We thank Drs Calugaru M. and Calugaru D. for their interest in our
article,1 and we welcome this opportunity to address their concerns.
The purpose of our study was to investigate the outcomes of intravitreal
antivascular endothelial growth factor (VEGF) therapy in eyes with both
neovascular age-related macular degeneration (AMD) and diabetic
retinopathy (DR) as higher levels of VEGF due to concomitant DR in eyes
with a...
We thank Drs Calugaru M. and Calugaru D. for their interest in our
article,1 and we welcome this opportunity to address their concerns.
The purpose of our study was to investigate the outcomes of intravitreal
antivascular endothelial growth factor (VEGF) therapy in eyes with both
neovascular age-related macular degeneration (AMD) and diabetic
retinopathy (DR) as higher levels of VEGF due to concomitant DR in eyes
with active neovascular AMD may lead to a higher consumption of anti-VEGF
molecules, thus impairing the efficacy of treatment.1
As pointed out, in our series we included patients that had undergone
other treatments for DR, either before or during administration of anti-
VEGF drugs for neovascular AMD. This is an obvious limitation of our
retrospective study, even though all the patients included were treatment
na?ve for anti-VEGF agents.
We recorded that best corrected visual acuity, after a significant
improvement at 1 year, returned to baseline values at the last follow-up
visit, while mean central macular thickness (CMT) significantly decreased
from 408 ?m to 335 ?m. As pointed out, these results may suggest that
disease process could be still active and progressive requiring further
treatment. 2 In fact, at the end of follow up, CNV was still active in 39%
eyes, while 61% eyes developed an atrophic/fibrotic scar with no signs of
activities. On the other hand, CMT could have been influenced by the two
concomitant diseases, the diabetic retinopathy and the choroidal
neovascularization. In particular, we cannot exclude that some patients
underwent anti-VEGF treatment, DR-related macular edema.
We agree that, a lot of cytokines, chemokines, and growth factors may be
associated with DR pathophysiology.3,4 Further prospective studies should
consider the effects of these molecules and the use of non-specific anti-
VEGF substances which inhibits the up-regulation of the VEGF and
suppresses the expression of the whole panoply of the proinflammatory and
proangiogenic factors.
References
1. Bandello F, Corvi F, La Spina C, et al. Outcomes of intravitreal anti-
VEGF therapy in eyes with both neovascular age-related macular
degeneration and diabetic retinopathy. Br J Ophthalmol 2016;
http:/dx.doi.org/10.1136/bjophthalmol-2016- 308400.
2. 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;148:266-271.
3. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of
various cytokines after intravitreal triamcinolone versus bevacizumab for
diabetic macular edema. Am J Ophthalmol 2011;152:686-694.
4. Shah SU, Harless A, Bleau L, et al. Prospective randomized subject-
masked study of
intravitreal bevacizumab monotherapy versus dexamethasone implant
monotherapy in
the treatment of persistent diabetic macular edema. Retina. 2016 Apr 27.
[Epub ahead of print]
Outcomes of intravitreal anti-VEGF therapy in eyes with both
neovascular age-related macular degeneration and diabetic retinopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Outcomes of intravitreal anti-VEGF therapy in eyes with both
neovascular age-related macular degeneration and diabetic retinopathy.
Bandello et al. Br J Ophthalmol 2016; http:+/dx.
do...
Outcomes of intravitreal anti-VEGF therapy in eyes with both
neovascular age-related macular degeneration and diabetic retinopathy
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Outcomes of intravitreal anti-VEGF therapy in eyes with both
neovascular age-related macular degeneration and diabetic retinopathy.
Bandello et al. Br J Ophthalmol 2016; http:+/dx.
doi.org/10.1136/bjophthalmol-2015-308400.
Dear Editor
We would like to address several challenges arisen from the interesting
study by Bandello et al [1] and which can be summarized specifically as
follows:
1. The article was retrospectively conducted with the existence of a
selection bias due to previous treatments applied for diabetic retinopathy
(DR) in 12% of the patients (eg., paretinal photocoagulation [PRP] in 5%
and grid laser in 7% of the patients). Moreover, there were other
treatments than those with the antivascular endothelial growth factor
(VEGF) agents which were administered during follow-up (eg., dexamethasone
implant in 12%, PRP in 2%, photodynamic therapy in 15%, and stereotactic
radio in 2% of the eyes).
2. We analyzed the results of this study taking into account the
current assertion whereby the assessment should be guided by anatomical
measure data with visual changes as a secondary guide [2]. Thus, best
corrected visual acuity improved significantly at 1 year but returned to
baseline values at the end of the follow-up, while mean central macular
thickness (CMT) significantly decreased from 408 to 335 microns at last
follow-up visit. Of note, this CMT value is more than the cutoff (315.2
microns) for the upper level of normal foveal thickness (270+/- 22.5) [3]
plus 2 standard deviations and highlights unresolved macular edema
indicating that the disease process is still active and progressive
requiring further treatment.
3. The final anatomic results in eyes with both neovascular age-
related macular degeneration (AMD) and DR were poor. They revealed 39% of
the eyes with active choroidal neovascularization, 22% with predominantly
atrophic scar, and 39% of the eyes with predominantly fibrotic scar.
Additionally, one eye graded as severe non-proliferative DR progressed to
proliferative DR and finally was inactivated due to PRP.
4. The results of this series can be explained by the low frequency
of injections (a mean of 9.2) as well as the long duration of diabetes (a
mean of 22 years). Most likely there was a chronic retinal capillaropathy
due to permanent breakdown of the inner and outer blood-retinal barriers
following ischemic changes to the macular ganglion cell complex, close to
the foveola.
Altogether, the specific anti-VEGF agents represent the front-line
therapy for AMD and DR. Because o lot of cytokines, chemokines, and growth
factors may be associated with DR pathophysiology [4,5], the addition of a
non-specific anti-VEGF substance, eg., a corticosteroid implant, which
inhibits the up-regulation of the VEGF and suppresses the expression of
the whole panoply of the proinflammatory and proangiogenic factors, is
mandatory.
References
1. Bandello F, Corvi F, La Spina C, et al. Outcomes of intravitreal anti-
VEGF therapy in eyes with both neovascular age-related macular
degeneration and diabetic retinopathy. Br J Ophthalmol 2016;
http:/dx.doi.org/10.1136/bjophthalmol-2016-308400.
2. Freund KB, Korobelnik JF, Deveny R, et al. Treat-and-extend regimens
with anti-VEGF agents in retinal diseases. A literature review and
consensus recommendations. Retina 2015;35:1489-1506.
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;148:266-271.
4. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of
various cytokines after
intravitreal triamcinolone versus bevacizumab for diabetic macular
edema. Am J Ophthalmol
2011;152:686-694.
5. Shah SU, Harless A, Bleau L, et al. Prospective randomized subject-
masked study of
intravitreal bevacizumab monotherapy versus dexamethasone implant
monotherapy in the
treatment of persistent diabetic macular edema. Retina
2016;http:/dx.doi.org/10.1097/IAE
eLetter
Comment on: Risk factors for low vision related functioning in the Mycotic
Ulcer Treatment Trial: a randomised trial comparing natamycin with
voriconazole
Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Corresponding author
Dr. Jagat Ram, MS, FAMS
Professor and Head
Department of Ophthalmology
Post Graduate...
eLetter
Comment on: Risk factors for low vision related functioning in the Mycotic
Ulcer Treatment Trial: a randomised trial comparing natamycin with
voriconazole
Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Corresponding author
Dr. Jagat Ram, MS, FAMS
Professor and Head
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Email id: drjagatram@gmail.com
Conflict of interest and source of funding- None declared
Dear Editor,
We read with interest the recent paper by Rose- Nussbaumer and associates
[1] determining the risk factors for low vision-related quality of life
in patients with fungal keratitis. While the study is indeed interesting,
we herein address important issues, some of which warrant further
discussion. First, the authors stated in the abstract "Those who required
therapeutic penetrating keratoplasty had an average of 25.2 points
decrease on VFQ after correcting for treatment arm (95% CI ?31.8 to ?18.5,
p<0.001).". However, in the manuscript it is mentioned that "study
participants who required therapeutic penetrating keratoplasty (TPK) had
significantly worse VFQ scores than those who did not, with those having
undergone TPK scoring on average 25.5 points lower on VFQ (95% CI ?32.0 to
?18.9, p<0.001)." Second, since marital status is one of the robust
predictor of health outcomes, it should have been taken into account as it
may affect the quality of life in the study patients. It has been seen
that divorced and widowed men report higher rates of depressive symptoms
than married men [2]. Third, presence of other comorbidities like
diabetes, cancer, organic disorders/cognitive impairment or current use of
any medication due to a psychiatric disorder eg. antidepressants should be
ruled out. Moreover, use of topical nonselective beta-blockers or intake
of oral lipophilic beta blockers for hypertensives should also be
considered since they may lead to depression [3, 4] and subsequently
affect quality of life.
References
1. Rose- Nussbaumer J, Prajna NV, Krishnan T, et al. Br J Ophthalmol
2016;100:929-932.
2. Jang SN, Kawachi I, Chang J et al. Marital status, gender, and
depression: Analysis of the baseline survey of the Korean Longitudinal
Study of Ageing (KLoSA). Soc Sci Med 2009; 11(12): 1608-15.
3. Verbeek DE, van Riezen J, de Boer RA, van Melle JP, de Jonge P. A
review on the putative association between beta-blockers and depression.
Heart Fail Clin. 2011;7(1):89-99.
4. Augustin A, Sahel JA, Bandello F et al. Anxiety and depression
prevalence rates in age-related macular degeneration. Invest Ophthalmol
Vis Sci. 2007;48(4):1498-503.
eLetter
Comment on: The impact of donor age and endothelial cell density on graft
survival following penetrating keratoplasty
Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Corresponding author
Dr. Jagat Ram, MS, FAMS
Professor and Head
Department of Ophthalmology
Post Graduate Institute of Medical Education and Re...
eLetter
Comment on: The impact of donor age and endothelial cell density on graft
survival following penetrating keratoplasty
Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Corresponding author
Dr. Jagat Ram, MS, FAMS
Professor and Head
Department of Ophthalmology
Post Graduate Institute of Medical Education and Research, Chandigarh,
India, 160012
Email id: drjagatram@gmail.com
Conflict of interest and source of funding- None declared
Dear Editor,
We read with interest the recent paper by Wakefield and associates [1]
analysing if donor age and preoperative endothelial cell density (ECD)
affects corneal endothelial failure following penetrating keratoplasty
(PK). While the study is indeed interesting, we herein address important
issues, some of which warrant further discussion. First, the authors have
determined the overall 5-year graft survival rate due to endothelial
failure in all recipients. No mention has been made of the endothelial
cell density/loss at 5 years after surgery in all age groups. Was there
any significant difference in the endothelial cell density in all groups?
Second, diabetic status has been few of the factors affecting corneal
endothelial cell counts. In patients with diabetes (after adjusting age),
the cell count is lesser by 66 cells (95% CI, 6.3-125.9) compared with
controls [2]. Did the authors take into consideration the presence or
absence of diabetes mellitus in all groups since higher prevalence of
diabetes in the younger age group donors could have decreased the graft
survival ultimately making it comparable with the graft survival of
corneas from elderly donors. Third, cigarette smoking reduces endothelial
cell counts [3]. Smoking history should also have been considered while
comparing the graft survival rates in all the groups. Moreover, advanced
nuclear cataract and chronic pulmonary disease are significant risk
factors for reduced endothelial density. Although the mechanisms are
unknown, patients with these risk factors may have a poor endothelial
reserve [4]. The authors should therefore rule out all the aforementioned
factors before analyzing the results.
References
1. Wakefield MJ, Armitage WJ, Jones MNA, et al. Br J Ophthalmol
2016;100:986-989.
2. Sudhir RR, Raman R, Sharma T. Changes in the Corneal Endothelial Cell
Density and Morphology in Patients With Type 2 Diabetes Mellitus: a
Population Based Study, Sankara Nethralaya Diabetic Retinopathy And
Molecular Genetics Study (SN-DREAMS, Report 23). Cornea 2012; 0:1-4.
3. Ilhan N, Ilhan O, Coskun M, et al. Effects of Smoking on Central
Corneal Thickness and the Corneal Endothelial Cell Layer in Otherwise
Healthy Subjects. Eye Contact Lens. 2015; 10.1097/ICL.0000000000000212
4. Ishikawa A. Risk factors for reduced corneal endothelial cell density
before cataract surgery. J Cataract Refract Surg. 2002;28(11):1982-92.
Intravitreal bevacizumab for diabetic macular oedema: 5-year results
of the Pan-American collaborative retina study group.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Intravitreal bevacizamab for diabetic macular oedema: 5-year
results of the Pan-American collaborative retina study group. Arevalo et
al. Br J Ophthalmol published online on February 24,
2016...
Intravitreal bevacizumab for diabetic macular oedema: 5-year results
of the Pan-American collaborative retina study group.
Dan Calugaru, Mihai Calugaru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Intravitreal bevacizamab for diabetic macular oedema: 5-year
results of the Pan-American collaborative retina study group. Arevalo et
al. Br J Ophthalmol published online on February 24,
2016;doi:10.1136/bjophthalmol-2015-307950.
Dear Editor
The article by Arevalo et al [1] has several shortcomings that prevent the
validation and extrapolation of their results and that can be specifically
summarized as follows:
1. The study was retrospectively conducted with the existence of a
selection bias due to the lack of a uniform clear treatment schedule for
injections and reinjections, the decision to treat being left at the
discretion of the treating physicians. Additionally, a total of 113 eyes
were diagnosed with proliferative diabetic retinopathy and treated with
panretinal photocoagulation at least 6 months before undergoing
intravitreal bevacizumab (IVB) for diabetic macular oedema (DME).
2. The assessment of the final outcomes should be made taking into
account the current assertion whereby evaluation of the outcomes has to be
guided by the anatomical measure data with the visual changes as a
secondary guide [2]. Accordingly, the visual and anatomic improvements of
this study were poor. Thus, while early visual gains due to IVB were not
maintained 5 years after treatment, the central macular thickness (CMT)
decreased significantly from 403.5 to 313.7 microns over 5 years follow-
up. Importantly, this value is much more than the cutoff (252 microns) for
the upper level of normal foveal thickness (212 ? 20 ?m)(3) plus 2
standard deviations. Of note, the proportion of eyes considered "dry" on
optical coherence tomography as per criterion of foveal thickness ? 260
?m was 29.4%, the rest of the eyes having unresolved macular oedema.
3. The results of this study could be explained by the low frequency
of injections (a mean of 8.4 IVB injections per eye over 5 years) as well
as the long duration of diabetes (a mean of 15.8 years). Most likely there
was a chronic retinal capillaropathy due to permanent irreversible
breakdown of the inner and outer blood retinal barriers. The vascular
endothelial growth factor (VEGF) is one proven contributor to macular
oedema in diabetic retinopathy. Besides, a panoply of proinflammatory and
proangiogenic cytokines, chemokines, and growth factors may be associated
with pathophysiology of DME [4,5].
Altogether, the specific anti-VEGF drugs represent the front-line
therapy for the treatment of DME but VEGF inhibition only may not be
sufficient to decrease inflammatory response. Therefore, addition of a non
-specific anti-VEGF substance, i.e., intravitreal steroid injection is
mandatory. Otherwise, patients will be impeded to achieve maximal visual
and anatomic benefits.
References 1. Arevalo JF, Lasave AF, Wu L, et al. Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan American collaborative retina study group. Br J Ophthalmol 2016, online first published on February 24, 2016; doi:10.1136/bjophthalmol-2015-307950. 2. Freund KB, Korobelnik JF, Deveny R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases. A literature review and consensus recommendations. Retina 2015;35:1489-1506. 3. Chan A, Duker JS, Ko TH, et al. Normal macular thickness measurements in healthy eyes using optical coherence tomography. Arch Ophthalmol 2006;124:193-198. 4. Sohn HJ, Han DH, Kim IT, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol2011;152:686-694. 5. Shah SU, Harless A, Bleau L, et al. Prospective randomized subject- masked study of intravitreal bevacizumab monotherapy versus dexamethasone implant monotherapy in the treatment of persistent diabetic macular edema. Retina 2016, online first published on April 27, 2016; doi:10.1097/IAE 0000000000001038.
I read with interest the article by Kuroda et al.[1] The authors
explored new possibilities of anterior segment imaging using a posterior
segment swept-source optical coherence tomography device without
noteworthy modifications. Interestingly, it was possible to obtain high-
resolution images of the conjunctiva, episclera, and the sclera near the
limbus that seemingly allow unequivocal identificati...
I read with interest the article by Kuroda et al.[1] The authors
explored new possibilities of anterior segment imaging using a posterior
segment swept-source optical coherence tomography device without
noteworthy modifications. Interestingly, it was possible to obtain high-
resolution images of the conjunctiva, episclera, and the sclera near the
limbus that seemingly allow unequivocal identification of anatomical
boundaries. The authors used this technique to examine eyes with anterior
scleritis/episcleritis.
However, I was not so impressed when I read through the methods
section of the paper. Contralateral eyes of patients were included as
controls. This is certainly problematic, considering that some of the
subjects had systemic inflammatory disease. In patients with overt
bilateral disease, both eyes were included in the analysis. As a result,
the measurements are not independent,[2] and the use of basic statistical
tests such as the Mann-Whitney or Kruskal-Wallis tests is not legitimate.
All these tests require independence of observations. Advanced statistical
methods[3] such as generalized estimating equations[4] or paired
comparison[5] would be necessary to obtain statistically valid results.
Another significant weakness of the methodology is that the thickness
of tissues was not measured perpendicularly to the ocular surface. This
makes data prone to bias and increases the variability. Moreover, the
internal limits of the sclera in Figures 2B and 4B are not very distinct,
and one wonders how accurate the measurements of this boundary are in
other eyes in the study, if these photos are representative.
To sum up, the images displayed are promising, yet, the scientific
rigour of the paper is much less compelling.
References
1. Kuroda Y, Uji A, Morooka S, et al. Morphological features in
anterior scleral inflammation using swept-source optical coherence
tomography with multiple B-scan averaging. Br J Ophthalmol Published
Online First: 7 July 2016. doi: 10.1136/bjophthalmol-2016-308561
2. Ray WA, O'Day DM. Statistical analysis of multi-eye data in
ophthalmic research. Invest Ophthalmol Vis Sci 1985; 26:1186-8.
3. Fan Q, Teo YY, Saw SM. Application of advanced statistics in
ophthalmology. Invest Ophthalmol Vis Sci 2011; 52:6059-65.
4. Hanley JA, Negassa A, Edwardes MD, et al. Statistical analysis of
correlated data using generalized estimating equations: an orientation. Am
J Epidemiol 2003; 157:364-75.
5. Murdoch IE, Morris SS, Cousens SN. People and eyes: statistical
approaches in ophthalmology. Br J Ophthalmol 1998; 82:971-3.
Dear Editor,
We thank Drs Gupta and Ram for their interest in our recent paper on the
anatomical effects of dexamethasone intravitreal implant (DEX implant) in
eyes with diabetic macular oedema [1] and appreciate the opportunity to
respond to their comments. Their letter highlights various patient- and
treatment-related factors that potentially might have influenced the
retinal findings described in our analysis. We pro...
Dear Editor,
We thank Drs Gupta and Ram for their interest in our recent paper on the
anatomical effects of dexamethasone intravitreal implant (DEX implant) in
eyes with diabetic macular oedema [1] and appreciate the opportunity to
respond to their comments. Their letter highlights various patient- and
treatment-related factors that potentially might have influenced the
retinal findings described in our analysis. We provide here some further
clarification on the specific points raised in their letter.
Firstly, the MEAD study data do not allow us to determine with certainty
the treatment-free interval preceding DEX implant injection. However, we
can confirm that all enrolled patients were required to discontinue
intravitreal anti-VEGF and triamcinolone treatment at least 3 and 6
months, respectively, prior to study entry. Also, ranibizumab was not
available at the start of the study (2004) and only 7% of patients had
received prior anti-VEGF therapy. Moreover, randomization is likely to
have minimized any imbalance between the treatment groups. Secondly,
patients presenting with epiretinal membrane or vitreomacular traction
syndrome at the initial screening visit were excluded from study entry.
Thirdly, regarding the issue of insulin and oral hypoglycaemic use and
changes in antidiabetic treatment during the study, randomization
presumably minimized any influence these factors might have had on study
outcomes. Fourthly, the study was not designed to assess the comparative
efficacy of the 0.35 mg and 0.7 mg implants. However, since HbA1c assays
over the course of the study showed no significant difference in glycaemic
control between the three treatment arms, the MEAD findings indicate that
the two implants are of comparable efficacy in reducing macular oedema.
Finally, for information on the effects of DEX implant on lens status the
reader is referred to the primary paper of the MEAD Study Group [2].
Ronald P. Danis, M.D.
Srinivas Sadda, M.D.
Xiao-Yan Li, M.D.
Harry Cui, MS.
Yehia Hashad, M.D.
Scott M. Whitcup, M.D.
Fundus Photograph Reading Center, Department of Ophthalmology and
Visual Sciences, University of Wisconsin-Madison, 2870 University Avenue,
Madison, Wisconsin 53711.
E-mail: rpdanis@wisc.edu
References 1. Danis RP, Sadda S, Li XY, et al. Anatomical effects of
dexamethasone intravitreal implant in diabetic macular oedema: a pooled
analysis of 3- year phase III trials. Br J Ophthalmol 2016;100:796-801. 2.
Boyer DS, Yoon YH, Belfort R, et al. Three-year, randomized, sham-
controlled trial of dexamethasone intravitreal implant in patients with
diabetic macular edema. Ophthalmology 2014;121:1904-14.
Conflict of Interest:
RPD and SS have received grant support and consulting fees from Allergan, Inc. X-YL and YH are employees of Allergan, Inc.
We thank Drs. Uzun and Pehlivan for their interest and comments to
our article.[1]
We compared and correlated the central choroidal thickness to the
different choridal parameters at different times between 9:00 h and 18:00
h. We compared the findings between 09:00 h and 12:00 h, 09:00 h and 15:00
h, 09:00 h and 18:00 h, 12:00 h and 15:00 h, 12:00 h and 18:00 h, and
15:00 h and 18:00 h. There were...
We thank Drs. Uzun and Pehlivan for their interest and comments to
our article.[1]
We compared and correlated the central choroidal thickness to the
different choridal parameters at different times between 9:00 h and 18:00
h. We compared the findings between 09:00 h and 12:00 h, 09:00 h and 15:00
h, 09:00 h and 18:00 h, 12:00 h and 15:00 h, 12:00 h and 18:00 h, and
15:00 h and 18:00 h. There were significant strong correlations between
the fluctuation range of central choroidal thickness (fCCT) and those of
luminal area and total choroidal area at all times (r >0.8, P
<0.001). There was no significant correlation between the fCCT and the
fluctuation range of stromal area (fSA) at 09:00 h and 18:00 h, 12:00 h
and 18:00 h, and 15:00 h and 18:00 h (P >0.1). There were significant
correlations between the fCCT and the fSA at 09:00 h and 12:00 h, 09:00 h
and 15:00 h but the correlations were relatively weak (r = 0.428, P =
0.010; r = 0.383, P = 0.023; respectively). There was a moderate
correlation between fCCT and fSA at 12:00 h and 15:00 h (r = 0.635, P
<0.001), however, no significant difference in the mean choroidal
parameters was found during this interval (P = 1.000 for all choroidal
parameters, repeated ANOVA with the Bonferroni test for post hoc
analysis). Thus, these results reconfirm our main conclusion that that the
diurnal variations in the choroidal thickness are mainly due to the
fluctuations in the luminal area.
There was no significant correlation between age and the choroidal
parameters in the partial regression analyses in which the axial length
was set as the control variable. However, we reported earlier that the age
was significantly and negatively correlated with the total choroidal area,
luminal area, stromal area, and the ratio of luminal to stromal area.[2]
The differences in the distribution of age of the participants and the
sample size between the two studies may explain this discrepancy. The
mean age of 30.5 ? 9.11 (mean ? SD) years (range, 21 - 52 years) in the
present study was younger with a smaller range than that in the previous
report with a mean age of 55.9 ? 18.8 years (range 22 - 90 years). The
sample size of the previous study was 180 which was larger than that of
the present study (n = 38). No significant difference in the choroidal
parameters was found between the sexes.
Again, we thank you for your interest.
1. Kinoshita T, Mitamura Y, Shinomiya K, et al. Diurnal variations in
luminal and stromal areas of choroid in normal eyes. Br J Ophthalmol. 2016
Jun 13. pii: bjophthalmol-2016-308594. doi: 10.1136/bjophthalmol-2016-
308594.
2. Sonoda S, Sakamoto T, Yamashita T, et al. Luminal and stromal areas of
choroid determined by binarization method of optical coherence tomographic
images. Am J Ophthalmol 2015;159:1123-31.
Effects of switching from ranibizumab to aflibercept in eyes with
exudative age-related macular degeneration
Dan C?lug?ru, Mihai C?lug?ru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Effects of switching from ranibizumab to aflibercept in eyes with
exudative age-related macular degeneration. Barthelmes et al. Br J
Ophthalmol published online on March 18, 2016;doi:10.1136/bjophthalmol-
20...
Effects of switching from ranibizumab to aflibercept in eyes with
exudative age-related macular degeneration
Dan C?lug?ru, Mihai C?lug?ru
Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Effects of switching from ranibizumab to aflibercept in eyes with
exudative age-related macular degeneration. Barthelmes et al. Br J
Ophthalmol published online on March 18, 2016;doi:10.1136/bjophthalmol-
2015-308090.
Dear Editor
The interesting article by Barthelmes et al [1] carries several
shortcomings that prevent the validation and extrapolation of their
results and that can be specifically summarized as follows:
1. The study was retrospectively conducted with the existence of a
bias due to the lack of a uniform definite treatment scheme for injections
and reinjections, the decision to treat being left at the discretion of
the treating physicians, Additionally, 26 eyes were switched back to the
original treatment and two different treatment regimens were chosen,
namely, the treat-and-extend approach in 59% of the eyes and the monthly
pro re nata algorithm to the rest of the eyes.
2 The aggressiveness of the neovascular age-related macular
degeneration (nAMD) was graded taking into account the fluoreiscein
angiography features. The assessment process should have included the
optical coherence tomography (OCT) data as well.
3. The analysis of the final outcomes of this study should have been
carried out considering the current assertion according to which
evaluation of the outcomes has to be guided by the anatomical measure data
with the visual changes as a secondary guide [2] and not vice versa as
Barthelmes et al [1] have approached.
4. There were no data on the proportion of eyes considered "dry" on
OCT as per criterion of foveal thickness < 320 ?m [3] nor on the
anatomical types of the macular edema (subretinal fluid/cystic changes
within neurosensory retina). Except for the morphological types of the
choroidal neovascular membrane lesions presented in details, nothing was
stated referring to the other anatomical types of the neovascular
maculopathy including serous and/or hemorrhagic detachment of the
neurosensory retina or retinal pigment epithelium (RPE), retinal hard
exudates, subretinal and sub-RPE fibrovascular proliferation, and
subretinal fibrosis, before and after switching to aflibercept (Eylea;
Regeneron Pharmaceuticals Tarrytown, NY, USA.
5. The design of this study has been deprived of a real washout
period which is essential between the two periods of treatment in terms of
aliased effects. Given that this washout period was not precisely
delimited, the impact of the significant carryover effects may be
confounded with direct treatment effects, in the sense that these effects
could not be estimated separately being able to bias the interpretion of
data analysis.
Altogether, regardless of the anti-VEGF agents used (ranibizumab
[Lucentis, Genentech Inc., South San Francisco, CA, USA]/bevacizumab
[Avastin, Genentech Inc.,]/aflibercept), the efficacy of therapy depends
primarily on the precociousness of the therapy after nAMD onset.
References
1. Barthelmes D, Campain A, Nguyen P, et al. Effects of switching from
ranibizumab to aflibercept in eyes with exudative age-related macular degeneration. Br J Ophthalmol2016, online first published on March 18, 2016;doi:10.1136/bjophthalmol-2015-308090..
2. Freund KB, Korobelnik JF, Deveny R, et al. Treat-and-extend regimens
with anti-VEGF agents in retinal diseases. A literature review and consensus
recommendations. Retina 2015;35:1489-1506..
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 Ophthalmol2009;148:266-271.
Dear Editor,
We have read and reviewed the article entitled as "Diurnal variations in
luminal and stromal areas of choroid in normal eyes'' by Kinoshita et al.
with great interest [1]. The authors analyzed systemic blood pressure,
heart rate, intraocular pressure, central choroidal thickness (CCT), total
cross-sectional choroidal area, the luminal areas, stromal areas and the
ratio of luminal area to total choroidal area...
Dear Editor,
We have read and reviewed the article entitled as "Diurnal variations in
luminal and stromal areas of choroid in normal eyes'' by Kinoshita et al.
with great interest [1]. The authors analyzed systemic blood pressure,
heart rate, intraocular pressure, central choroidal thickness (CCT), total
cross-sectional choroidal area, the luminal areas, stromal areas and the
ratio of luminal area to total choroidal area (L/C ratio) of 38 healthy
participants every 3 hours between 06:00 and 21:00. They found that there
were significant diurnal variations in the CCT, total choroidal area,
luminal area and L/C ratio with the maximum values at 6:00 hours and the
minimum values at 15:00 hours. We express our gratitude to the authors,
and appreciate their valuable contributions to the literature. However, we
would like to ask the authors two important points regarding the study.
Choroid is the most vascular structure of the eye, and it has the
highest blood flow of any tissue per unit weight in human body.
Additionally, numerous studies have demonstrated that choroid has a unique
anatomical structure, and neurovascular configuration [2]. Owing to
advancements in technology, ability to obtain fast, high-resolution, high-
quality imaging of choroid with reproducible results made the
investigators to focus on this important structure.
Kinoshita et al. investigated the choroid, and the relationship of
structure of choroid with systemic and local factors, and demonstrated the
diurnal variation of those parameters. They compared all those
investigated parameters, and particularly the parameters measured between
06:00 and 15:00 with each other. It is a fact that the vast majority of
the studies investigating the choroid were performed during working hours.
Accordingly, we would like to ask the authors whether they investigated
the parameters, particularly the ones related to choroid in different time
intervals, for instance between 09:00 and 12:00, or 09:00 and 15:00, or
12:00 and 15:00; since we suppose that such an assessment may guide
investigators for further studies on choroid.
Second, we suggest that considering age and gender differences of the
participants regarding choroid-related parameters might provide
significant contribution to the paper and the literature.
References
1 Kinoshita T, Mitamura Y, Shinomiya K, et al. Diurnal variations in
luminal and stromal areas of choroid in normal eyes. Br J Ophthalmol 2016;
doi: 10.1136/bjophthalmol-2016-308594.
2 Nickla DL, Wallman J. The multifunctional choroid. Prog Retin Eye Res
2010;29:144-68.
We thank Drs Calugaru M. and Calugaru D. for their interest in our article,1 and we welcome this opportunity to address their concerns. The purpose of our study was to investigate the outcomes of intravitreal antivascular endothelial growth factor (VEGF) therapy in eyes with both neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR) as higher levels of VEGF due to concomitant DR in eyes with a...
Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Outcomes of intravitreal anti-VEGF therapy in eyes with both neovascular age-related macular degeneration and diabetic retinopathy. Bandello et al. Br J Ophthalmol 2016; http:+/dx. do...
eLetter Comment on: Risk factors for low vision related functioning in the Mycotic Ulcer Treatment Trial: a randomised trial comparing natamycin with voriconazole Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS Department of Ophthalmology Post Graduate Institute of Medical Education and Research, Chandigarh, India, 160012 Corresponding author Dr. Jagat Ram, MS, FAMS Professor and Head Department of Ophthalmology Post Graduate...
eLetter Comment on: The impact of donor age and endothelial cell density on graft survival following penetrating keratoplasty Parul Chawla Gupta, MS; Jagat Ram, MS, FAMS Department of Ophthalmology Post Graduate Institute of Medical Education and Research, Chandigarh, India, 160012 Corresponding author Dr. Jagat Ram, MS, FAMS Professor and Head Department of Ophthalmology Post Graduate Institute of Medical Education and Re...
Intravitreal bevacizumab for diabetic macular oedema: 5-year results of the Pan-American collaborative retina study group. Dan Calugaru, Mihai Calugaru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Intravitreal bevacizamab for diabetic macular oedema: 5-year results of the Pan-American collaborative retina study group. Arevalo et al. Br J Ophthalmol published online on February 24, 2016...
Dear Editor,
I read with interest the article by Kuroda et al.[1] The authors explored new possibilities of anterior segment imaging using a posterior segment swept-source optical coherence tomography device without noteworthy modifications. Interestingly, it was possible to obtain high- resolution images of the conjunctiva, episclera, and the sclera near the limbus that seemingly allow unequivocal identificati...
Dear Editor, We thank Drs Gupta and Ram for their interest in our recent paper on the anatomical effects of dexamethasone intravitreal implant (DEX implant) in eyes with diabetic macular oedema [1] and appreciate the opportunity to respond to their comments. Their letter highlights various patient- and treatment-related factors that potentially might have influenced the retinal findings described in our analysis. We pro...
Dear Editor,
We thank Drs. Uzun and Pehlivan for their interest and comments to our article.[1] We compared and correlated the central choroidal thickness to the different choridal parameters at different times between 9:00 h and 18:00 h. We compared the findings between 09:00 h and 12:00 h, 09:00 h and 15:00 h, 09:00 h and 18:00 h, 12:00 h and 15:00 h, 12:00 h and 18:00 h, and 15:00 h and 18:00 h. There were...
Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration Dan C?lug?ru, Mihai C?lug?ru Department of Ophthalmology, Univ of Medicine Cluj-Napoca/Romania
Re: Effects of switching from ranibizumab to aflibercept in eyes with exudative age-related macular degeneration. Barthelmes et al. Br J Ophthalmol published online on March 18, 2016;doi:10.1136/bjophthalmol- 20...
Dear Editor, We have read and reviewed the article entitled as "Diurnal variations in luminal and stromal areas of choroid in normal eyes'' by Kinoshita et al. with great interest [1]. The authors analyzed systemic blood pressure, heart rate, intraocular pressure, central choroidal thickness (CCT), total cross-sectional choroidal area, the luminal areas, stromal areas and the ratio of luminal area to total choroidal area...
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