The Open Ophthalmology Journal




ISSN: 1874-3641 ― Volume 13, 2019

Incidence of Retinal Pigment Epithelial Tears and Associated Risk Factors After Treatment of Age-Related Macular Degeneration with Intravitreal Anti-VEGF Injections§



Theodoros Empeslidis, Athanasios Vardarinos, Vasileios Konidaris, Soon Wai Ch'ng, Bharat Kapoor, James Deane , Konstantinos T Tsaousis*
Ophthalmology Department, Medical Retina Unit, Leicester Royal Infirmary, Leicester, UK

Abstract

Purpose :

To study the incidence and risk factors for retinal pigment epithelium tears following intravitreal anti-vascular endothelial growth factor (VEGF) injections.

Methods :

Retrospective longitudinal study. 4027 intravitreal anti-VEGF injections in 628 patients (676 eyes) for choroidal neovascularisation associated with age related macular degeneration in a period of 18 months were studied.

Results :

Seventeen patients (mean age 83.95±5.84) developed retinal pigment epithelium tears. The incidence rate was 0.4%. Fibrovascular pigment epithelium detachment (PED) was previously observed in all cases. In 88 % (15/17) of AMD patients that had a RPE tear, PED height was found to be less than 400 microns at presentation. In 5 of 7 patients with RPE tear grade <4, continuing of anti-VEGF treatment resulted to improvement of visual acuity.

Conclusion :

Critical risk factors for RPE tears are presence of PED as well as advanced age. Visual improvement appears to depend more on the extent and location of the RPE tear and less on the PED height.

Keywords: Age-related macular degeneration, anti-vascular endothelial growth factor, intravitreal, retinal pigment epithelium tears.


Article Information


Identifiers and Pagination:

Year: 2014
Volume: 8
First Page: 101
Last Page: 104
Publisher Id: TOOPHTJ-8-101
DOI: 10.2174/1874364101408010101

Article History:

Received Date: 7/10/2014
Revision Received Date: 18/10/2014
Acceptance Date: 18/10/2014
Electronic publication date: 31 /12/2014
Collection year: 2014

Article Metrics:

CrossRef Citations:
0

Total Statistics:

Full-Text HTML Views: 1359
Abstract HTML Views: 1009
PDF Downloads: 253
Total Views/Downloads: 2621

Unique Statistics:

Full-Text HTML Views: 594
Abstract HTML Views: 587
PDF Downloads: 172
Total Views/Downloads: 1353
Geographical View

© Empeslidis et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Ophthalmology Department, Medical Retina, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UK; Tel: +44116 258 5928; Fax: +44 258 6763; E-mail: konstantinos.tsaousis@gmail.com§ The work has been partially presented at the 12th EURETINA Congress, 6– 9 September 2012, Milan, Italy.





INTRODUCTION

Retinal pigment epithelium (RPE) tears are defined as well-demarcated areas of bare choroid, visible immediately adjacent to a hyper pigmented area which represents the redundant and retracted RPE. (Fig. 1A) In optical coherence tomography (OCT), RPE tears are defined as an interruption of the hyper reflective RPE layer with elevation of the torn RPE flap and increased choroidal depth signals posterior to the RPE tear (Fig. 1B).

Fig. (1)

A: Color fundus photograph showing an RPE tear. B: OCT of the same patient illustrating clearly the increase of the choroidal depth signal in areas of RPE absence (white arrows).



Since they were first described by Hoskin et al. [1Hoskin A, Bird AC, Sehmi K. Tears of detached retinal pigment epithelium. Br J Ophthalmol 1981; 65: 417-22.], tears of the RPE have been recognized increasingly as a cause of severe central visual loss in age related macular degeneration (AMD). As a general rule, RPE tears are part of the natural history of a pigment epithelial detachment (PED) that has developed as a result of occult choroidal neovascularization, retinal angiomatous proliferation, or polypoidal choroidal vasculopathy [2Michels S, Aue A, Simader C, Geitzenauer W, Sacu S, Schmidt-Erfurth U. Retinal pigment epithelium tears following verteporfin therapy combined with intravitreal triamcinolone. Am J Ophthalmol 2006; 141: 396-98., 3Gutfleisch M, Heimes B, Schumacher M , et al. Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD. Eye (Lond) 2011; 25: 1181-6.]. In addition, tears may occur spontan-eously, following photodynamic laser treatment, laser photocoagulation, and YAG laser posterior capsulotomy [4Decker WL, Sanborn GE, Ridley M, Annesley WH Jr, Sorr EM. Retinal pigment epithelial tears. Ophthalmology 1983; 90: 507-12.-6Vardarinos A, Empeslidis T, Periysamy K , et al. Tear of retinal pigment epithelium following YAG laser posterior capsulotomy in a patient on Anti-VEGF Treatment for AMD Six Months' Follow-Up. Case Rep Ophthalmol 2012; 3: 221-5.]. RPE tears are classified according to the criteria of Sarraf et al. grade 1 (diameter smaller than 200 μm), grade 2 (diameterbetween 200 μm and 1 disc diameter), grade 3 (diameter > 1 disc diameter) and grade 4 (Grade 3 tears that involve the foveal centre) [7Sarraf D, Reddy S, Chiang A, Yu F, Jain A. A new grading system for retinal pigment epithelial tears. Retina 2010; 30: 1039-45.]. RPE tears have also been described in eyes with PED after anti-vascular endothelial growth factor (VEGF) treatment [8Dhalla MS, Blinder KJ, Tewari A, Hariprasad SM, Apte RS. Retinal pigment epithelial tear following intravitreal pegaptanib sodium. Am J Ophthalmol 2006; 141: 752-4.-10Smith BT, Kraus CL, Apte RS. Retinal pigment epithelial tears in ranibizumab treated eyes. Retina 2009; 29: 335-9.]. Reported incidence of RPE tears in the literature ranges from 1.8% to 27%, in both natural history and interventional series [11Cunningham ET Jr, Feiner L, Chung C, Tuomi L, Ehrlich JS. Incidence of retinal pigment epithelial tears after intravitreal ranibizumab injection for neovascular age-related macular degeneration. Ophthalmology 2011; 118: 2447-52.]. The overall incidence of RPE tears was even lower (0.7-5.1%) in the phase III randomised multicenter clinical trials of ranibizumab for the treatment of neovascular AMD (MARINA, ANCHOR and PIER trials) [12Lommatzsch A, Heimes B, Gutfleisch M, Spital G, Zeimer M, Pauleikhoff D. Serous pigment epithelial detachment in age-related macular degeneration comparison of different treatments. Eye (Lond) 2009; 23: 2163-8.]. Several studies have also shown risk factors associated with RPE tears such as height of PED on OCT and size of the baseline PED lesions [13Doguizi S, Ozdek S. Pigment epithelial tears associated with anti-vegf therapy incidence, long-term visual outcome, and relationship with pigment epithelial detachment in age-related macular degeneration. Retina 2013; [Epub ahead of print]]. Recent attention has been paid to the suspicion that RPE tears occur more commonly after anti-VEGF therapy, but this relationship has not been clearly established. Patients with pre-existing subfoveal tears of the RPE have been excluded from prospective trials of anti-VEGF therapy and hence their response to subsequent anti-VEGF therapy is not well-understood.

In the present study we describe the incidence rate and risk factors for RPE tears following intravitreal anti-VEGF treatment in a single institution. In addition we investigate the effect of continuing anti-VEGF treatment after RPE tear development.

METHODS

A longitudinal, retrospective study was undertaken of the medical records of patients who attended the retina service at the Leicester Royal Infirmary between May 2010 and December 2011. Eligibility criteria for the study included: identification of occult subretinal CNV on indocyanine green angiography (ICGA), treatment with intravitreal injections of ranibizumab (Lucentis; Genentech, Inc, South San Francisco, CA) or bevacizumab (Avastin; Genentech) and follow up of at least 12 months. Exclusion criteria were: other previous treatment (laser, photodynamic therapy), ocular abnormalities other than AMD affecting visual function or treatment outcome. The treatment plan included a 3-monthly loading phase of intravitreal injections. Further injections provided depending on the OCT detection of subretinal fluid (SRF), intraretinal fluid (IRF), and persistence or recurrence of PED. Patients were evaluated on a regular basis (maximum intervals of 3 months) for at least 12 months.

RPE tears were diagnosed based on fundus examination, Spectral Domain optical coherence tomography (OCT) (3D OCT-1000, Topcon Corporation, Tokyo, Japan), and fundus fluorescein angiography (FFA). RPE tears were then classified according to the criteria of Sarraf. In our service, intravitreal anti-VEGF injections were continued even after a RPE tear development, except from grade 4 tears.

Data were collected retrospectively, and the completed data forms were analyzed with Microsoft Excel 2010 for Windows (Microsoft Corporation, Redmond, WA, USA).

RESULTS

A total of 628 patients (mean age 80.9±7.3 years), 676 eyes and 4027 injections were analysed. RPE tears developed in 17 cases (0.4%) (12 women). Mean age of this group of patients was 83.94±5.84 years. 14/17 of the patients that developed RPE tear were over 80 years old.

15/17 patients had a PED height of less than 400 microns at presentation and developed RPE tears within 6 months after the intravitreal anti-VEGF treatment initiation. 14 patients developed RPE tear earlier than the sixth intravitreal injection.

The visual outcome was poor in 10 patients, as they had Grade 4 RPE tears. The remaining 7 patients had Grade 1-3 RPE tears and visual acuity slightly improved in 5 of them with the continuation of their anti-VEGF treatment (Table 1).

Table 1.

Visual acuity (LogMAR) of patients that developed RPE tear and continued anti-VEGF treatment.




DISCUSSION

In terms of visual prognosis in RPE tears, even if the short-term visual prognosis is relatively unchanged by RPE tears, they are associated with a slow decrease in vision in the long term, often resulting in a severe visual disability. RPE tears are associated with subretinal bleeding and development of disciform scars that lead to this poor visual prognosis. However, few reports have described that anti-VEGF can improve the outcome of this condition [14Coco RM, Sanabria MR, Hernandez AG, Fernandez Munoz M. Retinal pigment epithelium tears in age-related macular degeneration treated with antiangiogenic drugs a controlled study with long follow-up. Ophthalmologica 2012; 228: 78-83.-17Rouvas AA, Ladas ID, Georgalas I, Vergados I, Papakonstantinou D, Kotsolis AI. Ranibizumab for the treatment of exudative age-related macular degeneration associated with retinal pigment epithelial tear. Retina 2011; 31: 1083-8.]. Repopulation of the RPE after pigment epithelium tear has been described as one potential avenue for post-tear visual gains by Peiretti et al. [18Peiretti E, Iranmanesh R, Lee JJ, Klancnik JM, Sorenson JA, Yannuzzi LA. Repopulation of the retinal pigment epithelium after pigment epithelial rip. Retina 2006; 26: 1097-9.], in a patient with RPE tear and polypoidal choroidal neovascularisation. There are suggestions that persistent anti-VEGF therapy is important to continue to suppress the neovascular activity in cases of RPE tears grade 3 or lower [19Garg S, Brod R, Kim D, Lane RG, Maguire J, Fischer D. Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration. Clin Experiment Ophthalmol 2008; 36: 252-6.-21Bartels S, Barrelmann A, Book B , et al. Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration Function recovery under intensive therapy. Ophthalmologe 2013; [Epub ahead of print]]. Therefore, in these cases the possible clinical benefits tend to appear at 3 months’ time. For grade 4 RPE tears, macular surgery with macular translocation or an RPE graft could be an option [22Polito A, Cereda M, Romanelli F, Pertile G. Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear long-term results. Br J Ophthalmol 2011; 95: 74-8., 23Zayit-Soudry S, Moroz I, Loewenstein A. Retinal pigment epithelial detachment. Surv Ophthalmol 2007; 52: 227-43.]. It is debatable if a more aggressive or alternatively a more reserved treatment regime would result in better visual results.

The overall incidence rate reported in our study (0.4%) was comparable to the reported literature. Presence of fibrovascular PED appears to be a significant risk factor for the development of RPE tears in AMD. Large PED diameter and vertical height on OCT (>400 μm) have been shown to increase the risk of RPE tear. However, our study shows that 88% (15/17) of the RPE tears developed from PEDs with height less than 400 μm. This finding is very interesting and implies that PED height may not be such a decisive risk factor for RPE tears development. Since the mean age of our cases was over 80 years, one can hypothesize that the integrity of the RPE is an additional factor leading to tearing of older people compromised retinal pigment epithelium. Saraff’s RPE tear classification system comprises a solid base for the study of the entity and in our opinion additional parameters as age and RPE thickness could attribute to an even more complete explanation and prognosis of this devastating condition.

It has also been shown that RPE tears always developed relatively close to the initiation of the anti-VEGF treatment (1-3 months). The mean number of injections before the diagnosis of a new RPE tear in our study was 7.2. RPE tears might be initiated during anti-VEGF therapy, as a result of tractional forces at the level of RPE [24Nagiel A, Freund KB, Spaide RF, Munch IC, Larsen M, Sarraf D. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography. Am J Ophthal-mol 2013; 156: 981-8.]. The time association between the development of RPE tears and the initiation of anti-VEGF treatment cannot prove a causative relation, but it should be taken into consideration as a complication of the treatment.

Further studies are needed to address when patients with RPE tears should receive treatment. Retreatment decisions are complex, given that fluid leakage may occur not only due to choroidal neovascular activity, but also secondary to the absence of RPE, which functions to pump out fluid from the subretinal space.

A workable limitation of the current study is its retrospective nature. Nevertheless, the study was conducted in a large referral center where the accuracy of data is assured. Another limiting factor could be considered the inclusion of two eyes for some patients. However, all of our cases were unilateral so no further analysis was needed.

In conclusion, this study demonstrates that a considerable risk factor for RPE tears development is a previously diagnosed PED. In the majority of our cases, PED height was not as critical factor as the patient’s age, showing a possible age dependent resistance of the RPE to stretching caused by the PED.

Large randomised controlled clinical studies may be necessary to establish the burden of possible risk factors as well as to define the optimum management after a retinal pigment epithelium tear in patients with age related macular degeneration.

CONFLICT OF INTEREST

The authors confirm that this article content has no conflict of interest.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Hoskin A, Bird AC, Sehmi K. Tears of detached retinal pigment epithelium. Br J Ophthalmol 1981; 65: 417-22.
[2] Michels S, Aue A, Simader C, Geitzenauer W, Sacu S, Schmidt-Erfurth U. Retinal pigment epithelium tears following verteporfin therapy combined with intravitreal triamcinolone. Am J Ophthalmol 2006; 141: 396-98.
[3] Gutfleisch M, Heimes B, Schumacher M , et al. Long-term visual outcome of pigment epithelial tears in association with anti-VEGF therapy of pigment epithelial detachment in AMD. Eye (Lond) 2011; 25: 1181-6.
[4] Decker WL, Sanborn GE, Ridley M, Annesley WH Jr, Sorr EM. Retinal pigment epithelial tears. Ophthalmology 1983; 90: 507-12.
[5] Gass JD. Retinal pigment epithelial rip during krypton red laser photocoagulation. Am J Ophthalmol 1984; 98(6): 700-6.
[6] Vardarinos A, Empeslidis T, Periysamy K , et al. Tear of retinal pigment epithelium following YAG laser posterior capsulotomy in a patient on Anti-VEGF Treatment for AMD Six Months' Follow-Up. Case Rep Ophthalmol 2012; 3: 221-5.
[7] Sarraf D, Reddy S, Chiang A, Yu F, Jain A. A new grading system for retinal pigment epithelial tears. Retina 2010; 30: 1039-45.
[8] Dhalla MS, Blinder KJ, Tewari A, Hariprasad SM, Apte RS. Retinal pigment epithelial tear following intravitreal pegaptanib sodium. Am J Ophthalmol 2006; 141: 752-4.
[9] Chan CK, Meyer CH, Gross JG , et al. Retinal pigment epithelial tears after intravitreal bevacizumab injection for neovascular age-related macular degeneration. Retina 2007; 27: 541-1.
[10] Smith BT, Kraus CL, Apte RS. Retinal pigment epithelial tears in ranibizumab treated eyes. Retina 2009; 29: 335-9.
[11] Cunningham ET Jr, Feiner L, Chung C, Tuomi L, Ehrlich JS. Incidence of retinal pigment epithelial tears after intravitreal ranibizumab injection for neovascular age-related macular degeneration. Ophthalmology 2011; 118: 2447-52.
[12] Lommatzsch A, Heimes B, Gutfleisch M, Spital G, Zeimer M, Pauleikhoff D. Serous pigment epithelial detachment in age-related macular degeneration comparison of different treatments. Eye (Lond) 2009; 23: 2163-8.
[13] Doguizi S, Ozdek S. Pigment epithelial tears associated with anti-vegf therapy incidence, long-term visual outcome, and relationship with pigment epithelial detachment in age-related macular degeneration. Retina 2013; [Epub ahead of print]
[14] Coco RM, Sanabria MR, Hernandez AG, Fernandez Munoz M. Retinal pigment epithelium tears in age-related macular degeneration treated with antiangiogenic drugs a controlled study with long follow-up. Ophthalmologica 2012; 228: 78-83.
[15] Konstantinidis L, Ambresin A, Zografos L, Mantel I. Retinal pigment epithelium tears after intravitreal injection of ranibizumab for predominantly classic neovascular membranes secondary to age-related macular degeneration. Acta Ophthalmol 2010; 88: 736-41.
[16] Lesniak SP, Fine HF, Prenner JL, Roth DB. Long-term follow-up of spontaneous retinal pigment epithelium tears in age-related macular degeneration treated with anti-VEGF therapy. Eur J Ophthalmol 2011; 21: 73-6.
[17] Rouvas AA, Ladas ID, Georgalas I, Vergados I, Papakonstantinou D, Kotsolis AI. Ranibizumab for the treatment of exudative age-related macular degeneration associated with retinal pigment epithelial tear. Retina 2011; 31: 1083-8.
[18] Peiretti E, Iranmanesh R, Lee JJ, Klancnik JM, Sorenson JA, Yannuzzi LA. Repopulation of the retinal pigment epithelium after pigment epithelial rip. Retina 2006; 26: 1097-9.
[19] Garg S, Brod R, Kim D, Lane RG, Maguire J, Fischer D. Retinal pigment epithelial tears after intravitreal bevacizumab injection for exudative age-related macular degeneration. Clin Experiment Ophthalmol 2008; 36: 252-6.
[20] Lalwani GA, Rosenfeld PJ, Fung AE , et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration year 2 of the PrONTO Study. Am J Ophthalmol 2009; 148: 43-58.
[21] Bartels S, Barrelmann A, Book B , et al. Tear in retinal pigment epithelium under anti-VEGF therapy for exudative age-related macular degeneration Function recovery under intensive therapy. Ophthalmologe 2013; [Epub ahead of print]
[22] Polito A, Cereda M, Romanelli F, Pertile G. Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear long-term results. Br J Ophthalmol 2011; 95: 74-8.
[23] Zayit-Soudry S, Moroz I, Loewenstein A. Retinal pigment epithelial detachment. Surv Ophthalmol 2007; 52: 227-43.
[24] Nagiel A, Freund KB, Spaide RF, Munch IC, Larsen M, Sarraf D. Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography. Am J Ophthal-mol 2013; 156: 981-8.

Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Webmaster Contact: info@benthamopen.net
Copyright © 2019 Bentham Open