In their article Doctors Agrawal and McKibbin evaluate the one-year
frequency and the clinical outcome data of Putscher’s retinopathy through
the British Ophthalmological Surveillance Unit. [1] All their 15 cases
were visually symptomatic. Twelve cases were associated with trauma and 3
cases with acute pancreatitis. The authors conclude that the incidence of
Purtsher’s retinopathy is low (0.24 case...
In their article Doctors Agrawal and McKibbin evaluate the one-year
frequency and the clinical outcome data of Putscher’s retinopathy through
the British Ophthalmological Surveillance Unit. [1] All their 15 cases
were visually symptomatic. Twelve cases were associated with trauma and 3
cases with acute pancreatitis. The authors conclude that the incidence of
Purtsher’s retinopathy is low (0.24 cases per million population) in the
United Kingdom, and that in half of the cases visual acuity improves by at
least 2 Snellen lines in 6 months.
The authors’ data, however, need careful interpretation. We investigated
the clinical characteristics, histological features and prognostic
significance of retinopathy of pancreatitis (Purtscher’s retinopathy
associated with acute pancreatitis) in several studies. [2][3] We found
that most of our cases were visually asymptomatic, since the patients were
in severe or terminal status in intensive care units. We also found that
retinopathy of pancreatitis was an indicator of multi-organ failure and
lethal outcome. Our data suggest that pancreatitis associated Purtscher’s
retinopathy is more common than reported by Doctors Agrawal and McKibbin,
and that the visual outcome may be worse than found by the authors who
used data reported by ophthalmologists. One may suppose that the reporting
ophthalmologists might have seen only those cases which were associated
with less severe systemic damage, and therefore the patients were able to
realise their visual symptoms. It is probable that Purtscher’s retinopathy
is more frequent than reported by the authors for the United Kingdom, and
that the visual outcome is different from that indicated in their article,
if all cases are considered.
Correspondence to: Gábor Holló, Department of Ophthalmology,
Semmelweis University, Budapest; hg@szem1.sote.hu
The author has no commercial interest in any product mentioned in the
article or the comment.
References
1.Agrawal A, McKibbin M. Purtscher’s retinopathy: epidemiology,
clinical features and outcome. Br J Ophthalmol 2007;91:1456-1459.
2.Holló G, Bobek I. Clinicopathology of a case with retinopathy of
pancreatitis. Acta Ophthalmol (Copenh) 1993;71:422-425.
3.Holló G, Tarjányi M, Varga M, et al. Retinopathy of pancreatitis
indicates multiple-organ failure and poor prognosis in severe acute
pancreatitis. Acta Ophthalmol (Copenh) 1994;72:114-117.
Re: van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong
PTVM, Simonsz HJ Risk of bilateral visual impairment in individuals with
amblyopia: the Rotterdam study BJO 2007;91 (11): 1450
Josefin Nilsson The negative impact of amblyopia from a population
perspective: untreated amblyopia almost doubles the lifetime risk of
bilateral visual impairment. BJO 2007;91 (11): 1417
Re: van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong
PTVM, Simonsz HJ Risk of bilateral visual impairment in individuals with
amblyopia: the Rotterdam study BJO 2007;91 (11): 1450
Josefin Nilsson The negative impact of amblyopia from a population
perspective: untreated amblyopia almost doubles the lifetime risk of
bilateral visual impairment. BJO 2007;91 (11): 1417
Dear Editor
It is not surprising that amblyopes are at higher risk of bilateral
visual impairment since impaired visual functions of the fellow eye have
been previously demonstrated. Leguire et al warned that “In future
studies of amblyopia, whether in children or in adults, caution is advised
in assuming that the nonamblyopic eye is normal because acuity is normal.”
[2] Johnson found that both amblyopic and fellow eyes had central
scotomata, even after apparently successful treatment, [3] and concluded
that “ocular effects of amblyopia may not be strictly limited to the
amblyopic eye.” [4] Anomalous optic discs, reduced axial lengths,[5] and
anatomic abnormalities involving the axial length to optic disc area have
been reported as present to different degrees in amblyopic and fellow
eyes.[6,7] Moreover, amblyopia is commonly associated with systemic
disorders such as prematurity and low birth weight[8] even in the absence of
retinopathy. [9] These anatomic and functional factors put both eyes at
risk makes them more susceptible to vision loss.
Nilsson’s editorial implies that lack of screening and treatment of
amblyopia cause a lifelong handicap[10] and that treatment offer a
significant cost / benefit gain.[11,12] These beliefs employed several
unsupported assumptions. Among them is that treatment results in final
visual acuity sufficient to perform all tasks and that untreated amblyopia
has a financial handicap equivalent to workman’s compensation scales for
loss of an eye. Actually, treatment of severe amblyopia rarely results in
functionally useful vision.[13] PEDIG studies showed that approximately 25
percent of their treated patients had no or very limited improvement at
the end of their initial observation period.[14,15] Initial successes were
reduced by an anticipated 50 percent rate of recidivism.[16,17]
Furthermore, the assumption that improved Snellen acuity reflects
functional improvement is challenged by findings that reading speed is
significantly less than normal even when final acuity was comparable with
the controls. [18]
A retrospective demographic investigation concluded that “No
functionally or clinically significant differences existed between people
with and without amblyopia in educational outcomes, behavioral
difficulties or social maladjustment, participation in social activities,
unintended injuries (school, workplace, or road traffic accidents as
driver), general or mental health and mortality, paid employment, or
occupation based social class trajectories.”[19]
There is an absolute need for effective allocation of medical
resources.[20] Increased bilateral vision impairment among people with
initial anatomic ocular defects in both eyes must motivate efforts to
prevent those prenatal conditions leading to impaired ocular anatomy.
Respectfully submitted,
Philip Lempert, MD
References
1. van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong PTVM,
Simonsz HJ Risk of bilateral visual impairment in individuals with
amblyopia: the Rotterdam study BJO 2007;91 (11): 1450
2. Leguire LE, Rogers GL, Bremer DL Amblyopia: the normal eye is not
normal. J Pediatr Ophthalmol Strabismus 1990;27(1):32-38
3. Johnson DA Relative scotomata in the "normal" eye of functionally
patients. A scanning laser ophthalmoscope (SLO) micreperimetric study.
Binocul Vis Strabismus Q. 2007;22(1):17-48.
4. Johnson DA The use of the scanning laser ophthalmoscope in the
evaluation of amblyopia (an American Ophthalmological Society thesis).
Trans Am Ophthalmol Soc. 2006;104:414-36.
5. Lempert P. Porter L. Dysversion of the optic disc and axial length
measurements in a presumed amblyopic population J Amer Acad Ped
Ophthalmol Strabismus 1998;2:207-213
6. Lempert P. Axial length – disc area ratio in esotropic amblyopia. Arch
Ophthalmol 2003; 121:821-824
7. Lempert P The axial length / disc area ratio in anisometropic hyperopic
amblyopia: A hypothesis for decreased unilateral vision associated with
hyperopic anisometropia. Ophthalmology 2004:111:304-308
8. Holmström G, M el Azazi M, Kugelberg U Ophthalmological follow up of
preterm infants: a population based, prospective study of visual acuity
and strabismus Br J Ophthalmol 1999;83:143-150
9. O’Connor AR, Stephenson TJ, Johnson A, Tobin MJ, Ratib S, Moseley
M, Fielder AR Visual function in low birthweight children . British
Journal of Ophthalmology 2004: 88 (9): 1149 - 1153
10. Josefin Nilsson The negative impact of amblyopia from a population
perspective: untreated amblyopia almost doubles the lifetime risk of
bilateral visual impairment. BJO 2007;91 (11): 1417
11. Joish VN, Malone DC, Miller JM. A cost-benefit analysis of vision
screening methods for preschoolers and school-age children. J AAPOS
2003;7:283-290
12. Membreno JH, Brown MM, Brown GC, Sharma S, Beauchamp GR. A cost-
utility analysis of therapy for amblyopia.Ophthalmology. 2002;109(12):2265
-2271.
13. Ingram RM Amblyopia: the need for a new approach Brit J. Ophthalmol
1979:63:236-237
14. PEDIG A randomized trial of atropine vs. patching for treatment of
moderate amblyopia in children. Arch Ophthalmol 2002;120:268-278
15. Pediatric Eye Disease Investigator Group. The course of moderate
amblyopia treated with patching in children: experience of the amblyopia
treatment study. Am J Ophthalmol. 2003;136(4):620-629
16. Simons K. Amblyopia characterization, treatment, and prophylaxis.
Surv Ophthalmol. 2005;50(2):123-66
17. Rutstein RP, Fuhr PS Efficacy and stability of amblyopia therapy. Optom
Vis Sci 1992;69(10):747-754
18.Stifter E, Burggasser G, Hirmann E, Thaler A, Radner W. Monocular and
binocular reading performance in children with microstrabismic amblyopia.
Br J Ophthalmol. 2005;89(10):1324-9
19. J S Rahi, P M Cumberland, and C S Peckham Does amblyopia affect
educational, health, and social outcomes? Findings from 1958 British birth
cohort BMJ 2006; 332: 820-825
20. Woolf SH Potential Health and Economic Consequences of Misplaced
Priorities. JAMA 2007;197(5) 523-526
We read with great interest the report by Raftery et al on
Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost
effectiveness. The authors raise the very pertinent point in respect to
a single company owning two competing drugs and the inherent cost to tax
payers. The authors conclude their abstract with "Public pressure may be
the most potent weapon in persuading Genentech to license bevaciz...
We read with great interest the report by Raftery et al on
Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost
effectiveness. The authors raise the very pertinent point in respect to
a single company owning two competing drugs and the inherent cost to tax
payers. The authors conclude their abstract with "Public pressure may be
the most potent weapon in persuading Genentech to license bevacizumab
for AMD".
We would like to suggest what forms this public pressure may take.
The pharmaceutical industry claims to educate the medical profession on
conditions and its drugs to treat them. Should we be relying on a
business to give us unbiased evaluations of products it is selling? Most
doctors who accept free lunches and merchandise will claim to be
unaffected.
However, doctors who have frequent contact with drug representatives are
more willing to prescribe new drugs, do not like ending consultations
with advice only, and are more likely to agree to prescribe a drug that
is not clinically indicated. [1] Doctors are now dependent on drug
companies for education and funding for research.
Research funded by drug companies has been found to be less likely to be
published than research funded by other sources. Studies sponsored by
pharmaceutical companies were found to be four times more likely to have
outcomes favouring the sponsor than were studies with other sponsors.
[2]
We have an unhealthy relationship with the pharmaceutical industry
which undermines our ability to make patient centered decisions. To
prevent more profit centered drugs coming to market rather than patient
centered drugs, we as a profession must take responsibility. When
published financial reports indicate pharmaceutical industry spending in
marketing is three times that of Research and Development, alarm bells
should be ringing.
To reduce this influence we must no longer accept free lunches,
merchandise or holidays, look for alternate means of funding research
and educational meetings and most of all become educated on the role
drug companies play in our decision making. Accepting our need for the
pharmaceutical industry should not mean accepting dependence upon them,
if we wish to see drugs such as bevacizumab being licensed it is time we
make our boundaries clear.
Suggested reading: The Truth About the Drug Companies by Marcia
Angell (Former Editor of the New England Journal of Medicine)
www.nofreelunch.org
References
1. Watkins C, Moore L, Harvey I, Carthy P, Robinson E, Brawn R.
Characteristics of general practitioners who frequently see drug
industry
representatives: national cross sectional survey. BMJ 2003;326: 1178-9
2. Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical
industry sponsorship and research outcome and quality: systematic
review.
BMJ 2003;326: 1167-70
We appreciated the paper by Iriyama et al.[1] The authors have
investigated the role of anti vascular endothelial growth factor (VEGF)
antibodies on retinal ganglion cells in rats. It is an interesting and
relevant paper considering the clinical use of anti-VEGF antibodies in a
variety of ocular conditions.[2] However, there are a couple of issues
that require further clarification.
We appreciated the paper by Iriyama et al.[1] The authors have
investigated the role of anti vascular endothelial growth factor (VEGF)
antibodies on retinal ganglion cells in rats. It is an interesting and
relevant paper considering the clinical use of anti-VEGF antibodies in a
variety of ocular conditions.[2] However, there are a couple of issues
that require further clarification.
The authors demonstrate, in figure 1, that bevacizumab (AvastinTM;
Genentech Inc. San Francisco, CA) is unable to bind to murine VEGF and
they provide evidence by doing Western blot on rat ocular tissue (retina
and choroid) using anti-rat VEGF antibody (R&D systems, Minneapolis) and
bevacizumab. Membranes were developed using rabbit anti mouse IgG and
anti-goat IgG. Authors demonstrate that only anti rat VEGF antibody was
able to detect rat VEGF and not bevacizumab. Although the authors have
not mentioned it in their paper, the anti-rat VEGF antibody that the
authors used is raised in goat according to the information provided by
the source. It justifies the use of anti-goat secondary antibody. It is
not clear why and where they used anti-mouse IgG. On the other hand,
bevacizumab is a humanized antibody and it should be detected by
anti-human IgG 3, which was not used by the authors. This might explain
why they could not detect bevacizumab binding with rat VEGF. Consistent
with this argument, Bock et al. in a recent paper[4] have been able to
show that bevacizumab binds to murine VEGF. They used a similar
technique (Western blot), and by using anti-human IgG were able to
detect bevacizumab bound to the murine VEGF. They further confirmed
their results using additional techniques such as ELISA (again utilizing
anti-human IgG) and surface Plasmon resonance (BIAcore assay).
Also, the figure legend of Figure 2 does not match the figure, nor
does the legend for Figure 4. It seems figures have switched.
Rajesh K Sharma, MD, PhD
Kakarla V Chalam, MD, PhD, MBA, FACS
Department of Ophthalmology
University of Florida, College of Medicine
Jacksonville FL
References
1. Iriyama A, Chen YN, Tamaki Y et al. Effect of anti-VEGF antibody on retinal ganglion cells in rats. Br.J.Ophthalmol. 2007;91:1230-3.
2. Aggio FB, Farah ME, Silva WC et al. Intravitreal
bevacizumab for exudative age-related macular degeneration after multiple treatments.
Graefes Arch.Clin.Exp.Ophthalmol. 2006.
3. Heiduschka P, Fietz H, Hofmeister S et al. Penetration of bevacizumab through the retina after intravitreal injection in the monkey.
Invest Ophthalmol.Vis.Sci. 2007;48:2814-23.
4. Bock F, Onderka J, Dietrich T et al. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis.
Invest Ophthalmol.Vis.Sci. 2007;48:2545-52.
We read with great interest the report by Alwitry et al [1] on severe
decompression retinopathy after medical treatment of acute angle closure.
The authors have speculated that the mechanism of the ‘preretinal’
haemorrhage in this case was similar to the scattered ‘intraretinal’
haemorrhages seen in ocular decompression retinopathy. Although we agree
with them that the haemorrhage was caused by sudd...
We read with great interest the report by Alwitry et al [1] on severe
decompression retinopathy after medical treatment of acute angle closure.
The authors have speculated that the mechanism of the ‘preretinal’
haemorrhage in this case was similar to the scattered ‘intraretinal’
haemorrhages seen in ocular decompression retinopathy. Although we agree
with them that the haemorrhage was caused by sudden lowering of
intraocular pressure (IOP), we believe that the exact pathophysiological
mechanism, as well the clinical signs, in this case were different from
the condition originally described by Fechtner et al [2].
It can be hypothesised that a pupillary block caused the volume of
aqueous humor in the posterior chamber to increase markedly. The vitreous
gel was therefore pushed toward the posterior pole. Following medical
therapy the pupillary block was reversed and the aqueous humor moved
rapidly through the pupil from the posterior chamber to the anterior
chamber. This coupled with decreased aqueous production due to
administration of aqueous suppressants allowed the vitreous body to move
forward rapidly. This induced a rapid posterior vitreous detachment (PVD),
disrupting small vessels on the retinal surface or optic disc, and
resulted in the subhyaloid haemorrhage. In the present case the very short
duration of raised IOP makes significant impairment of autoregulation of
retinal vasculature unlikely and the absence of multiple intraretinal
haemorrhages rules out a general compromise of mechanical stability of
retinal capillaries. Obana et al [3] were the first to demonstrate a
subhyaloid haemorrhage caused by PVD induced after laser iridectomy for
primary angle-closure glaucoma and it should be distinguished from ocular
decompression retinopathy.
This leads to an interesting conclusion that a sudden lowering of IOP
may cause posterior segment bleeding by three different mechanisms. Ocular
decompression retinopathy is caused by overwhelming of capacitance of
retinal capillaries and results in multiple intraretinal haemorrhages. The
second mechanism and clinical picture is similar to a central retinal vein
occlusion [4,5]. A sudden change in hydrostatic equation between the
posterior and anterior chambers, induces a rapid PVD and may result in
subhyaloid haemorrhage, as in this case.
Figure 1 Three different mechanisms of posterior segment
bleeding after sudden lowering of intraocular pressure
References
1. Alwitry A, Khan K, Rotchford A et al. Severe decompression
retinopathy after medical treatment of acute primary angle closure. Br J
Ophthalmol 2007;91:121
2. Fechtner RD, Minckler D, Weinreb RN et al. Complications of
glaucoma surgery. Ocular decompression retinopathy. Arch Ophthalmol
1992;110:965-8
3. Obana A, Gohto Y, Ueda N, Miki T, Cho A, Suzuki Y. Retinal and
subhyaloid hemorrhage as a complication of laser iridectomy for primary
angle-closure glaucoma. Arch Ophthalmol. 2000 Oct;118:1449-51
4. Suzuki R, Nakayama M, Satoh N. Three types of retinal bleeding as
a complication of hypotony after trabeculectomy. Ophthalmologica.
1999;213:135-8
5. Dev S, Herndon L, Shields MB. Retinal vein occlusion after
trabeculectomy with mitomycin C. Am J Ophthalmol. 1996 Oct;122:574-5
I read with interest the article by Pedroza-Seres M and associates
who assessed the pathogenic roles of peripheral CD57+ natural killer T
(NKT) cell in pars planitis.[1] The authors compared the frequencies of
CD57+ NKT cell in peripheral blood between pars planitis patients and
healthy controls, and then evaluated the effector-related surface
molecules and functions of CD57+ NKT cells derived from pa...
I read with interest the article by Pedroza-Seres M and associates
who assessed the pathogenic roles of peripheral CD57+ natural killer T
(NKT) cell in pars planitis.[1] The authors compared the frequencies of
CD57+ NKT cell in peripheral blood between pars planitis patients and
healthy controls, and then evaluated the effector-related surface
molecules and functions of CD57+ NKT cells derived from patients. The
authors conclude that CD57+ NKT cell subsets may function as memory-effector T cells during pars planitis immunopathogenesis. My experience of
using similar methods to investigate the phenotypes and functions of
CD8brightCD56+ T cells in Behçet uveitis supports the notion that
NK-typed CD8+ T cells play an effector role in chronic uveitis.[2] I would
like to offer my opinion to their interpretation of experimental results.
I observed that CD8bright CD56+ cells in peripheral blood were composed of
more than 95% TCRαβ cells and that CD8dimCD56+ cells consisted of
natural killer cells and γδTCR+ cells.[2,3] Because the authors used the
different gate of CD8 expression in figure 1 and 3, it is possible to
overestimate the frequencies of peripheral CD8+CD57+ T cells including
CD8dim populations. Likewise CD56+ cells, CD8dimCD57+ cells may not be
TCRαβcells, which require confirmation of TCR expression.
As shown in Figure 4 and Table 3, the authors found that CD57+CD8+ T cells
significantly produced IL-4 after nonspecific stimulation. However, these
results are not compatible with the idea that terminally differentiated NK-typed CD8+ T cells are polarized to produce cytokines, like CD56+CD8+ T cells.[2] Apoptosis of ex vivo CD57+CD8+ T cells may contribute to these
findings because of smaller cell counts after stimulation (thick lines).
The authors described that stimulared or unstimulated immune cells were
used for intracellular staining of perforin. Because CD8+CD56+ T cells
shed the preformed intracellular
perforin after in vitro stimulation, the authors should measure the
amounts of intracellular perforin in unstimulated cells.
I agree with the authors that NK-typed CD8+ T cells exert potent effector
functions over conventional CD8+ T cells. CD56+ T cells are recruited into
eye, particularly in Behçet uveitis, which are different from other
etiologies of uveitis.[3] Moreover, these cells show phenotypical or
functional changes after immunosuppresive treatments.[4] However, I did not
observe upregulation of CD56+ T cells in aqueous or peripheral blood in
patients with intermediate uveitis.[3] The specific roles of CD57+CD8+ T
cells in pars planitis pathogenesis are not definite because the authors
did not evaluate phenotypical or functional differences of CD57+CD8+ T
cells according to the disease activity or compare their results with
other etiologies of uveitis. Therefore, further investigations are needed
to identify the pathogenic roles of CD57+CD8+ T cells in pars planitis.
References
1. Pedroza-Seres M, Linares M, Voorduin S, et al. Pars planitis is
associated with an increased frequency of effector-memory CD57+ T cells.
Br J Ophthalmol 2007;91:1393-8.
2. Ahn JK, Chung H, Lee DS, Yu YS, Yu HG. CD8brightCD56+ T cells are
cytotoxic effectors in patients with active Behçet's uveitis. J
Immunol 2005;175:6133-42.
3. Yu HG, Lee DS, Seo JM, et al. The number of CD8+ T cells and NKT cells
increases in the aqueous humor of patients with Behçet's uveitis.
Clin Exp Immunol 2004;137:437-43.
4. Ahn JK, Park YG, Park SW, et al. Combined low dose cyclosporine and
prednisone down-regulate natural killer cell-like effector functions of
CD8brightCD56+ T cells in patients with active Behçet's uveitis.
Ocul Immunol Inflamm 2006;14:267-275.
We read with interest the article by Aisenbrey et al [1] who have described the results of surgical treatment of peripapillary choroidal neovascularisation in eight patients.
As reported, peripapillary choroidal neovascularisation is a relatively uncommon entity that can be a variant of macular choroidal neovascularisation in elderly patients.
Accordingly to the MPSG[2], early small peripapilla...
We read with interest the article by Aisenbrey et al [1] who have described the results of surgical treatment of peripapillary choroidal neovascularisation in eight patients.
As reported, peripapillary choroidal neovascularisation is a relatively uncommon entity that can be a variant of macular choroidal neovascularisation in elderly patients.
Accordingly to the MPSG[2], early small peripapillary choroidal neovascularisation should be first treated with red thermal laser photocoagulation. If applied by an experienced specialist the risk of burning the interpapillomacular bundle is limited.
However, the therapeutical approach is more delicate for laser resistant, extended and/or very exsudative peripapillary choroidal neovascularisation.
In their study, Aisenbrey et al report good clinical outcome after surgical treatment. Nevertheless, as published by Rosenblatt et al [3], photodynamic therapy with Verteporfin can also be a good option because of its efficacy and very limited risk. This is also our clinical experience.
Figure 1 shows the left eye of a male patient in his early seventies with very exsudative peripapillary choroidal neovascularisation before and one year after one photodynamic therapy with Verteporfin. The current parameters for choroidal neovascularisation and a spot of 4200 µ covering a great part of the optic nerve were used. This case looks very similar to the illustrated case of Aisenbrey et al, except the fact that we first unsuccessfully tried to treat the lesion with thermal laser.
Figure 1: left eye of a male patient in his early seventies with very exsudative peripapillary choroidal neovascularisation before (a) and one year after one photodynamic therapy with Verteporfin (b).
Figure 1a
Figure 1b
In our experience with Verteporfin we have never noted any clinical damage to the optic nerve after partial exposition and it has been shown by Schmidt-Erfurth et al [4] that optic nerve can be exposed to a light dose twice as high as conventionally used without showing histopathological alterations.
Regarding the potential major risks of the surgical approach of peripapillary choroidal neovascularisation we suggest that PDT could be the first therapeutical choice in these cases.
References
1. Aisenbrey S, Gelisken F, Szurman P, et al. Surgical treatment of
peripapillary choroidal neovascularisation. Br J Ophthalmol 2007;91:1027- 1030.
2. The Macular Photocoagulation Study Group. Laser photocoagulation
for neovascular lesions nasal to the fovea. Results from clinical trials for lesions secondary to ocular histoplasmosis or idiopathic causes.
Macular Photocoagulation Study Group. Arch. Ophthalmol. 1995; 113:56-61.
3. Rosenblatt BJ, Shah GK, Blinder K. Photodynamic therapy with
verteporfin for peripapillary choroidal neovascularisation. Retina. 2005; 25:33-37.
4. Schmidt-Erfurth U, Laqua H, Schlotzer-Schrehard U, et al.
Histopathological changes following photodynamic therapy in human eyes.
Arch. Ophthalmol. 2002 Jun; 120(6):835-44.
I commend the authors for yet another treatment for this potentially
disabling and common affliction.
I note that one important component of this treatment requires the mapping
of the site of the erosion during an attack with this area being singled
out for the localised 4-6mm of treatment. However, in most patients that
I have treated over the years the area of erosion is healed by the time
they seek...
I commend the authors for yet another treatment for this potentially
disabling and common affliction.
I note that one important component of this treatment requires the mapping
of the site of the erosion during an attack with this area being singled
out for the localised 4-6mm of treatment. However, in most patients that
I have treated over the years the area of erosion is healed by the time
they seek ophthalmic care (microerosions) and at the most there may be
left some intraepithelial microcysts but no epithelial defect. I would
have thought that this would make it difficult to ascertain where the
treatment should be applied in these cases. The patients who present with
a large epithelial defect (macro-erosions), in whom the mapping of
involved epithelium is possible, are in the minority in my practice.
Perhaps the authors are seeing a selection bias in their cases and it
would be interesting if they could indicate whether they would treat these
“microerosions” and if so where on the cornea.
They also describe using a dry surgical sponge to debride the treated area
resulting in a single sheet removal of the treated area. In my
experience, attempted removal of the loose sheet of epithelium in a
recurrent erosive patient most often results in removal of the entire
corneal epithelium which can be seen to be non-adherent out to the limbus
in all directions. It would be useful if the authors could indicate how
they restrict the removal of the treated epithelium only without ending up
removing the entire corneal epithelium.
We thank Dr. Camras for his interest in our report on levels of
bimatoprost and its free acid in the aqueous humour of cataract patients
after a single topical dose of bimatoprost [1] and welcome the opportunity
to respond to his comments. We are in agreement with Dr. Camras that the
results of our study [1] and those of his previously reported study [2]
are similar, showing low nanomolar concentrat...
We thank Dr. Camras for his interest in our report on levels of
bimatoprost and its free acid in the aqueous humour of cataract patients
after a single topical dose of bimatoprost [1] and welcome the opportunity
to respond to his comments. We are in agreement with Dr. Camras that the
results of our study [1] and those of his previously reported study [2]
are similar, showing low nanomolar concentrations of 17-phenyl PGF2alpha
(bimatoprost acid) in the aqueous humour. There is no question that
bimatoprost acid is a metabolite of bimatoprost. The issue is whether
bimatoprost acid levels account for the IOP-lowering activity of
bimatoprost. The evidence suggests that they are insufficient to do so. As
Dr. Camras stated in his correspondence: “bimatoprost yields peak free
acid concentrations in the aqueous 3 to 6 times lower than latanoprost
acid”. It is accepted that the biological effects of latanoprost are
exerted by latanoprost acid: the relatively high concentration of
latanoprost acid achieved after latanoprost dosing [1-3] is sufficient to
activate a substantial proportion of the prostaglandin FP receptors
present in the target tissues and account for the IOP-lowering effect of
latanoprost. It is difficult to understand, however, how the much lower
levels of bimatoprost acid achieved could be believed to account for the
IOP-lowering effect of bimatoprost, particularly since bimatoprost has
reduced IOP more effectively than latanoprost in some clinical studies
[4,5] and is effective in patients who fail to respond to latanoprost
[6,7].
Dr. Camras contends that there is overwhelming evidence that
bimatoprost acid is more potent than latanoprost acid at prostaglandin FP
receptors, but the 10 references he cites to support this statement [8-17]
include 3 studies in which bimatoprost acid and latanoprost acid were not
compared [8-10], 3 reviews from a single laboratory that reported greater
functional potency of bimatoprost acid compared with latanoprost acid in
the cat iris sphincter preparation [11-13], and a study that found 3-fold
lower functional potency of bimatoprost acid compared with latanoprost
acid in human trabecular meshwork cells (EC50 of 112 nM vs 34.7 nM) [14].
Dr. Camras fails to note that the study showing very high functional
potency of bimatoprost acid in human HEK-293 cells [15] used transfected
cells with overexpression of the FP receptor. Bimatoprost acid was
reported to be very potent in stimulating phosphoinositide hydrolysis in
nontransfected mouse 3T3 and rat A7r5 cells [16]. However, in other
studies by the same laboratory, bimatoprost acid was 10-fold less potent
in mobilizing intracellular Ca++ in these cell lines [9,18]. Reported
potency values in human ciliary muscle cells were 3.8 nM and 3.6 nM for
bimatoprost acid and 124 nM and 198 nM for latanoprost acid [16,17], but
bimatoprost acid was less effective than latanoprost acid in stimulating
MAP kinase at 100 nM [17]. In summary, review of the literature does not
reveal compelling evidence that bimatoprost acid is more potent than
latanoprost acid. In fact, in human trabecular meshwork cells as well as
human fibroblasts expressing endogenous, nontransfected prostaglandin FP
receptors, bimatoprost acid and latanoprost acid have shown similar
functional potency [1,14,16]. The results with trabecular meshwork cells
are more clinically relevant because one pathway by which bimatoprost is
believed to reduce IOP is through effects on the trabecular meshwork [19].
Wan et al [20] have shown that bimatoprost produces a decrease in outflow
facility, which is blocked by a prostamide antagonist, in a human anterior
segment organ culture model.
Camras et al proposed that the 22 nM aqueous humour concentration of
bimatoprost acid is sufficient to lower IOP based on its agonist potency.
Following his line of reasoning, the 100 nM aqueous humour concentration
reported for latanoprost acid should not be sufficient to account for the
IOP lowering, based on EC50 potency values of 124 nM and 198 nM in ciliary
muscle cells. In fact, the data suggest that aqueous humour concentrations
of bimatoprost acid are not sufficient to activate the FP receptor for
effective diurnal IOP lowering, particularly taking into account the
aqueous humour concentration of latanoprost acid and respective agonist
potencies. The most plausible explanation for the greater efficacy of
bimatoprost, despite lower levels of bimatoprost acid in the aqueous
humor, is that bimatoprost reduces IOP through a mechanism other than or
in addition to production of bimatoprost acid. There is excellent evidence
from animal studies that the intact bimatoprost molecule has biological
activity distinct from the activity of prostaglandin FP agonists [21]. For
example, in a dissociated cat iris preparation, a specific population of
cells responds to bimatoprost with an increase in calcium levels, and a
separate and distinct population of cells responds to bimatoprost acid
with an increase in calcium levels [22]. The selective stimulation of
different cells in the same preparation by bimatoprost and prostaglandin
FP agonists suggests the involvement of receptors for bimatoprost distinct
from prostaglandin FP receptors. The recent identification of an
antagonist that blocks the effects of bimatoprost, but not bimatoprost
acid or latanoprost acid, in the cat iris preparation has provided
additional evidence for biological activity of bimatoprost mediated
through novel receptors [23]. Although studies in prostaglandin FP
receptor knockout mice have shown that the intact FP receptor gene is
needed for the IOP response to bimatoprost in the mouse eye [24,25], the
IOP response does not appear to be mediated by interaction of bimatoprost
acid with prostaglandin FP receptors, because there is minimal hydrolysis
of bimatoprost in the mouse eye [25]. Instead, intact bimatoprost may
interact with an alternatively spliced prostaglandin FP receptor
pharmacologically distinct from the well-characterized FP receptor [26].
The mechanism of action of bimatoprost is of considerable interest
because bimatoprost appears to be the most effective medication now
available for reducing IOP [4,27]. Further drug discovery may well aim to
develop drugs that take advantage of a similar mechanism of action. For
this reason it is important to consider the data from both clinical and
laboratory studies and to be open-minded in reaching reasonable
conclusions. To assume that the mechanism of action of bimatoprost is the
same as that of latanoprost and ignore or misinterpret evidence
inconsistent with that assumption is neither good science nor helpful to
clinical advancements in lowering IOP.
References
1. Cantor LB, Hoop J, Wudunn D, et al. Levels of bimatoprost acid in
the aqueous humour after bimatoprost treatment of patients with cataract.
Br J Ophthalmol 2007;91:629-32.
2. Camras CB, Toris CB, Sjoquist B, et al. Detection of the free acid
of bimatoprost in aqueous humor samples from human eyes treated with
bimatoprost before cataract surgery. Ophthalmology 2004;111:2193-8.
3. Sjöquist B, Stjernschantz J. Ocular and systemic pharmacokinetics
of latanoprost in humans. Surv Ophthalmol 2002;47(Suppl 1):S6-12.
4. Denis P, Lafuma A, Khoshnood B, et al. A meta-analysis of topical
prostaglandin analogues intra-ocular pressure lowering in glaucoma
therapy. Curr Med Res Opin 2007;23:601-8.
5. Dirks MS, Noecker RJ, Earl M, et al. A 3-month clinical trial
comparing the IOP-lowering efficacy of bimatoprost and latanoprost in
patients with normal-tension glaucoma. Adv Ther 2006;23:385-94.
6. Gandolfi SA, Cimino L. Effect of bimatoprost on patients with
primary open-angle glaucoma or ocular hypertension who are nonresponders
to latanoprost. Ophthalmology 2003;110:609-14.
7. Williams RD. Efficacy of bimatoprost in glaucoma and ocular
hypertension unresponsive to latanoprost. Adv Ther 2002;19:275-81.
8. Sharif NA, Kelly CR, Williams GW. Bimatoprost (Lumigan®) is an
agonist at the cloned human ocular FP prostaglandin receptor: real-time
FLIPR-based intracellular Ca2+ mobilization studies. Prostaglandins Leukot
Essent Fatty Acids 2003;68:27-33.
9. Sharif NA, Williams GW, Kelly CR. Bimatoprost and its free acid
are prostaglandin FP receptor agonists. Eur J Pharmacol 2001;432:211-3.
10. Kelly CR, Williams GW, Sharif NA. Real-time intracellular Ca2+
mobilization by travoprost acid, bimatoprost, unoprostone, and other
analogs via endogenous mouse, rat, and cloned human FP prostaglandin
receptors. J Pharmacol Exp Ther 2003;304:238-45.
11. Stjernschantz JW. From PGF2a-isopropyl ester to latanoprost: a
review of the development of Xalatan: the Proctor Lecture. Invest
Ophthalmol Vis Sci 2001;42:1134-45.
12. Resul B, Stjernschantz J, Selén G, et al. Structure-activity
relationships and receptor profiles of some ocular hypotensive
prostanoids. Surv Ophthalmol 1997;41(Suppl 2):S47-S52.
13. Stjernschantz J, Albert D, Hu D, et al. Mechanism and clinical
significance of prostaglandin-induced iris pigmentation. Surv Ophthalmol
2002;47(Suppl 1):S162-S175.
14. Sharif NA, Kelly CR, Crider JY. Human trabecular meshwork cell
responses induced by bimatoprost, travoprost, unoprostone, and other FP
prostaglandin receptor agonist analogues. Invest Ophthalmol Vis Sci
2003;44:715-21.
15. Sharif NA, Kelly CR, Crider JY. Agonist activity of bimatoprost,
travoprost, latanoprost, unoprostone isopropyl ester and other
prostaglandin analogs at the cloned human ciliary body FP prostaglandin
receptor. J Ocul Pharmacol Ther 2002;18:313-24.
16. Sharif NA, Kelly CR, Crider JY, et al. Ocular hypotensive FP
prostaglandin (PG) analogs: PG receptor subtype binding affinities and
selectivities, and agonist potencies at FP and other PG receptors in
cultured cells. J Ocul Pharmacol Ther 2003;19:501-15.
17. Sharif NA, Crider JY, Husain S, et al. Human ciliary muscle cell
responses to FP-class prostaglandin analogs: phosphoinositide hydrolysis,
intracellular Ca2+ mobilization and MAP kinase activation. J Ocul
Pharmacol Ther 2003;19:437-55.
18. Kelly CR, Williams GW, Sharif NA. Real-time intracellular Ca2+
mobilization by travoprost acid, bimatoprost, unoprostone, and other
analogs via endogenous mouse, rat, and cloned human FP prostaglandin
receptors. J Pharmacol Exp Ther 2003;304:238-45.
19. Brubaker RF. Mechanism of action of bimatoprost (Lumigan). Surv
Ophthalmol 2001;45(Suppl 4):S347-51.
20. Wan Z, Woodward DF, Stamer WD. Bimatoprost effects on
conventional drainage tissues. Invest Ophthalmol Vis Sci 2007;48:E-
Abstract 3919. Full manuscript in press.
21. Chen J, Senior J, Marshall K, et al. Studies using isolated
uterine and other preparations show bimatoprost and prostanoid FP agonists
have different activity profiles. Br J Pharmacol 2005;144:493-501.
22. Spada CS, Krauss AH, Woodward DF, et al. Bimatoprost and
prostaglandin F(2 alpha) selectively stimulate intracellular calcium
signaling in different cat iris sphincter cells. Exp Eye Res 2005;80:135-
45.
23. Woodward DF, Krauss AH, Wang JW, et al. Identification of an
antagonist that selectively blocks the activity of prostamides
(prostaglandin-ethanolamides) in the feline iris. Br J Pharmacol
2007;150:342-52.
24. Ota T, Aihara M, Narumiya S, et al. The effects of prostaglandin
analogues on IOP in prostanoid FP-receptor-deficient mice. Invest
Ophthalmol Vis Sci 2005;46:4159-63.
25. Crowston JG, Lindsey JD, Morris CA, et al. Effect of bimatoprost
on intraocular pressure in prostaglandin FP receptor knockout mice. Invest
Ophthalmol Vis Sci 2005;46:4571-7.
26. Liang Y, Li C, Guzman VM, Woodward DF. Identification of
alternatively spliced variants of human prostaglandin FP receptor mRNA
[Abstract 639.4]. Presented at: Experimental Biology 2005 and XXXV
International Congress of Physiological Sciences, March 31-April 6, 2005;
San Diego, CA.
27. Cantor LB, Hoop J, Morgan L, et al. Intraocular pressure-lowering
efficacy of bimatoprost 0.03% and travoprost 0.004% in patients with
glaucoma or ocular hypertension. Br J Ophthalmol 2006;90:1370-3.
We would like to thank the authors Hornby and Gilbert for their
interesting letter referring to our case report of bilateral colobomatous
microphthalmos with orbital cyst.[1] Their remarks and view are relevant
and demand further clarification.
Because our intention was to investigate more in depth the origin of
the cyst fluid and wall and because of space limitations, we were not able
to...
We would like to thank the authors Hornby and Gilbert for their
interesting letter referring to our case report of bilateral colobomatous
microphthalmos with orbital cyst.[1] Their remarks and view are relevant
and demand further clarification.
Because our intention was to investigate more in depth the origin of
the cyst fluid and wall and because of space limitations, we were not able
to provide additional data about the documented vitamin A deficiency (VAD)
during pregnancy in our histopathologic case report.[2] We will provide
these here. The mother had a history of a biliopancreatic diversion
(Scopinaro procedure) which resulted in a diminished absorption in order
to induce weight loss. However, this operation is associated with a risk
to develop nutritional deficiencies, especially of fat-soluble vitamins
(A,D,E,K), and this in up to 6 percent of cases.[3] In our case, from the
16th week of gestation onwards, the vitamin A status of the mother had
been monitored along with other nutritional parameters (Table 1).
Subsequently, she had been hospitalized for intravenous administration of
a multivitamin preparation, extra vitamin B12 and iron, together with oral
suppletion of folic acid and multivitamins. Despite such maximal repletion
there had been a documented hypovitaminosis A at least from week 16 until
the 24th week of gestation. From week 28 of gestation she had been
hospitalized for parenteral nutrition to further support her vitamin
status. The father was healthy, and no consanguinity was present. History
of any eye abnormalities in the family was negative. It is very likely
that a depletion of vitamin A during conception and the first weeks of
pregnancy was present because vitamin A has a depot within the liver, as
such preventing an acute drop in its plasma level. Futhermore plasma
vitamin A level do not decrease during pregnancy under normal physiologic
conditions. Therefore, ocular development probably occurred in the
context of a vitamin A deficiency.
Previous research done by Hornby et al. pointed out a possible link
between VAD during pregnancy and an increased incidence of microphthalmos
in newborns, in particular in cases with a genetic recessive
predisposition to the teratogenic effects of varying degrees of VAD during
pregnancy.[4] Cools et al. reported the presence of bilateral congenital
microphthalmos in two newborns in a series of nine cases of
biliopancreatic diversion–related adverse neonatal outcome.[3] In one
of them, VAD occurred during pregnancy. Excess as shortage of vitamin A
during gestation may result in an anomalous development of the organism
(e.g. teratogenicity of vitamin A analogues such as isotretinoin),
especially of the eyes.[5] Accumulating data are providing further
evidence to support a possible link between VAD and congenital
microphthalmos and consider vitamin A level as a possible nutritional risk
factor for abnormal development such as folic acid in the prevention of
neural tube defects. This may have implications in preconceptional
evaluation, especially for women with a history of bypass surgery.
Parenteral nutrition as preconceptional treatment may be sufficient to
replete vitamin and nutrient stores in these cases.
References
1. Hornby SJ, Gilbert C. Vitamin A deficiency and possible link with
colobomatous malformations. Br J Ophthalmol July 2007 eLetter
2. Decock, C. E., Breusegem, C. M., Van Aken, E. H, and Leroy, B. P.
High beta-trace protein concentration in the fluid of an orbital cyst
associated with bilateral colobomatous microphthalmos. Br.J Ophthalmol.
91(6), 836-837. 2007.
3. Cools M, Duval ELIM, Jespers A. Adverse neonatal outcome after
maternal biliopancreatic diversion operation: report of 9 cases. Eur J
Pediatr 2006;165:199-202
4. Hornby SJ, Ward SJ, Gilbert CE. Eye birth defects in humans may be
caused by a recessively-inherited genetic predisposition to the effects of
maternal vitamin A deficiency during pregnancy. Med Sci Monit.
2003;9(11):HY23-6.
5. Dickman ED, Thaller C, Smith SM. Temporally-regulated retinoic
acid depletion produces specific neural crest, ocular and nervous system
defects. Development 1997;124:3111-21.
Dear Editor,
In their article Doctors Agrawal and McKibbin evaluate the one-year frequency and the clinical outcome data of Putscher’s retinopathy through the British Ophthalmological Surveillance Unit. [1] All their 15 cases were visually symptomatic. Twelve cases were associated with trauma and 3 cases with acute pancreatitis. The authors conclude that the incidence of Purtsher’s retinopathy is low (0.24 case...
Re: van Leeuwen R, Eijkemans MJC, Vingerling JR, Hofman A, de Jong PTVM, Simonsz HJ Risk of bilateral visual impairment in individuals with amblyopia: the Rotterdam study BJO 2007;91 (11): 1450
Josefin Nilsson The negative impact of amblyopia from a population perspective: untreated amblyopia almost doubles the lifetime risk of bilateral visual impairment. BJO 2007;91 (11): 1417
Dear Editor
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Dear Editor
We read with great interest the report by Raftery et al on Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost effectiveness. The authors raise the very pertinent point in respect to a single company owning two competing drugs and the inherent cost to tax payers. The authors conclude their abstract with "Public pressure may be the most potent weapon in persuading Genentech to license bevaciz...
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We appreciated the paper by Iriyama et al.[1] The authors have investigated the role of anti vascular endothelial growth factor (VEGF) antibodies on retinal ganglion cells in rats. It is an interesting and relevant paper considering the clinical use of anti-VEGF antibodies in a variety of ocular conditions.[2] However, there are a couple of issues that require further clarification.
The author...
Dear Editor,
We read with great interest the report by Alwitry et al [1] on severe decompression retinopathy after medical treatment of acute angle closure. The authors have speculated that the mechanism of the ‘preretinal’ haemorrhage in this case was similar to the scattered ‘intraretinal’ haemorrhages seen in ocular decompression retinopathy. Although we agree with them that the haemorrhage was caused by sudd...
Dear Editor
I read with interest the article by Pedroza-Seres M and associates who assessed the pathogenic roles of peripheral CD57+ natural killer T (NKT) cell in pars planitis.[1] The authors compared the frequencies of CD57+ NKT cell in peripheral blood between pars planitis patients and healthy controls, and then evaluated the effector-related surface molecules and functions of CD57+ NKT cells derived from pa...
Dear Editor
We read with interest the article by Aisenbrey et al [1] who have described the results of surgical treatment of peripapillary choroidal neovascularisation in eight patients.
As reported, peripapillary choroidal neovascularisation is a relatively uncommon entity that can be a variant of macular choroidal neovascularisation in elderly patients. Accordingly to the MPSG[2], early small peripapilla...
Dear Editor
I commend the authors for yet another treatment for this potentially disabling and common affliction. I note that one important component of this treatment requires the mapping of the site of the erosion during an attack with this area being singled out for the localised 4-6mm of treatment. However, in most patients that I have treated over the years the area of erosion is healed by the time they seek...
Dear Editor,
We thank Dr. Camras for his interest in our report on levels of bimatoprost and its free acid in the aqueous humour of cataract patients after a single topical dose of bimatoprost [1] and welcome the opportunity to respond to his comments. We are in agreement with Dr. Camras that the results of our study [1] and those of his previously reported study [2] are similar, showing low nanomolar concentrat...
Dear Editor,
We would like to thank the authors Hornby and Gilbert for their interesting letter referring to our case report of bilateral colobomatous microphthalmos with orbital cyst.[1] Their remarks and view are relevant and demand further clarification.
Because our intention was to investigate more in depth the origin of the cyst fluid and wall and because of space limitations, we were not able to...
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