronal
serial sections.
In discussing our findings of reduced cortical thickness in this
glaucoma patient,
Dr. Sloper refers to the lack of evidence for visual cortex changes even
following enucleation in non-human primates. However, following unilateral
enucleation in non-human primate, there is in fact evidence of
cytoarchitectural changes in ocular dominance columns of the visual cortex
[5]. Furthermore, retinal ganglion cell degeneration involving both eyes
has been shown to lead to reduced cortical ribbon thickness. [6] While in
this case, injury to vision centers in the brain may be secondary to
retinal ganglion cell loss by anterograde transsynaptic degeneration,
primary injury to the visual cortex leading to retrograde degeneration of
retinal ganglion cells cannot be excluded. [7]
Degenerative changes at multiple levels of the visual system were
observed in this patient with advanced glaucoma. Additional cases of
glaucoma patients and controls are needed to characterize these changes
further.
References
1. Gupta N, Ang L-C , Noël de Tilly L, Yücel Y H. Human Glaucoma and
Neural Degeneration in the Intracranial Optic Nerve, Lateral Geniculate
Nucleus and Visual Cortex of the Brain. British J Ophthalmol 2006; 90: 674
-678.
2. Weber AJ, Chen H, Hubbard WC, Kaufman PL. Experimental glaucoma
and cell size, density, and number in the primate lateral geniculate
nucleus. Invest Ophthalmol Vis Sci 2000; 41:1370-1379.
3. Yücel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N. Atrophy of
relay neurons in magno- and parvocellular layers in the lateral geniculate
nucleus in experimental glaucoma. Invest Ophthalmol Vis Sci 2001; 42:3216-
3222.
4. Yücel YH, Zhang Q, Weinreb RN, Kaufman PL, Gupta N. Effects of
retinal ganglion cell loss on magno-, parvo-, koniocellular pathways in
the lateral geniculate nucleus and visual cortex in glaucoma. Prog Retin
Eye Res 2003; 22: 465-481.
5. Haseltine EC, DeBruyn EJ, Casagrande VA. Demonstration of ocular
dominance columns in Nissl-stained sections of monkey visual cortex
following enucleation. Brain Res, 1979;176: 153-158.
6. Cragg BG. The development of synapses in kitten visual cortex
during visual deprivation, Exp Neurol, 1975; 46: 445-451.
7. Johnson H, Cowey A. Transneuronal retrograde degeneration of
retinal ganglion cells following restricted lesions of striate cortex in
the monkey. Exp Brain Res. 2000;132:269-275.
We read with great interest the “Bullying and eye patching”
commentary by Williams and co-workers in which they report on the
psychosocial implications of early versus late treatment of amblyopia.[1]
In their birth cohort study, they found that early detection (screening at
the age of 3 years and 1 month) and subsequent early treatment of
amblyopia resulted in fewer reports of bullying victimisatio...
We read with great interest the “Bullying and eye patching”
commentary by Williams and co-workers in which they report on the
psychosocial implications of early versus late treatment of amblyopia.[1]
In their birth cohort study, they found that early detection (screening at
the age of 3 years and 1 month) and subsequent early treatment of
amblyopia resulted in fewer reports of bullying victimisation by age 8
years. On this basis, they appraised pre-school vision screening and
suggested that the timing of treatment should be as early as possible, so
as to lessen the likelihood of bullying. Whilst the literature suggests
that sustained bullying in childhood may have adverse psychosocial
consequences in adulthood,[2] and whilst we agree that prevention of
bullying is important, there is no evidence indicating that the
experiences of children who undergo patching treatment for amblyopia have
adverse consequences in terms of children’s longer term well-being.
There is certainly a growing body of evidence suggesting that
patching is associated with peer victimisation.[1,3-4] In a study we
recently conducted, we found that children not only reported experiences
of bullying, but also feelings of stigmatisation regardless of whether
they were subjected to victimisation.[5] This resulted in negative
psychosocial outcomes for some children. However, whether bullying and or
feelings of stigmatisation have longer term psychosocial sequelae remains
unanswered. Ideally, prospective longitudinal studies are needed to
investigate the long term psychosocial consequences of patching for
amblyopia. Although Williams and her colleagues have conducted a
prospective study, they have only assessed bullying at one point in time
(at 8.5 years of age) and do not appear to have asked children what they
perceived as the cause of their victimisation. Without at least the
child’s perspective on this, it is impossible to ascertain whether these
experiences relate to patching. Furthermore, amblyopia treatment usually
always ceases well before the end of the first decade of life. Hence,
patching, the source of a child’s differentness within a group of peers,
also ceases early in life. It is possible that short-term patching does
not necessarily have an adverse effect on an individual’s psychosocial
well-being in the long-term. There is also evidence that the removal of a
stigmatising feature can have positive implications for an individual. For
instance, it has been reported that psychosocial functioning improves with
corrective surgery for strabismus.[6-9] More research is needed to
investigate whether this similarly relates to patching.
We agree with the authors that bullying and other psychosocial
factors should form part of treatment outcome measures; however there is
need for future research to also be attentive to the longer term effects
of patching treatment for amblyopia. Given the nature of this birth cohort
study, the ALSPAC Study team may be able to address this in follow-up
studies.
Konstandina Koklanis PhD
Zoran Georgievski BAppSc(Orth)Hons
References
1. Williams C, Horwood J, Northstone K, et al. The timing of patching
treatment and a child's wellbeing. British Journal of Ophthalmology
2006;90:670-671.
2. Olweus D. Victimisation by peers: Antecedents and long-term
outcomes. In: Rubin KH, Asendorpf J, eds. Social Withdrawal, Inhibition
and Shyness in Childhood.
Hillsdale, NJ: Lawrence Erlbaum. 1993.
3. Packwood E, Cruz O, Rychwalski P, Keech R. The psychosocial
effects of amblyopia study. Journal of the American Association for
Pediatric Ophthalmology and Strabismus 1999;3:15-17.
4. Horwood J, Waylen A, Herrick D, et al. Common visual defects and
peer victimization in children. Investigative Ophthalmology and Visual
Science 2005;46:1177-1181.
5. Koklanis K, Abel L, Aroni R. The psychosocial impact of amblyopia
and its treatment: A multidisciplinary study. Clinical and Experimental
Ophthalmology in press.
6. Burke J, Leech C, Davis H. Psychosocial implications of strabismus
surgery in adults. Journal of Pediatric Ophthalmology and Strabismus
1997;34:159-164.
7. Satterfield D, Keltner J, Morrison T. Psychosocial aspects of
strabismus study. Archives of Ophthalmology 1993;111:1100-1105.
8. Jackson S, Harrad R, Morris M, Rumsey N. The psychosocial benefits
of corrective surgery for adults with strabismus. British Journal of
Ophthalmology 2006;90:883-888.
9. Menon V, Saha J, Tandon R, et al. Study of psychosocial aspects of
strabismus. Journal of Pediatric Ophthalmology and Strabismus 2002;39:203-
208.
Gupta et al. state that both magnocellular and parvocellular cells
from
the lateral geniculate nucleus (LGN) of a patient with glaucoma are
significantly smaller than those in three control subjects. However it
would
appear that the authors have used the sample sizes and standard deviation
of
the cell samples from each individual to make comparisons between
subjects.
This is statistically invalid...
Gupta et al. state that both magnocellular and parvocellular cells
from
the lateral geniculate nucleus (LGN) of a patient with glaucoma are
significantly smaller than those in three control subjects. However it
would
appear that the authors have used the sample sizes and standard deviation
of
the cell samples from each individual to make comparisons between
subjects.
This is statistically invalid, as these samples contain no estimate of the variability between individuals. The P values of <0.0001 quoted for
differences between the patient with glaucoma and the control subjects are
erroneous. The basis for making comparisons of LGN size between different
subjects has been described[1] and requires a single mean value to be used
for each sample in each subject for comparisons between groups of
subjects.
In this instance the comparison is between groups of 1 and 3; these are
too
small to allow a meaningful statistical comparison. This does not of
course
mean that transneuronal shrinkage of LGN cells does not occur as a result
of
ganglion cell loss in glaucoma, but the present findings do not
demonstrate it
in man.
Of more concern is the statement that in the visual cortex of the
glaucoma patient "cortical ribbon thickness reduction was easily
discernable
compared to controls". The only evidence presented to support this is
photographs of single sections through the primary visual cortex in the
one
glaucomatous subject and one control. Given possible differences in
shrinkage during processing, differences in apparent thickness due to
obliquity in sectioning and inter-individual variability this is
meaningless.
Comparable differences in apparent cortical thickness are visible in
different
parts of primary visual cortex as illustrated in a standard textbook of
ophthalmology (Figs 15.105 and 15.108)[2] where they are almost certainly
due to differences in obliquity of sectioning. The demonstration of
changes in
cortical thickness secondary to retinal ganglion cell degeneration would
be a
novel and important observation, particularly as I am not aware of any
good
evidence for this even following enucleation in experimental primates.
However, the demonstration of central visual pathway changes in patients
with glaucoma will require the analysis of substantial numbers of patients
and controls to obtain meaningful results.
References
1. Headon MP, Sloper JJ, Hiorns RW and Powell TPS. Effects of
monocular
closure at different ages on deprived and undeprived cells in the primate
lateral geniculate nucleus. Dev Brain Res 1985 18: 57-78.
2. Central visual pathways. In: Bron AJ, Tripathi RC and Tripathi
BJ. Wolff’s
anatomy of the eye and orbit, 8th Edition, London, Arnold, 2001.
We read with great interest the article by Chiba and co-workers about
the possible effect on intraocular pressure (IOP) induced by non-steroidal
anti-inflammatory (NSAID) ophthalmic solution in patients affected by
primary open angle glaucoma (POAG) or ocular hypertension (OH) and treated
with latanoprost [1].
In 2003, Kashiwagi and Tsukahara (two co-authors of
the above-mentioned Chiba et al...
We read with great interest the article by Chiba and co-workers about
the possible effect on intraocular pressure (IOP) induced by non-steroidal
anti-inflammatory (NSAID) ophthalmic solution in patients affected by
primary open angle glaucoma (POAG) or ocular hypertension (OH) and treated
with latanoprost [1].
In 2003, Kashiwagi and Tsukahara (two co-authors of
the above-mentioned Chiba et al. paper) have already published a similar
study conducted on a very small number of healthy volunteers (thirteen
Japanese young adults), concluding that the co-administration of bromfenac
significantly inhibited latanoprost induced IOP reduction [2]. In June
2005, we have published an article on the same topic, but carried out on
thirty-two POAG patients [3]. This paper described discrepant results as
compared to those obtained by both Chiba and co-workers [1], and Kashiwagi
and Tsukahara [2]. In fact, within our Caucasian glaucomatous study group,
diclofenac eyedrops significantly enhances the ocular hypotensive effect
of latanoprost.
We have tried to explain the contradictory data obtained
in 2003 by Kashiwagi and Tsukahara [2], in comparison with our results [3]
and those achieved by Sponsel et al. in 2002 [4], also indicating several
possible bias of the first mentioned trial. Finally, we have speculatively
discussed the reliable pathophysiological causes of this more marked,
latanoprost-induced IOP reduction in NSAID-treated POAG patients [3]
mainly considering that: i. therapeutic and side-effect profiles of
latanoprost is explainable by its prevalent action on FP, EP and TP
prostaglandin (PG) receptors [5-7]; ii. in human cultured ciliary muscle
(CM) cells the same NSAID level, obtained after drug topical
administration, inhibits the PGs synthesis [8]; iii. in experimental
models, an up-regulation of PG receptors occurs via cyclooxygenases
inhibition [9-11].
Rationally, we have concluded that a NSAID-related fall
in endogenous PGs synthesis could be responsible for a PG receptors over-
expression, increasing the IOP-lowering effect of topical PG analogues.
The effect of this pharmacological interaction, essentially based on the
well-known plasticity of PG receptors system [9-13], should be
realistically investigated only in patients with a definite and definitive
diagnosis of glaucoma, such as POAG patients studied by ours in 2005 [3].
In fact, only in glaucomatous CM cells an over-expression of PG receptors
occurs [12], whereas these receptors are scarcely present in the same
cells of healthy subjects [13] and, reliably, also in CM of OH patients.
This hypothesis has been developed starting from different points of view
respect to Chiba et al. [1], whose paper has also briefly commented by Alm
in an Editorial published in the same BJO issue [14].
In our opinion, none of the investigations existing in the current
literature are able to conclusively verify the possibility of an
interaction between NSAIDs and PG analogues. Particularly, the recent
study of Chiba et al. is characterized by an insufficient and
heterogeneous patient's recruitment (just nine POAG and four OH subjects),
resembling the crucial weak-point of Kashiwagi and Tsukahara trial, which
was previously conducted on healthy volunteers [1,2].
Curiously, Chiba
and co-workers have not considered these biases. On the contrary, they
have emphasized, at the top of the Discussion section, that their "study
clearly demonstrated that ophthalmic NSAID inhibits the IOP reduction by
latanoprost ophthalmic solution in glaucomatous eyes", partially or
totally ignoring: i. the results of other Authors who had utilized a more
numerous and / or homogeneous study populations [3, 4, 15]; ii. the possible
variability of PG receptors expression in different ethnic groups [16,
17].
References
1. Chiba T, Kashiwagi K, Chiba N, Tsukahara S. Effect of non-
steroidal anti-inflammatory ophthalmic solution on intraocular pressure
reduction by latanoprost in patients with primary open angle glaucoma or
ocular hypertension. Br J Ophthalmol 2006; 90: 314-17.
2. Kashiwagi K, Tsukahara S. Effect of non-steroidal anti-
inflammatory ophthalmic solution on intraocular pressure reduction by
latanoprost. Br J Ophthalmol 2003; 87: 297-301.
3. Costagliola C, Parmeggiani F, Antinozzi PP, Caccavale A,
Cotticelli L, Sebastiani A. The influence of diclofenac ophthalmic
solution on the intraocular pressure-lowering effect of topical 0.5%
timolol and 0.005% latanoprost in primary open-angle glaucoma patients.
Exp Eye Res 2005; 81: 610-15.
4. Sponsel WE, Paris G, Trigo Y, Pena M, Weber A, Sanford K, McKinnon
S. Latanoprost and brimonidine: therapeutic and physiologic assessment
before and after oral nonsteroidal anti-inflammatory therapy. Am J
Ophthalmol 2002; 133: 11-8.
5. Stjernschantz J, Selen G, Astin M, Resul B. Microvascular effects
of selective prostaglandin analogues in the eye with special reference to
latanoprost and glaucoma treatment. Prog Retin Eye Res 2000; 19: 459-96.
6. Weinreb RN, Toris CB, Gabelt BT, Lindsey JD, Kaufman PL. Effects
of prostaglandins on the aqueous humor outflow pathways. Surv Ophthalmol
2002; 47: S53–S64.
7. Stjernschantz J. Studies on ocular inflammation and development of
a prostaglandin analogue for glaucoma treatment. Exp Eye Res 2004; 78: 759
-66.
8. Yousufzai SY, Abdel-latif AA. Endothelin-1 stimulates the release
of arachidonic acid and prostaglandins in cultured human ciliary muscle
cells: activation of phospholipase A2. Exp Eye Res 1997; 65: 73-81.
9. Li DY, Varma DR, Chemtob S. Up-regulation of brain PGE2 and PGF2
alpha receptors and receptor-coupled second messengers by cyclooxygenase
inhibition in newborn pigs. J Pharmacol Exp Ther 1995; 272: 15-9.
10. Li DY, Abran D, Peri KG, Varma DR, Chemtob S. Inhibition of
prostaglandin synthesis in newborn pigs increases cerebral microvessel
prostaglandin F2 alpha and prostaglandin E2 receptors, their second
messengers and vasoconstrictor response to adult levels. J Pharmacol Exp
Ther 1996; 278: 370-7.
11. Hardy P, Bhattacharya M, Abran D, Peri KG, Asselin P, Varma DR,
Chemtob S, Bhatthacharya M. Increases in retinovascular prostaglandin
receptor functions by cyclooxygenase-1 and -2 inhibition. Invest
Ophthalmol Vis Sci 1998; 39: 1888-98.
12. Husain S, Kaddour-Djebbar I, Abdel-Latif AA. Alterations in
arachidonic acid release and phospholipase C-beta(1) expression in
glaucomatous human ciliary muscle cells. Invest Ophthalmol Vis Sci 2002;
43: 1127-34.
13. Mukhopadhyay P, Geoghegan TE, Patil RV, Bhattacherjee P, Paterson
CA. Detection of EP2, EP4, and FP receptors in human ciliary epithelial
and ciliary muscle cells. Biochem Pharmacol 1997; 53, 1249-55.
14. Alm A. Can NSAIDs and prostaglandin analogues be combined? Br J
Ophthalmol 2006; 90: 259-60.
15. Miyake K, Ota I, Maekubo K, Ichihashi S, Miyake S. Latanoprost
accelerates disruption of the blood-aqueous barrier and the incidence of
angiographic cystoid macular edema in early postoperative pseudophakias.
Arch Ophthalmol 1999; 117: 34-40.
16. Stein M, O'Malley K, Kilfeather S. Ethnic differences in cyclic
AMP accumulation: effect on alpha 2, beta 2, and prostanoid receptor
responses. Clin Pharmacol Ther 1990; 47: 360-5.
17. Oguma T, Palmer LJ, Birben E, Sonna LA, Asano K, Lilly CM. Role
of prostanoid DP receptor variants in susceptibility to asthma. N Engl J
Med 2004; 351: 1752-63.
We read with interest the extended report by Hassell and colleagues
[1] demonstrating the adverse effect of quality of life in mild visual
impairment (<6/12) and worse. Their demonstration of the impact of
Age Related Macular Degeneration (AMD) on quality of life indices is an
important illustration of the difficulties experienced by the visually
impaired.
We read with interest the extended report by Hassell and colleagues
[1] demonstrating the adverse effect of quality of life in mild visual
impairment (<6/12) and worse. Their demonstration of the impact of
Age Related Macular Degeneration (AMD) on quality of life indices is an
important illustration of the difficulties experienced by the visually
impaired.
We have reported a similar experience in West Glamorgan (Wales,
United Kingdom) [2]. Our study comprised of 66 patients registered as
blind/partially sighted (59.1% because of AMD). The demographic
characteristics mirrored this study (mean age 81.33 (SD 9.87); 69.7%
female). We utilised an alternative index to the Impact of Vision
Impairment (IVI) questionnaire, the National Eye Institute Visual
Function
Questionnaire (NEI-VFQ 25) [3]. This has similar categories including
general health, general vision, ocular pain, near activities, distance
activities, social functioning, mental health, role difficulties,
dependency, colour vision, peripheral vision.
Hassell et al demonstrated a statistically significant restriction
in leisure and work, social and consumer interaction and household and
personal care difficulties between those with a mild/moderate compared
to the severely impaired group. This was our experience in the analogous
categories of social functioning (NEI-VFQ score 36.49% for the blind vs.
50% for the partially sighted; p = 0.0005) and dependency (NEI-VFQ score
30.07% for the blind vs. 46.98% for the partially sighted; p = 0.0003).
Furthermore, percentage scores in our study were less than 50% for all
categories except general health, ocular pain and peripheral vision for
the blind and partially sighted. Of the studies that have utilised the
NEI-VFQ in order to determine the extent of visual function, none have
previously demonstrated mean scores as low as our study (Brody et al
2001[4]; Klein et al 2001[5]). Hassell et al have therefore not only
demonstrated a worse quality of life in the severely visually impaired
(<6/60), but reinforce the important fact that all those with visual
impairment experience difficulties.
A second interesting finding in their paper was the absence of
correlation between duration of visual impairment and adaptation. We
found that the NEI-VFQ scores for those living alone were better than
for individuals living with someone for numerous categories including near
vision activities (20.9% vs. 15.3%, p=0.03), distant vision activities
(27.9% vs. 20.1%, p=0.056) and dependency (46.3 vs. 31.4%, p=0.004)
(Williams GP, Pathak-Ray V and Austin MW 2001, Unpublished Data).
This may imply that living alone forces people to adapt. We
interpreted this finding with caution however as a number of the people
'living with someone' resided in a nursing/residential home. This may
have occurred as a result living alone causing difficulties with coping in
the first instance.
Finally, their paper was undertaken before people had received low
vision services. Depressingly, our study found that there was incomplete
delivery of formal low visual aid assessment (n=44, 66%); of these 70%
found them to be of use. We therefore agree with the authors that not
only should there be consideration of referral to low visual services, but
adequate delivery and support is required in order to for it to be
effective.
Mr Geraint P Williams BSc, MRCOphth
Mrs Vanita Pathak-Ray FRCS (Ed)
Mr Michael W Austin FRCS, FRCOPhth
References
[1] Hassell JB, Lamoureux EL and Keefe JE. Impact of age related
macular degeneration on quality of life. British Journal of
Ophthalmology
2006;90:593-596
[2] Williams GP, Pathak-Ray V, Austin MW, Lloyd AP, Millngton IM
and
Bennett A. Quality of life and visual rehabilitation: an observational
study of low vision in West Glamorgan. Eye 2006 Feb 3 [Epub ahead of
print]
[3] Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S and
Hays
RD. Development of the 25-item National Eye Institute Visual Function
Questionnaire. Archives of Ophthalmology, 2001. 119(7):1050-8.
[4] Brody BL, Gamst AC, Williams RA, Smith AR, Lau PW, Dolnak D et
al. Depression, Visual Acuity, Comorbidity, and Disability Associated
with Age-related Macular Degeneration. Ophthalmology 2001;108(10)1893-
1900
[5] Klein R, Moss SE, Klein BEK, Gutierrez P and Mangione CM. The
NEI-VFQ-25 in People With Long Term Type-1 Diabetes Mellitus. Archives
of
Ophthalmology 2001;119:733-740.
We read with great interest the article published by Pate JC (1) in
your journal and the editorial (2), regarding polymicrobial infection of
cornea. Our centre is a tertiary level eye care centre in northern India
and also the apex centre for eye care of the country. We, in our
country come across a large number of fungal keratitis cases compared to
that
reported in western studies. Though the author...
We read with great interest the article published by Pate JC (1) in
your journal and the editorial (2), regarding polymicrobial infection of
cornea. Our centre is a tertiary level eye care centre in northern India
and also the apex centre for eye care of the country. We, in our
country come across a large number of fungal keratitis cases compared to
that
reported in western studies. Though the authors rightly state that the
findings
reported by them may not be generalized to populations like ours, we
would like to share our view. As a part of a recent project on fungal
keratitis, we
studied 76 eyes of presumed fungal keratitis in the last 1 year duration
prospectively. The pattern of polymicrobial infection was analyzed as
well.
The criteria mentioned for diagnosing the co-infection by Pate JC
(1)
were similar in our study. Of a total 76 eyes only 20 (26%) were proven
to have fungal keratitis by culture. Of these 20, pure fungal
infection was detected only in 5 (25%) and the remaining 15 had
bacterial co-infection (75%). The isolation of yeast is much
less in our country in contrast to that of western literature. Also
there
is intracountry variation in geographical distribution of filamentous
fungi such as Aspergillus and Fusarium. At our center, in northern
India,
the isolation of Aspergillus heads the list.
While the authors reported bacterial co-infection in 10% and 20% of
Moniliaceous and Dematiaceous filamentous fungi respectively, we found
66% and 100%. However, we feel that high percentages of co-
infection in our study could be attributed to small sample size.
The authors have also commented that the prevalence
may be due to a number of factors such as nonconformity in microbial co-
isolation, climatic effect, history of trauma, ocular
surface integrity, and prior therapy. The first factor was ruled
out in our study as the microbial co-isolation was carefully evaluated
in
our microbiology lab. The climatic effect did not show any correlation.
It
is not possible to comment on ocular surface as a negligible number of
eyes
with ulcer had associated ocular surface abnormalities. Though, 60%
&
86.6% of eyes with polymicrobial co-infection revealed a history of
trauma
and prior drug therapy respectively the same could not be compared with
that of growth without co-infection as the number of eyes was only 5. We
are in concurrence with our earlier reports (3,4) and that of the
authors
(1,2) that coexistence of Staphylococcal infection is most commonly
found
along with fungal infection . The authors have expressed their view that
there may be a mutual alliance for the co-pathogens. Tuft (2) has
commented about the super infection with a second organism which is
attributed to the inhibition of the local immune response by the topical
corticosteroid. This is an important aspect to note as the patients with
keratitis when referred to the tertiary center with extensive and non
responsive infection are found to be on topical corticosteroid sometime
or
other during course of the disease.
At the end, we congratulate the authors for bringing this important
issue to light so that clinicians may effectively manage polymicrobial
co-infection.
Table 1.
Isolate
Proven fungal case
Bacterial co-infection
Moniliaceous filamentous fungi
15
10 (66%)
Dematiaceous filamentous fungi
5
5 (100%)
Total
20
15
References
1. Pate J C, Jones DB, Wilhelmus KR. Prevalence and spectrum of
bacterial co-infection during fungal keratitis. Br J Ophthalmol 2006;
90:289-92.
2. Tuft S. Polymicrobial infection and the eye- Has important
management implications. Br J Ophthalmol 2006; 90:57-58.
3. Satpathy G, Vishalakshi P. Ulcerative keratitis: microbial
keratitis and sensitivity pattern-a five year study. Ann Ophthalmol 1995;
27:301-6.
4. Khanal B, Deb M, Panda A, et al. Laboratory diagnosis in
ulcerative keratitis. Ophthalmic Res 2005; 37:123-7
I have just finished reading the interesting paper by Daniell et al
and, being one of the first authors (Secchi AG et al, AJO, 1990, 110,
137-
42) to become interested in the topical use of Cyclosporine A in
"allergic" conditions concerning the ocular surface, I would like to
make
a few comments - based above all on a 20-year experience in the
treatment
of vernal keratoconjunctivitis (VKC) with topi...
I have just finished reading the interesting paper by Daniell et al
and, being one of the first authors (Secchi AG et al, AJO, 1990, 110,
137-
42) to become interested in the topical use of Cyclosporine A in
"allergic" conditions concerning the ocular surface, I would like to
make
a few comments - based above all on a 20-year experience in the
treatment
of vernal keratoconjunctivitis (VKC) with topical Cyclosporine A as my
first line prescription in over 1,000 patients.
I am certainly not the only one to use this
approach. Colleagues throughout the world use
topical Cyclosporine A in the treatment of VKC and, particularly in the
limbal forms. The tarsal forms usually
improve in as little as ten days of treatment as far as symptoms are
concerned, the mucus disappears, the giant papillae remain on the
contrary more or less unchanged, as the corneal sterile ulcers do. No
side
effects have been noticed even after years of treatment, beside some
corneal mild epitheliopathy and a frequent burning sensation upon
instillation, which often disappears within a few weeks. My personal
experience is that topical Cyclosporine A, on the overall, really
changes
the life in most cases of VKC patients.
Allergic keratoconjunctivitis (AKC) seems to be a rather different
story. The effect of topical CsA
is minimal, well below that of topical steroids, and in many cases good
results are obtained only with systemic use of the drug.
The results presented by our Australian colleagues seems to be, in
VKC cases, opposite to our observations. No statistical difference has
been found between Restasis and the placebo, neither for symptoms nor
for
signs. The reason, in my opinion, is that a 0.05 % concentration of
Cyclosporine A such as that present in Restasis is far too low for being
active in VKC patients. We use with full satisfaction, as do our
colleagues, a 1 to 2 % concentration
in either olive or maize oil. In maintenance regimens even a 0.5% may be
active. Lower concentrations, on the contrary, are not effective at
all.
Restasis, as a major fact, is intended neither for VKC nor for AKC.
Its off-label use in these clinical conditions is substantially
ineffective, as our Australian colleagues have clearly confirmed.
I quite agree on the Authors' last sentence "not to recommend
Restasis
eye drops in steroid dependent allergic conjunctivits", but I strongly
disagree on "tempering our enthusiasm": It is not topical CyclosporineA
which has been shown not to be useful in VKC, it is Restasis! Will
Allergan eventually provide a stronger topical preparation of
Cyclosporine A? There
are millions of patients suffering for VKC in the world, and steroids
are not the answer while even last-
generation antiallergic multivalent drugs are most often not effective
enough!
Antonio G. Secchi MD
Professor of Ophthalmology and Director
Department of Ophthalmology
University of Padua, Italy
School of Medicine
ag.secchi@unipd.it
Reference:
AG Secchi, MS Tognon, A Leonardi
Topical Use of Cyclosporine in the Treatment of Vernal
Keratoconjunctivitis
Am J Ophthal 1990, 110, 137-142.
We are deeply concerned by the conclusion made
by Vu et al that “there was a harmful effect of higher LZ intake on AMD
among those with high level of linoleic acid intake. Based on these data LZ
supplementation could not be recommended”.1 It is
counterintuitive, and goes against the evidence currently available in the
literature.2,3 The most likely explanation is that their results
reflect the success of the public health messages put out to patients with AMD
about eating foods high in antioxidants, such as green leafy vegetables and
spinach. This important message is in danger of being undermined by such
pronouncements.
It is our opinion that the letters section
of a medical journal is not the place to publish contentious nutritional
epidemiological data. It is too complex, and the limitation on the number of
words does not allow an adequate disclosure of methods and results, or an appropriate
depth of discussion. The readers, therefore, are not able to properly interpret
the data. This type of article cannot be properly peer reviewed without the
submission of much more data than was given in this case.
There are a number of problems with this
study.The possibility of selection
bias is a particular concern where the study is evaluating only 65 % of the
original target population and is only examining crossectional data. The
statistical method used to calculate the odds ratios was not given, although it
could be assumed that a logistic regression model would have been applied. A close
examination of the results indicates that there were only 4 cases of late AMD
in the higher than median linoleic acid group (table 1). The odds ratio of 4.72
at a significance level of 0.005 for the effects of adjusted daily LZ intake on
the prevalence of late AMD was based on these four cases. Regardless of the
validity of the statistical methods, it needs to be borne in mind that a
conclusion with major public health implications was based on such few cases. The
food frequency questionnaire used in this study was not validated for the key
variables, linoleic acid and LZ intake.4 The use of a single self-reported
instrument for the estimation of lutein intake is subject to large biases and
error, and has the lowest validity for lutein as opposed to the other
carotenoids.5 These possible confounders are present in addition to
the possibility of a dietary change towards higher LZ intake after the
diagnosis of AMD.
Table1. The estimated numbers of subjects
based on reported Odds Ratios
.
Group
Low
linoleic
High
linoleic
OR
Late
AMD
32
4
0.11
Early
AMD
102
45
0.44
Any
AMD
134
49
0.35
Non
AMD
852
937
total
986
986
Table legend: These estimates were based on
the odds ratios (OR) reported for all participants graded using Wisconsin definitions. The median daily linoleic acid
intake of 7.17 g divides the population into equal numbers of 986 cases. The OR
is calculated as the ratio between high and low linolieic acid intake groups,
of the odds of disease occurring in each group. The odds itself is the ratio
between the number of cases with and without disease. Due to the large number
of cases without disease, compared to the number with disease, the OR can be
approximated by the simple ratio of the number of cases with disease between
high and low linoleic acid groups.
Notwithstanding this, in order to better
understand the significance of the results, we need to know (a) more details on
how linoleic acid and LZ intake were calculated, and in particular, the chief
food sources of these variables; (b) whether the separate food items confirm
the trend; (c) what the demographics of the subset of patients with an above
median linoleic acid and high LZ intake were; (d) how many of this subset were
aware of their diagnosis; (e) whether more patients with AMD returned the food
frequency questionnaire than those without; (f) and how the ophthalmologic
diagnosis of AMD was validated.
Strong conclusions made in this article are
not justified by the provided data. Their publication creates confusion and
undermines professional, government and public confidence in the validity of other
data with great potential public health benefits. It takes enormous time,
effort and resources to educate the public on preventative lifestyle changes.
We must ensure that the messages to the public remain clear and consistent, and
that new findings are put through a process of rigorous examination to confirm
their validity. It appears that, in this case, the process may have failed.
References
1.Vu,
H. T.Robman, L.McCarty, C. A.Taylor, H. R.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
2.Seddon
JM, Ajani AU, Sperduto RD, et al. Dietary carotenoids,
vitamins A, C, and E, and advanced age-related macular degeneration. Eye
Disease Case-Control Study Group. JAMA 1994;272:1413–1420.
3.Cho
E, Seddon JM, Rosner B, et al. Prospective study of intake of fruits,
vegetables, vitamins, and carotenoids and risk of age-related maculopathy. Arch
Ophthalmol 2004;122:883–892.
4.Hodge
A, Patterson AJ, Brown WJ, et al. The AntiCancer Council of Victoria FFQ: relative validity of nutrient
intakes compared with weighed food records in young to middle-aged women in a
study of iron supplementation. Aust N Z J Public Health 2000;24:576–583.
5.Natarajan
L,Flatt WF,Xlaoying S, et al Validity and systematic error in measuring
carotenoids consumption with dietary self reported instruments Am J EpidemiolMarch 2006 (in print)
We would like to commend authors for describing a modification to
surgical technique for insertion of Molteno tube implant that eliminates
the need for a donor patch scleral graft.1 The purpose of this
modification is laudable however we do envisage few surgical difficulties
with this modification. Firstly the creation of scleral tunnel using a
curved 20 gauge microvitreoretinal (MVR) blade creat...
We would like to commend authors for describing a modification to
surgical technique for insertion of Molteno tube implant that eliminates
the need for a donor patch scleral graft.1 The purpose of this
modification is laudable however we do envisage few surgical difficulties
with this modification. Firstly the creation of scleral tunnel using a
curved 20 gauge microvitreoretinal (MVR) blade creates risk of mismatch
between the curve of the globe and that of MVR blade and thus a risk of
inadvertent intraocular entry and damage to ciliary body or lens.
Secondly the entry created by 20 gauge MVR blade is likely to be
significantly larger than the outer diameter of the anterior chamber tube
leading to aqueous leak around the tube entry into AC. This may increase
the risk of shallow AC and hypotony in early post-operative period. This
may have contributed to the frequent occurrence of corneal decompensation
(20.6%) in this case series.
We believe that the traditional partial thickness scleral flap has
some benefits over the scleral tunnel technique. There is no need for the
scleral patch graft with partial thickness scleral flap. All glaucoma
surgeons and most general ophthalmologists are familiar with this
technique. Furthermore it allows the creation of AC entry under direct
supervision using 22 gauge bent needle, ensuring the accurate placement of
the tube in the AC and snug fit between the tube and entry site. Ability
to visualize the entry site is important particularly for Ophthalmologists
in their early years of Glaucoma surgery training.
Dr S P Deokule, MS, FRCSEd, FRANZCO
Prof ACB Molteno, FRCSEd
Refrences
1. J K Leong, P McCluskey, S Lightman, H MA Towler. Outcome of graft
free Molteno Tube Insertion. Br J Ophthalmol 2006;90:501-505
2. ACB Molteno, MMB Van Rooyen, R Bartholomew. Implants for draining
neovascular glaucoma. Br J Ophthalmol 1977;61:120-125.
We read with great interest the report by Singh et al,1 describing the management of
subretinal macular haemorrhage by vitrectomy, subretinal injection of tissue
plasminogen activator (tPA) and pneumatic tamponade. Our experience with this
techinque has also been positive, and this approa...
We read with great interest the report by Singh et al,1 describing the management of
subretinal macular haemorrhage by vitrectomy, subretinal injection of tissue
plasminogen activator (tPA) and pneumatic tamponade. Our experience with this
techinque has also been positive, and this approach has replaced intravitreal tPA injection after vitrectomy and partial fluid-gas
exchange, or pneumatic displacement without vitrectomy, as the preferred
management of submacular haemorrhage in our unit. In most cases, the
haemorrhage is sufficiently displaced by two weeks to allow angiographic
studies and definitive treatment decisions to be made.
There are some notable differences between our approach and
the methods described by the authors. The concentration of 12 µg per 0.1
ml is significantly lower than the concentration we have used, which is 50
µg per 0.1 ml. We are not aware of any study that showed an optimal
concentration of tPA for subretinal injection, but this concentration has been
shown to be safe in experimental in vivo studies.2-4The authors
would have needed to inject 0.4 ml to reach the target dosage of 48 µg,
which is a large volume for a subretinal injection. There could be an argument
for a smaller injection volume to minimise distortion of the retinal
architecture. We aim to inject at the edge of the haemorrhage, rather than
directly into the body of the clot, in order to avoid detaching the fovea
further. The injection is performed under direct vision, with the end point
being an encirclement of the haemorrhage by the newly introduced subretinal
fluid.
We have not found it necessary to create a separate retinotomy
before the injection of tPA. We have most commonly used
a 32-gauge needle (Glaser Subretinal Injector, BD Ophthalmic Systems, Warks, United
Kingdom), which enables a direct injection
into the subretinal space with minimal trauma. However, we have found that the
needle allowed a significant amount of reflux of tPA
into the vitreous cavity. More recently, we have used a 41-gauge subretinal
needle (Storz Retinal Cannula 20G/41G, Bausch & Lomb, Rochester, United States) with great success,
which allows a precise placement of the bleb with minimal reflux.
We prefer SF6 20 % tamponade as it is our
impression that the haemorrhage takes at least one week to be displaced. A
comparative study with air would be useful. We have used SF6 10 % for
smaller haemorrhages.
Without treatment, the prognosis for submacular haemorrhage
is poor. Pneumatic displacement offers the means for an effective displacement of
submacular haemorrhage. With intravitreous tPA injection 5, and non-vitrectomy pneumatic
displacements reporting high success rates,6 we agree with the
authors’ conclusion that further studies will be needed to elucidate the
best approach of managing this difficult problem.
References
1.Singh
RP, Patel C, Sears JE. Management of subretinal macular
haemorrhage by direct administration of tissue plasminogen activator.Br J Ophthalmol 2006;90(4):429-431.
2.Benner
JD, Morse LS, Toth CA, Landers MB, 3rd, Hjelmeland LM. Evaluation
of a commercial recombinant tissue-type plasminogen activator preparation in
the subretinal space of the cat.Arch
Ophthalmol 1991;109(12):1731-1736.
3.Irvine
WD, Johnson MW, Hernandez E, Olsen KR. Retinal toxicity of human tissue
plasminogen activator in vitrectomized rabbit eyes. Arch Ophthalmol 1991;109(5):718-722.
4.Johnson
MW, Olsen KR, Hernandez E, Irvine WD, Johnson RN. Retinal
toxicity of recombinant tissue plasminogen activator in the rabbit.Arch Ophthalmol 1990;108(2):259-263.
5.Hassan
AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage
with intravitreous tissue plasminogen activator injection and pneumatic
displacement. Ophthalmology 1999;106(10):1900-6; discussion 1906-1907.
6.Hattenbach
LO, Klais C, Koch FH, Gumbel HO. Intravitreous injection of tissue plasminogen
activator and gas in the treatment of submacular hemorrhage under various conditions.
Ophthalmology 2001;108(8):1485-1492.
Dear Editor,
We thank Dr. John Sloper for his comments regarding this clinical pathological case of advanced human glaucoma, visual field loss, and central visual system degeneration. [1] Dr. Sloper states "Gupta et al. state that both magnocellular and parvocellular cells from the lateral geniculate nucleus of a patient with glaucoma are significantly smaller than those in three control subjects." We respectf...
Dear Editor,
We read with great interest the “Bullying and eye patching” commentary by Williams and co-workers in which they report on the psychosocial implications of early versus late treatment of amblyopia.[1] In their birth cohort study, they found that early detection (screening at the age of 3 years and 1 month) and subsequent early treatment of amblyopia resulted in fewer reports of bullying victimisatio...
Dear Editor,
Gupta et al. state that both magnocellular and parvocellular cells from the lateral geniculate nucleus (LGN) of a patient with glaucoma are significantly smaller than those in three control subjects. However it would appear that the authors have used the sample sizes and standard deviation of the cell samples from each individual to make comparisons between subjects. This is statistically invalid...
Dear Editor,
We read with great interest the article by Chiba and co-workers about the possible effect on intraocular pressure (IOP) induced by non-steroidal anti-inflammatory (NSAID) ophthalmic solution in patients affected by primary open angle glaucoma (POAG) or ocular hypertension (OH) and treated with latanoprost [1].
In 2003, Kashiwagi and Tsukahara (two co-authors of the above-mentioned Chiba et al...
Dear Editor
We read with interest the extended report by Hassell and colleagues [1] demonstrating the adverse effect of quality of life in mild visual impairment (<6/12) and worse. Their demonstration of the impact of Age Related Macular Degeneration (AMD) on quality of life indices is an important illustration of the difficulties experienced by the visually impaired.
We have reported a similar exper...
Dear Editor,
We read with great interest the article published by Pate JC (1) in your journal and the editorial (2), regarding polymicrobial infection of cornea. Our centre is a tertiary level eye care centre in northern India and also the apex centre for eye care of the country. We, in our country come across a large number of fungal keratitis cases compared to that reported in western studies. Though the author...
Dear Editor,
I have just finished reading the interesting paper by Daniell et al and, being one of the first authors (Secchi AG et al, AJO, 1990, 110, 137- 42) to become interested in the topical use of Cyclosporine A in "allergic" conditions concerning the ocular surface, I would like to make a few comments - based above all on a 20-year experience in the treatment of vernal keratoconjunctivitis (VKC) with topi...
...
Dear Editor,
We would like to commend authors for describing a modification to surgical technique for insertion of Molteno tube implant that eliminates the need for a donor patch scleral graft.1 The purpose of this modification is laudable however we do envisage few surgical difficulties with this modification. Firstly the creation of scleral tunnel using a curved 20 gauge microvitreoretinal (MVR) blade creat...
Dear Sir,
We read with great interest the report by Singh et al,1 describing the management of subretinal macular haemorrhage by vitrectomy, subretinal injection of tissue plasminogen activator (tPA) and pneumatic tamponade. Our experience with this techinque has also been positive, and this approa...
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