IF in JCR CiteScore
Rank About IJO Current
Issue Featured Articles Articles In Press Recent Accepted
International Journal
of Ophthalmology
2017; 10(9): 1481-1482
·Comment and Response·
Comment on “Predictors of short-term outcomes
related to central subfield foveal thickness after intravitreal bevacizumab for
macular edema due to central retinal vein occlusion”
Dan Călugăru, Mihai Călugăru
Department of Ophthalmology, University of Medicine, Cluj-Napoca 400012,
Romania
Correspondence to: Mihai Călugăru.
Department of Ophthalmology, University of Medicine, Strada Brâncoveanu 11,
Cluj-Napoca 400012, Romania. mihai.calugaru@mail.dntcj.ro
Received: 2016-01-15
Accepted: 2017-03-07
Citation: Călugăru D, Călugăru M. Comment on “Predictors of short-term outcomes
related to central subfield foveal thickness after intravitreal bevacizumab for
macular edema due to central retinal vein occlusion”. Int J
Ophthalmol 2017;10(9):1481-1482
Dear Editor,
We read with great interest the article by Wang et al[1]
which investigated the predictive factors for short-term outcomes related to
central subfield foveal thickness (CSFT) after intravitreal bevacizumab (IVB;
Avastin, Genentech Inc., South Francisco, CA, USA) injections in 60 patients
with macular edema (ME) secondary to central retinal vein occlusion (CRVO). The
authors concluded that IVB significantly improved visual acuity and CSFT after
3mo. Older age and lower baseline CSFT were associated with a good 3mo
prognosis and were good predictors of short-term CSFT outcomes. There are some
issues related to this article, that we would like to address and that can be
summarized as follows: 1) The conclusion of the study that patients
>60-year-old achieved better cystoid macular edema (CME) resolution and
lower CSFT at 3mo compared with patients aged ≤60y is valid only for patients
with CME at baseline and a duration of CRVO >3mo (intermediate phase of
disease[2]) since onset i.e. an average of 4.63mo for
responders and an average of 3.01mo for incomplete responders. However, this
assertion of the authors does not match the early, acute phase of CRVO
patients. 2) There were a significant difference regarding the response to
treatment between patients with CME alone (36/60) and those presenting CME with
associated subretinal retinal fluid (SRF) (24/60) at baseline. The fact that
58.3% of CME cases and 98.3% of CME cases with SRF responded to treatment with
a complete resolution at 3mo brings into discussion two issues i.e. the
greater effect of bevacizumab in patients with CME and associated SRF (compared
with patients without SRF) and the beneficial and predictive impact of SRF in
resolving CME. Accordingly, the presence of cystic spaces alone might be more
disruptive to the retinal architecture in the absence of SRF. 3) The assertion
of the authors that younger age is associated with a bad 3mo prognosis and
might be predictive of late or incomplete response for foveal thickness
outcomes is well documented and with practical implications. It seems to be a
somewhat paradoxical and counter-intuitive finding due to generally healthier
ocular tissues in younger patients which should have caused these patients to
achieve better short-term outcomes related to CSFT after treatment.
Importantly, inflammatory cytokines may play an important role in the
pathogenesis of CRVO in younger patients, where vascular endothelial growth
factor (VEGF) inhibition alone may not be sufficient to decrease the
inflammatory response. Therefore, addition of a non-specific anti-VEGF
substance, i.e. intravitreal steroid injection, which inhibits the
expression of VEGF and suppresses the expression of the whole panoply of
cytokines, chemokines, and growth factors, is mandatory.
In 2015, we published a prospective clinical study[3] on
the 3y outcomes of bevacizumab treatment in patients with acute (≤1mo
after the occlusion was diagnosed) central/hemicentral retinal vein occlusions
(central/hemicentral RVOs). Of these patients, 50% had ischemic
central/hemicentral RVOs, 17.5% of the patients experienced SRF and no one had
CME. The results of this study showed, for the first time, evidence suggesting
that early treatment administered immediately after clinical onset of the
venous occlusion provided significant and sustained improvements in visual
acuity and foveal thickness with inactive disease (dry retina and stable visual
acuity for at least 6mo after the last injection) in most phakic patients with
acute central/hemicentral RVOs, making this treatment option a rational and
viable therapeutic strategy.
In conclusion central/hemicentral RVO has to be considered an ophthalmic
emergency. Therefore, therapy with anti-VEGF agents has to be promptly applied
as soon as possible after RVO onset. Every delay of therapy adversely
influences the deterioration of visual functions, which are difficult to
restore even with subsequent treatment. Regardless of the anti-VEGF agents used[4]
and regardless of the treatment approaches chosen (treat-and-extend/pro re
nata algorithm)[5], the efficacy of therapy depends primarily on
the precociousness of the therapy after RVO diagnosis.
ACKNOWLEDGEMENTS
Conflicts of Interest: Călugăru D, None;
Călugăru M, None.
REFERENCES
1 Wang MZ, Feng K, LuY, Qian F, Lu XR, Zang SW, Zhao L. Predictors of
short-term outcomes related to central subfield foveal thickness after
intravitreal bevacizumab for macular edema due to central retinal vein
occlusion. <ii>Int J Ophthalmol</ii> 2016;9(1):86-92. [PMC free article] [PubMed]
2 Hayreh SS, Klugman MR, Beri M, Kimura AE, Podhajsky P. Differentiation
of ischemic from non-ischemic central retinal vein occlusion during the early
acute phase.<ii> Graefes Arch Clin Exp Ophthalmol
</ii>1990;228(3):201-217. [CrossRef]
3 Călugăru D, Călugăru M. Intravitreal bevacizumab in acute
central/hemicentral retinal vein occlusions: three-year results of a prospectve
clinical study. <ii>J Ocul Pharmacol Ther</ii>
2015;31(2):78-86.<ii> [CrossRef] [PubMed]
</ii>4 Călugăru D, Călugăru M. Intravitreal aflibercept of macular
edema secondary to central retinal vein occlusion: 18-month results of the
phase 3 GALILEO study. <ii>Am J Ophthalmol </ii>
2015;159(3):607-608. [CrossRef] [PubMed]
5 Călugăru D, Călugăru M. Letter to the Editor: treat-and-extend
intravitreal bevacizumab for branch retinal vein occlusion.
<ii>Ophthalmic Surg Lasers Imaging Retina </ii> 2015;46(10):994. [CrossRef] [PubMed]
Author Reply to the Editor
Dear Editor,
We thank Dr. Călugăru D and Dr. Călugăru M for their comments on our
paper published by the International Journal of Ophthalmology[1].
We acknowledge and understand their comments, and would like to shed some light
on them.
Response: 1) We admit that our study has a few limitations, which
are already acknowledged in our paper, but there might be additional ones we
did not foresee. In our study, the duration of central retinal vein occlusion
(CRVO) ranged from 1 to 144wk, which was similar to some previous studies[2-3].
Because the acute phase of non-ischemic CRVO was already over when the patients
consulted, anti-vascular endothelial growth factor (VEGF) treatment could have
been delayed due to various reasons. We might agree that the conclusion of the
study is valid only for patients with cystoid macular edema (CME) at baseline
and a duration of CRVO >3mo, but maybe patients would benefit more from the
treatment if they receive it in the early phase, which still needs to be
confirmed. In our future studies, we will take into consideration the different
durations of CRVO among patients. But for now, our results do not allow
reaching further or more refined conclusions. 2) We asserted that the frequency
of CME alone decreased from 60% at baseline to 41.7% after 3mo of therapy and
that the frequency of CME with SRF decreased from 40% at baseline to 1.7% after
3mo of therapy. About 50% of patients with CME and more than 90% of patients
with subretinal retinal fluid (SRF) responded to treatment with a complete
resolution at 3mo. Furthermore, 9 of 25 patients with CME and SRF at baseline
showed CME alone after 3mo. These results strongly suggest that SRF is easier
to treat than CME, rather than CME with SRF. 3) Younger patients should achieve
better short-term central subfield foveal thickness (CSFT) outcomes after
treatment due to their generally healthier ocular tissues compared with older
patients. Although we could not exclude the effects of the small sample size,
the impact of age on the response to retinal thickness outcomes after
bevacizumab treatment should be considered. As we know, younger patients with
CRVO may present a higher frequency of inflammatory conditions compared with
older patients. Therefore, VEGF inhibition alone may not be sufficient to
decrease the inflammatory response, especially in younger patients with CRVO.
Accordingly, addition of an anti-angiogenic and anti-inflammatory agent may be
more effective in younger patients, but no anti-inflammatory agent was used in
the present study and we agree that additional studies are still necessary to
address this issue adequately.
REFERENCES
1 Wang MZ, Feng K, LuY, Qian F, Lu XR, Zang SW, Zhao L. Predictors of
short-term outcomes related to central subfield foveal thickness after
intravitreal bevacizumab for macular edema due to central retinal vein
occlusion. <ii>Int J Ophthalmol</ii> 2016;9(1):86-92. [PMC free article] [PubMed]
2 Chung EJ, Hong YT, Lee SC, Kwon OW, Koh HJ. Prognostic factors for
visual outcome after intravitreal bevacizumab for macular edema due to branch
retinal vein occlusion. <ii>Graefes Archive Clin Exp Ophthalmol
</ii>2008;246(9):1241-1247. [CrossRef] [PubMed]
3 Hoeh AE, Ruppenstein M, Ach T, Dithmar S. OCT patterns of macular
edema and response to bevacizumab therapy in retinal vein occlusion.
<ii>Graefes Archive Clin Exp Ophthalmol
</ii>2010;248(11):1567-1572. [CrossRef] [PubMed]
Mei-Zi Wang
Department of Ophthalmology, Beijing Tiantan Hospital, Capital Medical
University, Beijing 100050, China
Lin Zhao
Peking
University Eye Center, Peking University Third Hospital, Key Laboratory of Vision
Loss and Restoration, Ministry of Education, Beijing 100191, China
----------------------------------------------------------------------------------------------------------------------------------------
All rights reserved by Press of International Journal of Ophthalmology (IJO PRESS)