We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of i...
We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of inflammation in primary rhegmatogenous retinal detachment. Therefore, we challenge laser flare values beyond 100pc/ms. Measurements become easily disturbed by background lighting or cells leading to the necessity to exclude measurements falsified by artefacts.
It would be interesting to know details on the protocol the authors followed to exclude artefacts. Furthermore, we would appreciate an explanation for the unusual variation of the values and the discrepant data towards previous reports.(2,4)
Reference List
1. Mulder VC, Tode J, van Dijk EH, Purtskhvanidze K, Roider J, Van Meurs JC et al. Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol 2017. doi: 10.1136/bjophthalmol-2016-309134.
2. Conart JB, Kurun S, Ameloot F, Trechot F, Leroy B, Berrod JP. Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Acta Ophthalmol 2016.
3. Hoerster R, Hermann MM, Rosentreter A, Muether PS, Kirchhof B, Fauser S. Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol 2013;97:450-3.
4. Schroder S, Muether PS, Caramoy A, Hahn M, Abdel-Salam M, Diestelhorst M et al. Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Retina 2012;32:38-42.
Thank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preopera...
Thank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preoperative flare value above 100 pc/ms. These measurements were accurate because they showed small SD’s (e.g. mean 263.8± SD 2.8; mean 196.5±SD 3.5; mean 162.0±SD 6.0) and flare was also visible upon slit lamp examination. Therefore, because these values do occur in patients with a rhegmatogenous retinal detachment we feel that inclusion of these measurements is mandatory.
However, excluding patients with a preoperative flare value above 100 pc/ms from our regression and ROC analyses – as is suggested by dr. Schaub and colleagues – did not significantly improve the results from either centre 1 or centre 2. Logistic regression centre 1: OR 1.013; p = 0.446, centre 2: OR 1.035; p = 0.028. Sensitivity and specificity at a cut-off of 15 pc/ms dropped to 78 and 39% in centre 1, and 36% and 77% in centre 2 (p = 0.051).
A possible explanation for the discrepancy with the previous reports is our low prevalence of postoperative PVR (7.5% and 6.2% respectively) compared to the previous reports. All previous reports included consecutive patients and found prevalences of 10.3%(1), 14.9%(2) and 20% (3). Both the positive predictive value (PPV) and the odds ratio (OR) are affected by the prevalence. This means that even with comparable sensitivity and specificity the PPV and the OR will be lower when the prevalence is lower. In addition, different reports used different definitions of postoperative PVR. We used reoperation due to epiretinal membranes and/or subretinal strands within six months of initial surgery, as did Schröder et al.(1) Hoerster et al. based their findings on PVR grade C at 3 months postoperatively. While ten patients developed PVR only four (6%) needed a reoperation.(2) It is unclear from the report whether all four patients had a flare value > 15 pc/ms but if this were the case this would give a PPV of 20% and OR of 8 instead of the reported 40% and 30. Conart et al. used PVR grade B and C at 6 months as the outcome. Moreover, they included 20% patients with preoperative PVR grade C which influenced the postoperative number of patients with PVR. Both studies included flare values > 100 pc/ms which confirms that high values are not uncommon.(2,3)
The predictive value of the flare value thus depends on the patient group that is targeted. Our results indicate that there is a large overlap in flare values which makes selecting those patient at high risk for developing postoperative PVR (according to our definition) inaccurate.(4) Dependent on the implications of a positive test result (flare value > 15pc/ms) we should decide whether a false discovery rate of 60-90% is acceptable.
We agree with dr. Schaub and collegues that identifying patients with an increased risk of PVR would be of great benefit in studies of the treatment of PVR by “enriching” the study population. Unfortunately, in our study, we have not been able to validate preoperative flare measurements for this purpose.
Recently, however, we have shown that postoperative flare measurements may have that potential (Mulder et al, non published data, presented at the NOG Maastricht, March 29 2017), and we encourage other groups to validate these findings.
References
1 Schroder S, Muether PS, Caramoy A, et al. Anterior chamber aqueous flare is a strong predictor for proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Retina 2012;32(1):38-42.
2 Hoerster R, Hermann MM, Rosentreter A, et al. Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment. Br.J.Ophthalmol. 2013;97(4):450-453.
3 Conart JB, Kurun S, Ameloot F, et al. Validity of aqueous flare measurement in predicting proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment. Acta Ophthalmol. 2016;.
4 Mulder VC, Kluft C, van Etten PG, et al. Higher vitreous concentrations of dabigatran after repeated oral administration. Acta Ophthalmol. 2017;.
Dear Sir,
We read the article "Classification of diabetic macular odema using ultra-widefield angiography and implications for response to anti-VEGF therapy" by Xue K, et al1 with great interest. The authors aimed to classify Diabetic macular odema [DMO] using ultra-widefield flourescein angiography [UWFA] and evaluate response to anti-vascular endothelial growth factor [anti-VEGF]. They concluded that UWFA facilitates detection of peripheral ishemia. DMO group with significant peripheral ishemia responded well to anti-VEGF therapy than other groups. We congratulate the author for their lightening study about subject and would like to make some contributions about study.
The study did not mention the severity of diabetes of the patients enrolled in the study nor systemic comorbid conditions like glycemic control, systolic hypertension, protinuria1, which would alter the incidence of macular odema.2, 3
The study selected patients with DMO who have been given subthreshold micropulse diode laser. As it was not mentioned in the study, we wonder if the study desires to see the response of anti-VEGF in non-resolving macular odema patients alone. Also, it was to our surprise why patients with Panretinal photocoagulation were not excluded from the study while classifying the patients into 3 groups .
The classification of DMO into three groups was not clearly satisfying because there would be always a component of ishemia overlapping between t...
Dear Sir,
We read the article "Classification of diabetic macular odema using ultra-widefield angiography and implications for response to anti-VEGF therapy" by Xue K, et al1 with great interest. The authors aimed to classify Diabetic macular odema [DMO] using ultra-widefield flourescein angiography [UWFA] and evaluate response to anti-vascular endothelial growth factor [anti-VEGF]. They concluded that UWFA facilitates detection of peripheral ishemia. DMO group with significant peripheral ishemia responded well to anti-VEGF therapy than other groups. We congratulate the author for their lightening study about subject and would like to make some contributions about study.
The study did not mention the severity of diabetes of the patients enrolled in the study nor systemic comorbid conditions like glycemic control, systolic hypertension, protinuria1, which would alter the incidence of macular odema.2, 3
The study selected patients with DMO who have been given subthreshold micropulse diode laser. As it was not mentioned in the study, we wonder if the study desires to see the response of anti-VEGF in non-resolving macular odema patients alone. Also, it was to our surprise why patients with Panretinal photocoagulation were not excluded from the study while classifying the patients into 3 groups .
The classification of DMO into three groups was not clearly satisfying because there would be always a component of ishemia overlapping between the different groups. Third group was basically with neovascularisation according to the author, but ishemia is the basic driving cause for neovascularisation. Also, it was not mentioned about type of neovascularisation that was considered in the third group, Neovascularisation of disc [NVD] OR Neovasculasiation elsewhere [NVE]. Since neovascularisation at disc would suggest that there is global ishemia. So we feel second and third group were not clearly defined by authors in the study.
According to the study, group 2 i.e. with peripheral ishemic group responded better to anti-VEGF than other groups. We wonder how would this grouping alter the management of DMO in any way, as it is already known that DMO treated with anti-VEGF would improve vision and reduce the macular odema.4, 5
Financial Support and Sponsorship
Nil
Conflicts of Interest
There are no conflicts of interest
References:
1. Xue K etal. Classification of diabetic macular odema using ultra-widefield angiography and implications for response to anti-VEGF therapy. Br J Ophthalmol 2017; 101:559-563.
2. Early treatment for diabetic retinopathy study [ETDRS] research group .ETDRS design and baseline patient characteristics. ETDRS report number 7 .Ophthalmology 1991; 98: 741 - 756.
3. Ronald KLIEN, MD, MPH, Michaiel D. Knudston, MS, etal. WISCONSON EPIDEMIOLOGICAL STUDY OF DIABETIC RETINOPATHY, the twenty five year incidence of macular odema in persons with type 1 diabetes .Ophthalmology 2009; 116 [3]: 497-503.
4. Paul Mitchell MD, PhD, Francesco Bandello, MD, FEBO; etal. RESTORE STUDY. Ranibizumab monotherapy or combined with laser versus monotherapy for diabetic macular odema. Ophthalmology 2011; 118 [4]: 615-25.
5. Pascale Massin, MD, PhD, Francesco Bandello ,MD ,FEBO etal Safety and efficacy of Ranibizumab in Diabetic Macular Edema [RESOLVE STUDY]. Diabetes care 2010; 33: 2399-2405.
Dear Sir
Thanks for this notification
1. Preoperative and postoperative characteristics for the CF group are shown in Table 2 (line 13)
Answer: This was a typing error hoping if it will be corrected to: preoperative and postoperative characteristics for the AMG group are shown in Table 2
2. The study does not mention about the location postoperatively. How will the site of the ulcer change from central to paracentral and vice versa?
Answer: Eighteen from twenty patients in each group showed healing of the ulcer, and two cases in each group were sent for keratoplasty (from 4 to 8 days after intervention). So, there is no need to mention size of the ulcer. Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
So the description of the ulcer will be changed from peripheral to central.
There was no need to mention this as the ulcers healed.
3. There is no mention about the complications studied. Descemetocele and perforations occurred preoperatively.
Answer: Three cases with perforation and one case with descemetocele were referred to immediate keratoplasty, and other ulcers healed, so there were no complications to be mentioned. Regarding other complications in secondary outcome measures, there were no complications and this was mentio...
Dear Sir
Thanks for this notification
1. Preoperative and postoperative characteristics for the CF group are shown in Table 2 (line 13)
Answer: This was a typing error hoping if it will be corrected to: preoperative and postoperative characteristics for the AMG group are shown in Table 2
2. The study does not mention about the location postoperatively. How will the site of the ulcer change from central to paracentral and vice versa?
Answer: Eighteen from twenty patients in each group showed healing of the ulcer, and two cases in each group were sent for keratoplasty (from 4 to 8 days after intervention). So, there is no need to mention size of the ulcer. Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
So the description of the ulcer will be changed from peripheral to central.
There was no need to mention this as the ulcers healed.
3. There is no mention about the complications studied. Descemetocele and perforations occurred preoperatively.
Answer: Three cases with perforation and one case with descemetocele were referred to immediate keratoplasty, and other ulcers healed, so there were no complications to be mentioned. Regarding other complications in secondary outcome measures, there were no complications and this was mentioned in the discussion section in the second paragraph of the last page.
Dear Editor,
I read with interest the above randomised clinical study published by
Abdulhalim et al in BrJ Ophthal 2015;99:59-63.
The main outcome measures were location, size and depth of the lesion,
epithelialisation time and persistence of infection. Secondary outcome
measures include visual acuity and other complications.
Table 1 states Demographic data and preoperative characteristics for
conjunctival flap group.
Table 2 states Demographic data and preoperative characteristics for
amniotic transplant group.
However in the narration in Results-it states preoperative and
postoperative characteristics for the CF group are shown in Table 1 (line
5) preoperative and postoperative characteristics for the CF group are
shown in Table 1. preoperative and postoperative characteristics for the CF
group are shown in Table 2 (line 13). This is very confusing.
Table 3 shows a comparison of CF group and AMG. Here the preoperative and
postoperative characteristics are all in one table.
The main outcome measures were location. The study does not mention about
the location postoperatively. How will the site of the ulcer change from
central to paracentral and vice versa? There is no mention about the size
and depth of the ulcer- which is also a parameter that was studied.There is
no mention about the complications studied. Descematocoele and perforations...
Dear Editor,
I read with interest the above randomised clinical study published by
Abdulhalim et al in BrJ Ophthal 2015;99:59-63.
The main outcome measures were location, size and depth of the lesion,
epithelialisation time and persistence of infection. Secondary outcome
measures include visual acuity and other complications.
Table 1 states Demographic data and preoperative characteristics for
conjunctival flap group.
Table 2 states Demographic data and preoperative characteristics for
amniotic transplant group.
However in the narration in Results-it states preoperative and
postoperative characteristics for the CF group are shown in Table 1 (line
5) preoperative and postoperative characteristics for the CF group are
shown in Table 1. preoperative and postoperative characteristics for the CF
group are shown in Table 2 (line 13). This is very confusing.
Table 3 shows a comparison of CF group and AMG. Here the preoperative and
postoperative characteristics are all in one table.
The main outcome measures were location. The study does not mention about
the location postoperatively. How will the site of the ulcer change from
central to paracentral and vice versa? There is no mention about the size
and depth of the ulcer- which is also a parameter that was studied.There is
no mention about the complications studied. Descematocoele and perforations
occured pre-operatively.
Was the visual acuity best corrected or uncorrected visual acuity.
I whole heartedly appreciate the work conducted by Chan Yun Kim et al in studying the treatment patterns and medication adherence of patients with glaucoma in South Korea.This study concluded that medication non adherence was seen more commonly in males , increased daily number of administration and increase in the number of eyedrops. We have also conducted a similar study at our centre in North India and would like to share our results .Our results are in agreement to the work conducted by Chan Yun Kim stating that increased number of instillation and increased number of eyedrops contribute significantly to medication non adherence. However, in our study we also found that medication adherence varies in different severity grades of glaucoma with severe stages being significantly more adherent than mild to moderate stages of glaucoma.Additionally, there was no difference found in medication adherence among males or females.
We again express our gratitude to the researcher in enlightening our minds regarding medication adherence in South Korean population.
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are li...
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are limitations including the lack of a standard algorithm of treatment and the impossibility to include other variables that might alter the final outcomes of the patients. Therefore, and as we also discussed, this imply that the conclusions presented must be taken with caution. Thus, when interpreting the results of a retrospective study it is important to understand and be aware of the possible bias and limitations, allowing the reader to take advantage of the many strengths of this design into incorporation of knowledge into their daily clinical practice. (4)
References.
1) Loya-Garcia D, Serna-Ojeda JC, Pedro-Aguilar L, et al. Non-traumatic corneal perforations: aetiology, treatment and outcomes. Br J Ophthalmol. 2017;101(5):634-639.
2) Jhanji V, Young AL, Mehta JS, et al. Management of corneal perforation. Surv Ophthalmol. 2011;56(6):522-38.
3) Dua HS, Gomes JA, King AJ, et al. The Amniotic Membrane in Ophthalmology. Surv Opthalmol 2004; 49:51-77.
4) Euser AM, Zoccali C, Jager KJ, et al. Cohort studies: prospective versus retrospective. Nephron Clin Pract. 2009;113(3):c214-7.
Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant. Iacono et al. Br
J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-201...
Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic
macular oedema after intravitreal dexamethasone implant. Iacono et al. Br
J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-2016-308726.
Dear Editor
We would like to address several challenges that have arisen from the
study by Iacono et al (1), which can be specifically summarized below.
1. The study was uncontrolled and was carried out on a small study
population. There was a selection bias attributable to the heterogeneous
prior treatments administered to the patients, namely, panretinal
photocoagulation (PRP), grid photocoagulation, focal laser
photocoagulation, and anti-vascular endothelial growth factor (VEGF)
injections. Nothing was stated regarding the existence of a washout period
between previous PRP, focal/grid laser treatment and the first
dexamethasone implant.
2. Three outer retinal layers (eg, the external limiting membrane,
the ellipsoid zone, and retinal pigment epithelium [RPE]) were thoroughly
investigated as potential predictors of vision loss/improvement. There are
no data on the qualitative status of the fourth outer retinal layers, that
is, the interdigitation zone, which corresponds to the contact cylinder
represented by the apices of the RPE cells that encase part of the cone
outer segments.
3. Nothing was stated referring to the prevalence of the
vitreoretinal interface abnormalities (eg, vitreomacular adhesion/traction
and epiretinal membranes) and their changes during the study as potential
predictive factors on anatomical and visual outcomes after dexamethasone
implant in eyes affected by recalcitrant diabetic macular oedema (DME)
associated with proliferative diabetic retinopathy.
4. In the assessment of the final results of this study we have
considered the current assertion that evaluation of outcomes has to be
guided by anatomical measure data with visual changes as a secondary guide
(2). Accordingly, the outcomes of this series are unsatisfactory. Despite
a mean gain of approximately 10 Early Treatment Diabetic Retinopathy Study
letters in visual acuity correlated with a significant improvement in the
integrity of the outer retinal layers, the central macular thickness (CMT)
decreased significantly to 423 microns after treatment, a value that is
more than the cutoff for the upper level of normal CMT (3). Persistence of
this high value of the CMT highlights unresolved macular edema and
indicates that the disease process is still active and progressive,
requiring further treatment with antiangiogenic agents.
5. The patients in the present study suffered from persistent DME
with a 30.3 months'duration of the disease, who have been treated with an
average of 2.2 dexamethasone implants within the 12-month follow-up, a
number of injections which has proved to be insufficient to obtain dryness
of the macula. These facts favored the delayed occurrence of a chronic
retinal capillaropathy owing to permanent breakdown of the inner and outer
blood-retinal barriers (eg, pigmentary changes in the fovea, poorly
controlled severe recurrent macular edema, telangiectatic vessels with
leakage, and epiretinal membrane formation). This permanent retinal
capillaropathy was temporarily relieved by reduction of oedematous
component with treatment. However, this condition is incurable owing to
the irreversible ischemic lesions to the macular ganglion cell complex,
close to the foveola, with macular oedema being a minor factor.
Altogether, regardless of the therapeutic agents chosen (anti-VEGF
agents/corticosteroids), the efficacy of therapy depends primarily on the
promptness of the treatment after DME diagnosis. Any delay in treatment
will adversely influence the restoration of visual functions, which are
difficult to correct even with subsequent treatment (4,5).
References
1. Iacono P, Parodi MB, Scaramuzzi M, et al. Morphological and functional
changes in recalcitrant diabetic macular oedema after intravitral
dexamethasone implant. Br J Ophthalmol 2016;
http:/dx.doi.org/10.1136/bjophthalmol-2016-308726.
2. Freund KB, Korobelnik JF, Devenyl R, et al. Treat-and-extend regimens
with anti-VEGF agents in retinal diseases. Aliterature review and
consensus recommendations. Retina 2015;35(8):1489-1506.
3. Gover S, Murthy RK, Brar VS, et al. Normative data for macular
thickness by high-definition spectral-domain optical coherence tomography
(spectralis). Am J Ophthalmol 2009;148(2):266-271.
4. Calugaru D. Calugaru M. Real-world outcomes of ranibizumab treatment
for diabetic macular edema in a United Kingdom National Health Service
setting. Am J Ophthalmol 2017;174:175-176.
5. Calugaru D, Calugaru M. Comments to: Long-term efficacy and safety of
intrvitreal dexamethasone implant for the treatment of diabetic macular
edema. Eur J Ophthalmol 2016;26(6):e171-e172.
Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
We would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and...
Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
We would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and complete dry macula at month 6; the changes of central macular thickness (CMT) and subfoveal choroidal thickness (CT) at month 6; and the explanation of the mechanism by which the subfoveal CT was reduced after aflibercept therapy.
3. At baseline, the two groups of polypoidal choroidal vasculopathy (PCV) (2) were not comparable because there have been significant differences regarding the polyp number, branch vascular network (BVN) leakage, and subfoveal CT. The comparison should have been conducted only after using the multivariate regression analyses for adjustment of the baseline differences.
4. The comparative analysis of the 3-month outcomes highlighted a significant difference between the two groups relating to the reductions in the subfoveal CT, which was significantly higher in the type 2 PCV and no differences with respect to the percentages of the dry macula as well as the changes in the best corrected visual acuity (BCVA) score and CMT. The significantly higher proportion of the patients with complete polyp regression in the type 1 PCV should be interpreted considering the polyp number existing at baseline which was significantly higher in the type 1 than in the type 2 patients.
5. At 6 months, there was no significant difference in changes between the two groups regarding the percentages of the dry macula, BCVA score, and CMT. However, the evaluation of the treatment efficacy of aflibercept revealed a significant decrease of the subfoveal CT relative to the baseline values in the two types of PCV with a significantly greater reduction in the type 2 idiopathic PCV than the type 1 polypoidal choroidal neovascularisation. Conceivably, suppression of the choroidal vascular hyperpermeability and the vasoconstriction induced by aflibercept (3) may be more prominent in the type 2 PCV patients having a thicker choroid with abnormally enlarged and permeable choroidal vessels.
Altogether, in the short-term, the significant subfoveal CT thinning by aflibercept does not seem to result in visual deleterious changes. However, in the long-term, the prolonged inhibition of the vascular endothelial growth factor (VEGF) using aflibercept may affect the integrity of the choriocapillaris (CC) taking into account the key role played by the VEGF-A in the regulation of the survival and permeability of the CC. In addition, through the fragment cristalizable (Fc) domain, aflibercept can bind to the Fc receptor of both CC endothelial cells and red blood cells, leading to complement mediated cell death (4). Thus, the choroidal vascular impairment may affect the integrity of RPE and the outer retina with subsequent visual damaging effects because the choroid is involved in maintaining perfusion of the outer retinal layers and is the sole source of metabolic exchange for the fovea.
References
1. Jeong S, Sagong M. Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Br J Ophthalmol 2016; http:/ dx. doi. org/ 10.1136/bjophthalmol-2016-309144.
2. Calugaru D. Calugaru M. Comparison of time to retreatment and visual function between ranibizumab and aflibercept in age-related macular degeneration. Am J Ophthalmol 2017;174:181-182.
3. Hata M, Oishi A, Tsujikawa A, et al. Efficacy of intravitreal injection of aflibercept in neovascular age-related macular degeneration with or without vascular hyperpermeability. Invest Ophthalmol Vis Sci 2014;55:7874-7880.
4. Julien S, Biesemeier A, Taubitz T, Schraermeyer U. Different effects of intravitreally injected ranibizumab and aflibercept on retinal and choroidal tissues of monkey eyes. Br J Ophthalmol 2014;98:Z813-825.
Dear Editor,
We read your article titled- Non-traumatic corneal perforations: aetiology, treatment and outcomes: with great interest. Corneal perforation is an acute ophthalmic emergency. This review describes the aetiology, plausible location and the multiple ways to approach the management of this condition in a very a systematic manner.
We do appreciate the organised mode of stratification and care of non- traumatic corneal perforation presented in the article. However, although the results are interesting, we feel that caution should be exercised when drawing conclusions from this data.
Initially, in results there are 127 eyes of 116 patients under the review. However, while describing the anatomical location of the perforation, only 102 eyes have been accounted for, with no records for the remaining 25 eyes. This would change the calculated p value significantly.
Similarly, where the initial treatments for perforations were being reviewed 133 eyes were mentioned as treated, thus including six extra unaccounted for eyes to the total. This would seriously jeopardise the authenticity of the calculated results.
Hence, there appears to be serious doubts regarding the validity of the conclusions of this review. A clearer and more detailed explanation or a recalculation of the results is warranted in this regard.
We noticed the article entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment" by Mulder and associates with interest.(1)
Several studies have been published concluding that elevated aqueous flare values seem to be associated with increased risk for PVR redetachment.(2-4) Schroeder et al reported that values >15 photon counts per milliseconds (pc/ms) increases the risk for PVR 16-fold.(4) Hoerster et al showed that the odds ratio for PVR development with preoperative flare values >15pc/ms was 30.7 (p=0.0001) with a sensitivity of 80% and specificity of 79%.(3) Conart et al verified these findings (OR 12.3, p<0.0001 for later PVR in flare values >15 pc/ms).(2)
In contrast Mulder et al concluded on their data compilation that laser flare measurements are inaccurate in predicting PVR.(1) Logistic regression analyses showed a significant increase in odds with increasing flare at least for the second centre (1) supporting the notion that high flare measurements herald PVR. However, the large variation precluded sufficient sensitivity and specificity to separate between groups. We assume the reason for the large variation is that high-level outliers were included. For center 2 only the highest and the lowest values were excluded, no information is provided for center 1. Values of 100pc/ms, here up to 312pc/ms, are uncommon for the low-level type of i...
Show MoreThank you for your interest in our publication entitled "Preoperative aqueous humour flare values do not predict proliferative vitreoretinopathy in patients with rhegmatogenous retinal detachment".
As per request, we would like to provide more details on our protocol.
As described in our discussion, centre 1 used the mean of ten correct measurements making sure these measurements did not differ more than 2 standard deviations from each other. In centre 2, seven correct measurements were recorded of which the highest and lowest value were discarded leaving an average of five measurements. A correct measurement meant that the background readings did not differ more than 15% (indicated by the code ‘BG’ on the output) and that single “cell/C” measurements were replaced by an additional measurement. In addition, measurements with a small signal to noise ratio (indicated by the code ‘s/n’) were avoided as much as possible. However, with low flare values this was not always feasible. The flare meters were located in a room with blinds (centre 1) and a room without windows (centre 2); computer screens and lights were turned off during measurements. Both flare meters were calibrated monthly to assure correct readings. We therefore believe that the included mean values are artefact free.
Despite the exclusion of patients with additional conditions such as AMD, CRVO and preoperative PVR grade C or higher, we did end up with patients with a preopera...
Show MoreDear Sir,
Show MoreWe read the article "Classification of diabetic macular odema using ultra-widefield angiography and implications for response to anti-VEGF therapy" by Xue K, et al1 with great interest. The authors aimed to classify Diabetic macular odema [DMO] using ultra-widefield flourescein angiography [UWFA] and evaluate response to anti-vascular endothelial growth factor [anti-VEGF]. They concluded that UWFA facilitates detection of peripheral ishemia. DMO group with significant peripheral ishemia responded well to anti-VEGF therapy than other groups. We congratulate the author for their lightening study about subject and would like to make some contributions about study.
The study did not mention the severity of diabetes of the patients enrolled in the study nor systemic comorbid conditions like glycemic control, systolic hypertension, protinuria1, which would alter the incidence of macular odema.2, 3
The study selected patients with DMO who have been given subthreshold micropulse diode laser. As it was not mentioned in the study, we wonder if the study desires to see the response of anti-VEGF in non-resolving macular odema patients alone. Also, it was to our surprise why patients with Panretinal photocoagulation were not excluded from the study while classifying the patients into 3 groups .
The classification of DMO into three groups was not clearly satisfying because there would be always a component of ishemia overlapping between t...
Dear Sir
Show MoreThanks for this notification
1. Preoperative and postoperative characteristics for the CF group are shown in Table 2 (line 13)
Answer: This was a typing error hoping if it will be corrected to: preoperative and postoperative characteristics for the AMG group are shown in Table 2
2. The study does not mention about the location postoperatively. How will the site of the ulcer change from central to paracentral and vice versa?
Answer: Eighteen from twenty patients in each group showed healing of the ulcer, and two cases in each group were sent for keratoplasty (from 4 to 8 days after intervention). So, there is no need to mention size of the ulcer. Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
Regarding site of the ulcer; some paracentral ulcer are creeping and/or enlarging in size to involve the central part.
So the description of the ulcer will be changed from peripheral to central.
There was no need to mention this as the ulcers healed.
3. There is no mention about the complications studied. Descemetocele and perforations occurred preoperatively.
Answer: Three cases with perforation and one case with descemetocele were referred to immediate keratoplasty, and other ulcers healed, so there were no complications to be mentioned. Regarding other complications in secondary outcome measures, there were no complications and this was mentio...
Dear Editor,
I read with interest the above randomised clinical study published by
Abdulhalim et al in BrJ Ophthal 2015;99:59-63.
The main outcome measures were location, size and depth of the lesion,
epithelialisation time and persistence of infection. Secondary outcome
measures include visual acuity and other complications.
Table 1 states Demographic data and preoperative characteristics for
conjunctival flap group.
Table 2 states Demographic data and preoperative characteristics for
amniotic transplant group.
However in the narration in Results-it states preoperative and
postoperative characteristics for the CF group are shown in Table 1 (line
5) preoperative and postoperative characteristics for the CF group are
shown in Table 1. preoperative and postoperative characteristics for the CF
group are shown in Table 2 (line 13). This is very confusing.
Table 3 shows a comparison of CF group and AMG. Here the preoperative and
postoperative characteristics are all in one table.
The main outcome measures were location. The study does not mention about
Show Morethe location postoperatively. How will the site of the ulcer change from
central to paracentral and vice versa? There is no mention about the size
and depth of the ulcer- which is also a parameter that was studied.There is
no mention about the complications studied. Descematocoele and perforations...
Dear sir/maam
I whole heartedly appreciate the work conducted by Chan Yun Kim et al in studying the treatment patterns and medication adherence of patients with glaucoma in South Korea.This study concluded that medication non adherence was seen more commonly in males , increased daily number of administration and increase in the number of eyedrops. We have also conducted a similar study at our centre in North India and would like to share our results .Our results are in agreement to the work conducted by Chan Yun Kim stating that increased number of instillation and increased number of eyedrops contribute significantly to medication non adherence. However, in our study we also found that medication adherence varies in different severity grades of glaucoma with severe stages being significantly more adherent than mild to moderate stages of glaucoma.Additionally, there was no difference found in medication adherence among males or females.
We again express our gratitude to the researcher in enlightening our minds regarding medication adherence in South Korean population.
Dear editor.
We thank Sarmad et al. for their interest in our publication. Our study is a retrospective review of several variables regarding non-traumatic corneal perforations (1). In handling clinical records for a retrospective analysis, missing variables represent a common problem. In relation to the location of corneal perforation, information was not available in 25 eyes thus the number does not match. Hence, in consideration of this inevitable flaw we decided not to include the anatomical location of perforation into the model presented in the manuscript, therefore all the variables included in this statistical model had no missing values.
Clinical treatment of corneal perforation is often complex and a single intervention may not address the patient full pathology, therefore more than one treatment is frequently used. (2) This explains the increased number of initial treatments in the first clinical intervention, one example of this scenario are the patients needing simultaneous tectonic penetrating keratoplasty to restore ocular integrity and concurrent amniotic membrane transplantation to aid in the control of ocular surface. (2)(3)
These two situations might not be precise in our manuscript, but we take the opportunity of this letter to clarify them. However, that is unquestionably far from compromising the validity of the conclusions. Definitely, as any retrospective study, and as we mention in the discussion of our article, there are li...
Show MoreMorphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Morphological and functional changes in recalcitrant diabetic macular oedema after intravitreal dexamethasone implant. Iacono et al. Br J Ophthalmol 2016;http:/dx.doi.org/10.1136/bjophthalmol-201...
Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Short-term efficacy of intravitreal aflibercept depending on angiographic classification of polypoidal choroidal vasculopathy. Jeong and Sagong. Br J Ophthalmol 2016; http: /dx.doi. org/ 10.1136/bjophthalmol-2016-309144.
Dear Editor
Show MoreWe would like to address several challenges that have arisen from the study by Jeong and Sagong (1), which can be specifically summarized below.
1. The study included a relatively small sample size of cases examined with a fairly short follow-up period.
2. Several relevant data are missing in the study. For example, the anatomic types of macular edema (diffuse/cystic changes within neurosensory retina/subretinal/sub retinal pigment epithelium (RPE) fluid/ mixed type) at baseline and at months 3 and 6; the qualitative status of the 4 outer retinal layers (eg, the external limiting membrane band, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelial band) at presentation as well as the magnitude of changes (disruption/absence) during the study as potential predictors of visual loss/improvement after aflibercept (Eylea; Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA) treatment; the percentages of patients with complete polyp regression and...
Dear Editor,
We read your article titled- Non-traumatic corneal perforations: aetiology, treatment and outcomes: with great interest. Corneal perforation is an acute ophthalmic emergency. This review describes the aetiology, plausible location and the multiple ways to approach the management of this condition in a very a systematic manner.
We do appreciate the organised mode of stratification and care of non- traumatic corneal perforation presented in the article. However, although the results are interesting, we feel that caution should be exercised when drawing conclusions from this data.
Initially, in results there are 127 eyes of 116 patients under the review. However, while describing the anatomical location of the perforation, only 102 eyes have been accounted for, with no records for the remaining 25 eyes. This would change the calculated p value significantly.
Similarly, where the initial treatments for perforations were being reviewed 133 eyes were mentioned as treated, thus including six extra unaccounted for eyes to the total. This would seriously jeopardise the authenticity of the calculated results.
Hence, there appears to be serious doubts regarding the validity of the conclusions of this review. A clearer and more detailed explanation or a recalculation of the results is warranted in this regard.
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