We were interested to read the letter by Patel et al. reporting the
unusual and striking fundus appearance of retinal arteriolar calcification
in association with chronic renal failure.[1] However, we feel that two
important conditions have been omitted from the comment, which merit
further discussion.
First, Monckeberg’s sclerosis, which in its classic form is
characterised by ‘pipe-stem’...
We were interested to read the letter by Patel et al. reporting the
unusual and striking fundus appearance of retinal arteriolar calcification
in association with chronic renal failure.[1] However, we feel that two
important conditions have been omitted from the comment, which merit
further discussion.
First, Monckeberg’s sclerosis, which in its classic form is
characterised by ‘pipe-stem’ calcific deposition in the medial coat of
muscular arteries in middle-aged and elderly individuals,[2] and is
described with widespread systemic distribution.[3,4] Interestingly
though, a juvenile form is seen, particularly in association with chronic
renal failure and diabetes.[5] The pathological mechanism of Monckeberg’s
sclerosis is uncertain, but is thought to encompass elements both of
dystrophic and metastatic calcification.[6] In the reported case, it
would be of interest to know if there was any evidence of vascular
calcification elsewhere in this individual, or whether it was localised to
the retinal arterioles only.
Secondly, Senior-Loken syndrome (renal-retinal syndrome,
nephronophthisis associated with retinitis pigmentosa or retinal aplasia)
is also germane to this discussion.[7] Nephronophthisis is a major cause
of progressive medullary cystic renal disease leading to chronic renal
failure in adolescents.[8] It is associated with a variable retinal
phenotype, a reflection of both clinical and genetic heterogeneity. When
associated with retinitis pigmentosa, there is an absence of the classic
bone spicule pigmentation, but optic nerve head pallor and attenuation of
the blood vessels is seen. Also, electroretinographic alterations have
been reported in nephronophthisis despite normal a normal fundus
examination.[9] In view of the phenotypic overlap seen with the reported
case, results of electroretinography would be pertinent to the discussion.
We would also advocate a molecular genetic analysis at the known loci
associated with Senior-Loken syndrome, which could potentially reveal an
interesting new allelic variant.
Finally, whilst the fundus photograph elegantly demonstrates the
stark changes seen in the retinal vasculature, this evidence could be
further augmented with the addition of an ultrasound B-scan image
demonstrating the pathognomonic echogenic features of intra-ocular
calcification.
Moin Mohamed
Vision Research Group
Molecular Medicine Unit
University of Leeds
Martin McKibbin
Eye Clinic
St James’s University Hospital
Beckett Street
Leeds
References
(1) Patel DV, Snead MP, and Satchi K. Retinal arteriolar calcification in a patient with chronic renal failure. Br J Ophthalmol 2002;86:1063
(2) Juergens JL et al. Peripheral vascular diseases. 5th edition. Philadelphia: W Saunders. 1980. pp.238-240.
(3) Lachman AS, Spray TL, Kerwin DM, Shugoll GI, Roberts WC. Medial
calcinosis of Monckeberg. A review of the problem and a description of a
patient with involvement of peripheral, visceral and coronary arteries. Am
J Med 1977 Oct;63(4):615-22.
(3) Castillo BV Jr, Torczynski E, Edward DP. Monckeberg's sclerosis in
temporal artery biopsy specimens. Br J Ophthalmol 1999 Sep;83(9):1091-2.
(4) Monckeberg's sclerosis: an
unusual presentation. Top C, Cankir Z, Silit E, Yildirim S, Danaci M. Angiology 2002 Jul-Aug;53(4):483-6.
(5) Byts' IuV, Holdobina OV, Dosenko VIe, Dudko MO, Larionova NA. The
current concepts of the pathogenesis of Monckeberg-type arteriosclerosis.
Fiziol Zh 2000;46(2):64-72.
(7) Gusmano R, Ghiggeri GM, Caridi G. Nephronophthisis-medullary cystic disease: clinical and genetic aspects. J Nephrol 1998 Sep-Oct;11(5):224-8.
(8) Orssaud C, Kleinknecht C, Habib R, Broyer M. Hereditary chorioretinal
degeneration and nephronophthisis. The role of Senior-Loken syndrome.
Ophtalmologie 1989 Sep-Dec;3(4):270-2.
We read with interest the remarks of Crowston et al. [1] on our
article entitled "Value of two mortality assessment techniques for organ
cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We
showed that the TUNEL technique revealed a far higher percentage of
endothelial cells (ECs) irreversibly engaged in a cell death process than
that obtained by trypan blue staining.
We read with interest the remarks of Crowston et al. [1] on our
article entitled "Value of two mortality assessment techniques for organ
cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We
showed that the TUNEL technique revealed a far higher percentage of
endothelial cells (ECs) irreversibly engaged in a cell death process than
that obtained by trypan blue staining.
The two techniques were performed sequentially: after observation of
trypan blue staining, corneas were immediately fixed in formaldehyde for
TUNEL. Crowston et al. suggest that the trypan blue itself and/or the time
spent outside the organ-culture medium before fixing in formaldehyde may
have caused an artefactual increase in the percentage of TUNEL-positive
ECs. Two arguments counter this remark:
1. The trypan blue staining procedure is identical to that used in all
European cornea banks that use organ culture during endothelial
examination(s) of grafts. Neither the low concentration of trypan blue
(0.4%) nor the short exposure time (about 1 minute) nor the short
incubation in the presence of 0.9% NaCl has ever been incriminated in ECs
over-mortality in routine practice.[3] Moreover, the innocuity of
injections of trypan blue into the anterior chamber, a common feature
during cataract surgery, has been well demonstrated.[4]
2. The time spent outside the organ-culture medium before fixing in
formaldehyde, a period required for vital staining and microscopic
examination of the endothelium, lasts only a few minutes. The cornea
remains under the microscope for about one minute only, the time needed
for image acquisition. Such rapidity is possible by using a prototype
automatic analyser of the endothelium, which we developed and have
recently published.[5] This is very probably insufficient time for DNA
fragmentation to occur in the proportion we observed. Moreover, the fixing
of the endothelial layer in 10% formaldehyde is immediate, and prevents
any continuation of fragmentation phenomena. On balance, it is highly
unlikely that the succession of markings is responsible for the
discrepancy between the positivity percentages of the two techniques. In
addition, we chose not to perform the two techniques simultaneously on
paired corneas or on the halves of one cornea because we wanted to
superimpose the two stains on the same cornea and thus obtain a double
cell staining.
The second remark by Crowston et al. is particularly interesting. We
too were surprised by the high percentage of TUNEL-positive ECs (mean
12.7%, SD 16.4). This may imply that all the cells died within 8 days,
which was evidently not the case. We believe this apparent contradiction
can be explained by the following theory. The TUNEL staining is positive
during a relatively long window (24-48 hours [6]). The TUNEL index,
measured at a given moment, provides a global view of all the cells with
fragmented DNA. However, the DNA fragmentation may be at different stages,
and the cells very likely spread according to a Gaussian distribution.
Therefore the cells, which are TUNEL-positive at a given moment, will not
all die instantaneously and simultaneously. Only the cells furthest to the
right on the curve will die in the very short term, and it is probably
these that are liable to be revealed by trypan blue. If it were possible
to perform TUNEL on two consecutive days, the percentage of positive cells
revealed would probably be very similar, but a large majority of the
positive cells recorded on the second day would have already been counted
on day one... It is, however, undeniable that the cells TUNEL-positive at a
given moment will all die eventually. In other words, we believe that, at
the end of storage, corneas contain a number of ECs engaged in an
irreversible cell-death process far more extensive than the highly
unreliable trypan blue staining technique suggests.
References
(1) Crowston JG, Healey PR, Maloof A, et al . Quantifying corneal
endothelial cell death. Br J Ophthalmol 2002;86:1068.
(2) Gain P, Thuret G, Chiquet C, et al . Value of two mortality assessment
techniques for organ cultured corneal endothelium: trypan blue versus
TUNEL technique. Br J Ophthalmol 2002;86:306-10.
(3) Sperling S. Evaluation of the endothelium of human donor corneas by
induced dilation of intercellular spaces and trypan blue. Graefes Arch
Clin Exp Ophthalmol 1986;224:428-34.
(4) Norn MS. Per operative trypan blue vital staining of corneal
endothelium. Eight years' follow up. Acta Ophthalmol 1980;58:550-5.
(5) Gain P, Thuret G, Kodjikian L, et al. Automated tri-image analysis of
stored corneal endothelium. Br J Ophthalmol 2002;86:801-8.
(6) Mesner PW, Epting CL, Hegarty JL, et al. A timetable of events during
programmed cell death induced by trophic factor withdrawal from neuronal
PC12 cells. J Neurosci 1995;15:7357-66.
We read with interest the remarks of Crowston et al. [1] on our
article entitled "Value of two mortality assessment techniques for organ
cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We
showed that the TUNEL technique revealed a far higher percentage of
endothelial cells (ECs) irreversibly engaged in a cell death process than
that obtained by trypan blue staining.
We read with interest the remarks of Crowston et al. [1] on our
article entitled "Value of two mortality assessment techniques for organ
cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We
showed that the TUNEL technique revealed a far higher percentage of
endothelial cells (ECs) irreversibly engaged in a cell death process than
that obtained by trypan blue staining.
The two techniques were performed sequentially: after observation of
trypan blue staining, corneas were immediately fixed in formaldehyde for
TUNEL. Crowston et al. suggest that the trypan blue itself and/or the time
spent outside the organ-culture medium before fixing in formaldehyde may
have caused an artefactual increase in the percentage of TUNEL-positive
ECs. Two arguments counter this remark:
1. The trypan blue staining procedure is identical to that used in all
European cornea banks that use organ culture during endothelial
examination(s) of grafts. Neither the low concentration of trypan blue
(0.4%) nor the short exposure time (about 1 minute) nor the short
incubation in the presence of 0.9% NaCl has ever been incriminated in ECs
over-mortality in routine practice.[3] Moreover, the innocuity of
injections of trypan blue into the anterior chamber, a common feature
during cataract surgery, has been well demonstrated.[4]
2. The time spent outside the organ-culture medium before fixing in
formaldehyde, a period required for vital staining and microscopic
examination of the endothelium, lasts only a few minutes. The cornea
remains under the microscope for about one minute only, the time needed
for image acquisition. Such rapidity is possible by using a prototype
automatic analyser of the endothelium, which we developed and have
recently published.[5] This is very probably insufficient time for DNA
fragmentation to occur in the proportion we observed. Moreover, the fixing
of the endothelial layer in 10% formaldehyde is immediate, and prevents
any continuation of fragmentation phenomena. On balance, it is highly
unlikely that the succession of markings is responsible for the
discrepancy between the positivity percentages of the two techniques. In
addition, we chose not to perform the two techniques simultaneously on
paired corneas or on the halves of one cornea because we wanted to
superimpose the two stains on the same cornea and thus obtain a double
cell staining.
The second remark by Crowston et al. is particularly interesting. We
too were surprised by the high percentage of TUNEL-positive ECs (mean
12.7%, SD 16.4). This may imply that all the cells died within 8 days,
which was evidently not the case. We believe this apparent contradiction
can be explained by the following theory. The TUNEL staining is positive
during a relatively long window (24-48 hours [6]). The TUNEL index,
measured at a given moment, provides a global view of all the cells with
fragmented DNA. However, the DNA fragmentation may be at different stages,
and the cells very likely spread according to a Gaussian distribution.
Therefore the cells, which are TUNEL-positive at a given moment, will not
all die instantaneously and simultaneously. Only the cells furthest to the
right on the curve will die in the very short term, and it is probably
these that are liable to be revealed by trypan blue. If it were possible
to perform TUNEL on two consecutive days, the percentage of positive cells
revealed would probably be very similar, but a large majority of the
positive cells recorded on the second day would have already been counted
on day one... It is, however, undeniable that the cells TUNEL-positive at a
given moment will all die eventually. In other words, we believe that, at
the end of storage, corneas contain a number of ECs engaged in an
irreversible cell-death process far more extensive than the highly
unreliable trypan blue staining technique suggests.
References
(1) Crowston JG, Healey PR, Maloof A, et al . Quantifying corneal
endothelial cell death. Br J Ophthalmol 2002;86:1068.
(2) Gain P, Thuret G, Chiquet C, et al . Value of two mortality assessment
techniques for organ cultured corneal endothelium: trypan blue versus
TUNEL technique. Br J Ophthalmol 2002;86:306-10.
(3) Sperling S. Evaluation of the endothelium of human donor corneas by
induced dilation of intercellular spaces and trypan blue. Graefes Arch
Clin Exp Ophthalmol 1986;224:428-34.
(4) Norn MS. Per operative trypan blue vital staining of corneal
endothelium. Eight years' follow up. Acta Ophthalmol 1980;58:550-5.
(5) Gain P, Thuret G, Kodjikian L, et al. Automated tri-image analysis of
stored corneal endothelium. Br J Ophthalmol 2002;86:801-8.
(6) Mesner PW, Epting CL, Hegarty JL, et al. A timetable of events during
programmed cell death induced by trophic factor withdrawal from neuronal
PC12 cells. J Neurosci 1995;15:7357-66.
We were interested to read the approach taken by Sahni and Clark [1]
to facilitate the effective Argon laser treatment of trichiasis. They
have ably reviewed the complications of trichiasis, the different forms of
management of trichiasis, the advantages of Argon laser treatment in the
management of trichiasis, the technique of Argon laser trichiasis therapy,
and the limitations of lash laser the...
We were interested to read the approach taken by Sahni and Clark [1]
to facilitate the effective Argon laser treatment of trichiasis. They
have ably reviewed the complications of trichiasis, the different forms of
management of trichiasis, the advantages of Argon laser treatment in the
management of trichiasis, the technique of Argon laser trichiasis therapy,
and the limitations of lash laser therapy.
We take issue with the authors in two areas. Firstly, the almost certain
consequence of using a duration of laser treatment of 0.1 second is that
if the laser "takes", the lash will disappear within the space of a few
laser shots, effectively precluding the effective destruction of that
particular lash follicle. We have particularly made it a point that when
teaching trainees the technique of lash laser, we ensure that the energy
burst lasts long enough to commence visible lash destruction as well as
destruction of the subcutaneous lash, as the burn is directed towards the
lash follicle. Thus, we always use a duration of several seconds, or even
continuous energy, and aim to achieve initiation of effective lash
destruction above the lid level after the first shot, or certainly within
three shots. Thus, one- to three-second-duration bursts may be required,
depending on the individual lash. Just a few more shots will effectively
and completely destroy the subcutaneous lash and its follicle.
Secondly, the article by Bartley and Lowry quoted by the authors,
describes using a "drop of ink from a fountain pen" to facilitate lash
laser.[2] Presumable in the interests of sterility, Sahni and Clark have
used the ink from a "blue skin marker pen" to allow improved absorption of
Argon laser energy. While using a fresh marker pen for each patient may
be relatively efficient, it could not be regarded as cost effective. By
contrast, in a procedure described by us in 1994,[3] we found that
transferring a tiny drop of the patient's own blood, whether still liquid
or already coagulated, to the lash base on the lid margin is a simple,
rapid, cheap, safe and highly effective method of getting the laser
reaction started when the lashes are pale. We have found that the
required amount of blood is invariably present on the patient's own lid
skin at the site of local anaesthetic infiltration. We usually transfer
it by picking it up with a sterile drawing-up needle. This is achieved
remarkably easily on the laser slit lamp, which allows adequate
magnification for the accurate siting of the transferred blood.
Geoffrey A. Wilcsek
Ian C. Francis
The Ocular Plastics Unit
Prince of Wales Hospital and the University of New South
Wales Randwick Sydney, Australia
References
(1) Sahni J, Clark D. Argon laser and trichiasis: a helpful tip.
Br J Ophthalmol 2001;85:761
(2) Bartley GB, Lowry JC. Argon laser treatment of trichiasis.
Am J Ophthalmol 1992;113:71-4
(3) Ghabrial R, Francis IC, Kappagoda MB. Autologous blood facilitation of
lid laser treatment. Aust NZ J Ophthalmol 1994.
Regarding the editorial by Khaw et al.[1]
we are surprised that after quite a few years now non-
penetrating filtering surgery (NPFS) remains only
partly understood by many ophthalmologists. There are
at present two main NPFS: viscocanalostomy as
described by Stegmann, in which outflow filtration is at
least in theory not subconjunctival, and deep
sclerectomy with or without an implant or even wi...
Regarding the editorial by Khaw et al.[1]
we are surprised that after quite a few years now non-
penetrating filtering surgery (NPFS) remains only
partly understood by many ophthalmologists. There are
at present two main NPFS: viscocanalostomy as
described by Stegmann, in which outflow filtration is at
least in theory not subconjunctival, and deep
sclerectomy with or without an implant or even with
viscoelastics, the success of which depends on
several outflow routes - an important one being
subconjunctival. Careful postoperative follow up
becomes therefore mandatory and is at least as
important as the procedure itself. If needed
subconjunctival injection of antimetabolites, needling or use of lasers for
goniopuncture, iris
desincarceration and attempts of possible bleb
reduction or closure of possible seidel may be
required. It also becomes evident that
antimetabolites play an important role in high risk
cases for filtration failure undergoing NPFS (apart
from viscocanolostomy as describd by Stegmann).
Furthermore in our hospital we have been using
antimetabolites also in cases requiring low
postoperative IOP such as normal tension glaucoma
since 1994. We do not understand the comment made
stating that greater care should be taken with
antimetabolites used during NPFS, since we
intraoperatively use these agents before the deeper
scleral flap is being excised or even created. Thus
at this stage this does not differ with
trabeculectomy. Later on the anterior chamber is not
entered and furthermore the deep scleral flap which
has been exposed to antimetabolites is being excised
making the danger of intraoperative intraocular
penetration considerably less than with
trabeculectomy (even with unintended macroperforation
during NPFS).
Additional sutures are added in cases of accidental
macroperforaton so that the incidence of early
significant hypotony in the hands of experienced
surgeons with NPFS is not high. Moreover
postoperative suturelysis may then be required in
these cases if the sutures have been made too tight
or too numerous.
References are being made to the article by Brart et al. However how
reliable is it to compare the
efficacy of two procedures without giving the same
chances of success to both? Intraoperative
antimetabolites were used for all trabeculectomies
and yet never with NPFS. Yet strangely enough,
postoperative antimetabolites as well as needling
with an attempt to lift the scleral flap in some,
were used in both groups. The author also writes in
the discussion that patients with successful drainage
at 6 and 12 months following viscocanalostomy had
evidence of subconjunctival drainage of aqueous as
opposed to eyes without successful drainage. Later on
he further states that 'with our viscocanalostomy
technique, the subconjunctival route is the main
pathway' and 'observation of the disappearance of
subconjunctival blebs in our patients with drainage
failure after viscocanalostomy appears to suggest
that subconjunctival fibrosis is responsible'.
Clearly, if antimetabolites are being used in
trabeculectomies, it should be used in NPFS before
any reliable conclusions can be drawn.
Goniopunture was also only done after 18 months which
of course will not be of great help if the outflow
route after the trabeculodescemet's membrane has
scarred down. Thus to promote good filtration in
addition to intraoperative and postoperative use of
antimetabolites, goniopuncture can help in enhancing
and thus in maintaining a flow under the scleral flap.
Using lasers for suturelysis in trabeculectomies or
for goniopuncture in NPFS is part of the
armementarium we have in glaucoma surgery. The final
aim for the patient is not to know whether the
procedure is penetrating or not, but rather how
effective it is so that the discussion on whether or
not to use goniopunture is futile.
For ophthalmologists performing NPFS, the later is
compared to trabeculectomy what phacoemulsification
was to extracapsular cataract extraction. They will
never go back to it unless obliged to do so. However
it is clear that there is a learning curve to this
surgery and that it is not as forgiveful as is
trabeculectomy.
E. Ravinet, MD
A. Mermoud, MD
Reference
(1) Khaw PT, Wells AP, Lim KS. Surgery for glaucoma in the 21st
century. Br J Ophthalmol 2002;86:
710-711.
Thank you very much for your response to our article on Acanthamoeba
and contact lens disinfecting solutions. You are absolutely right, indeed,
standard methods for testing of anti-Acanthamoeba effectivity of biocides
are urgently needed. However, as such standards are not yet available, we
used three different concentrations of amoebae, namely 103, 104, and 105
per ml (as stated in the Materials...
Thank you very much for your response to our article on Acanthamoeba
and contact lens disinfecting solutions. You are absolutely right, indeed,
standard methods for testing of anti-Acanthamoeba effectivity of biocides
are urgently needed. However, as such standards are not yet available, we
used three different concentrations of amoebae, namely 103, 104, and 105
per ml (as stated in the Materials and Methods section of our article)
intending to cover the whole range of concentrations we found in the
literature.
You are right in what you stated on the various contact-lens
solutions, however, it was our aim to compare all three different systems
available on the market in spite of knowing that they would not all be
optimal in their effectivity.
We fully agree to the measures you recommend, however, they depend on
the compliance of the contact lens users. It is a problem of costs on one
hand: the user wants to safe money by overwearing the lenses, not
replacing the lens boxes and economizing with the lens solutions. One the
other hand it is a problem of comfort, as using multipurpose or one step
solutions is more comfortable. So we tried to give realistic
recommendations, which help to minimize the risk, but are still user-
friendly.
I read with interest the article by Hiti et al.[1] on the susceptibility of Acanthamoeba to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. The association between acanthamoeba keratitis and contact lens wear is now firmly established. Thus, the use of contact lens disinfecting solutions effective at killing Acanthamoeba organisms is important in pr...
I read with interest the article by Hiti et al.[1] on the susceptibility of Acanthamoeba to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. The association between acanthamoeba keratitis and contact lens wear is now firmly established. Thus, the use of contact lens disinfecting solutions effective at killing Acanthamoeba organisms is important in preventing corneal infections. I would like to make a few comments on this article.
The lack of standard methods for testing disinfecting solutions against Acanthamoeba represents a critical problem when sensitivity assays are set up.[2] The authors say that 1 ml of disinfectant per well was applied in 24-well plates, but the amount of acanthamoeba suspension distributed in each well is missing. PHMB (0.0005 %) was found to be ineffective against A.hatchetti and A. lenticulta cysts after 8 hours' exposure. This is not surprising. Indeed, at concentrations (0.5 to 15 µg/ml) used in commercial contact lens solutions, PHMB is almost ineffective against amoeba cysts.[3-6] PHMB concentrations ranging from 45 to 90 µg/ml are needed to kill 99.9 % of Acanthamoeba cysts in under 1 hour of exposure.[7]
The authors observed that a one-step 3 % H2O2 system with catalase was ineffective against Acanthamoeba cysts after 8 hours' exposure. Silvany et al.[4] reported similar results. Because the catalyst is present from the very beginning of the disinfection step, the H2O2 is neutralised long before any disinfection can occur. Therefore, adequate exposure time before neutralisation is crucial.
The authors also found that a two-step 0.6 % H2O2 system was effective against A. castellanii and A. hatchetti cysts after 8 hours' exposure. However, Zanetti et al.[6] observed that an equivalent dilution of 3 % H2O2 was ineffective against the cysts of a corneal isolate of A. castellanii after 9 hours' exposure. These variations in susceptibility may depend on inherent strain differences.[2] Therefore, unlike the authors, I would not recommend the two-step 0.6 % H2O2 system as a safe disinfectant against Acanthamoeba. From previous data,[6,8-9] I suggest that the following measures should result in less contact lens case and contact lens contamination, thereby possibly reducing the risk of microbial keratitis.
-Naturally: wash hands before handling contact lenses.
-Use "one day" disposable contact lenses. If other types are preferred:
(a)Use a two-step 3% H2O2 system and neutralize after 9 hours' exposure (overnight).
(b)Replace the contact lens case regularly (preferably fortnightly).
References
(1) Hiti K, Walochnik J, Haller-Schober EM, et al. Viability of Acanthamoeba after exposure to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. Br J Ophthalmol 2002;86:144-6.
(2) Meisler MD, Rutherford I. Acanthamoeba and disinfection of soft contact lenses. Rev Infect Dis 1991;13:S410-2.
(3) Hugo ER, McLaughlin WR, Oh K, et al. Quantitative enumeration of Acanthamoeba for evaluation of cyst inactivation in contact lens care solutions. Invest Ophthalmol Vis Sci 1991;32:655-7.
(4) Silvany RE, Dougherty JM, McCulley JP. Effect of currently available contact lens disinfection systems on Acanthamoeba castellanii and Acanthamoeba polyphaga. Ophthalmology 1990;97:286-90.
(5) Silvany RE, Dougherty JM, McCulley JP. Effect of contact lens preservatives on Acanthamoeba. Ophthalmology 1991;98:854-7.
(6) Zanetti S, Fiori PL, Pinna A, et al. Susceptibility of Acanthamoeba castellanii to contact lens disinfecting solutions. Antimicrob Agents Chemother 1995;39:1596-8.
(7) Burger RM, Franco RJ, Drlica K. Killing Acanthamoebae with polyaminopropyl biguanide:quantitation and kinetics. Antimicrob Agents Chemother 1994;38:886-8.
(8) Grey TB, Cursons RTM, Sherwan JF, et al. Acanthamoeba, bacterial, and fungal contamination of contact lens storage cases. Br J Ophthalmol 1995;79:601-5.
(9) Pinna A, Sechi LA, Zanetti S, et al.Bacillus cereus keratitis associated with contact lens wear. Ophthalmology 2001;108:1830-4.
Dr Newsham's effort to inform parents of children with amblyopia about occlusion therapy is laudable but incomplete. Ethical considerations of informed consent require full disclosure of all aspect of the proposed treatment. In the current instance this compels inclusion of the following points:
1. Occlusion therapy has never been scientifically validated with a randomized, controlled study.
Dr Newsham's effort to inform parents of children with amblyopia about occlusion therapy is laudable but incomplete. Ethical considerations of informed consent require full disclosure of all aspect of the proposed treatment. In the current instance this compels inclusion of the following points:
1. Occlusion therapy has never been scientifically validated with a randomized, controlled study.
2. The dose / response relationship has never been defined. Flynn et al. stated that 'Success was not related to the duration of occlusion therapy, type of occlusion used'. [1] The variety of treatment protocols accentuate another dilemma 'owing to our paucity of knowledge on the dose-effect relation - a situation one finds hard to imagine for any
comparably established therapy outside ophthalmology. In other words we have no understanding of the dose-effect relation of occlusion in amblyopia therapy'. [2]
3.The application of 'greater levels of occlusion being prescribed for more severe amblyopia is
compromised by the observation 'that success was related to the depth of visual loss before treatment'.[4]
4. The benefits of treatment are likely to deteriorate following cessation of patching. [5]
5. Visual acuity normally improves as children become more mature, literate, and familiar with vision testing protocols. [6]
This is also true for amblyopic eyes. In amblyopic children between 3 and 7 years old without treatment visual acuity was
shown to consistently improve in each older age group. [7]
6. Both the occluded and the amblyopic eyes improve at the same rate during treatment. [8]
7. Success in amblyopia treatment is usually defined as improvement by a minimum of three lines. [9]Many of the successfully treated patients, by that criterion, will still not have normal vision at the end of presumably successful treatment. One quarter of treated patients with initial acuity better than 20/100 do not even achieve these limited goals. The comments about achieving normal vision may raise expectations that will not be achieved.
Moreover, it is not clear that performance on reading an eyechart is a complete indicator of visual function. Acuity
improvement with occlusion may not be accompanied by improved performance on the other tests - such as vernier acuity
or contrast sensitivity. [10]
8. Occlusion therapy does have potential adverse effects beyond disruption of family and social life [11] and interference with
education. [12]
9.Despite decades of occlusion therapy the prevalence of amblyopia in the adult population is similar to that of the school-age population. [13] Moreover, 'the prevalence of unilateral amblyopia was not found to be statistically different by age group'. [14] This suggests that long term benefits of conventional therapy are not demonstrated in demographic studies.
Patients and their families should be provided with comprehensive information concerning proposed treatments in order to make appropriate judgements. Physicians are obliged to make this information accurate and inclusive.
References
(1) Flynn JT, Schiffman J, Feuer W, Corona A The therapy of amblyopia: an analysis of the results of amblyopia therapy utilizing the pooled data of published studies. Trans Am Ophthalmol Soc 1998;96:431-50; discussion 450-3.
(2) Simonsz HJ, Polling JR, Voorn R, van Leeuwen J, Meester H, Romij C, Dijkstra BG. Electronic monitoring of treatment
compliance in patching for amblyopia. Strabismus 1999 Jun;7(2):113-23.
(3) Newsham D. A randomised controlled trial of written information: the effect on parental non-concordance with occlusion
therapy. Br J Ophthalmol 2002;86:787-91.
(4) Beardsell R, Clarke S, Hill M. Outcome of occlusion treatment for amblyopia. J Pediatr Ophthalmol Strabismus 1999
Jan-Feb;36(1):19-24.
(5) von Noorden GK, Attiah F Alternating penalization in the prevention of amblyopia recurrence. Am J Ophthalmol 1986 Oct 15;102(4):473-5.
(6) Robinson BE, Oladeji MM, Bobier WR. Visual acuity assessment in preschool children in Oxford County. ARVO 2000 Abstract # 4955.
(7) The Pediatric Eye Disease Investigator Group. The clinical profile of moderate amblyopia in children younger than 7 years. Arch Ophthalmol 2002;120:281-7. (Table 3 Baseline characteristics according to age at enrollment).
(8) Dorey SE, Adams GG, Lee JP, Sloper JJ. Intensive occlusion therapy for amblyopia. Br J Ophthalmol 2001 Mar;85(3):310-3.
(9) The Pediatric Eye Disease Investigator Group. A randomized trial of atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 2002;120:268-78.
(10) Levi DM, Polat U, Hu YS. Improvement in Vernier acuity in adults with amblyopia. Practice makes better. Invest Ophthalmol Vis Sci 1997 Jul;38(8):1493-510.
(11) Snowdon SL, Stewart-Brown SL. Amblyopia and Disability: A Qualitative Study. Health Services Research
Unit: University of Oxford.
(12) Yang LL, Lambert SR. Reappraisal of occlusion therapy for severe structural abnormalities of the optic disc and macula. J Pediatr Ophthalmol Strabismus 1995 ;32(1):37-41.
(13) Buch H, Vinding T, La Cour M, Nielsen NV. The prevalence and causes of bilateral and unilateral blindness in an elderly urban Danish population. The Copenhagen City Eye Study. Acta Ophthalmol Scand 2001 Oct;79(5):441-9.
(14) Brown SA, Weih LM, Fu CL, Dimitrov P, Taylor HR, McCarty CA. Prevalence of amblyopia and associated refractive errors in an adult population in Victoria. Australia Ophthalmic Epidemiol 2000
Dec;7(4):249-58.
Poon et al.[1] in their excellent article have reiterated the efficacy of autologous serum in the treatment of persistent epithelial defects (PEDs) of the cornea. We would like to invite the attention of the authors to certain aspects of the study.
The authors have considered a period of one week for labeling an epithelial defect to be persistent. However, most studies on a similar subject have tak...
Poon et al.[1] in their excellent article have reiterated the efficacy of autologous serum in the treatment of persistent epithelial defects (PEDs) of the cornea. We would like to invite the attention of the authors to certain aspects of the study.
The authors have considered a period of one week for labeling an epithelial defect to be persistent. However, most studies on a similar subject have taken the criterion to be two weeks.[2]
It is generally recommended that a 'wash out' period of a least two weeks be given with preservative free artificial tears3 and only those epithelial defects that remain either static or demonstrate an increase in size in this period be included in the study. The authors have not mentioned such a 'wash out' period being included in the protocol. When using autologous serum drops most investigators have not used any other therapeutic modality at the same time to enhance epithelialization apart from preservative free lubricants. The use of therapeutic contact lenses in five cases by the authors makes it difficult to evaluate the actual contribution of serum drops in the healing of the epithelial defect in these cases. Further, the use of serum drops in the immediate post operative period in two patients with poor ocular surface undergoing keratoplasty without waiting for the corneal epithelial defect to heal by itself cannot be extrapolated to making a comment on the beneficial effect of autologous serum. Also the rationale behind the use of 100 % serum when previous studies have proved the efficacy of a 20 % solution[2] is not clear. The 100 % concentration of serum can cause stickiness, which would be inconvenient to the patients and may reduce compliance. The use of the slit lamp micrometer by the authors for measuring the epithelial defects may not be accurate because of its inherent inter-observer and intra-observer variations. A better method would be measuring the area of the defect instead of the greatest dimensions by the use of digital photographs and area measuring software such as Image Pro PlusTM available from Media Cybernetics.
References
(1) Poon AC, Geerling G, Dart JKG, et al. Autologous Serum eye drops for dry eyes and epithelial defects: clinical and in vitro toxicity studies. Br J Ophthalmol 2001;85:1188-97.
(2) Tsubota K, Goto E, Shimmura S, et al. Treatment of persistent epithelial defect by autologous serum application. Ophthalmology 1999;106:1984-9.
(3) Gordon JF, Johnson P, Musch DC. Topical fibronectin ophthalmic solution in the treatment of persistent defects of the corneal epithelium. Am J Ophthalmol 1995;119:281-7.
Vajpayee and colleagues have criticised several aspects of our study and justified their views with unrepresentative quotations from the literature.
Choice of time period before an epithelial defect can be described as "persistent".
There is no accepted definition of persistent epithelial defect (PED) that includes a time period. We favour the definition given in one text"......
Vajpayee and colleagues have criticised several aspects of our study and justified their views with unrepresentative quotations from the literature.
Choice of time period before an epithelial defect can be described as "persistent".
There is no accepted definition of persistent epithelial defect (PED) that includes a time period. We favour the definition given in one text"... when the epithelium fails to regrow over a defect within the expected time course".[1] For the purpose of a study the time course must be specified. Vajpayee et al. Prefer 2 weeks [2] whereas in another recent paper 10 days was chosen with the proviso that the study treatment could start earlier if there was progression to perforation.[3] The penalty for patients at high risk of corneal melt, in the presence of a persistent defect, is substantial. In our study 2/13 patients had an epithelial defect for less than 2 weeks before inclusion in the study; Vajpayee et al. can ignore the data from these patients if they wish.
Wash-out period with preservative-free artificial tears
No "wash-out period" was used in this study, as we were trying to identify whether serum would have an additional effect on epithelial healing over preservative-free artificial tears and conventional therapy in patients with severe ocular surface disease. We were not trying to compare the efficacy of serum against preservative-free lubricants in healing PEDs. Conventional therapy was continued as serum alone could not fully address all the ocular surface problems, including aqueous tear deficiency and eyelid trauma, so that giving serum without continuing the other modalities may have caused harm to some of the patients. Other studies have adopted similar protocols with a PED defined as a defect that persisted "...despite conventional treatment such as artificial tears or extended wear contact lenses" with no wash out period [2] or that allowed a reduction in the 10 day wash out period if corneal ulceration progressed.[3] In a clinical study some ethical committees may not condone the treatment of persistent defects without non-preserved antibiotic prophylaxis against bacterial keratitis.
Keratoplasty patients being treated without waiting for the corneal epithelial defect to heal by itself
These patients had both failed previous grafts because of corneal perforation resulting from PEDs and one patient had recurrent epithelial breakdown, responding to the re-introduction of serum drops, after their initial withdrawal. We thought that, for some readers, this might be useful data to add to this descriptive study.
The rationale behind the use of 100 % serum when previous studies have proved the efficacy of a 20 % solution
The previous study Vajpayee et al. quote is, like ours and all the other studies on this subject, a descriptive study and no more proves that serum drops at 20 % work than does our own with 50% and 100%. Other studies, all uncontrolled, have used from 20% to 30% serum [2,4] for both persistent defect and dry eye. All these studies use empirical regimens for serum concentration and dosing frequency. Unlike Vajpayee et al., we have some patients (one reported in the study) who prefer 100 % serum to 50 %. Vajpayee et al. are probably also unaware of our study demonstrating that 100 % serum is less toxic that 50 % serum to cultured corneal epithelial cells;[5] this provides some laboratory data to support the use of 100 % serum. Lastly, the manufacture of 100 % serum requires less handling, reducing the risk of contamination.
The use of the slit lamp micrometer
Vajpayee et al. have missed the point that the treatment end point was closure of the defect, for which their proposed technique is inappropriate, rather than rate of closure, for which it would be ideal.
The deficiencies in our study are not the points that Vajpayee et al. have made but the fact that it was uncontrolled. The study was planned as a randomised controlled trial but could not be carried out as such for the reasons alluded to in the last paragraph. These regulatory problems are being overcome in the UK. We should all hope to see randomised treatment trials carried out in this area as well as the laboratory studies necessary to support the clinical application of serum.
John Dart
Alex Poon
References
(1) Macaluso DC, Feldman ST. Persistent epithelial defects and sterile ulceration. Pathogenesis of sterile corneal erosions and ulcerations. In Vol 1, Chapter 10; 204 of Krachmer J, Mannis M, Holland E, (Eds) Cornea; fundamentals of cornea and external disease. St Louis 1007: Mosby.
(2) Tsubota K, Goto E, Simmer S, Shimazaki J. Treatment of persistent epithelial defect by autologous serum application. Ophthalmology 1999;106:1984-9.
(3) Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology 2000;107:1347-51.
(4) Fox RI, Chan R, Michelson J, Belmont J, Michelson P. Beneficial effect of artificial tears made with autologous serum in patients with keratoconjunctivitis sicca. Arthritis Rheum 1984;29:577-83.
(5) Geerling G, Daniels JT, Dart JK, Cree IA, Khaw PT. Toxicity of natural tear substitutes in a fully defined culture model of human corneal epithelial cells. Investigative Ophthalmology & Visual Science 2001;42(5):948-56.
Dear Editor
We were interested to read the letter by Patel et al. reporting the unusual and striking fundus appearance of retinal arteriolar calcification in association with chronic renal failure.[1] However, we feel that two important conditions have been omitted from the comment, which merit further discussion.
First, Monckeberg’s sclerosis, which in its classic form is characterised by ‘pipe-stem’...
Dear Editor
We read with interest the remarks of Crowston et al. [1] on our article entitled "Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We showed that the TUNEL technique revealed a far higher percentage of endothelial cells (ECs) irreversibly engaged in a cell death process than that obtained by trypan blue staining.
...
Dear Editor
We read with interest the remarks of Crowston et al. [1] on our article entitled "Value of two mortality assessment techniques for organ cultured corneal endothelium: trypan blue versus TUNEL technique".[2] We showed that the TUNEL technique revealed a far higher percentage of endothelial cells (ECs) irreversibly engaged in a cell death process than that obtained by trypan blue staining.
...
Dear Editor
We were interested to read the approach taken by Sahni and Clark [1] to facilitate the effective Argon laser treatment of trichiasis. They have ably reviewed the complications of trichiasis, the different forms of management of trichiasis, the advantages of Argon laser treatment in the management of trichiasis, the technique of Argon laser trichiasis therapy, and the limitations of lash laser the...
Dear Editor
Regarding the editorial by Khaw et al.[1] we are surprised that after quite a few years now non- penetrating filtering surgery (NPFS) remains only partly understood by many ophthalmologists. There are at present two main NPFS: viscocanalostomy as described by Stegmann, in which outflow filtration is at least in theory not subconjunctival, and deep sclerectomy with or without an implant or even wi...
Dear Dr Pinna,
Thank you very much for your response to our article on Acanthamoeba and contact lens disinfecting solutions. You are absolutely right, indeed, standard methods for testing of anti-Acanthamoeba effectivity of biocides are urgently needed. However, as such standards are not yet available, we used three different concentrations of amoebae, namely 103, 104, and 105 per ml (as stated in the Materials...
Dear Editor
I read with interest the article by Hiti et al.[1] on the susceptibility of Acanthamoeba to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. The association between acanthamoeba keratitis and contact lens wear is now firmly established. Thus, the use of contact lens disinfecting solutions effective at killing Acanthamoeba organisms is important in pr...
Dear Editor
Dr Newsham's effort to inform parents of children with amblyopia about occlusion therapy is laudable but incomplete. Ethical considerations of informed consent require full disclosure of all aspect of the proposed treatment. In the current instance this compels inclusion of the following points:
1. Occlusion therapy has never been scientifically validated with a randomized, controlled study.
...Dear Editor
Poon et al.[1] in their excellent article have reiterated the efficacy of autologous serum in the treatment of persistent epithelial defects (PEDs) of the cornea. We would like to invite the attention of the authors to certain aspects of the study. The authors have considered a period of one week for labeling an epithelial defect to be persistent. However, most studies on a similar subject have tak...
Dear Editor
Vajpayee and colleagues have criticised several aspects of our study and justified their views with unrepresentative quotations from the literature.
Choice of time period before an epithelial defect can be described as "persistent".
There is no accepted definition of persistent epithelial defect (PED) that includes a time period. We favour the definition given in one text"......
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