We read with interest the recent study by Krebs et al. demonstrating the limitations of StratusOCT mapping software in the context of age-related macular degeneration (AMD).[1] We wish to applaud the authors for their study - while the limitations of StratusOCT automated analysis have previously been reported,[2] the fact remains that many ophthalmologists may not be well acquainted with these errors. We agree wi...
We read with interest the recent study by Krebs et al. demonstrating the limitations of StratusOCT mapping software in the context of age-related macular degeneration (AMD).[1] We wish to applaud the authors for their study - while the limitations of StratusOCT automated analysis have previously been reported,[2] the fact remains that many ophthalmologists may not be well acquainted with these errors. We agree with the authors and wish to underline the importance of these errors in this era of optical coherence tomography (OCT)-guided retreatment regimens for anti-angiogenic agents and increasing adoption of quantitative OCT measurements as secondary outcome parameters in clinical trials.[3]
In their study, the authors present evidence that automated Stratus software provides correct results in only 57.1% of eyes with AMD.[1] These results are consistent with previous reports and in line with clinical experience.[2] As mentioned in the discussion, manual placement of boundaries on OCT scans may represent a solution to this problem. We wish to thank the authors for mentioning our custom OCT grading software termed “OCTOR” as one possible software tool to perform this kind of analysis. The authors comment that "this software is not commercially available or supported by the StratusOCT". However, OCTOR was designed specifically with StratusOCT in mind and readily handles raw exported StratusOCT images. OCTOR is publicly available and can be downloaded from www.diesel.la. This software facilitates manual segmentation of OCT images and allows quantitative analysis of any area of interest in these images e.g. retina, subretinal fluid, subretinal tissue, or pigment epithelium detachment.[4] Furthermore, the most recent version of the Stratus OCT software (version 5.0) enables users to manually correct errant boundaries.
In their discussion, the authors comment that "manually set boundary lines would add subjectivity to the retinal thickness measurements". Recent research demonstrating both the accuracy and reproducibility of manual grading with OCTOR software in the setting of neovascular AMD suggests that manual grading does not necessarily add subjectivity to retinal thickness measurements.[5] Instead, manually corrected boundaries allow for more reliable data than the frequently erroneous automated boundary detection of the StratusOCT software. We recently used the manual grading software OCTOR to quantify the volumes of the neurosensory retina, subretinal fluid, subretinal tissue, and pigment epithelial detachments. Intergrader comparisons showed a high level of agreement and a strong correlation between measurements for all spaces (weighted Kappa= 0.72-0.97; ICC = 0.92-0.99). Although these values were obtained by graders who had undergone a formal certification program in our reading center, in our experience OCT grading can be learned both more quickly, and more easily, than grading of fluorescein angiography. This hypothesis is supported by the level of agreement between measurements in our study which was appreciably better than that which has been reported elsewhere for fluorescein angiography.[6]
Although significant progress is being made, the complex morphology of neovascular AMD presents a challenge to the development of automated OCT interpretation software. As automated segmentation algorithms improve, it will be necessary to assess their efficacy in a quantitative manner against a 'gold standard'. We believe that the accuracy of manual segmentation by trained human graders is such that it could serve as a 'gold standard' against which to compare the results of automated analysis.
In conclusion, we wish to commend the authors for highlighting this area, which is likely to be of critical importance as the next generation of OCT technology is incorporated into the diagnosis and management of neovascular AMD.
LICENCE FOR PUBLICATION:
The Corresponding Author has the right to grant on behalf of all authors, and does grant on behalf of all authors, an exclusive licence on a worldwide basis to the BMJ Publishing Group Ltd to permit this article (if accepted) to be published in BJO and any other BMJPGL products and sublicences such use and exploit all subsidiary rights, as set out in our licence (http://bjo.bmj.com/ifora/licence.pdf).
COMPETING INTERESTS:
Drs. Walsh and Sadda are co-inventors of Doheny intellectual property related to spectral domain optical coherence tomography that has been licensed by Topcon Medical Systems.
FUNDING:
Supported in part by NIH Grant EY03040 and NEI Grant R01 EY014375
References
1. Krebs I, Haas P, Zeiler F, Binder S. Optical coherence tomography: limits of the retinal-mapping program in age-related macular degeneration. Br J Ophthalmol 2008;92:933-5.
2. Sadda SR, Wu Z, Walsh AC, et al. Errors in retinal thickness measurements obtained by optical coherence tomography. Ophthalmology 2006;113:285-93.
3. Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol 2007;143:566-83.
4. Sadda SR, Joeres S, Wu Z, et al. Error correction and quantitative subanalysis of optical coherence tomography data using computer-assisted grading. Invest Ophthalmol Vis Sci 2007;48:839-48.
5. Joeres S, Tsong JW, Updike PG, et al. Reproducibility of quantitative optical coherence tomography subanalysis in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci 2007;48:4300-7.
6. Holz FG, Jorzik J, Schutt F, et al. Agreement among ophthalmologists in evaluating fluorescein angiograms in patients with neovascular age-related macular degeneration for photodynamic therapy eligibility (FLAP-study). Ophthalmology 2003;110:400-5.
We appreciate Dr. Kadyan’s letter regarding our study “Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ)” [1]. He requests clarification on several issues and, to the best of our ability we will attempt to respond to each in turn.
Regarding the proportion of cases and controls diagnosed with glauco...
We appreciate Dr. Kadyan’s letter regarding our study “Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ)” [1]. He requests clarification on several issues and, to the best of our ability we will attempt to respond to each in turn.
Regarding the proportion of cases and controls diagnosed with glaucoma, this information appears in Table 1 of the published manuscript.
Regarding exclusion criteria for the control group, as stated in the published manuscript the controls were randomly selected from patients seen in the Department of Ophthalmology clinic for reasons other than NAION; there were no other exclusionary criteria. With respect to the other ocular diagnoses of the control group, we did not collect this information. We also do not have information on the results of any sleep studies the study participants may have obtained.
Finally, regarding which of the specific sleep apnea syndrome symptoms in the SA-SDQ were associated with NAION, it appears that the cases reported more frequent loud snoring (or bothering others), having nose block up when wanting to sleep, and snoring/breathing getting worse when sleeping on the back compared to controls. There were no statistically significant differences for the other SAS specific items nor for any of the non-SAS items (e.g., body mass index, smoking status). Furthering these analyses to create a weighted score is an interesting idea and something we may consider pursuing in the future.
Regards,
Gerald McGwin, Jr., M.S., Ph.D.
Cynthia Owsley, Ph.D., M.S.P.H.
Departments of Epidemiology and Ophthalmology
University of Alabama at Birmingham
Birmingham, Alabama
References
1. Li J, McGwin G, Vaphiades, Owsley C. Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ). Br J Ophthalmol. 2007;91:1524-7.
We thank Dr Munier and Dr Satgé for their interest in our work on
“Aggressive metastasising adenocarcinoma of the retinal pigment epithelium
with trisomy 21” [1] and welcome the opportunity to respond to their
comments.
We are in agreement with Dr Munier and Dr Satgé that life-threatening
ophthalmic tumours must be kept in mind while taking care of patients with
Down syndrome. Despite an imp...
We thank Dr Munier and Dr Satgé for their interest in our work on
“Aggressive metastasising adenocarcinoma of the retinal pigment epithelium
with trisomy 21” [1] and welcome the opportunity to respond to their
comments.
We are in agreement with Dr Munier and Dr Satgé that life-threatening
ophthalmic tumours must be kept in mind while taking care of patients with
Down syndrome. Despite an important progress in life expectancy, solid
tumours of the eye and ocular adnexa remain very rare in these patients
[2].
In our case report we describe a 37-year-old man with trisomy 21 who
presented with a longstanding blind eye with opaque media. Histopathology
revealed an aggressive adenocarcinoma of the retinal pigment epithelium
(RPE) with marked invasion of the choroid, retina, sclera, orbital and
cranial optic nerve and subarachnoid space. The tumour seeded into the
lumbar spinal-cord space, and metastatic foci developed in the parietal
lobe and cerebellopontine angle [1].
However, the aggressive behaviour of this tumour is clearly atypical
for the usual tumour reported as RPE adenocarcinoma in the literature. The
fact that aggressive tumor extension and metastasis occur in a middle-aged
patient with trisomy 21 is quite remarkable.
Although the most frequent malignant intraocular tumor in blind eyes
with opaque media is choroidal melanoma [3], other malignancies with
invasive features and metastatic potential, such as adenocarcinoma of the
RPE, must be considered in the clinical management, even in patients with
Down syndrome.
References
1. Heindl LM, Naumann GOH, Kruse FE, Holbach LM. Aggressive metastasising
adenocarcinoma of the retinal pigment epithelium with trisomy 21. Br J
Ophthalmol 2008;92:389-91.
2. Satgé D, Lacombe D, Vekemans M, Bonnet A, Réthoré MO, Munier F. A
survey of ocular tumors in Down syndrome alone or associated with another
genetic affection. Int J Disabil Human Dev 2006;5:311-7.
3. De Gottrau P, Holbach LM, Naumann GOH. Clinicopathological review of
1146 enucleations (1980-90). Br J Ophthalmol 1994;78:260-5.
How often should we do visual fields in the first 2 years? Chauhan
and co-workers [1] recommend 3 visual fields per year. It will have an 80%
power of detecting a rate of loss of 2 dB/year in an eye with moderate
variability. Is this a significant improvement over 2 fields per year? In
order to answer that we should look at the efficacy of increasing the
frequency of field examinations versus prolongin...
How often should we do visual fields in the first 2 years? Chauhan
and co-workers [1] recommend 3 visual fields per year. It will have an 80%
power of detecting a rate of loss of 2 dB/year in an eye with moderate
variability. Is this a significant improvement over 2 fields per year? In
order to answer that we should look at the efficacy of increasing the
frequency of field examinations versus prolonging the duration of the
follow-up. From regression theory it is clear that the ability to detect a
statistically significant slope is determined by the variability of
measurement (MD), the number of observations/examinations and the span
along the X-axis (duration of follow-up). Furthermore, increasing the
duration is much more efficient than increasing the frequency of
examinations. Thus, 5 examinations in 1.7 years will not be able to detect
the same slope as 5 examinations in 5 years! The total amount of change
(rate * duration) will be much lower, and, as pointed out by the authors,
the amount of change affects power. Planning of a longitudinal study is a
useful parallel. Extensive tables, based on regression theory, on the
effect of number of examinations and duration of the study on the
precision of the estimate of the linear regression line have been
published.[2]From these tables it can be seen that five measurements,
evenly spread over 27 months, have the same power to detect a
statistically significant slope as seven measurements over 24 months. Thus
a visual field every 6 month’ the first two years would seem to be an
optimal frequency, if the goal is to determine if the slope of the
regression line is statistically significant or not.
References
[1] Chauhan BC, Garway-Heath DF, Goñi FJ, Rossetti L, Bengtsson B,
Viswanathan AC, and Heijl A. Practical recommendations for measuring rates
of visual field change in glaucoma. Br J Ophthalmol. 2008;92:569-73.
[2] Schlesselman JJ. Planning a longitudinal study: II. Frequency of
measurement and study duration. J Chron Dis. 1973;26:561-570.
Vitreous buffering capacity as a mechanism for silicone oil optic neuropathy
Dear editors
I read with interest the article concerning silicone oil optic
neuropathy
by Knecht et al in October issue of BJO. In that article they
suggest
an active transport of silicone oil into the optic nerve as a mechanism
for optic neuropathy. [1] I would like to suggest a new mechanism based
on buffering capacity...
Vitreous buffering capacity as a mechanism for silicone oil optic neuropathy
Dear editors
I read with interest the article concerning silicone oil optic
neuropathy
by Knecht et al in October issue of BJO. In that article they
suggest
an active transport of silicone oil into the optic nerve as a mechanism
for optic neuropathy. [1] I would like to suggest a new mechanism based
on buffering capacity of normal vitreous as a cause of silicone oil
optic neuropathy.
Conway et al demonstrated buffering capacity for bovine vitreous, when
it was incubated with 5%CO2 -95% air mixture. [2]
Buffering capacity of vitreous is largely dependent on bicarbonate-
CO2 system. This system is the most important buffer in the
extracellular fluid. [3] If we consider vitreous as like as the plasma
regarding its
CO2 content, we will need 5%CO2 over the vitreous to demonstrate vitreous
buffering effect. (5%*760mm Hg=38mm Hg so closed to normal 40mmHg P CO2 of
plasma)
Water in vitreous cavity may have buffering capacity comparable to
vitreous itself. Remember that 99% of normal vitreous is water.In the
presence of carbonic anhydrase as the catalyst and 40 mmHg of P CO2 in
nearby blood and interstitial tissue, which is in dynamic equilibrium
with this water, this buffering capacity is expected either for normal
vitreous or balanced salt solution.
Buffering capacity is also dependent on volume of buffer, so with
replacement of water content of vitreous with silicone oil the buffering
capacity might be decreased significantly or even lost.
Retinal nerve fiber in contact with a fluid which doesn't support PH
homeostasis will be at risk for more degeneration, and silicone oil-associated optic nerve degeneration could occur. [4]
Mehdizadeh M MD
Shiraz University of Medical Sciences
Shiraz, IRAN
References
1. Knecht P, Groscurth P, Ziegler U,et al. Is silicone oil optic
neuropathy caused by high intraocular pressure alone? A semi-biological
model.Br J Ophthalmol. 2007;91:1293-5
2. Conway M D,Jermak CM,Peyman GA
et al.Buffering capacity of bovine vitreous. Retina 2008;28: 150-153
3.
Berne R M Levy M N :Principles of physiology.St Louis C.V.Mosby
1990:470
4. Budde M, Cursiefen C, Holbach LM, et al. Silicone
oil-associated optic nerve degeneration. Am J Ophthalmol 2001; 131:
392-4
We read with interest the study from Moutray et al[1] that found
Optical Coherence Tomography (OCT) measures are not robust markers for
visual function. We have looked at 20 patients with wet age related
macular degeneration (AMD) and compared visual function and OCT measures
using the new generation of Fourier Domain 3D OCT. We also find no
significant correlation between OCT measurements of central...
We read with interest the study from Moutray et al[1] that found
Optical Coherence Tomography (OCT) measures are not robust markers for
visual function. We have looked at 20 patients with wet age related
macular degeneration (AMD) and compared visual function and OCT measures
using the new generation of Fourier Domain 3D OCT. We also find no
significant correlation between OCT measurements of central foveal
thickness, maximum retinal thickness and distance LogMar acuity, near
vision and contrast sensitivity. We believe that this data is relevant to
the use of ranibizumab in the UK.
The licence for the use of ranibizumab (Lucentis) in the UK is for a
loading phase of one injection per month for three consecutive months,
followed by a maintenance phase in which patients should be monitored for
visual acuity every month. If the patient experiences a loss of greater
than 5 letters in visual acuity (EDTRS) or one Snellen line equivalent,
ranibizumab should be administered.
The PrONTO[2] study however, used visual and OCT criteria to make
retreatment decisions. Retreatment was carried out if there was a loss of
5 letters in conjunction with fluid in the macula as detected by OCT, or
an increase in OCT central retinal thickness of at least 100 microns along
with other non- OCT guided criteria. More than a quarter of the study
participants did not lose 5 letters of vision but had an increase in OCT
central retinal thickness of at least 100 microns. Results from this study
still showed a comparable proportion of patients (35% vs 33%) gaining 15
letters or more compared to the MARINA[3] trial where monthly dosing was
carried out regardless of vision or OCT findings.
These studies suggest that visual function alone does not relate to
the presence or absence of intraretinal and/or subretinal fluid in a
significant proportion of patients which may signify the recurrence of the
CNV. We therefore believe that Moutray et al’s study adds weight to the
argument that visual function and OCT measurements should jointly be
considered as criteria for retreatment with ranibizumab in order to
maintain the level of vision achieved after the loading phase.
References
1. Moutray T, Alarbi M, Mahon G, et al. Relationships between clinical
measures of visual function, fluorescein angiographic and optical
coherence tomography features in patients with subfoveal choroidal
neovascularisation. British Journal of Ophthalmology 2008;92(3):361-364.
2. Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence
tomography-guided, variable dosing regimen with intravitreal ranibizumab
(Lucentis) for neovascular age-related macular degeneration. American
Journal of Ophthalmology 2007;143(4):566-583.
3. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. New England Journal of Medicine
2006;355(14):1419-1431.
A metastizing adenocarcinoma of the retinal pigment epithelium in a 37-year-old man with Down syndrome (DS) has recently been reported in the
British Journal of Ophthalmology [1]. In the article the authors underlined
an unusual and atypical aggressive behaviour of the tumour which was the
first well documented adenocarcinoma of the retinal pigment epithelium
with metastases. Although solid tumours are...
A metastizing adenocarcinoma of the retinal pigment epithelium in a 37-year-old man with Down syndrome (DS) has recently been reported in the
British Journal of Ophthalmology [1]. In the article the authors underlined
an unusual and atypical aggressive behaviour of the tumour which was the
first well documented adenocarcinoma of the retinal pigment epithelium
with metastases. Although solid tumours are globally less frequent in
persons with DS than in the general population [2] this does not seem to
apply to ocular neoplasms. Including Heindl's et al report 30 cases of
primary or secondary malignant tumours of the eye and orbit have been
reported so far, two thirds being retinoblastoma [3]. Unfortunately, but
interestingly, some neoplasms in patients with DS may have a rapid
progression as observed in a low grade glioma [4]. The reason for this
unfavourable course in some patients remains unknown. Nonetheless, as
ocular malignant neoplasm could be more frequent in children and adults
with DS, and since some of these tumours may have an unexpected aggressive
behaviour, we want to attract attention on them to allow a precocious
diagnosis and early treatment.
The study on tumors in DS is supported by the Fondation Jérôme
Lejeune.
References
1. Heindl LM, Naumann GO, Kruse FE, Holbach LM. Aggressive
metastasising adenocarcinoma of the retinal pigment epithelium with
trisomy 21. Br J Ophthalmol. 2008;92:389-91
2. Patja K, Pukkala E, Sund R, Iivanainen M, Kaski M. Cancer
incidence of persons with Down syndrome in Finland: a population-based
study. Int J Cancer. 2006;118:1769-72
3. Satgé D, Lacombe D, Vekemans M, Bonnet A, Réthoré M-O, Munier F. A
survey of ocular tumors in Down syndrome alone or associated with another
genetic affection. Int J Disabil Human Dev 2006;5:311-7
4. Satgé D, Monteil P, Sasco AJ, Vital A, Ohgaki H, Geneix A, Malet
P, Vekemans M, Réthoré MO. Aspects of intracranial and spinal tumors in
patients with Down syndrome and report of a rapidly progressing Grade 2
astrocytoma. Cancer. 2001;91:1458-66
We thank Dr Ayata for the thoughtful comments of our article. He
had three questions that we would like to answer as follows:
1) Figure 1 was quite important for the paper because it shows the
exact
location of the macular pigment in monkeys (courtesy of Francois Delori,
PhD). We are sorry for the lack of the image in the on-line paper
version but it was probably due to the PDF saving...
We thank Dr Ayata for the thoughtful comments of our article. He
had three questions that we would like to answer as follows:
1) Figure 1 was quite important for the paper because it shows the
exact
location of the macular pigment in monkeys (courtesy of Francois Delori,
PhD). We are sorry for the lack of the image in the on-line paper
version but it was probably due to the PDF saving process.
2) We do not think there is any inconsistency between results and
conclusion because that was exactly what we expected. If a pseudohole is
a macular lesion where there is no loss of foveal tissue, the presence
of foveal AF indicates the absence of macular pigment in the fovea.
Being the pigment located in the outer plexiform layer and outer nuclear
layer in the fovea (fig 1), that means we were dealing with lamellar
rather than pseudo macular holes. Our paper just underlined the finding
that OCT alone is inadequate to differentiate pseudo from lamellar
holes. As to this respect AF imaging may be useful because reveals a
loss of foveal tissue.
3) We are aware of the different aspects of AF-imaging after dark
and
light adaptation. As Dr Ayata properly pointed out, the visible changes
in AF imaging in light and dark adapted eyes are minimal in the fovea
and the lack of macular pigment in lamellar macular hole is in the
fovea. The AF ratio was used to correlate AF intensities with residual
retinal thickness at the bottom of the defect. The reason why we did not
use raw images for AF quantitative measurements was related to the great
difficulties in visualizing foveal defect in non normalized images. The
ratio could have affected the results of these correlations but not the
presence of foveal AF itself.
We thank again Dr Ayata for his interest in our article.
Epigenetic regulation of tumor suppressor genes provides an
attractive mechanism for tumors in which mutations and structural changes
are rare. The latter may apply to uveal melanoma for which little is known
of the genes that contribute to tumor development. In the search for
genes, uveal melanoma is often compared to its counterpart in the skin,
cutaneous melanoma. One of the major cuteneous melan...
Epigenetic regulation of tumor suppressor genes provides an
attractive mechanism for tumors in which mutations and structural changes
are rare. The latter may apply to uveal melanoma for which little is known
of the genes that contribute to tumor development. In the search for
genes, uveal melanoma is often compared to its counterpart in the skin,
cutaneous melanoma. One of the major cuteneous melanoma genes is the p16
encoding CDKN2A gene for which mutations and deletions are the major
mechanisms of inactivation. Deletions and mutations in CDKN2A are however
rare in uveal melanoma; still p16 expression is lacking in half of the
cell lines[1]. Using methylation analysis and methylation inhibition in cell
culture, we have shown that the underlying mechanism of loss of p16
expression in these cell lines is methylation of CDKN2A. This observation
is not disputed but controversy arises when primary tumors are analyzed
and estimates are given for the extend of CDKN2A methylation in uveal
melanoma[2,3]. The study by Moulin et al is an example of a study that
displays some remarkable deviations from results we and others have
achieved previously[4,5]. We would like to comment on some of the technical
and biological factors that may contribute to the lack of consistency in
the results that are achieved in the field of uveal melanoma epigenetics.
The molecular mechanism of epigenetic gene regulation is complex and
characterized by multiple molecular events that are functionally
connected. Hence, the analysis of only one of these events will never be
sufficient to fully explain the downregulation of tumor suppressor genes.
Whereas tumor cell lines probably present the endpoint of epigenetic
silencing and commonly display a homogeneous methylation profile, primary
tumors in contrast frequently present a more heterogeneous pattern of
methylation. We presume that this heterogeneity is correlated with the
progress of epigenetic silencing. On the one hand it is possible that
only a fraction of the tumor cells carries methylated tumor suppressor
genes, on the other hand the degree of CpG methylation may vary over a
broad range, depending on the advance of the epigenetic silencing. Despite
this heterogeneity, methylation can be used as molecular marker and may
have an important role in the pathogenesis of uveal melanoma.
The heterogeneity of the methylation requires sensitive techniques to
reveal this methylation in primary tumors. With the advent of bisulfite
modification of DNA, the analysis of methylation has increased enormously.
Most commonly applied techniques are the methylation-specific PCR (MSP)
and bisulfite sequence analysis. MSP is a technique with a high
sensitivity that is based on PCR primers that are specific for methylated
and unmethylated DNA. A drawback of this method is the false positive rate
due to illegitimate polymerization of methylation-specific primers that
are hybridized to unmethylated DNA which is a common event due to the
error rate of the polymerase. Therefore, we propose that MSP requires
validation by an additional technique. Initially we have used restriction
enzyme analysis for validation of internal CpG’s [1]. Recently, we turned to
melting temperature analysis of bisulfite PCR reactions that amplify both
methylated and unmethylated DNA. Analysis of these PCR reactions provides
insight into the degree of methylation and the quantity of methylated and
unmethylated fractions in tumor tissue[6]. Reanalysis of primary uveal
melanoma with melting point analysis for CDKN2A (previously analyzed with
MSP) indicated that the methylated fraction rarely exceeded 10% of the
tumor DNA (unpublished). Because of this low percentage, most of the
tumors will not test positive with the assay used by Moulin et al.
Loss of p16 expression is observed in many tumors and marks a
critical event in tumor development. Epigenetic silencing of the CDKN2A
gene (or any other tumor suppressor gene of interest) in uveal melanoma
should therefore be recognized even if it is only present in a minority of
cells as it may represent the malignant component of the tumor.
References
1. van der Velden,P.A. et al. Promoter Hypermethylation: A Common
Cause of Reduced p16(INK4a) Expression in Uveal Melanoma. Cancer Res 61,
5303-5306 (2001).
2. Lamperska,K. et al. Expression of p16 in sporadic primary uveal
melanoma. Acta Biochim. Pol. 49, 377-385 (2002).
3. Edmunds,S.C., Kelsell,D.P., Hungerford,J.L. & Cree,I.A.
Mutational analysis of selected genes in the TGFbeta, Wnt, pRb, and p53
pathways in primary uveal melanoma. Invest Ophthalmol. Vis. Sci. 43, 2845-
2851 (2002).
4. Merhavi,E. et al. Promoter methylation status of multiple genes
in uveal melanoma. Invest Ophthalmol. Vis. Sci. 48, 4403-4406 (2007).
5. Moulin,A.P., Clement,G., Bosman,F.T., Zografos,L. &
Benhattar,J. Methylation of CpG island promoters in uveal melanoma. Br. J.
Ophthalmol. 92, 281-285 (2008).
6. Maat,W. et al. Epigenetic Inactivation of RASSF1a in Uveal
Melanoma. Invest Ophthalmol. Vis. Sci. 48, 486-490 (2007).
Thank you for your comments. Two cases with the exfoliation syndrome
and one with pigmentary glaucoma were included in our study. As you
mentioned, dilatation of the pupil often causes a rise of intraocular
pressure in such cases. However, none of the three individuals in our
study had a significant rise of intraocular pressure or progression of
glaucoma.
Sincerely,
George Sp...
Thank you for your comments. Two cases with the exfoliation syndrome
and one with pigmentary glaucoma were included in our study. As you
mentioned, dilatation of the pupil often causes a rise of intraocular
pressure in such cases. However, none of the three individuals in our
study had a significant rise of intraocular pressure or progression of
glaucoma.
Sincerely,
George Spaeth M.D.
We read with interest the recent study by Krebs et al. demonstrating the limitations of StratusOCT mapping software in the context of age-related macular degeneration (AMD).[1] We wish to applaud the authors for their study - while the limitations of StratusOCT automated analysis have previously been reported,[2] the fact remains that many ophthalmologists may not be well acquainted with these errors. We agree wi...
We appreciate Dr. Kadyan’s letter regarding our study “Non-arteritic anterior ischaemic optic neuropathy and presumed sleep apnoea syndrome screened by the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ)” [1]. He requests clarification on several issues and, to the best of our ability we will attempt to respond to each in turn. Regarding the proportion of cases and controls diagnosed with glauco...
Dear Editors
We thank Dr Munier and Dr Satgé for their interest in our work on “Aggressive metastasising adenocarcinoma of the retinal pigment epithelium with trisomy 21” [1] and welcome the opportunity to respond to their comments.
We are in agreement with Dr Munier and Dr Satgé that life-threatening ophthalmic tumours must be kept in mind while taking care of patients with Down syndrome. Despite an imp...
Dear Editors
How often should we do visual fields in the first 2 years? Chauhan and co-workers [1] recommend 3 visual fields per year. It will have an 80% power of detecting a rate of loss of 2 dB/year in an eye with moderate variability. Is this a significant improvement over 2 fields per year? In order to answer that we should look at the efficacy of increasing the frequency of field examinations versus prolongin...
Vitreous buffering capacity as a mechanism for silicone oil optic neuropathy
Dear editors
I read with interest the article concerning silicone oil optic neuropathy by Knecht et al in October issue of BJO. In that article they suggest an active transport of silicone oil into the optic nerve as a mechanism for optic neuropathy. [1] I would like to suggest a new mechanism based on buffering capacity...
Dear Editors
We read with interest the study from Moutray et al[1] that found Optical Coherence Tomography (OCT) measures are not robust markers for visual function. We have looked at 20 patients with wet age related macular degeneration (AMD) and compared visual function and OCT measures using the new generation of Fourier Domain 3D OCT. We also find no significant correlation between OCT measurements of central...
Dear Editor
A metastizing adenocarcinoma of the retinal pigment epithelium in a 37-year-old man with Down syndrome (DS) has recently been reported in the British Journal of Ophthalmology [1]. In the article the authors underlined an unusual and atypical aggressive behaviour of the tumour which was the first well documented adenocarcinoma of the retinal pigment epithelium with metastases. Although solid tumours are...
Dear Editor
We thank Dr Ayata for the thoughtful comments of our article. He had three questions that we would like to answer as follows:
1) Figure 1 was quite important for the paper because it shows the exact location of the macular pigment in monkeys (courtesy of Francois Delori, PhD). We are sorry for the lack of the image in the on-line paper version but it was probably due to the PDF saving...
Dear editor,
Epigenetic regulation of tumor suppressor genes provides an attractive mechanism for tumors in which mutations and structural changes are rare. The latter may apply to uveal melanoma for which little is known of the genes that contribute to tumor development. In the search for genes, uveal melanoma is often compared to its counterpart in the skin, cutaneous melanoma. One of the major cuteneous melan...
Dear Dr Radcliffe and colleagues,
Thank you for your comments. Two cases with the exfoliation syndrome and one with pigmentary glaucoma were included in our study. As you mentioned, dilatation of the pupil often causes a rise of intraocular pressure in such cases. However, none of the three individuals in our study had a significant rise of intraocular pressure or progression of glaucoma. Sincerely, George Sp...
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