Graefes Arch Clin Exp Ophthalmol DOI 10.1007/s00417-017-3618-9
LETTER TO THE EDITOR (BY INVITATION)
Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion Gesine B. Szurman 1 & Carsten H. Meyer 2 & Nicolas Feltgen 3 & Amelie Pielen 4 & Bernhard Spitzer 5 & Matus Rehak 6 & Georg Spital 7 & Spyridon Dimopoulos 8 & Peter Szurman 1 & Bevacizumab Study Group Venous Occlusion & Kai Januschowski 1,8
Received: 31 January 2017 / Accepted: 8 February 2017 # Springer-Verlag Berlin Heidelberg 2017
Dear Editor Calugaru and Calugaru address many important issues already addressed in our manuscript but also raise interesting new aspects. Therefore, we would like to discuss some points arisen und share additional information on our study. Three hundred and sixteen eyes with macular edema (ME) secondary to central retinal vein occlusion (CRVO) were treated with bevacizumab and finished the 24-week follow-up. Not 151 but 165 eyes (52.2%) finished the 48-week follow-up; this number is quite significant. Between 24 and 48 weeks, there is stabilization of the median visual acuity (VA), the median CRT, the percentage of eyes with a gain of at least 3 VA lines, and the percentage of eyes with no residual ME [1, 2]. Therefore,
* Kai Januschowski
[email protected] Bevacizumab Study Group Venous Occlusion 1
Eye Clinic Sulzbach, Knappschaftsklinikum Saar, Sulzbach 66280 , Germany
2
Department of Ophthalmology, Pallace Clinics, Aarau, Switzerland
3
University Eye Hospital, University of Goettingen, Goettingen, Germany
4
Hannover Medical School, University Eye Hospital, Munich, Germany
5
Department of Neurology and Bernstein Center for Computational Neuroscience, Charité, Berlin, Germany
6
University Eye Hospital, University of Leipzig, Leipzig, Germany
7
Department of Ophthalmology, St. Franziskus Hospital, Muenster, Germany
8
Centre for Ophthalmology, University Eye Clinic Tuebingen, Tuebingen, Germany
analysis of predictive factors was performed on the basis of the 24-week results of all 316 eyes included [3]. Exclusion criteria were laser photocoagulation, cyclodestructive interventions, cataract surgery, or other surgical procedures during the follow-up. Pretreatment with retinal photocoagulation or intravitreal injection with a steroid in 50 eyes (14%) was analyzed as prognostic factor for improvement of VA. We are convinced that this is important information and reflects the clinical reality well as the data from this large retrospective study was obtained from a clinical routine setting. However, a possible bias due to an insufficient washout period in eyes pretreated with intravitreal injection cannot be completely ruled out (25 eyes, 8%). This is an excellent point made by Calugaru et al. Duration of CRVO until the first injection could not be shown as a prognostic factor for visual improvement (multiple regression p = 0.830) [3]. However, analyzing the subgroup with a duration of CRVO until the first bevacizumab injection of 3 months or less (203 eyes, 64%), a shorter duration was significantly associated with a higher increase in VA lines (p < 0.05). Although one would like to analyze many more factors that could be interesting and go into much more detail, even a large group of patients such as the one in this study does not permit this, as was discussed with our statistics expert. Information about the perfusion status of the retina as a predictive factor for visual improvement would be interesting, as we indicated in our manuscript. However, analysis in this set of data was not possible because of varying time points of fluorescein angiography within the study cohort due to retinal haemorrhage, as pointed out in the discussion for the attentive reader [3]. Retreatment was considered at each follow-up visit based on BCVA, OCT, and morphological findings. With a mean
Graefes Arch Clin Exp Ophthalmol
number of injections of 2.7, the bevacizumab treatment resulted in a significant improvement of a mean of 2.5 visual acuity lines (12.5 letters) at 24 weeks (p < 0.05). In a previous study we were able to show with this data that a minimum of 3 injections was needed to gain a 3-line increase of BCVA at 24 weeks [1]. The prospective, randomized, double-masked study of Epstein and colleagues that performed fixed bevacizumab injections every 6 weeks also found a gain of 3 lines up to week 24 (14 letters) [4]. We made it a point in our study to address the problem of undertreatment and attributed this to patient adherence, and pointed out that the promising results of many prospective trials are not reflected by the clinical reality [2, 3]. We thank the authors for repeating this important point by alluding to many of their studies. Our study was to investigate predictive factors for functional improvement as important information for the clinical routine from a real-life setting: With this information, treating physicians can inform their patients about the gap between promises made by a controlled but artificial setting (prospective randomized trials) and real-life outcome.
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Januschowski K, Dimopoulos S, Szurman P, Feltgen N, Spitzer B, Pielen A, Rehak M, Spital G, Bevacizumab Study Group Venous Occlusion, Meyer CH, Szurman GB (2015) Injection scheme for intravitreal bevacizumab therapy for macular oedema due to central retinal vein occlusion: results of a multicenter study. Acta Ophthalmol 93:e400–e402 Szurman GB, Januschowski K, Szurman P, Feltgen N, Spitzer B, Pielen A, Rehak M, Spital G, Dimopoulos S, Bevacizumab Study Group Venous Occlusion, Meyer CH (2016) Injection scheme for intravitreal bevacizumab therapy for macular oedema due to central retinal vein occlusion: results of a multicentre study. Acta Ophthalmol [Epub ahead of print]. doi:10.1111/aos.12976 Januschowski K, Feltgen N, Pielen A, Spitzer B, Rehak M, Spital G, Dimopoulos S, Bevacizumab Study Group Venous Occlusion, Meyer CH, Szurman GB (2016) Predictive factors for functional improvement following intravitreal bevacizumab injections after central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol. doi:10.1007/s00417-016-3471-22016 Epstein DL, Algvere PV, von Wendt G et al (2012) Benefit from bevacizumab for macular edema in central retinal vein occlusion: twelve-month results of a prospective, randomized study. Ophthalmology 119:2587–2591
