Recent eLetters
Displaying 21-30 letters out of 403 published
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Multifocal-ERG in ARMD after intravitreal use of bevacizumab
Submit responseDear Editor,
In the article entitled 'Electrophysiological effects of intravitreal Avastin (bevacizumab) in the treatment of exudative age-related macular degeneration (ARMD)' by Karanjia et al (Br J Ophthalmol 2008), the authors examine the sensitivity of multifocal-electroretinogram (mfERG) at measuring changes in retinal electrical activity in response to Avastin treatment for ARMD. In this interesting paper the authors study the changes of P1 response amplitude and support that this is the first study to demonstrate a statistically significant change in retinal electrical activity post-bevacizumab in patients with ARMD. I would like to draw attention to the authors of this article that in our prospective study 'Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary mfERG and OCT study' by Moschos MM et al (Doc Ophthalmol 2007; 114:37-44) really for the first time we evaluated the macular function before and after intravitreal use of Avastin. In our paper based on the study of 18 eyes, 1 month after treatment the retinal response density of mfERG really shows an improvement but 3 months after treatment no difference was found between baseline and 3 months.
Our results show that there are anatomical correlates to support the concept of disease amelioration 1 month after treatment. This is mainly the decrease of macular thickness as measured by OCT in an extremely significant degree (p<0.001) the first month after treatment. On the contrary the mean visual acuity improved only by 0.03 the first month after treatment and by 0.02 three months after treatment. On the contrary the mfERG improvement did not follow the decrease of macular thickness and is significant only the first month after treatment. These findings show that the increase of visual acuity, as also the improvement of electrical responses of the macular area is disproportional to the decrease of macular thickness. This may be explained by the fact that macular edema is only a parameter that may affect visual acuity and electrophysiological responses in the beginning of the disease. Atrophy of the retina, particularly of the photoreceptors, atrophy of the pigment epithelium and scarring are all unmeasured variables, which influence vision [1, 2].
References
1. Moschos M, Brouzas D, Apostolopoulos M, et al. Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study. Doc Ophtalmol 2007;114:137-144.
2. Moschos M, Panayotidis D, Theodossiadis G, et al. Assessment of macular function by electroretinography in age-related macular degeneration before and after photodynamic therapy. J Fr Ophtalmologie 2004;27:1001-1006.
Marilita M Moschos, MD, PhD Department of Ophthalmology, University of Athens, Athens, Greece
Correspondence and reprints: Moschos M. Marilita MD, PhD 144, Kountouriotou Str 185 35 Piraeus Greece Tel : ++30 6944887319 Fax: ++30 210 4122139 E-mail: moschosmarilita@yahoo.fr
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Choroidal Perfusion
Submit responseDear EditorsThis is an interesting haematological syndrome. I would question calling the occurrence simultaneous when the vision loss was symptomatically sequential. Roughly 20% of normals have areas of absent choroidal filling in the early venous phase of the retinal circulation. These areas fill suddenly as the dye arrives in a normal manner; if there is true pathological delay such as occurs with giant cell arteritis the areas tend to fill slowly and from the edges. It can not be called pathological relative choroidal perfusion delay till the retinal circulation has reached the mid venous phase as defined by the vein being half filled with fluorescence. The most common cause for a delay from injection to the early venous phase is a mild vasovagal reaction or a reduced cardiac output in a patient with atrial fibrillation. The time from injection thus cannot be used to define choroidal perfusion delay.
Yours sincerely
Paul Beaumont
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O C T : limits of the retinal-mapping program in age-related macular degeneration
Submit responseDear EditorsWe 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 EY014375References
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.
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Authors' reply
Dear EditorsWe 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.
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Authors' response
Submit responseDear 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 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. -
Is a field every 4 month a significant improvement over a field every 6 months?
Submit responseDear 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 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
Submit responseVitreous 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, IRANReferences
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 -
OCT measurement and visual function
Submit responseDear 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 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. -
Awareness on eye tumours and Down syndrome
Submit responseDear 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 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
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Author's response
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 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.
Ferdinando Bottoni ,MD
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