I enjoyed reading Paskowitz et al.'s (1) important summary of
evidence indicating that in some specific types of retinal degeneration,
light deprivation may prove to be of protective value.
In respect of Stargardt Disease, they cite evidence from animal models
that light deprivation can prevent A2E accumulation in the RPE, thus
preventing the degeneration.
A worthwhile point to note is that the dest...
I enjoyed reading Paskowitz et al.'s (1) important summary of
evidence indicating that in some specific types of retinal degeneration,
light deprivation may prove to be of protective value.
In respect of Stargardt Disease, they cite evidence from animal models
that light deprivation can prevent A2E accumulation in the RPE, thus
preventing the degeneration.
A worthwhile point to note is that the destruction of A2E-laden RPE cells
is light-induced, and the absorption spectrum of A2E peaks at 435 nm. Blue
light is very much more effective in causing the death of A2E-containing
RPE cells than green light (2).
It would thus appear that while total light deprivation may be effective
in preventing A2E accumulation in RPE cells, protection specifically from
blue light may slow down or prevent the death of RPE cells which already
contain high levels of A2E. Filtering blue light is a strategy that is
more practical to apply than total protection from light.
Blue light may have an important role in driving the circadian cycle, as
well as for psychological well being (3). Some caution may therefore be
warranted in filtering out 100% of the blue light 100% of the time. Very
substantial blue light protection can, however, be considered.
As the authors caution, clinical trials are required to confirm
predictions arising from currently available evidence (1), but in addition
to protection from light in general to the greatest extent practicable,
protection specifically from blue light may be a strategy that proves to
slow down the progress of Stargardt disease.
References
1. Paskowitz, D.M., LaVail, M.M. and Duncan, J.L. Light and inherited
retinal degeneration. Br. J. Opthalmol. 2006;90:1060-1066.
2. Sparrow, J.R., Nakanishi, K. and Parish, C.A. The lipofuscin
fluorophore A2E mediates blue light induced damage to retinal pigment
epithelial cells. Invest. Ophthalmol. Vis. Sci. 2000;41:1981-1989.
3. Charman, W.M. Age, lens transmittance, and the possible effects of
light on melatonin suppression. Ophthalm. Physiol. Opt. 2003;23:181-187.
With great interest, we read the comments of Dr. Ziemssen and
colleagues regarding our World View paper discussing the results of the
international intravitreal bevacizumab safety survey[1]. Their letter
will certainly accentuate the importance of this topic to the ophthalmic
community; we would like to clarify several of the points raised.
In our paper, we have fully acknowledged the pur...
With great interest, we read the comments of Dr. Ziemssen and
colleagues regarding our World View paper discussing the results of the
international intravitreal bevacizumab safety survey[1]. Their letter
will certainly accentuate the importance of this topic to the ophthalmic
community; we would like to clarify several of the points raised.
In our paper, we have fully acknowledged the purpose and
limitations
of our survey and expect that readers will accept the survey for what it
is: an attempt to gather timely information on the real-world global use
of intravitreal bevacizumab in order to provide a snapshot of safety
information. As we have stated before, our goal was to discover any
alarming serious adverse events that were associated with intravitreal
bevacizumab therapy; events that may not have appeared anomalous to any
one center because of a low rate of occurrence, but which could be
concerning in the aggregate. As stated in our report, our novel use of
the
internet provided an opportunity to collect such timely information on a
therapy that was growing exponentially in popularity and to share these
findings with the ophthalmologic community.
Dr. Ziemssen and colleagues have used this opportunity to point out
the many ways our survey did not meet the standards of a well-designed
prospective study. Again, our survey was never intended to be a
prospective study with pre-defined parameters and methods of
measurement.
Rather, it was a retrospective survey of clinical experience that did
not
require each site to perform a detailed chart review and request
research
approval from their institutions.
Concerns were raised regarding the definition of the study population.
The
study population was intended to be representative of the real-world
situation in which patients are treated as deemed appropriate by their
physicians. Therefore, the only prerequisite for inclusion in the survey
was having received intravitreal bevacizumab. Regarding a non-response
bias, we addressed this as the first point when discussing the
limitations
of the study.
With respect to a selection bias of participating physicians, the
email alerting our peers of the web address was distributed by the
listserves of both the American Society of Retina Specialists and the
Retina Society. Both organizations have extensive membership rosters
including international members. While we would like to believe that the
full memberships of these organizations are "friended peers," we accept
that only some are known to us, and of the 72 respondents, many were
previously unfamiliar and including three centers from Germany. The
project was furthermore presented at several
international meetings with invitations to participate. The survey was
completely "open access" and no password was required. Furthermore,
participants were encouraged to alert other colleagues of the survey's
existence.
Our paper already addressed the effect of observer bias considering
no systematic chart review was required. While standardized grading
systems are important and necessary for prospective trials, it would be
nearly impossible to perform a retrospective multi-center trial of this
scale since physicians and institutions collect variable information
using
myriad methods and techniques. Truly concerning adverse events such as
severe uveitis, endophthalmitis, or systemic thromboembolic events
should
be adequately significant to treating physicians for them to recall such
occurrences and details without requiring a chart review. Furthermore we
did not state that there was a "low rate of voluntary reports about
undesired side effects". Rather we stated the possibility of "under-
reporting" as a limitation of the study - which is not the same as Dr.
Ziemssen suggests.
In reply to the valid query regarding intravitreal bevacizumab
practice patterns, we share the following information. Of 68 centers
responding to practice pattern questions at the bottom of Figure 2, 17
groups check blood pressure both before and after injections, 9 check
only
before, 2 only after, and 40 groups do not check blood pressure either
before or after injection. 42 of 68 groups did ask patients to return
within one week of injection. Of the 26 groups who did not ask patients
to
return, 20 groups called the patients within the first week, 6 did not.
When asked about follow up appointments, 4 groups asked patients to
return
in 2 weeks, 24 groups in 4 weeks, and 5 groups in 2 weeks. The
questionnaire did not ask groups rechecking patients within 1-7 days
about
the interval for subsequent appointments, although 8 indicated that they
had patients return between 4-6 weeks following treatment.
We acknowledge that computers and information technology are used
in
the health care arena and are indeed superior to spontaneous human
reporting or manual review for detecting anomalous data as shown in the
paper by
Murff and colleagues reports, cited by Dr. Ziemssen and colleagues[2].
As Murff reviewed, computers and information technology are frequently
used for error detection in hospital laboratories by setting programs
with
predetermined error margins such as a platelet count of <70,000/IL
for
thrombocytopenia. Murff does not report any use of the world wide
internet
for adverse event monitoring.
We concur with the authors that an intensive high-quality,
prospective safety study of intravitreal bevacizumab with clear
definitions, full-length questionnaires and uniform protocols is needed
to
define the safety profile, and are pleased to learn that Dr. Ziemssen
and
colleagues are undertaking their own internet based retrospective
efficacy
and safety survey.[3] [4]
This safety survey was initiated during an unprecedented time in
ophthalmology when no information had been reported about the safety of
intravitreal bevacizumab but during which thousands of these injections
were being performed worldwide. Much remains to be learned about the
safety, efficacy, and role of
intravitreal bevacizumab in ophthalmic disease worldwide and we look
forward to future reports.
Sincerely yours,
Anne Fung, Philip Rosenfeld and Elias Reichel
References
1.Fung AE, Rosenfeld PJ, Reichel E. The international intravitreal
bevacizumab safety survey: Using the internet to assess drug safety
worldwide. Br J Ophthalmol 2006.
2.Murff HJ, Patel VL, Hripcsak G, Bates DW. Detecting adverse events for
patient safety research: a review of current methodologies. J Biomed
Inform 2003;36(1-2):131-43.
3.www.avastin-rg.de
4.Ladewig MS, Ziemssen F, Jaissle G, et al. [Intravitreal bevacizumab
for
neovascular age-related macular degeneration]. Ophthalmologe
2006;103(6):463-70.
We read with interest the article by Fung et al. assessing
complications related to single or repeated intravitreal injections of
bevacizumab. [1] We congratulate the authors on studying this innovative
therapy via internet and greatly appreciate the effort to gather timely
information about the potentially related adverse events.
Using a product for an indication not in the approved labeling, the
ph...
We read with interest the article by Fung et al. assessing
complications related to single or repeated intravitreal injections of
bevacizumab. [1] We congratulate the authors on studying this innovative
therapy via internet and greatly appreciate the effort to gather timely
information about the potentially related adverse events.
Using a product for an indication not in the approved labeling, the
physicians have the responsibility to be well informed about the product
and its potential risks and to base its use on firm scientific rationale
and on sound medical evidence. [2] Informed consent must also depend on a
full discussion of all potential complications of the treatment proposed.
Unfortunately, some pitfalls in conducting this survey have restricted the
explanatory power of the presented results. [3]
The definition of the study population remains unclear as the authors
have abandoned a comprehensible sampling method. The vague distribution of
the e-mail request among undefined physicians did not exclude non-response
bias. It is not obvious whether other responders might have use
bevacizumab less successfully. Selection bias results when the sample
group is dominated by friended piers possibly not representative of the
whole population. An open access to the website and official announcements
by the scientific societies should be a prerequisite in future surveys.
The observer bias has to be assumed high as no standard and
systematic method of measuring the parameters e.g. blood pressure, [4] IOP
or signs of inflammations is warrented. In a questionnaire survey, it is
important to ensure that all the interviewers follow the same or at least
a similar monitoring protocol. It would have been interesting also to
analyse the behaviour of the treating physicians. Though asking for
returns within the first week, routinely measurements of blood pressure
and planning of control intervals (Fig.2) the authors did not mention the
answers to these questions.
Fung et al. did acknowledge the low rate of voluntary reports about
undesired side effects, however the inclusion of single patients was left
dependant on the mood of the participants. While some centers might have
excluded patients with pre-existing cardiovascular diseases, others might
have been less reserved. As the FDA commits off-label therapists to
maintain records of the product's use and effects, [2] it would have been
easily possible to request the exact number of dropouts in the follow-up
of 5.228 old-aged patients.
Computers and the internet have already widely used for monitoring
adverse events. [5] Physicians negligence of therapeutic problems [6] and
the superiority of chart review to computer monitoring [7,8] are,
therefore, well known issues. It would be also interesting to know, how
many of the presented, presumed adverse events, were reported to Medwatch,
the voluntary reporting system of the FDA´s Office of Drug Safety.
Subconjunctival haemorrhages were reported to be seen as common as
deaths after bevacizumab injection, but five times less common than
corneal abrasions. These rates appear awkward and cast doubts on the
report quality [9] and the clear definition of adverse events. [10] The
necessity of the questionnaires to be short [11] must not compromise the
integrity and conclusiveness of the survey. The mixture of different
numbers of injections per patient does not facilitate the interpretation
either. Last but not least, the authors should take into consideration the
individual benefit when estimating the safety profile of a drug. [12,13]
In summary, we congratulate Fung et al. on their efforts to specify
the safety profile and the scientific rationale of the most common off-
label drug in ophthalmology. They were successful in realizing such a big
collaboration project without any industrial support. Although different
biases are limiting the conclusions of this study, we want to encourage
the authors to carry on with the apparently planned full Avastin registry
to gather and offer more comprehensive information. That would meet the
needs of our patients, especially when FDA approved therapy is not
available or affordable.
F Ziemssen, S Grisanti, KU Bartz-Schmidt
University Eye Hospital Tuebingen
Schleichstr. 12, D-72076 Tuebingen, Germany
Focke.Ziemssen@med.uni-tuebingen.de
References
1. Fung AE, Rosenfeld PJ, Reichel E. The international intravitreal
bevacizumab safety survey: Using the internet to assess drug safety
worldwide.
Br J Ophthalmol. 2006;E-pub.
2. U.S. Food and Drug Administration. "Off-Label" and investigational
use of marketed drugs, biologics, and medical devices. Information sheets.
http://www.fda.gov/oc/ohrt/irbs/offlabel.html.
3. Leung WC. Conducting a survey. StudentBMJ. 2001;9:143-145.
4. Palatini P. Masked hypertension: how can the condition be
detected? Blood Press Monit. 2004;9:297-9.
5. Murff HJ, Patel VL, Hripcsak G, Bates DW. Detecting adverse events
for patient safety research: a review of current methodologies. J Biomed
Inform. 2003;36:131-43.
6. Figueiras A, Tato F, Fontainas J, Gestal-Otero JJ. Influence of
physicians' attitudes on reporting adverse drug events: a case-control
study. Med Care. 1999;37:809-14.
7. Jha AK, Kuperman GJ, Teich JM, et al. Identifying adverse drug
events: devel-opment of a computer-based monitor and comparison with chart
review and stimu-lated voluntary report. J Am Med Inform Assoc. 1998;5:305
-14.
8. Bates DW, Evans RS, Murff HJ et al. Detecting adverse events using
information technology. J Am Med Inform Assoc. 2003;10:115–128.
9. Kelly WN. The quality of published adverse drug event reports. Ann
Pharmacother. 2003;37:1774-8.
10. Yu KH, Nation RL, Dooley MJ. Multiplicity of medication safety
terms, definitions and functional meanings: when is enough enough? Qual
Saf Health Care 2005;14:358–363.
11. Edwards P, Roberts I, Sandercock P, Frost C. Follow-up by mail in
clinical trials: does questionnaire length matter? Control Clin Trials.
2004;25:31-52.
12. Sinclair JC, Cook RJ, Guyatt GH, Pauker SG, Cook DJ. When should
an effective treatment be used? Derivation of the threshold number needed
to treat and the minimum event rate for treatment. J Clin Epidemiol. 2001
54:253-62.
13. Irvine EJ. Measurement and expression of risk: optimizing
decision strategies. Am J Med. 2004 Suppl 5A:2S-7S
Stoutenbeek and Jansonius have demonstrated high rates of optometric
consultations in the Netherlands as a basis for screening populations at
risk of glaucoma .One of the aims of screening is understood to be the
early detection of morbidity. We recently published a review[1] of all
glaucoma patients registered blind at Manchester Royal Eye Hospital in
2003 and found that only 42% of these had their...
Stoutenbeek and Jansonius have demonstrated high rates of optometric
consultations in the Netherlands as a basis for screening populations at
risk of glaucoma .One of the aims of screening is understood to be the
early detection of morbidity. We recently published a review[1] of all
glaucoma patients registered blind at Manchester Royal Eye Hospital in
2003 and found that only 42% of these had their referrals initiated by by
optometrists and that significant visual loss had occured prior to
referral. We were able to correlate poor uptake of optometric services
with socioeconomic deprivation.Laidlaw et al have already shown a
reduction in glaucoma referrals to hospital eye services following the
imposition of the sight test fee in the UK[2].
The high rates of optometric review may well be conducive to
screening in the Netherlands. However access is certainly not universal
and may still leave the most vulnerable at risk.
References
1.Henson DB & Thampy R. Preventing blindness from glaucoma.BMJ
2005;331:120-121
2.Laidlaw DAH, Bloom PA, Hughes AO, Sparrow JM, Marmion VJ. The sight
test fee: effect on ophthalmology referrals and rate of glaucoma
detection. BMJ 1994;309: 634-6.
We read with great interest the scientific report published in your
journal by Zaidi AA et al(1) regarding their experience with pneumatic
retinopexy. We express our willingness to share our experience with a
unique complication mentioned by the authors. Giant retinal tear was
observed in one patient in the study by the author, which required scleral
buckle with vitrectomy.
We read with great interest the scientific report published in your
journal by Zaidi AA et al(1) regarding their experience with pneumatic
retinopexy. We express our willingness to share our experience with a
unique complication mentioned by the authors. Giant retinal tear was
observed in one patient in the study by the author, which required scleral
buckle with vitrectomy.
A 32-year-old male presented to our vitreoretinal service with
retinal detachment in the right eye. On examination he had bilateral high
myopia with right eye subtotal rhegmatogenous retinal detachment with
superonasal (1’o clock position) horse shoe tear (HST). His best corrected
visual acuity (BCVA) was counting fingers close to face in the affected
eye and 6/18 in left eye (OS). His refractive status OS was -13.0DS/-
2.75DC@60°. We performed superior 90° scleral buckling along with 360°
band. Injection of 0.4cc of SF6 gas (sulfur hexafluoride gas) was done for
fish mouthing of tear. Residual subretinal (SRF) fluid was present on
first postoperative day. The very next day (2nd postoperative day), a
superotemporal giant retinal tear (GRT) was noticed extending from the
site of primary HST. Patient underwent pars plana vitrectomy (PPV) with
endolaser photocoagulation and silicone oil injection. The retina was
found to be attached in the subsequent follow ups. Silicone oil was
removed (SOR) 3 months later and the patient maintained BCVA of 6/18 OD
till date (6 months post-SOR).
Pneumatic retinopexy (PR) is a promising alternative technique to
scleral buckling for selected cases of retinal detachment.(2,3) Pneumatic
retinopexy may also be effectively used in treating GRT with mobile
flap.(4,5) Exceptional case reports are also available in which multiple
breaks up to five clock hours apart have been successfully treated with
PR(6) . But vitreous condensation and traction with new retinal tears and
detachments in operated cases of pneumatic retinopexy is also well
documented in literature.(7) Collaborative Pneumatic Retinopexy Study
showed new/missed retinal breaks in 7% which occurred within the first
three postoperative months.(8) But we could not find a similar reference
or case report in literature in which a GRT was documented as a
complication, till the article by Zaidi AA et al(1) which prompted us to
share our experience.
Our case was slightly different from the patient in this report since
we performed scleral buckling along with gas injection as a primary
procedure. But still it was not sufficient to prevent the extension of the
tear. SF6 will expand 2.5 times its volume in 48 hours and this may make
the early postoperative period highly vulnerable for such
complications.(9) Gas injection in eyes with extensive lattice
degeneration, stiff fixed folds or a history of a giant retinal tear in
the fellow eye is generally not recommended as this procedure increases
the risk of further separation of already compromised vitreous base in
such patients. Though it is widely accepted that retina with significant
traction is not a good case for PR, our case and the author’s article
reiterate once again the significance of careful patient selection before
retinal tamponade with intravitreal gas.
References
1. Zaidi et al. Pneumatic retinopexy: success rate and complications.
Br J Ophthalmol.2006; 90: 427-428.
2. Tornambe PE et al. Pneumatic retinopexy. Surv Ophthalmol. 1988 Jan
-Feb; 32 (4):270-81. Review.
3. Eter N, Boker T, Spitznas M. Long-term results of pneumatic
retinopexy. Graefes Arch Clin Exp Ophthalmol. 2000 Aug; 238(8):677-81.
4. Irvine AR, Lahey JM. Pneumatic retinopexy for giant retinal tears.
Ophthalmology. 1994 Mar; 101(3):524-8.
5. Ando F, Hirose H, Nagasaka T. Treatment of retinal detachment with
giant tear by pneumatic retinopexy. Eur J Ophthalmol. 1993 Oct-Dec;
3(4):201-6.
6. Tornambe PE. Bilateral retinal detachment repaired with bilateral
pneumatic retinopexy. Case report. Arch Ophthalmol. 1987 Nov;
105(11):1489.
7. Dreyer RF. Sequential retinal tears attributed to intraocular gas.
Am J Ophthalmol. 1986 Aug 15; 102(2):276-8.
8. Hilton GF, Kelly NE, Salzano TC, et al. Pneumatic retinopexy: a
collaborative report of the first 100 cases. Ophthalmology 1987; 94:307-
14.
9. Abrams GW, Swanson DE, Sabates WI, GoldmanAI. The results of
sulfur hexafluoride gas in vitreous surgery. Am J Ophthalmol. 1982 Aug; 94
(2):165-71.
We read with keen interest the article by Atmaca-Sonmez et al on
"Persistent detachment of the fovea after non-buckling repair of
rhegmatogenous retinal detachment".[1] As stated in the article the
presence of persistent detachment of the fovea and localised delayed
subretinal fluid absorption (DSRFA) has been noted quite frequently after
scleral buckling and pneumatic retinopexy, after the advent of...
We read with keen interest the article by Atmaca-Sonmez et al on
"Persistent detachment of the fovea after non-buckling repair of
rhegmatogenous retinal detachment".[1] As stated in the article the
presence of persistent detachment of the fovea and localised delayed
subretinal fluid absorption (DSRFA) has been noted quite frequently after
scleral buckling and pneumatic retinopexy, after the advent of optical
coherence tomography (OCT). Wolfensberger concluded that the
presence of persistent subretinal fluid was virtually nonexistent after
vitrectomy with gas tamponade in his prospective study.[2]
We have seen the presence of localised DSRFA in a 35 year old male
who had undergone belt buckling with vitrectomy, endodrainage and silicone
oil endotamponade for rhegmatogenous retinal detachment due to a posterior
retinal tear in his left eye. This patient had complaints of distortion
and defective vision 4 months after surgery. Best-corrected vision was
20/60. On examination the fovea looked normal but multiple small rounded
lesions around 1/4th disc areas were seen temporal to the fovea simulating
pigment epithelial detachments. OCT (Zeiss Stratus Model 3000)
showed multiple areas of localized neurosensory detachment ranging from ¼
to ½ disc area in the area of previous retinal detachment. The
fovea also showed the presence of localized sub retinal fluid
(SRF).
This instance shows that persistent subretinal fluid can occur in the
presence of silicone oil also apart from cases of scleral buckling,
pneumatic retinopexy and vitrectomy with gas tamponade as earlier
reported.
References
1. P Atmaca-Sonmez, M W Johnson, D N Zacks. Persistent detachment of
the fovea after non-buckling repair of rhegmatogenous retinal detachment.
Br J Ophthalmol 2006; 90: 920 - 1.
2. Wolfensberger TJ. Foveal reattachment after macula-off retinal
detachment occurs faster after vitrectomy than after buckle surgery.
Ophthalmology 2004;111:1340 - 3.
Figure 1: Fundus image showing the silicone oil reflex (Black arrow) at the fovea and multiple bleb like elevations temporal to it (White arrow)
Figure 2: OCT pictures showing the persistant subfoveal fluid (Green arrow) and loculated neurosensory detachments (Red arrows)
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.
Dear Editor,
I enjoyed reading Paskowitz et al.'s (1) important summary of evidence indicating that in some specific types of retinal degeneration, light deprivation may prove to be of protective value. In respect of Stargardt Disease, they cite evidence from animal models that light deprivation can prevent A2E accumulation in the RPE, thus preventing the degeneration. A worthwhile point to note is that the dest...
Dear Editor:
With great interest, we read the comments of Dr. Ziemssen and colleagues regarding our World View paper discussing the results of the international intravitreal bevacizumab safety survey[1]. Their letter will certainly accentuate the importance of this topic to the ophthalmic community; we would like to clarify several of the points raised.
In our paper, we have fully acknowledged the pur...
Dear Editor,
We read with interest the article by Fung et al. assessing complications related to single or repeated intravitreal injections of bevacizumab. [1] We congratulate the authors on studying this innovative therapy via internet and greatly appreciate the effort to gather timely information about the potentially related adverse events. Using a product for an indication not in the approved labeling, the ph...
Dear Editor,
Stoutenbeek and Jansonius have demonstrated high rates of optometric consultations in the Netherlands as a basis for screening populations at risk of glaucoma .One of the aims of screening is understood to be the early detection of morbidity. We recently published a review[1] of all glaucoma patients registered blind at Manchester Royal Eye Hospital in 2003 and found that only 42% of these had their...
Dear Editor,
We read with great interest the scientific report published in your journal by Zaidi AA et al(1) regarding their experience with pneumatic retinopexy. We express our willingness to share our experience with a unique complication mentioned by the authors. Giant retinal tear was observed in one patient in the study by the author, which required scleral buckle with vitrectomy.
A 32-year-old m...
Dear Editor,
We read with keen interest the article by Atmaca-Sonmez et al on "Persistent detachment of the fovea after non-buckling repair of rhegmatogenous retinal detachment".[1] As stated in the article the presence of persistent detachment of the fovea and localised delayed subretinal fluid absorption (DSRFA) has been noted quite frequently after scleral buckling and pneumatic retinopexy, after the advent of...
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...
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