Response to E-letter.
Thank very much for reading our article. It is true that oral insulin
analogues can lead to increased growth hormone, increasing its effect over
diabetic retinopathy, but previously it should exist a blood-retina
barrier (BRB), despite in patients with preexisting diabetic retinopathy
the BRB rupture exist in some amount. It is possible that oral insulin
analogues can affect the diabetic retinopathy...
Response to E-letter.
Thank very much for reading our article. It is true that oral insulin
analogues can lead to increased growth hormone, increasing its effect over
diabetic retinopathy, but previously it should exist a blood-retina
barrier (BRB), despite in patients with preexisting diabetic retinopathy
the BRB rupture exist in some amount. It is possible that oral insulin
analogues can affect the diabetic retinopathy level, but in patients
without diabetic retinopathy the BRB should be intact. In the present
study we demonstrate two findings, the first is the number of patients
with any-DR who increased selectively in two age groups: in patients with
age between 41-50 and patients with age between 51-60; and the second
finding is that patients with advanced-DR, showed an increase in the 31-
40, 41-50, 51-60 and 61-70 age groups. In all groups the HbA1c increased
progressively since 2008 to 2014. Can the insulin analogues do any
effects? It is difficult to give an answer. Attending our knowledge is a
possibility, but I say you a question. What is the more important effect
over the diabetic retinopathy the bad glycemic levels or the treatment by
insulin or analogues, due this bad control? In fact, is very difficult to
answer this question, in our initial studies long time ago ( ), the
insulin is an independent factor in diabetic retinopathy development, but
when we apply multivariate analysis using logistic regression the insulin
is a confounding risk factor overlapped to glycemic levels. Respect our
conclusion about a poor control of glycemic levels in the previously cited
age groups is a reality in our Country, it seems it exists a relaxation in
diabetes control exercised by patients, and all staff involved in the
treatment of diabetes should strive to re-educate patients with diabetes,
reminding how important is the glycemic control to prevent serious
complications such as diabetic retinopathy. Finally thank you very much
for your contribution to our problem.
References.
1. Romero-Aroca P, Salvat-Serra M, Mendez-Marin I, Martinez-Salcedo I.
[Is microalbuminuria a risk factor for diabetic retinopathy?]. J Fr
Ophtalmol. 2003;26(7):680-4.
2. Romero-Aroca P, Calvino-Dominguez O, del Castillo-Dejardin D.
[Epidemiologic study of diabetic retinopathy in a primary care unit]. Arch
Soc Esp Oftalmol. 2000;75(3):147-52.
3. Romero-Aroca P, Espeso-Sentis O, Sarda-Aure P, del Castillo-Dejardin D.
[Relationship between microalbuminuria and diabetic retinopathy in type 1
diabetes mellitus]. Rev Clin Esp. 2000;200(7):351-4.
We read with interest the article titled "Predictive factors for
treatment failure in patients with presumed ocular tuberculosis in an area
of low endemic prevalence" by Agarwal et al published in Br J Ophthalmol
2016;100:348-355.
We wanted to point out few things regarding the article -
The diagnosis of ocular tuberculosis was presumptive in most cases. The
authors have used clinical guide...
We read with interest the article titled "Predictive factors for
treatment failure in patients with presumed ocular tuberculosis in an area
of low endemic prevalence" by Agarwal et al published in Br J Ophthalmol
2016;100:348-355.
We wanted to point out few things regarding the article -
The diagnosis of ocular tuberculosis was presumptive in most cases. The
authors have used clinical guidelines from an article by Gupta et
alignment published in 2007.[1]The same authors have published revised
criterion in 2010.[2]It would have been more appropriate to use the latter
more recent guidelines.
The authors do not provide a break-up of the morphological forms of
posterior uveitis considered as tubercular in the present series. Few
categories of posterior uveitis such as serpiginous choroiditis and
vasculitis may have been included as ocular tuberculosis only on basis of
Quantiferon gold test positivity. All patients with these diagnosis may
not actually be due to active tubercular infection.[3] Rather only a
subset of these patients may be due to active tuberculosis. Thus it is
difficult to analyse treatment failure in cases where the aetiology is not
very certain.
The findings of the authors of higher failure rate of Anti-tubercular
therapy (ATT) in those given higher doses of immunosuppressives could also
indicate that the disease process is not due to active tubercular
infection. The ATT has probably no role in the management of these
disorders and it is actually the immunosuppression that is working. The
failure may be due to inadequate or rapid withdrawal of immunosppression.
Thus it may not be prudent to attribute failure to some property of
tubercular infection when the diagnosis of tuberculosis itself is probable
or questionable.
The authors donot mention if any cases had side-effects of the anti-
tubercular medication or if any patients dropped out.
The authors mention that the decision to start ATT was based on discretion
of physician. Although from the article it appears that the onus of
starting ATT was with the treating ophthalmologist as it was started only
on basis of ocular findings and QFT-G positivity even in the absence of
systemic evidence of tuberculosis.
The authors mention in the end that the evidence base for benefit of oral
steroids in TB-associated uveitis is weak. However we feel that the
contrary, i.e. evidence of benefit of ATT in certain cases of presumed
ocular tuberculosis is weak as in most studies ATT has been given in
combination with steroids and not alone.
References
1: Gupta V,Gupta A,Rao NA.Intraocular tuberculosis--an update.Surv
Ophthalmol 2007;52:561-87.
2: Gupta A, Bansal R, Gupta V, Sharma A, Bambery P. Ocular signs
predictive of tubercular uveitis.Am J Ophthalmol. 2010 Apr;149(4):562-70.
doi: 10.1016/j.ajo.2009.11.020. Epub 2010 Feb 10.
3: Nazari Khanamiri H, Rao NA.Serpiginous choroiditis and infectious
multifocal serpiginoid choroiditis. Surv Ophthalmol. 2013 May-
Jun;58(3):203-32.
I read with great interest the article by Romero- Aroca et al. titled "Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population" [1]. Insulin usage has found to be a risk factor for progression of DRP. Authors conclude this result as relaxation of patients in metabolic control. Beside this conclusion, insulin analogues may directly cause progression of DRP. Insulin and its analogues stimulate ins...
I read with great interest the article by Romero- Aroca et al. titled "Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population" [1]. Insulin usage has found to be a risk factor for progression of DRP. Authors conclude this result as relaxation of patients in metabolic control. Beside this conclusion, insulin analogues may directly cause progression of DRP. Insulin and its analogues stimulate insulin like growth hormone-1 (IGF-1) receptors, like growth hormone. There is a strong relationship between growth hormone and progression of DRP. Diabetic retinopathy regresses after surgical ablation or spontaneous infarction of pituitary gland [2]. Growth hormone deficiency is a protective factor for development of diabetic retinopathy in dwarfs [3]. Development of diabetic retinopathy is significantly higher in pubertal subjects than pre -pubertal subjects, despite the same glycemic control [4]. Thus, insulin analogues may cause progression of DRP through growth hormone-like effect. But I hypothesize that insulin analogues may cause progression of DRP only after deterioration of inner blood retinal barrier [5]. Hyperglycemia is a major risk factor for development of DRP. High blood glucose levels cause inner blood-retinal barrier deterioration by polyol pathway, non-enzymatic protein glycation and oxidative stress. Insulin analogues decrease blood glucose level and protect pericytes and inner blood-retinal barrier. When inner blood-retinal barrier is intact, insulin analogues may pass into the retinal tissue in very small amounts. After impairment of inner blood retinal barrier, insulin analogues may pass into the retinal tissue in much more amounts. Thus, insulin analogues may pass retinal tissue after impairment of inner blood retinal barrier and cause progression of DRP by growth hormone like effect. But before impairment, analogues can not pass through inner blood retinal barrier to cause progression of DRP, even delay onset of DRP by decreasing high blood glucose that impair pericytes.
References
1. Romero-Aroca P, de la Riva-Fernandez S, Valls-Mateu A, Sagarra-Alamo R, Moreno-Ribas A, Soler N. Changes observed in diabetic retinopathy: eight- year follow-up of a Spanish population. Br J Ophthalmol. 2016 Jan 14.
2. Adams, D.A., Rand, R.W., Roth, N.H., Dashe, A.M., Gipstein, R.M., Heuser, G. Hypophysectomy in diabetic retinopathy. The relationship between the degree of pituitary ablation and ocular response. Diabetes. 1974;23:698???707.
3. Merimee, T.J. A follow-up study of vascular disease in growth-hormone-deficient dwarfs with diabetes. N Engl J Med. 1978;298:1217???1222.
4. Murphy, R.P., Nanda, M., Plotnick, L., Enger, C., Vitale, S., Patz, A. The relationship of puberty to diabetic retinopathy. Arch Ophthalmol. 1990;108:215???218.
5. Kaya A, Kar T, Aksoy Y, Ozalper V, Basbug B. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier. Med Hypotheses. 2013 Dec;81(6):1012-4. 4.
We have read and reviewed the article entitled as "Short-term
choroidal thickness changes in patients treated with either ranibizumab or
aflibercept: a comparative study'' by Kim et al. with interest.1 The
authors analyzed 240 eyes of 240 treatment-naive neovascular AMD patients
who treated with three-monthly injections of either ranibizumab
(ranibizumab group) or aflibercept (aflibercept group). Th...
We have read and reviewed the article entitled as "Short-term
choroidal thickness changes in patients treated with either ranibizumab or
aflibercept: a comparative study'' by Kim et al. with interest.1 The
authors analyzed 240 eyes of 240 treatment-naive neovascular AMD patients
who treated with three-monthly injections of either ranibizumab
(ranibizumab group) or aflibercept (aflibercept group). They analyzed the
choroidal thickness (CT) alterations between the time of diagnosis and 3
months later, and compared them between two groups. They demonstrated a
greater decrease in CT in eyes treated with aflibercept compared to the
eyes treated with ranibizumab. We would like to ask for further details,
and contribute to the article.
As mentioned in the discussion section of the paper, a number of
factors including diurnal variation, refractive error, axial length (AL),
diabetes mellitus, hypertension, and consumption of water or coffee might
affect CT. However, we wonder intraocular pressure (IOP), use of local or
systemic drugs, smoking, sleep and exercise status, consumption of alcohol
before optical coherence tomography (OCT), and whether body mass index,
and systemic blood pressure of the patients were taken into consideration.
We also wonder lightening of the test room since all of the aforementioned
factors have been shown to affect CT significantly.2 3
For instance, Sanchez-Cano et al. demonstrated a strong negative
correlation between subfoveal CT and AL in healthy adults.4 In addition
Saeedi et al. showed a negative correlation between mean CT and IOP.5 On
the other hand, intravitreal ranibizumab and aflibercept may cause a
significant increase in IOP6-8, and a significant alteration in CT.
Therefore, IOP must be analyzed on control examinations just before OCT
measurements.
Additionally CT shows a significant diurnal variation. The choroid could
increase its thickness by 50% in an hour, and quadruple its thickness in a
few days.4 Kee et al. found that the choroid could thin very rapidly, by
about 100 micron, in 3-4 h in young chicks.9 Usui et al. showed that CT
might show a diurnal variation up to 65 micron in healthy individuals.10
It is highly likely that all those parameters could affect the data
obtained from the study, and the results of the statistical tests.
Therefore, one should act with suspicion towards the results of this
study.
REFERENCES
1 Kim JH, Lee TG, Chang YS, et al. Short-term choroidal thickness
changes in patients treated with either ranibizumab or aflibercept: a
comparative study. Br J Ophthalmol 2016. doi: 10.1136/bjophthalmol-2015-
308074. [Epub ahead of print].
2 Akay F, Gundogan FC, Yolcu U, et al. Choroidal thickness in
systemic arterial hypertension. Eur J Ophthalmol 2016;26:152-7.
3 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye
Res 2010; 29:144-68.
4 Sanchez-Cano A, Orduna E, Segura F, et al. Choroidal thickness and
volume in healthy young white adults and the relationships between them
and axial length, ammetropy and sex. Am J Ophthalmol 2014;158:574-83.e1.
5 Saeedi O, Pillar A, Jefferys J, et al. Change in choroidal
thickness and axial length with change in intraocular pressure after
trabeculectomy. Br J Ophthalmol 2014;98:976-9.
6 Dedania VS, SJ Bakri. Sustained elevation of intraocular pressure
after intravitreal anti-vegf agents: What is the evidence? Retina
2015;35:841-58.
7 Freund KB, Hoang QV, Saroj N. Intraocular pressure in patients with
neovascular age-related macular degeneration receiving intravitreal
aflibercept or ranibizumab. Ophthalmology 2015;122:1802-10.
8 Hoang QV, Tsuang AJ, Gelman R, et al. Clinical predictors of
sustained intraocular pressure elevation due to intravitreal anti-vascular
endothelial growth factor therapy. Retina 2013;33:179-87.
9 Kee CS, Marzani D, Wallman J. Differences in time course and visual
requirements of ocular responses to lenses and diffusers. Invest
Ophthalmol Vis Sci 2001;42:575-83.
10 Usui S, Ikuno Y, Akiba M, et al. Circadian changes in subfoveal
choroidal thickness and the relationship with circulatory factors in
healthy subjects. Invest Ophthalmol Vis Sci 2012;53:2300-7.
We read with great interest the study titled as "Comparison of
trabeculectomy versus Ex-PRESS: 3-year follow-up" by Gonzalez-Rodriguez et
al [1].We congratulate their efforts for conducting the study with a
follow up of 3 years, making the results more significant.They concluded
that success rates, mean IOP, number of anti-glaucoma medications and
final visual acuities were similar between the two groups after 3 years.
T...
We read with great interest the study titled as "Comparison of
trabeculectomy versus Ex-PRESS: 3-year follow-up" by Gonzalez-Rodriguez et
al [1].We congratulate their efforts for conducting the study with a
follow up of 3 years, making the results more significant.They concluded
that success rates, mean IOP, number of anti-glaucoma medications and
final visual acuities were similar between the two groups after 3 years.
The positive points in favour of Ex-PRESS implant, are its standardized
pore size leading to more predictable filtration and consequently
avoidance of hypotony & other complications and a shorter learning
curve.
Interestingly many studies have also claimed that Ex-PRESS has a
faster visual recovery. In fact, the authors showed from their first year
data that by one month the Ex-PRESS group reached the baseline acuity
whereas in the trabeculectomy group, acuity remained significantly lower
from baseline at each study visit from day 1 to 6 months. However, when
excluding patients who needed a repeat glaucoma procedure, the acuity was
found to be better in Ex-PRESS group compared to Trabeculectomy group at
all time points. In our opinion, this data would have been more promising
had the authors mentioned the test-retest variability as well as the
confidence intervals of the visual acuity measurements in either group.
The e?ects of the Ex-PRESS device on cornea were previously evaluated by
the authors in their 1 year results [2]. We are keen to know their
findings with regards to corneal health at last follow-up.
The results of this study are consistent with other published
reports, proving that, there is actually no difference in success rates
between Ex-PRESS and trabeculectomy [3,4]. Though Ex-PRESS implant is
considered to be another good option in our surgical armamentarium, the
significant cost difference needs to be considered in conjunction with
e?cacy and safety, if Ex-PRESS is to supersede trabeculectomy [5].
REFERENCES -
1. Gonzalez-Rodriguez JM, et al. Br J Ophthalmol 2015
2. Wagschal et al. Prospective Randomized Study Comparing Ex-PRESS to
Trabeculectomy: 1-Year Results. J Glaucoma 2015;24:624-629.
3. Netland PAet al. Randomized, prospective, comparative trial of EX-
PRESS glaucoma filtration device versus trabeculectomy (XVT study). Am J
Ophthalmol 2014;157:433-40.e3.
4. Dahan E, Ben Simon GJ, Lafuma A. Comparison of trabeculectomy and
Ex-PRESS implantation in fellow eyes of the same patient: a prospective,
randomised study. Eye (Lond) 2012;26:703-10.
5. Buys YM. Trabeculectomy with ExPRESS: weighing the benefits and
cost. CurrOpin Ophthalmol 2013;24:111-18.
With great interest,We have read the article by Chidambara1 and
partners on characteristics and quantification of vascular changes in
macular telangiectasia type 2( MacTel 2) on optical coherence tomography
angiography(OCTA).The authors concluded that OCTA helps understand the
pathology and disease progression better in MacTel 2.We commend their
interesting and important work on this subject.However, w...
With great interest,We have read the article by Chidambara1 and
partners on characteristics and quantification of vascular changes in
macular telangiectasia type 2( MacTel 2) on optical coherence tomography
angiography(OCTA).The authors concluded that OCTA helps understand the
pathology and disease progression better in MacTel 2.We commend their
interesting and important work on this subject.However, we have a question
for the authors concerning intra- and inter-observer variation and the
reproducibility of the OCTA examination.
As far as I know, reproducibility and repeatability are indicators of
the applicability of any instrument as a diagnostic tool in clinical
practice2.OCTA is extremely sensitive to motion, some images had
significant artifacts even with the motion correction algorithm. Operator
learning curve, media opacity, and patient cooperation were factors in
poor-quality images3.If the subjects had repeated instances of unstable
fixation,the image would appear with white ambiguous lines.The analysis
software would mistake these white ambiguous lines for blood vessels and
would overestimate the retinal vessel density.Therefore,intra- and inter-
observer variation would be relatively large. I think the authors should
perform a reproducibility analysis to prove the stability of the OCTA
system examination.If such an analysis had been performed and intra- and
inter- observer variation exceeded a certain percent,the results of this
study might have been shown to be unreliable.
REFERENCES
1. Chidambara L, Gadde SGK, Yadav NK, et al. Characteristics and
quantification of vascular changes in macular telangiectasia type 2 on
optical coherence tomography angiography. Br J Ophthalmol 2016:2015-
307941.
2. Carpineto P, Mastropasqua R, Marchini G, et al. Reproducibility and
repeatability of foveal avascular zone measurements in healthy subjects by
optical coherence tomography angiography. Br J Ophthalmol 2015.
3. Hwang TS, Gao SS, Liu L, et al. Automated Quantification of Capillary
Nonperfusion Using Optical Coherence Tomography Angiography in Diabetic
Retinopathy. JAMA OPHTHALMOL 2016:1-7.
We read with great interest the article entitled "Smoking was associated with poor response to intravenous steroids therapy in Graves' ophthalmopathy" by Xing et al [1]. Cigarette smoking is known to be the most important risk factor for the development or deterioration of GO, and it is associated with poor response to treatment for GO. However, the exact mechanisms which prove deleterious effect of cigarette smoking on GO rem...
We read with great interest the article entitled "Smoking was associated with poor response to intravenous steroids therapy in Graves' ophthalmopathy" by Xing et al [1]. Cigarette smoking is known to be the most important risk factor for the development or deterioration of GO, and it is associated with poor response to treatment for GO. However, the exact mechanisms which prove deleterious effect of cigarette smoking on GO remain poorly understood.
It has been suggested that smoke-induced generation of reactive oxygen species (ROS) may play a role in the pathogenesis of GO, either through direct contact with the paranasal sinuses, or indirectly through the bloodstream [2]. Previously, we had revealed that smokers had significant higher urinary 8-OHdG (product of oxidative DNA damage) than never smokers in GO patients [3]. Recently , we observed that cigarette smoke extract (CSE)-induced more cytotoxicity and ROS accumulation in a dose-dependent manner in the GO orbital fibroblasts as compared to those of normal controls. The increased generation of ROS, especially the superoxide anions and hydrogen peroxide, can stimulate orbital fibroblasts proliferation and induce the production of pro-inflammatory cytokines, being key pathological features of GO [4]. More importantly, we also noted that cigarette smoke-mediated oxidative stress could induce fibrotic-related genes expression, including apolipoprotein J, fibronectin, and connective tissue growth factor (CTGF) in the GO orbital fibroblasts (169%, 180%, and 170%, respectively) , and these inductions could be inhibited by pretreatment with antioxidants.
Apolipoprotein J, fibronectin, and CTGF are all important fibrogenic factors. Especially, CTGF is critical for TGF-beta-mediated fibroblast-myofibroblast transdifferentiation and subsequent extracellular matrix deposition [5], which may contribute to the tissue remodeling and fibrosis process in GO. Besides, CSE has been reported to stimulate adipocyte differentiation in GO orbital fibroblasts either by synergizing with ROS or interleukin -1 [2,6]. Collectively, previous reports and our current findings may explain, in part, why smoking is associated with poor response to immunosuppressive therapy in GO.
References
1. Xing L, Ye L, Zhu W, Shen L, Huang F, Jiao Q, Zhou X, Wang S, Wang
W, Ning G. Smoking was associated with poor response to intravenous
steroids therapy in Graves' ophthalmopathy. Br J Ophthalmol. 2015;99:1686-
91.
2. Yoon JS, Lee HJ, Chae MK, Lee SY, Lee EJ. Cigarette smoke extract- induced adipogenesis in Graves' orbital fibroblasts is inhibited by quercetin via reduction in oxidative stress. J Endocrinol. 2013;216:145- 56.
3. Tsai CC, Cheng CY, Liu CY, Kao SC, Kau HC, Hsu WM, Wei YH. Oxidative stress in patients with Graves' Ophthalmopathy: Relationship between oxidative DNA damage and clinical evolution. Eye (Lond). 2009;23:1725-30.
4. Tsai CC, Cheng CY, Liu CY, Kao SC, Kau HC, Hsu WM, Wei YH.
Oxidative stress in patients with Graves' Ophthalmopathy: Relationship
between oxidative DNA damage and clinical evolution. Eye (Lond).
2009;23:1725-30.
6. Cawood TJ, Moriarty P, O'Farrelly C, O'Shea D. Smoking and thyroid -associated ophthalmopathy: a novel explanation of the biological link. Journal of Clinical Endocrinology and Metabolism. 2007;92:59-64.
We read with great interest the article entitled "Pathogenesis of
thyroid eye disease: review and update on molecular mechanisms" by Khong
et al [1]. We would like to contribute to the article with our novel
findings.
In our previous study, we first demonstrated the up-regulation of
mRNA and protein expression of fibrosis-related genes including
fibronectin, apolipoprotein J and connective tissue growth factor...
We read with great interest the article entitled "Pathogenesis of
thyroid eye disease: review and update on molecular mechanisms" by Khong
et al [1]. We would like to contribute to the article with our novel
findings.
In our previous study, we first demonstrated the up-regulation of
mRNA and protein expression of fibrosis-related genes including
fibronectin, apolipoprotein J and connective tissue growth factor (CTGF),
in the orbital fibroblasts from patients with TED, as compared with those
of normal controls [2]. In addition, the expression of CTGF in orbital
fibroblasts can be modulated by oxidative stress. Recently, we further
revealed that the enhanced expression of CTGF in TED orbital fibroblasts
correlated with the clinical activity score and ophthalmopathy index,
suggesting that increased levels of CTGF are pathologically significant
[unpublished data].
CTGF, a cysteine-rich matricellular protein of the CCN family, has
been implicated in mediating various cellular processes, including
adhesion, proliferation, differentiation, and migration, and extracellular
matrix production, all of which are common features of tissue remodelling
and fibrosis. Evidence has been increased suggesting that over-expression
of CTGF has been noted in numerous fibrotic disorders, including
pulmonary, renal, hepatic, skin, cardiac, and ocular fibrosis.
Inflammation often dominates the early course of TED, followed by
remodeling of orbital connective tissue, including accumulation of
extracellular matrix and fibrosis. Fibrosis process represents a relative
quiescent stage in the disease course of TED; however, it may cause much
of the substantial morbidity of the patients including severe lid
retraction, restrictive strabismus, proptosis, exposure keratopathy, and
compressive optic neuropathy. Current knowledge about the inflammatory
process of TED has been rapidly expanding, however, only limited studies
have addressed the fibrosis process of this disease. Elucidation of the
molecular mechanisms that initiate and regulate the process of fibrosis,
especially the role of CTGF in TED, is crucial for the development of
novel treatments.
References
1. Khong JJ, McNab AA, Ebeling PR, Craig JE, Selva D. Pathogenesis of
thyroid eye disease: review and update on molecular mechanisms. Br J
Ophthalmol 2016;100:142-50.
2. Tsai CC, Wu SB, Chang PC, Wei YH. Alteration of Connective Tissue
Growth Factor (CTGF) Expression in Orbital Fibroblasts from Patients with
Graves' Ophthalmopathy. PLoS One 2015;10:e0143514.
Optic disc edema in astronauts following long-duration space flight
We commend Morgan and colleagues for their discussion of optic disc
changes during and after long-duration space flight (LDSF). 1 They note
that astronauts after LDSF have developed clinical features (disc edema,
globe flattening) similar to those of idiopathic intracranial hypertension
(IIH) that may persist for many months post flight and sugg...
Optic disc edema in astronauts following long-duration space flight
We commend Morgan and colleagues for their discussion of optic disc
changes during and after long-duration space flight (LDSF). 1 They note
that astronauts after LDSF have developed clinical features (disc edema,
globe flattening) similar to those of idiopathic intracranial hypertension
(IIH) that may persist for many months post flight and suggest that these
changes result from increased intracranial pressure (ICP) "which persists
for months and years after their return to Earth."1
Cephalad microgravity fluid shifts may increase head and neck venous
pressure, thus inhibiting cerebrospinal fluid (CSF) drainage into the
venous system, increasing CSF pressure and leading to changes similar to
those seen in patients with IIH. However, lumbar puncture opening pressure
(LPOP) has been only moderately elevated (21 to 28.5 cm H20) in the 4
astronauts examined from 12 to 60 days post-mission.2 Although LPOP may
have been higher during the mission, we doubt these post-flight pressures
are sufficiently high to sustain disc edema for months post-mission.
As Morgan et al. note, microgravity exposure may disrupt flow within
the orbital optic nerve subarachnoid space (ONSAS), causing accumulation
of toxic metabolites and creating a ball-valve like effect that allows CSF
to enter the ONSAS but inhibits outflow, thus increasing pressure within
that compartment.3 In theory, either one or both ON sheaths may be
affected in a given astronaut, with or without increased ICP. Of seven
astronauts with disc edema, four have displayed disc asymmetry. One of
these had unilateral disc edema associated with an LPOP of 18 cmH20 1 week
after space flight.4 We also have observed persistent asymmetric disc
edema 6 months following LDSF in an astronaut with LPOP's of 22 and 16 cm
H20 performed 7 days and 1 year post mission respectively, again
suggesting ON sheath compartmentalization (manuscript in preparation). We
thus believe that increased ICP may not be the sole, or even primary,
cause of persistent optic disc changes post LDSF.
Thomas H. Mader MD
C. Robert Gibson OD
Andrew G. Lee MD
Prem S. Subramanian, MD, PhD
Neil R. Miller MD
References
1. Morgan WH, Balaratnasingam C, Lind CRP, Colley S, Kang MH, House
PH, Yu D. Cerebrospinal fluid pressure and the eye. Br J Ophthalmol
2015; 0:1-7.
2. Mader TH, Gibson CR, Pass AF, et al. Optic disc edema, globe
flattening, choroidal folds, and hyperopic shifts observed in astronauts
after long-duration space flight. Ophthalmology 2011;118:2058-69.
We thank Cheng and Tham for their interest in our systematic review
of global variations and time trends in primary open angle glaucoma
(POAG).[1] The comments raise some important issues relating to the
assimilation of evidence from observational studies, particularly in
summarising estimates of chronic disease prevalence.
Cheng and Tham have questioned our inclusive approach, which resu...
We thank Cheng and Tham for their interest in our systematic review
of global variations and time trends in primary open angle glaucoma
(POAG).[1] The comments raise some important issues relating to the
assimilation of evidence from observational studies, particularly in
summarising estimates of chronic disease prevalence.
Cheng and Tham have questioned our inclusive approach, which resulted
in us having a greater number of studies, number of POAG cases and
population denominator, and led to more precise estimates of POAG
prevalence compared to their earlier review.[2] The purpose of our more
complex approach was to explicitly model and quantify the heterogeneity
between population surveys, which used different survey methods and case
definitions of POAG. By quantifying these differences we are able to
provide estimates of POAG prevalence standardised to studies which use
optimal methods, i.e., that did not rely on intraocular pressure and
routinely performed visual field assessments on all participants, while
allowing studies with suboptimal methods to contribute to overall
estimates by accounting for the differences in study methods. This is
particularly important when attempting to appreciate time trends in POAG,
given changes in study methods over time. Moreover it allows greater
global representation of studies, allowing more recent studies,
particularly from less developed countries often with suboptimal methods,
to contribute. This would not have been the case if a more exclusive
approach had been adopted.
Cheng and Tham also raise the issue of examining response rates.
However, we examined differences in response rates in our earlier
review,[3] and found that these had little effect on our prevalence
estimates. We acknowledge in the paper the difficulty of extracting
response rates, as these are not routinely reported, and sometimes
confused with participation rates, i.e., the number who took part and
completed an examination out of those who agreed to take part. In general,
our experience is that assessment of study quality of observational
studies is complex, compared to established methods in experimental
studies. Attempts were made to judge the quality of studies on criteria
such as response rates and methods used. However, it is difficult to
extract measures of study quality in a meaningful way; for example well-
designed studies may have low response rates. Our experience suggests that
subjective assessments of study quality can sometimes be arbitrary and may
not capture characteristics which may influence the outcome of interest.
Hence, we have chosen an approach which seeks to understand variability by
explicitly modelling differences in study methods. We believe that this
makes for a fuller assessment, providing evidence based guidance for the
conduct of future studies. For instance, our work suggests that a recent
shift away from routine visual field testing, perhaps as an inadvertent
consequence of recent ISGEO guidelines,[4] may have artefactually
influenced prevalence estimates; such an effect would not have been
identified and quantified by a more exclusive approach.
Cheng and Tham also question whether our more inclusive strategy may
have led to lower global estimates of POAG prevalence; 2.2% (95% CrI 1.8%
to 2.8%) in our study [1] versus 3.1% (1.7% to 5.3%) in their earlier
review.[2] However, we would like to point out that these estimates are
not dissimilar, with our more precise estimate being encapsulated within
the much wider confidence interval of their earlier estimate.[2] That our
estimate is marginally lower may in part be attributable to our different
ethnic/regional categorization of studies, particularly amongst Asians.
The earlier review simply treated Asians as one population.[2] However, we
found evidence suggesting that the age specific prevalence differed across
Asian populations,[1] which needs to be accounted for when deriving global
estimates, especially given the large population size of Asia. Moreover,
our review includes more recent studies from Asian populations, where POAG
numbers are high given the large population, but age-specific prevalence
is actually lower compared to other ethnic groups. We feel that our
modelling approach is justified and provides an important corrective to
earlier work. For example, the earlier review suggested urban-rural
differences in disease prevalence,[2] where we showed no effect as urban-
rural associations were inextricably linked to ethnicity and the ethnic
specific associations with age.[1]
We hope that these estimates provide greater certainty and
transparency so we understand how the global and regional estimates of
POAG prevalence are derived. Greater precision allows for more accurate
and appropriate planning of health care service needed to care for those
with the condition. We also believe that our work will assist with the
design of future population based studies, which seek to describe the
population prevalence of glaucoma.
Authors: Dr Alicja R Rudnicka,* Dr Venediktos V Kapetanakis,* Miss
Michelle P Y Chan,# Professor Paul J Foster,#** Professor Derek G Cook,*
Professor Christopher G Owen
*Population Health Research Institute, St George's, University of
London, Cranmer Terrace, London, SW17 0RE, UK
#Division of Genetics and Epidemiology, UCL Institute of
Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK
**NIHR Biomedical Research Centre Moorfields Eye Hospital NHS
Foundation Trust, 162 City Road, London EC1V 2PD, UK.
References:
1. Kapetanakis VV, Chan MP, Foster PJ, Cook DG, Owen CG, Rudnicka AR.
Global variations and time trends in the prevalence of primary open angle
glaucoma (POAG): a systematic review and meta-analysis. Br J Ophthalmol
2015.
2. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global
prevalence of glaucoma and projections of glaucoma burden through 2040: a
systematic review and meta-analysis. Ophthalmology 2014; 121(11):2081-
2090.
3. Rudnicka AR, Mt-Isa S, Owen CG, Cook DG, Ashby D. Variations in
primary open-angle glaucoma prevalence by age, gender, and race: a
Bayesian meta-analysis. Invest Ophthalmol Vis Sci 2006; 47(10):4254-4261.
4. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and
classification of glaucoma in prevalence surveys. Br J Ophthalmol 2002;
86(2):238-242.
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