We read with interest the report by Espina et al(1) regarding changes
occurring in outer retinal tubulation (ORT) during the course of
intravitreal anti-VEGF treatment.(2) These authors retrospectively
describe ORT changes observed during and after anti-VEGF treatment and
correlated these changes to disease activity or presence of retinal fluid
in 31 patients with neovascular age-related macular degeneration (AMD)
with...
We read with interest the report by Espina et al(1) regarding changes
occurring in outer retinal tubulation (ORT) during the course of
intravitreal anti-VEGF treatment.(2) These authors retrospectively
describe ORT changes observed during and after anti-VEGF treatment and
correlated these changes to disease activity or presence of retinal fluid
in 31 patients with neovascular age-related macular degeneration (AMD)
with a median follow-up time of 11 months.(1) They noted ORT changes in 10
of 33 eyes with ORT detected at baseline and subsequent anti-VEGF
treatment suggesting that some ORT contain vascular elements.(1) We
address the latter issue here.
We recently showed (2, 3) histology and electron microscopy from 77
ORT cross-sections identified in 53 human donor eyes (40 exudative AMD and
13 geographic atrophy), and compared to spectral domain optical coherence
tomography (SD-OCT) scans from 43 eyes with ORT from 34 patients.
Additionally, we published a direct clinicopathologic correlation of ORT
in one patient.(3) ORT is a gliotic formation of Muller cells and
surviving photoreceptors, almost all cones, located in the outer nuclear
layer.(2, 4) Cone photoreceptors degenerate by losing their outer
segments, followed by inner segment retraction, with only the external
limiting membrane formed by Muller cells left at the end-stage.(5) Thus,
ORT undergo a natural evolution independent of anti-VEGF treatment,
because our sample did not contain treated eyes, and we did not observe
any vascular elements within these ORTs.
Others have reached similar conclusions about the ongoing
degeneration of ORT as a natural progression of AMD, not secondary to anti
-VEGF treatment,(6) and despite treatment with optimal visual outcomes,
the prevalence of ORT has increased.(7)
To determine ORT dynamics longitudinally, a metric for measuring ORT
changes, including size, shape, and eccentricity, in multiple closely
spaced SD-OCT scans will be necessary. On the basis of extensive
histology, ORT represents a distinctive process of neurodegeneration,
observable in living patients, with a widely available imaging technology.
References
1. Espina M, et al. (2015) Outer retinal tubulations response to anti-VEGF
treatment. The British journal of ophthalmology.
2. Schaal KB, et al. (2015) Outer retinal tubulation in advanced age-
related macular degeneration: Optical coherence tomographic findings
correspond to histology. Retina 35(7):1339-1350.
3. Litts KM, et al. (2015) Clinicopathological correlation of outer
retinal tubulation in age-related macular degeneration. JAMA ophthalmology
133(5):609-612.
4. Curcio CA, Medeiros NE, & Millican CL (1996) Photoreceptor loss in
age-related macular degeneration. Investigative ophthalmology & visual
science 37(7):1236-1249.
5. Litts KM, Messinger JD, Freund KB, Zhang Y, & Curcio CA (2015)
Inner segment remodeling and mitochondrial translocation in cone
photoreceptors in age-related macular degeneration with outer retinal
tubulation. Investigative ophthalmology & visual science 56(4):2243-
2253.
6. Gildener-Leapman JR, Srivistava S, Ehlers JP, & Kaiser PK (2015)
Prevalence of outer retinal tubulation after anti-VEGF therapy for age-
related macular degeneration. Ophthalmic surgery, lasers & imaging
retina 46(3):345-348.
7. Dirani A, Gianniou C, Marchionno L, Decugis D, & Mantel I (2015)
Incidence of outer retinal tubulation in ranibizumab-treated age-related
macular degeneration. Retina 35(6):1166-1172.
Dear Editor,
After reading the article entitled "Ranibizumab 0,5 Treat-and-Extend
regimen for diabetic macular oedema: the RETAIN study" by Prunte et al
(1), there are several considerations that we would like to bring to your
attention.
From the data provided, we noticed how 48.3% of patients in the "pro re
nata" (PRN) regime required <=9 injections over a two-year period. On
the other hand, this condition in "treat...
Dear Editor,
After reading the article entitled "Ranibizumab 0,5 Treat-and-Extend
regimen for diabetic macular oedema: the RETAIN study" by Prunte et al
(1), there are several considerations that we would like to bring to your
attention.
From the data provided, we noticed how 48.3% of patients in the "pro re
nata" (PRN) regime required <=9 injections over a two-year period. On
the other hand, this condition in "treat-and-extend" (T&E) groups only
occurs in 9.92% of the cases (with/without laser, 11.12%/8.74%
respectively).
Referencing another trial for diabetic macular oedema (DMO) with anti-VEGF
therapy, DRCR.net Protocol T (2), 56.36% of the patients received
bilateral treatment. Based on the number of medical visits, total costs
and potential overexposure (there is a growing concern about adverse
events (3)), bilateral treatment brings a correction factor worth to be
considered.
Regarding medical visits, any other monitoring regimen different from
monthly medical visit during the course of two years would clearly alter
this analysis. For instance, the recommendation issued by The Royal
College of Ophthalmology (4): If the patient is stabilized, in year 2
onwards, period between follow up appointments may be increased gradually,
ultimately to a maximum of 12-16 weeks.
The prospect of a better outcome offered by the T&E (vs PRN) in macular
degeneration is where its main strength lies (5). However after reviewing
the DMO results, we believe that the proposed intervention in real
medicine would only make sense after providing enough context to make the
patient fully aware of his options. Otherwise we would be assuming that an
intravitreal injection would be chosen over multiple visits to the
ophthalmologist, which is unlikely.
Clinical caseloads is a major challenge, but should not be addressed by a
strategy that requires the patient to undergo invasive treatments more
often than might be necessary.
References
1. Prunte C, Fajnkuchen F, Mahmood S, et al. Ranibizumab 0.5 mg treat
-and-extend regimen for diabetic macular oedema: the RETAIN study. Br J
Ophthalmol Published Online First: 17 October 2015. doi:
10.1136/bjophthalmol-2015-307249
2. The Diabetes Retinopathy Clinical Research Network. Aflibercept,
bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med
2015;372:1193-203. doi: 10.1056/NEJMoa1414264
3. Avery RL, Gordon GM. Systemic Safety of Prolonged Monthly Anti-Vascular
Endothelial Growth Factor Therapy for Diabetic Macular Edema: A Systematic
Review and Meta-analysis. JAMA Ophthalmol Published online first; 29
October 2015. doi:10.1001/jamaophthalmol.2015.4070
4. Royal College of Ophthalmologists. Diabetic Retinopathy Guidelines,
2013. https://www.rcophth.ac.uk/wp-content/uploads/2014/12/2013-SCI-301-
FINAL-DR-GUIDELINES-DEC-2012-updated-July-2013.pdf (accesed 24 October
2015)
5. Chin-Yee D, Eck T, Fowler S, et al. A systematic review of as needed
versus treat and extend ranibizumab or bevacizumab treatment regimens for
neovascular age-related macular degeneration. Br J Ophthalmol Published
Online First: 29 October 2015. doi:10.1136/bjophthalmol-2015-306987
We would like to thank Craig et al for their interest in our article.[1] TILDA was designed to provide accurate and reliable information regarding ageing in the Republic of Ireland in order to inform policy. Ophthalmic assessment, which included retinal photography, was a small component of the broader TILDA study.
1. We agree with Craig et al that mydriatic photography is preferable, when attempting to identify and grade age-rel...
We would like to thank Craig et al for their interest in our article.[1] TILDA was designed to provide accurate and reliable information regarding ageing in the Republic of Ireland in order to inform policy. Ophthalmic assessment, which included retinal photography, was a small component of the broader TILDA study.
1. We agree with Craig et al that mydriatic photography is preferable, when attempting to identify and grade age-related macular degeneration (AMD) in epidemiological studies. Unfortunately, this is not always feasible.
2. We believe, however, that the observed 2.2% prevalence of late AMD (in our sample) in the 75 years and over age-group, alluded to by Craig et al, is not attributable to our photographic technique. To illustrate our contention in this regard, we have done some example calculations (below), making diverse assumptions about prevalence among the participants whom we were unable to grade, thereby simulating several possible scenarios. Indeed, our own belief is that non-response bias, a feature of most social surveys, may be an important contributing factor, if indeed prevalence is under-estimated in our study. TILDA participants had the option of either a home-based or health centre assessment, and only the latter group were graded for AMD. Participants who opted for home-based assessment were more likely to be older, rate their health as poor, walk more slowly, more likely to self-report a disability than those who opted for health centre assessment.[2] Thus, the TILDA sample for our study was a relatively younger and healthier cohort, and the low prevalence of late AMD, which we reported, may reflect this. The high percentage of gradable photographs (over 96% in our sample, despite the lack of dilation) is also a likely consequence of this non-response bias.
3. Excluding ungradable participants, 9 out of 402 participants in our sample, aged 75 years and over, had late AMD - a prevalence rate of 2.2%. If dilation had been feasible, and all 108 ungradable participants had been successfully graded in consequence, how would this have affected the estimated prevalence?
Thirty of these 108 participants were aged 75 years and over, and including these, we would have had 432 rather than 402 in this age group in our sample:
a. Assuming that 30.8% of the 30 extra participants had late AMD (this figure of 30.8% comes from the over-80 subgroup in the Reykjavik Eye Study,[3]and represents by far the highest prevalence of late AMD of any subgroup listed in Table 7 of our article[1]), then 9 extra participants (30.8% of 30) in our study would have been classified as late AMD, and our estimated prevalence rate would then have been 18/432=4.2% rather than the 2.2% which we reported.
b. Assuming 18.5% of these 30 participants had late AMD (18.5%, from the 85+ age group in the Blue Mountains Eye Study,[4] being the next highest figure in our Table 7), we would have reported 5 or 6 extra cases of late AMD, resulting in a prevalence of 14/432=3.2% or 15/432=3.5%.
c. Assuming 7.1% prevalence (Beaver Dam Eye Study[5] which, like our study, and unlike both of the above studies, had 75 years and over as the oldest age grouping) the estimated prevalence would have been 11/432=2.5%.
In conclusion, we concur with Craig et al that non-mydriatic photography represents a limitation of our study, which we acknowledged in our article.[1] However, we believe non-response bias is more likely to account for the lower-than-expected prevalence of late AMD in the 75 years and over subgroup of the TILDA sample.
Funding: TILDA is funded by the Irish Department of Health, The Atlantic Philanthropies, and Irish Life plc. KOA and JMN are funded by the European Research Council (ERC). JMN is also funded by the Howard Foundation, Cambridge, UK. TP is funded by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
Competing Interest: JMN and SB do consultancy work for nutraceutrical companies in a personal capacity and as directors of Nutrasight Consultancy Limited. All other authors report no potential conflict of interest.
Contributors: KOA wrote the initial draft. All authors contributed to writing and critical revision of the article.
Reference List
[1] Akuffo KO, Nolan J, Stack J, Moran R, Feeney J, Kenny RA, et al. Prevalence of age-related macular degeneration in the Republic of Ireland. Br J Ophthalmol 2015 Aug;99(8):1037-44.
[2] Cronin H, O'Regan C, Finucane C, Kearney P, Kenny RA. Health and aging: development of the Irish Longitudinal Study on Ageing health assessment. J Am Geriatr Soc 2013 May;61 Suppl 2:S269-S278.
[3] Jonasson F, Arnarsson A, Sasaki H, Peto T, Sasaki K, Bird AC. The prevalence of age-related maculopathy in iceland: Reykjavik eye study. Arch Ophthalmol 2003 Mar;121(3):379-85.
[4] Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study. Ophthalmology 1995 Oct;102(10):1450-60.
[5] Klein R, Klein BEK, Linton KLP. Prevalence of Age-Related Maculopathy - the Beaver Dam Eye Study. Ophthalmology 1992;99(6):933-43.
The authors thank Mr Moreker for his letter regarding our series. We
agree that these are often complex cases and that each patient should be
assessed holistically and discussed individually, ideally in a
multidisciplinary setting. We do not check haemoglobin levels in all the
patients referred to us, in part because severe anaemia in otherwise well
children is rare in the UK population, but we agree that this should be...
The authors thank Mr Moreker for his letter regarding our series. We
agree that these are often complex cases and that each patient should be
assessed holistically and discussed individually, ideally in a
multidisciplinary setting. We do not check haemoglobin levels in all the
patients referred to us, in part because severe anaemia in otherwise well
children is rare in the UK population, but we agree that this should be
done pre-operatively in children where anaemia is suspected.
We acknowledge that a proportion of lymphatic malformations demonstrate a
venous component and that it is vital to exclude any intracranial vascular
connections before embarking on the injection of a sclerosing agent. In
our series, contrast was injected into the malformation and digital
subtraction imaging performed in every case prior to injection.
Yours sincerely,
Dr Alex M Barnacle BM MRCP FRCR
Consultant Interventional Radiologist
Great Ormond Street Hospital for Children
London
UK
Dear Editor,
We read the article entitled ''Evaluation of choroidal thickness in
retinitis pigmentosa using enhanced depth imaging optical coherence
tomography'' by Dilsher S. Dhoot and associates (1), and would like to
offer our comments. The authors presented, in this prospective, case-
control study of choroidal imaging with enhanced depth imaging spectral
domain optical coherence tomography in patients with retinitis...
Dear Editor,
We read the article entitled ''Evaluation of choroidal thickness in
retinitis pigmentosa using enhanced depth imaging optical coherence
tomography'' by Dilsher S. Dhoot and associates (1), and would like to
offer our comments. The authors presented, in this prospective, case-
control study of choroidal imaging with enhanced depth imaging spectral
domain optical coherence tomography in patients with retinitis pigmentosa
(RP) compared with age and refractive error-matched controls with no
clinical retinal or glaucomatous disease (1). The authors established that
in-vivo evidence of significantly thinner choroids in patients with RP
compared to age and refraction-matched controls (1). We congratulate and
applaud their interesting and important work, but we believe that some
concerns must be addressed.
The choroid is a highly vascular tissue, and it is known that the
choroidal thickness (CT) is affected from intraocular pressure, blood
pressure, smoking, and the use of certain drugs (2). The choroid is also
affected from microvascular changes and dyslipidemia (3). But, it is
understood from the present study that the authors did not exclude the
subjects having systemic diseases such as hypercholesterolemia,
hypertension, diabetes mellitus, and obstructive sleep apnea. The authors
also empasized that age and refractive error were matched before comparing
CT between the groups. However, we noticed that they did not define the
axial length, which is known to be an important factor for the assessment
of CT. Some authors reported the correlations between subfoveal CT and
axial length and refractive error (4). Refractive error is associated with
axial length, but it is not stable throughout life. Therefore, adjusting
axial length with refractive error would be more accurate, especially in
elderly patients.
In conclusion, we congratulate the authors on their study, which
establishes CTs of RP patients and allows comparison of CTs between
healthy controls.
References
1. Dhoot DS, Huo S, Yuan A, Xu D, Srivistava S, Ehlers JP, Traboulsi E,
Kaiser PK. Evaluation of choroidal thickness in retinitis pigmentosa using
enhanced depth imaging optical coherence tomography. Br J Ophthalmol
2013;97:66-69.
2. Mrejen S, Spaide RF. Optical coherence tomography: imaging of the
choroid and beyond. Surv Ophthalmol 2013;58(5):387-429.
3. Wong IY, Wong RL, Zhao P, Lai WW. Choroidal thickness in relation to
hypercholesterolemia on enhanced depth imaging optical coherence
tomography. Retina 2013;33(2):423-428.
4. Li XQ, Larsen M, Munch IC. Subfoveal choroidal thickness in relation to
sex and axial length in 93 Danish university students. Invest Ophthalmol
Vis Sci 2011;52(11):8438-8441.
Dear Editor, I read, with interest, the article entitled: Validity and repeatability of the Aladdin ocular biometer [1] and it appears to contain errors in the reporting of Bland-Altman 95% Limits of Agreement (LoAs). Figures 1,2 and 3 all contain the following statement in their legends: "The dotted lines represent the upper and lower 95% limits of agreement."
These statements are, I believe, incorrect. The "dotted lines" are c...
Dear Editor, I read, with interest, the article entitled: Validity and repeatability of the Aladdin ocular biometer [1] and it appears to contain errors in the reporting of Bland-Altman 95% Limits of Agreement (LoAs). Figures 1,2 and 3 all contain the following statement in their legends: "The dotted lines represent the upper and lower 95% limits of agreement."
These statements are, I believe, incorrect. The "dotted lines" are curved: an unusual feature for Bland-Altman LoAs [2,3]. The 95% LoAs are meant to be population estimates of a range in which 95% of the values will be found. For example, for the repeatability analysis of Axial Length measurements shown in Figure 1, only 12 of the 22 points lie within the purported LoAs. If the 95% LoAs were good estimates then the chance of a sample having only 12 (or fewer) of the 22 points within it, would be 0.000000036. So, the dotted lines are not good estimates of the 95% LoAS. The dotted lines may represent something else, like the 95% confidence intervals for the population limits for the fitted regression line.
For these 22 points as plotted, the mean of differences was 0.004 mm with a 95% CI from -0.008 to 0.016mm. (Note, this is different from the values of "0.00 mm with a 95% CI of 0.05 mm" reported by Mandel et al [1]. They may have confused "confidence intervals" with "LoAs"). The lower LoA is -0.050 mm with a 95%CI from -0.038 to -0.074 mm and the upper LoA is 0.057 mm with a 95%CI from 0.045 to 0.082 mm.[4]
I think Mandal et al [1] have made similar errors with reporting their LoAs in their other data sets. It may not affect their overall conclusions about the merits of Aladdin biometry, but it would be useful to have this issue clarified.
1. Mandal P, Berrow EJ, Naroo SA, Wolffsohn JS, Uthoff D, Holland D, et al. Validity and repeatability of the Aladdin ocular biometer. Br J Ophthalmol 2014;98(2):256-8.
2. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;327(8476):307-10.
3. Altman DG, Bland JM. Measurement in medicine: the analysis of method comparison studies. The Statistician 1983;32:307-17.
4. Carkeet A. Exact parametric confidence intervals for Bland-Altman limits of agreement. Optom Vis Sci 2015;92(3):e71-80.
We read with interest the article by Akuffo et al reporting the
prevalence of age related macular degeneration (AMD) in the Republic of
Ireland and congratulate them on their findings. The authors report a
recent meta-analysis demonstrating considerable heterogeneity in the
prevalence of AMD across studies of European ancestry (1), with 20%
variability being explained by the age-ranges used and 50% by study
characterist...
We read with interest the article by Akuffo et al reporting the
prevalence of age related macular degeneration (AMD) in the Republic of
Ireland and congratulate them on their findings. The authors report a
recent meta-analysis demonstrating considerable heterogeneity in the
prevalence of AMD across studies of European ancestry (1), with 20%
variability being explained by the age-ranges used and 50% by study
characteristics. The TILDA age-specific prevalence for AMD in the over 75-
year age group of 2.2% seems lower than we would expect. The authors
report the measured prevalence was similar to that in the National Health
and Nutrition Examination Survey (2). We would like to highlight this
study shared one similar methodology that we feel may contribute to the
low prevalence: that of non-mydriatic 45-degree digital colour fundus
photography. The use of high resolution mydriatic stereo/non-stereoscopic
digital imaging has been shown to be comparable at detecting AMD lesions
when compared to film-based stereoscopic photographs (3), but the use of
45-degree non-mydriatic photography has several shortcomings. It reduces
colour contrast and increases the frequency of poor quality/ungradable
images, especially in individuals with small pupils and media opacities
(3). It has been shown to have a low sensitivity (70%) for detecting AMD
when compared to 30-degeree colour photography (4). Despite this, in the
TILDA study over 96% of photographs were deemed gradable which is higher
than some published rates (5). We understand dilation was not possible as
AMD grading was not the only aim, but we would like to emphasise that when
feasible, the use of mydriatic colour fundus photography is the preferred
option for detecting AMD in epidemiological studies. It makes comparison
to other published prevalence rates easier to interpret which was one of
the fundamental ideas behind standardising prevalence studies with the use
of The International Classification System.
1. Rudnicka AR, Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG.
Age and gender variations in age-related macular degeneration prevalence
in populations of European ancestry: a meta-analysis. Ophthalmology. 2012
Mar;119(3):571-80. PubMed PMID: 22176800.
2. Klein R, Chou CF, Klein BE, Zhang X, Meuer SM, Saaddine JB. Prevalence
of age-related macular degeneration in the US population. Arch Ophthalmol.
2011 Jan;129(1):75-80. PubMed PMID: 21220632.
3. Klein R, Meuer SM, Moss SE, Klein BE, Neider MW, Reinke J. Detection of
age-related macular degeneration using a nonmydriatic digital camera and a
standard film fundus camera. Arch Ophthalmol. 2004 Nov;122(11):1642-6.
PubMed PMID: 15534124.
4. Lim JI, Labree L, Nichols T, Cardenas I. Comparison of nonmydriatic
digitized video fundus images with standard 35-mm slides to screen for and
identify specific lesions of age-related macular degeneration. Retina.
2002 Feb;22(1):59-64. PubMed PMID: 11884880.
5. De Bats F, Vannier Nitenberg C, Fantino B, Denis P, Kodjikian L. Age-
related macular degeneration screening using a nonmydriatic digital color
fundus camera and telemedicine. Ophthalmologica Journal international
d'ophtalmologie International journal of ophthalmology Zeitschrift fur
Augenheilkunde. 2014;231(3):172-6. PubMed PMID: 24356326.
We read the article titled, "Significance of the hyperautofluorescent
ring associated with choroidal neovascularization in eyes undergoing anti-
VEGF therapy for wet age-related macular degeneration"[1] with great
interest. Our paper "Evaluation of fundus autofluorescence patterns in Age
-related Macular Degeneration" is presently under review. After reading
the above article we retrospectively analyze...
We read the article titled, "Significance of the hyperautofluorescent
ring associated with choroidal neovascularization in eyes undergoing anti-
VEGF therapy for wet age-related macular degeneration"[1] with great
interest. Our paper "Evaluation of fundus autofluorescence patterns in Age
-related Macular Degeneration" is presently under review. After reading
the above article we retrospectively analyzed our data.
We studied 80 eyes of 68 patients with choroidal neovascularization (CNV)
due to AMD. FAF images were classified as: Presence of
hyperautofluorescent(HAF) ring around the lesion complex (Group 1) and
absence of HAF ring around the lesion complex (Group 2). Horizontal extent
of sub retinal fluid was measured.
Out of 80 eyes, 32 eyes (40%) showed a HAF ring. In a subgroup of 36
treatment naive eyes, 14 eyes (38.88%) had HAF ring. There was no
statistically significant difference between the horizontal extent of sub
retinal fluid (SRF) at baseline in group 1 [2219?1387.39 micron (median-
1969.5)] and group 2 [2230.18 ? 1580.92 micron (median- 1939.5)]. Mean
best corrected visual acuity was 1.16 ? 0.46 logMAR units in group 1 and
0.95 ? 0.54 in group 2 and the difference between the groups was not
significant.
In the study by Camacho et al, HAF ring was noted in 38.1% of cases of wet
AMD the presence of which was shown to have prognostic significance[1]. We
also found similar percentage of cases with HAF ring. However, in our
study presence of HAF ring did not correlate with the baseline visual
acuity or the extent of SRF. This could be due to the smaller sample size
in our study. We could not comment on the integrity of inner segment-
outer segment junction, as we did not have post treatment SD-OCT images of
the cases. Further studies on FAF patterns in AMD and their prognostic
significance might give us more information.
References
1. Camacho N, Barteselli G, Nezgoda JT, et al. Significance of the
hyperautofluorescent ring associated with choroidal neovascularisation in
eyes undergoing anti-VEGF therapy for wet age-related macular
degeneration. The British journal of ophthalmology 2015;99(9):1277-83 doi:
10.1136/bjophthalmol-2014-306226[published Online First: Epub Date]|.
The large single center experience of Barnacle et al does convince
one of the need to use sclerotherapy and withhold surgery in such cases.
But lymphatic malformations are the most varied in terms of presentations.
Each malformation is different and it is not possible to club the various
kinds of seemingly one type of malformations ,together, in one group ;
nor would it be possible to state which modality should be fi...
The large single center experience of Barnacle et al does convince
one of the need to use sclerotherapy and withhold surgery in such cases.
But lymphatic malformations are the most varied in terms of presentations.
Each malformation is different and it is not possible to club the various
kinds of seemingly one type of malformations ,together, in one group ;
nor would it be possible to state which modality should be first choice
of therapy ,since every malformation will behave differently
Traditionally malformations were classified as lymphatic if there was
no flow. (1)This can be judged by the absence of enhancement on contrast
as suggested by some authors. But in one of our cases the orbital
lymphatic malformation happened to have a small veinous element as well as
described In some imaging studies (2) and sometimes such malformations
may show low degree of enhancement if there is a significant venous
component or feeder vessel. In our case of a one year old female child ,
there was no indication of a connection with any other tissue on MRI and
CT Scan .It is known that lymphatic malformations cross anatomic planes
and physiologic boundaries (3) and so the orbit brain plane crossing is a
possibility one must always rule out.
Encouraged by articles like the present one, which show good results
with various agents including bleomycin, doxycycline, Ethibloc, sodium
tetradecyl sulfate, ethanol, and OK-432 as well as Sildenafil, with
certain authors (4) preferring dual agent for macrocystic lesions and
single agent for macro cystic lesions and per cutaneous drainage as a
prerequisite ; we, like most others , had decided on sclerosis of our
patient who was already well investigated. But insistence on doing a
digital subtraction angiography revealed a connection with dural veinous
sinus.
There are various reports which describe complications (5). Hematoma
and thrombosis related complications are known but a dural sinus
thrombosis can have catastrophic sequelae .This in our case was averted by
a digital subtraction angiography which showed a low flow malformation
Further the child was discovered to be severely anaemic with
haemoglobin of 6 gms/dl ( iron deficiency related) and was transfused with
blood. Nutritional advice and iron supplements were given and the patient
was asked to follow up after a month.Surprisingly after blood transfusion
the malformation reduced in size.Hence the surgery or any other
sclerotherapy intervention was deferred. The child's parents did not
follow up as there was no swelling or any complaint. The child came with
another episode of increase in size after 6 months. Routine blood
examination for determining fitness for anaesthesia again revealed an
iron deficiency anaemia with haemoglobin of 8 gms/dl . She had defaulted
on iron syrup due to constipation and was malnourished.She was again given
hematinics and the swelling reduced again!
This probably means flow characteristics may vary even in low flow
situations and cause a variation in size of the mass in the orbit and a
hyperdynamic state like anaemia should be treated first . Digital
subtraction angiography may be indicated in cases which present with a
history of varying size of the lesion.
This probably would mean that each case needs to be examined in close
details and there would probably not be any one preferred treatment
modality as first choice and solutions probably need to be tailored
according to the case presenting to the surgeon , since each malformation
may be different and one of its kind
References :-
1)Harris GJ. Orbital vascular malformations: a consensus statement on
terminology and its clinical implications. Orbital Society. Am J
Ophthalmol. 1999 Apr;127(4):453-5. .
2)Garcia DD, Heran MK, Amadi AJ, Rootman J. Low outflow distensible venous
malformations of the anterior orbit: presentation, hemodynamic factors,
and management. Ophthal Plast Reconstr Surg. 2011 Jan-Feb;27(1):38-43.
3) Graeb DA, Rootman J, Robertson WD, Lapointe JS, Nugent RA, Hay EJ.
Orbital lymphangiomas: clinical, radiologic, and pathologic
characteristics. Radiology. 1990 May;175(2):417-21.
4)Hill RH, Shiels WE, Foster JA, Czyz CN, Stacey A, Everman KR, et al.
Percutaneous drainage and ablation as first line therapy for macrocystic
and microcystic orbital lymphatic malformations. Ophthal Plast Reconstr
Surg. 2012 Mar-Apr;28(2):119-25.
5)MacIntosh PW, Yoon MK, Fay A. Complications of intralesional bleomycin
in the treatment of orbital lymphatic malformations. Semin Ophthalmol.
2014 Sep-Nov;29(5-6):450-5.
We would like to acknowledge our appreciation for Dr. Peyman for
paying close attention to our article and raising important points. Now,
big-bubble deep anterior lamellar keratoplasty (DALK) is a corneal
transplantation technique of choice for corneal stromal pathologies not
involving endothelium such as keratoconus. The principle shortcoming of
this technique is that it is technically challenging. Any attempts to
incr...
We would like to acknowledge our appreciation for Dr. Peyman for
paying close attention to our article and raising important points. Now,
big-bubble deep anterior lamellar keratoplasty (DALK) is a corneal
transplantation technique of choice for corneal stromal pathologies not
involving endothelium such as keratoconus. The principle shortcoming of
this technique is that it is technically challenging. Any attempts to
increase the success rate of big-bubble formation should be commended as
it is a critical step and difficult for many surgeons. Our article aimed
to investigate the possible influence of patient- and surgery-related
variables on this rate in a homogeneous group of keratoconus patients who
were operated on by a single experienced surgeon.1 The exploratory
analysis revealed that among various factors, recipient sex and
trephination size significantly influenced the rate of achieving a bare
Descemet's membrane (DM).1
Following are points in response to the critiques posed by Dr. Peyman:
1) As mentioned in the Methods section, the influence of the independent
variables on the success rate of big-bubble formation was first
investigated using univariate analysis. Only the variables which had a
significant association at a univariate level were entered into multiple
regression analysis. In our final confirmatory analysis, there was a
limited number of variables including recipient sex, vertical corneal
diameter, corneal thickness, anterior chamber depth, and recipient
trephination size. Therefore, it is very unlikely that multiple
comparisons led to a false positive correlation between the variables.
Additionally, comparisons between the bare DM group and the manual
dissection group using Chi-square and Mann-Whitney tests revealed
significant differences between the two groups in terms of patient sex
distribution and recipient trephination size confirming the results
yielded by multiple regression analyses. This indicates that the
significant associations found in our study were not caused by chance.
2) Providing no evidence, Dr. Peyman anecdotally reports that when the
recipient trephination size is large, it is difficult to complete the
procedure as big-bubble DALK. However, Huang et al.2 used two different
recipient trephination sizes (7.75 mm and 8.25 mm) and reported that big-
bubble DALK was successfully completed in 89.4% of the 7.75-mm group and
in 84.8% of the 8.25-mm group (P=0.60). It is possible that due to some
technical problems Dr. Peyman has with large diameter trephines in DALK,
he has been convinced that the larger diameter of trephination could
potentially cause more failure of the procedure.
3) According to Dr. Peyman's experience, cutting the recipient cornea in a
case of incomplete small bubbles is difficult and could create holes or
ruptures in peripheral posterior layers. However, corneal surgeons who
master different techniques of DALK such as manual dissection technique
and Melle's technique can safely complete dissection using viscoelastic
materials or blunt spatula once the dissection plane is reached.
4) Dr. Peyman refers to a study by Dua et al.3 to explain the reason for
difficult expansion of the big bubble to the border of trephination when a
large trephine is used. In the initial article, Dua et al.3 revealed that
pre-Descemet posterior stromal layer (PDL) ended before the termination of
DM. In the subsequent study, however, they provided evidence that PDL
extends beyond the edge of the big bubble to insert into the trabecular
meshwork.4 Therefore, it is possible to separate posterior stroma from the
PDL far to the corneal periphery. We conducted a study comparing the rate
of achieving a bare DM during big-bubble DALK using central versus
peripheral air injection (the manuscript has been submitted). Using
surgical calipers, we precisely measured the size of achieved bubbles
which ranged from 7.0 to 10.5 mm. These data indicate the big bubble can
successfully be enlarged beyond that Dr. Peyman mentioned.
To summarize, DALK grafts employing a larger diameter recipient bed
provide several advantages including low graft astigmatisms, stable
postoperative refractive outcomes, and better graft biomechanics.2,6 Our
recent study adds a new advantage to the application of a large trephine
size in keratoconic eyes which increases the likelihood of successful big
bubble formation during Anwar's DALK technique.1
References
1- Feizi S, Javadi MA, Daryabari SH. Factors influencing big-bubble
formation during deep anterior lamellar keratoplasty in keratoconus. Br J
Ophthalmol. 2015; In press.
2- Huang T, Hu Y, Gui M, et al. Large-diameter deep anterior lamellar
keratoplasty for keratoconus: visual and refractive outcomes. Br J
Ophthalmol. 2015; 99:1196-1200.
3- Dua HS, Faraj LA, Said DG, et al. Human corneal anatomy redefined: a
novel pre-Descemet's layer (Dua's layer). Ophthalmology. 2013;120:1778-
1785.
4- Dua HS, Faraj LA, Branch MJ, et al. The collagen matrix of the human
trabecular meshwork is an extension of the novel pre-Descemet's layer
(Dua's layer). Br J Ophthalmol. 2014;98:691-697.
5- Feizi S, Einollahi B, Yazdani S, et al. Graft biomechanical properties
after penetrating keratoplasty in keratoconus. Cornea. 2012;31:855-858.
Sepehr Feizi, MD, MSc
Assistant Professor of Ophthalmology, Shahid Beheshti University of
Medical Sciences, Tehran, Iran.
Email: sepehrfeizi@yahoo.com
Conflict of Interest:
None declared
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We would like to acknowledge our appreciation for Dr. Peyman for paying close attention to our article and raising important points. Now, big-bubble deep anterior lamellar keratoplasty (DALK) is a corneal transplantation technique of choice for corneal stromal pathologies not involving endothelium such as keratoconus. The principle shortcoming of this technique is that it is technically challenging. Any attempts to incr...
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