Anti-VEGF and Retinal Dystrophies

Author(s): Maurizio Battaglia Parodi, Pierluigi Iacono*, Stefano Da Pozzo

Journal Name: Current Drug Targets

Volume 21 , Issue 12 , 2020

DOI : 10.2174/1389450121666200428103334

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The therapeutic approach based on anti-vascular endothelial growth factor (anti-VEGF) molecules can be used to treat two important complications of retinal dystrophies: choroidal neovascularization and macular edema. The macular involvement in retinal dystrophies can lead to further visual deterioration in patients at a young age and already affected by functional limitations. The study reports the effect of anti-VEGF treatment in several subforms of retinal dystrophies, critically discussing advantages and limitations.

Keywords: Choroidal neovascularization, macular edema retinitis pigmentosa, best vitelliform macular dystrophy, stargardt disease, pattern dystrophy, anti-VEGF.

[1]
Marano F, Deutman AF, Leys A, Aandekerk AL. Hereditary retinal dystrophies and choroidal neovascularization. Graefes Arch Clin Exp Ophthalmol 2000; 238(9): 760-4.
[http://dx.doi.org/10.1007/s004170000186] [PMID: 11045344]
[2]
Battaglia Parodi M, Iacono P, Bandello F. Antivascular endothelial growth factor in hereditary dystrophies. Dev Ophthalmol 2010; 46: 107-10.
[http://dx.doi.org/10.1159/000320013] [PMID: 20703036]
[3]
Triolo G, Pierro L, Parodi MB, et al. Spectral domain optical coherence tomography findings in patients with retinitis pigmentosa. Ophthalmic Res 2013; 50(3): 160-4.
[http://dx.doi.org/10.1159/000351681] [PMID: 23989166]
[4]
Hirakawa H, Iijima H, Gohdo T, Tsukahara S. Optical coherence tomography of cystoid macular edema associated with retinitis pigmentosa. Am J Ophthalmol 1999; 128(2): 185-91.
[http://dx.doi.org/10.1016/S0002-9394(99)00100-2] [PMID: 10458174]
[5]
Iwakiri R, Okinami S, Hirata A. Two cases of retinitis pigmentosa associated with choroidal neovascularization. Nippon Ganka Gakkai Zasshi 2007; 111(8): 606-11.
[PMID: 17874536]
[6]
Cheng JY, Adrian KH. Photodynamic therapy for choroidal neovascularization in stargardt disease and retinitis pigmentosa. Retin Cases Brief Rep 2009; 3(4): 388-90.
[http://dx.doi.org/10.1097/ICB.0b013e31817f2e3f] [PMID: 25389856]
[7]
Battaglia Parodi M, De Benedetto U, Knutsson KA, et al. Juxtafoveal choroidal neovascularization associated with retinitis pigmentosa treated with intravitreal bevacizumab. J Ocul Pharmacol Ther 2012; 28(2): 202-4.
[http://dx.doi.org/10.1089/jop.2011.0140] [PMID: 22149640]
[8]
Miyata M, Oishi A, Oishi M, Hasegawa T, Ikeda HO, Tsujikawa A. Long-term efficacy and safety of anti-VEGF therapy in retinitis pigmentosa: a case report. BMC Ophthalmol 2018; 14: 18-248.
[http://dx.doi.org/10.1186/s12886-018-0914-z]
[9]
Artunay O, Yuzbasioglu E, Rasier R, Sengul A, Bahcecioglu H. Intravitreal ranibizumab in the treatment of cystoid macular edema associated with retinitis pigmentosa. J Ocul Pharmacol Ther 2009; 25(6): 545-50.
[http://dx.doi.org/10.1089/jop.2009.0089] [PMID: 20028262]
[10]
Yuzbasioglu E, Artunay O, Rasier R, Sengul A, Bahcecioglu H. Intravitreal bevacizumab (Avastin) injection in retinitis pigmentosa. Curr Eye Res 2009; 34(3): 231-7.
[http://dx.doi.org/10.1080/02713680802710692] [PMID: 19274531]
[11]
Moustafa GA, Moschos MM. Intravitreal aflibercept (Eylea) injection for cystoid macular edema secondary to retinitis pigmentosa - a first case report and short review of the literature. BMC Ophthalmol 2015; 15: 44.
[http://dx.doi.org/10.1186/s12886-015-0033-z] [PMID: 25925748]
[12]
Strong SA, Peto T, Bunce C, et al. Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa. Br J Ophthalmol 2020; 2: 10.
[http://dx.doi.org/10.1136/bjophthalmol-2019-315152]
[13]
Salom D, Diaz-Llopis M, García-Delpech S, Udaondo P, Sancho-Tello M, Romero FJ. Aqueous humor levels of vascular endothelial growth factor in retinitis pigmentosa. Invest Ophthalmol Vis Sci 2008; 49(8): 3499-502.
[http://dx.doi.org/10.1167/iovs.07-1168] [PMID: 18326689]
[14]
Khan KN, Mahroo OA, Islam F, Webster AR, Moore AT, Michaelides M. Functional and anatomical outcomes of choroidal neovascularization complicating BEST1-related retinopathy. Retina 2017; 37(7): 1360-70.
[http://dx.doi.org/10.1097/IAE.0000000000001357] [PMID: 27764019]
[15]
Battaglia Parodi M, Iacono P, Romano F, Bandello F. Spectral domain optical coherence tomography features in different stages of stages of Best vitelliform macular dystrophy. Retina 2018; 38(5): 1041-6.
[http://dx.doi.org/10.1097/IAE.0000000000001634] [PMID: 28376040]
[16]
Battaglia Parodi M, Romano F, Cicinelli MV, et al. Retinal vascular impairment in best vitelliform macular dystrophy assessed by means of optical coherence tomography angiography. Am J Ophthalmol 2018; 187: 61-70.
[http://dx.doi.org/10.1016/j.ajo.2017.12.013] [PMID: 29288639]
[17]
Battaglia Parodi M, Casalino G, Iacono P, Introini U, Adamyan T, Bandello F. The expanding clinical spectrum of choroidal excavation in macular dystrophies. Retina 2018; 38(10): 2030-4.
[http://dx.doi.org/10.1097/IAE.0000000000001805] [PMID: 28800018]
[18]
Guduru A, Gupta A, Tyagi M, Jalali S, Chhablani J. Optical coherence tomography angiography characterisation of Best disease and associated choroidal neovascularisation. Br J Ophthalmol 2018; 102(4): 444-7.
[PMID: 28765145]
[19]
Shahzad R, Siddiqui MA. Choroidal neovascularization secondary to Best vitelliform macular dystrophy detected by optical coherence tomography angiography. J AAPOS 2017; 21(1): 68-70.
[http://dx.doi.org/10.1016/j.jaapos.2016.08.018] [PMID: 27867022]
[20]
Battaglia Parodi M, Romano F, Arigo A, et al. Natural course of the vitelliform stage in best vitelliform macular dystrophy: a five-year follow-up study. Graefes Arch Clin Exp Ophthalmol 2020; 258(2): 297-301.
[http://dx.doi.org/10.1007/s00417-019-04454-4] [PMID: 31848692]
[21]
Padhi TR, Anderson BJ, Abbey AM, et al. Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes. Br J Ophthalmol 2018; 102(9): 1232-7.
[http://dx.doi.org/10.1136/bjophthalmol-2017-310497] [PMID: 29217515]
[22]
Allikmets R, Singh N, Sun H, et al. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 1997; 15(3): 236-46.
[http://dx.doi.org/10.1038/ng0397-236] [PMID: 9054934]
[23]
Koenekoop RK. The gene for Stargardt disease, ABCA4, is a major retinal gene: a mini-review. Ophthalmic Genet 2003; 24(2): 75-80.
[http://dx.doi.org/10.1076/opge.24.2.75.13996] [PMID: 12789571]
[24]
Battaglia Parodi M. Eredodistrofie Corioretiniche. Rome: Verduci Editore 2002; pp. 21-60.
[25]
Lee W, Xie Y, Zernant J, et al. Complex inheritance of ABCA4 disease: four mutations in a family with multiple macular phenotypes. Hum Genet 2016; 135(1): 9-19.
[http://dx.doi.org/10.1007/s00439-015-1605-y] [PMID: 26527198]
[26]
Arrigo A, Grazioli A, Romano F, et al. Multimodal evaluation of central and peripheral alterations in Stargardt disease: a pilot study. Br J Ophthalmol 2019.bjophthalmol-2019-315148.
[http://dx.doi.org/10.1136/bjophthalmol-2019-315148] [PMID: 31748334]
[27]
Franceschetti A, François J. Fundus flavimaculatus. Arch Ophtalmol Rev Gen Ophtalmol 1965; 25(6): 505-30.
[PMID: 4221555]
[28]
Armstrong JD, Meyer D, Xu S, Elfervig JL. Long-term follow-up of Stargardt’s disease and fundus flavimaculatus. Ophthalmology 1998; 105(3): 448-57.
[http://dx.doi.org/10.1016/S0161-6420(98)93026-3] [PMID: 9499775]
[29]
Klein R, Lewis RA, Meyers SM, Myers FL. Subretinal neovascularization associated with fundus flavimaculatus. Arch Ophthalmol 1978; 96(11): 2054-7.
[http://dx.doi.org/10.1001/archopht.1978.03910060442009] [PMID: 718494]
[30]
Pawlak D, Souied E, Mimoun G, Papp-Pawlak M, Coscas G, Soubrane G. [Fundus flavimaculatus and choroidal neovascularization. J Fr Ophtalmol 2006; 29(2): 188-94.
[http://dx.doi.org/10.1016/S0181-5512(06)73770-6] [PMID: 16523163]
[31]
Quijano C, Querques G, Massamba N, Soubrane G, Souied EH. Type 3 choroidal neovascularization associated with fundus flavimaculatus. Ophthalmic Res 2009; 42(3): 152-4.
[http://dx.doi.org/10.1159/000229030] [PMID: 19628956]
[32]
Rotenstreich Y, Fishman GA, Anderson RJ. Visual acuity loss and clinical observations in a large series of patients with Stargardt disease. Ophthalmology 2003; 110(6): 1151-8.
[http://dx.doi.org/10.1016/S0161-6420(03)00333-6] [PMID: 12799240]
[33]
Valmaggia C, Niederberger H, Helbig H. Photodynamic therapy for choroidal neovascularization in fundus flavimaculatus. Retina 2002; 22(1): 111-3.
[http://dx.doi.org/10.1097/00006982-200202000-00022] [PMID: 11884891]
[34]
Souied EH, Pawlak D, Algan M, Sayag D, Coscas G, Soubrane G. Photodynamic therapy for choroidal neovascularization on late-onset fundus flavimaculatus. Am J Ophthalmol 2005; 140(2): 312-4.
[http://dx.doi.org/10.1016/j.ajo.2005.01.024] [PMID: 16086955]
[35]
Japiassú RM, Moura Brasil OF, Maia HS, Maia AS, Brasil OM. Photodynamic therapy for bilateral and simultaneous choroidal neovascularization in stargardt disease. Retin Cases Brief Rep 2008; 2(1): 9-11.
[http://dx.doi.org/10.1097/ICB.0b013e3180467837] [PMID: 25389604]
[36]
Kim HH, Carvounis PE, Albini TA, Holz ER, Mieler WF. Photodynamic therapy for bilateral subfoveal choroidal neovascularization complicating stargardt macular dystrophy. Retin Cases Brief Rep 2008; 2(1): 6-8.
[http://dx.doi.org/10.1097/ICB.0b013e318033907f] [PMID: 25389603]
[37]
Braun B, Schneider U, Hasler P, Prünte C. Combination therapy of PDT and triamcinolone in CNV associated with fundus flavimaculatus. Klin Monatsbl Augenheilkd 2007; 224(4): 353-5.
[http://dx.doi.org/10.1055/s-2007-962838] [PMID: 17458813]
[38]
Querques G, Bocco MC, Soubrane G, Souied EH. Intravitreal ranibizumab (Lucentis) for choroidal neovascularization associated with Stargardt’s disease. Graefes Arch Clin Exp Ophthalmol 2008; 246(2): 319-21.
[http://dx.doi.org/10.1007/s00417-007-0689-z] [PMID: 17934751]
[39]
Tejerina AN, García-Pous M, Pozos EP, Esteban MC, Boronat JM. Ranibizumab for choroidal neovascularization in fundus flavimaculatus. Retin Cases Brief Rep 2008; 2(3): 250-2.
[http://dx.doi.org/10.1097/ICB.0b013e31816b31d1] [PMID: 25390102]
[40]
Koh V, Naing T, Chee C. Fundus flavimaculatus and choroidal neovascularization in a young patient with normal electroretinography: case report. Can J Ophthalmol 2012; 47(3): e3-5.
[http://dx.doi.org/10.1016/j.jcjo.2012.03.003] [PMID: 22687319]
[41]
Battaglia Parodi M, Munk MR, Iacono P, Bandello F. Ranibizumab for subfoveal choroidal neovascularisation associated with Stargardt disease. Br J Ophthalmol 2015; 99(9): 1268-70.
[http://dx.doi.org/10.1136/bjophthalmol-2014-305783] [PMID: 25740804]
[42]
Roy R, Kumar A, Ghosh S, Lobo A, Agarwal P. All that glitters are not flecks: inflammatory choroidal neovascularization in fundus flavimaculatus. Ocul Immunol Inflamm 2015; 23(2): 188-90.
[http://dx.doi.org/10.3109/09273948.2013.873810] [PMID: 24484270]
[43]
Radu RA, Hu J, Yuan Q, et al. Complement system dysregulation and inflammation in the retinal pigment epithelium of a mouse model for Stargardt macular degeneration. J Biol Chem 2011; 286(21): 18593-601.
[http://dx.doi.org/10.1074/jbc.M110.191866] [PMID: 21464132]
[44]
Cicinelli MV, Battista M, Starace V, Battaglia Parodi M, Bandello F. Monitoring and Management of the Patient with Stargardt Disease. Clin Optom (Auckl) 2019; 11: 151-65.
[http://dx.doi.org/10.2147/OPTO.S226595] [PMID: 31819694]
[45]
Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. 4th ed. St. Louis: CV Mosby 1997; pp. 314-25.
[46]
Francis PJ, Schultz DW, Gregory AM, et al. Genetic and phenotypic heterogeneity in pattern dystrophy. Br J Ophthalmol 2005; 89(9): 1115-9.
[http://dx.doi.org/10.1136/bjo.2004.062695] [PMID: 16113362]
[47]
Marmor MF, Byers B. Pattern dystrophy of the retinal pigment epithelium. Am J Ophthalmol 1976; 13: 112-6.
[PMID: 8794711]
[48]
Taillanter-Francoz N, Remy C, Bonnet M, Baserer T. Choroidal neovessels associated with reticular dystrophy of the pigment epithelium (case report). Bull Soc Ophtalmol Fr 1981; 81(4-5): 539-41.
[PMID: 6167375]
[49]
Marano F, Deutman AF, Pinckers AJ, Aandekerk AL, Rijneveld WJ. Reticular dystrophy of the retinal pigment epithelium and choroidal neovascularization. A fluorescein and ICGV study. Acta Ophthalmol Scand 1997; 75(1): 22-7.
[http://dx.doi.org/10.1111/j.1600-0420.1997.tb00243.x] [PMID: 9088395]
[50]
Battaglia Parodi M, Da Pozzo S, Ravalico G. Photodynamic therapy for choroidal neovascularization associated with pattern dystrophy. Retina 2003; 23(2): 171-6.
[http://dx.doi.org/10.1097/00006982-200304000-00006] [PMID: 12707595]
[51]
Parodi MB, Liberali T, Pedio M, et al. Photodynamic therapy of subfoveal choroidal neovascularization secondary to reticular pattern dystrophy: three-year results of an uncontrolled, prospective case series. Am J Ophthalmol 2006; 141(6): 1152-4.
[http://dx.doi.org/10.1016/j.ajo.2006.01.038] [PMID: 16765697]
[52]
Battaglia Parodi M. Choroidal neovascularization in fundus pulverulentus. Acta Ophthalmol Scand 2002; 80(5): 559-60.
[http://dx.doi.org/10.1034/j.1600-0420.2002.800521.x] [PMID: 12390174]
[53]
Parodi MB, Iacono P, Cascavilla M, Zucchiatti I, Kontadakis DS, Bandello F. Intravitreal bevacizumab for subfoveal choroidal neovascularization associated with pattern dystrophy. Invest Ophthalmol Vis Sci 2010; 51(9): 4358-61.
[http://dx.doi.org/10.1167/iovs.10-5237] [PMID: 20375343]
[54]
Mimoun G, Caillaux V, Querques G, Rothschild PR, Puche N, Souied EH. Ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy: one-year results. Retina 2013; 33(3): 513-21.
[http://dx.doi.org/10.1097/IAE.0b013e3182753adb] [PMID: 23400081]
[55]
Empeslidis T, Vardarinos A, Deane J, Banerjee S. Intravitreal ranibizumab in the treatment of butterfly-shaped pattern dystrophy associated with choroidal neovascularization: a case report. Case Rep Ophthalmol 2012; 3(1): 77-82.
[http://dx.doi.org/10.1159/000336987] [PMID: 22529806]
[56]
Vaclavik V, Tran HV, Gaillard MC, Schorderet DF, Munier FL. Pattern dystrophy with high intrafamilial variability associated with Y141C mutation in the peripherin/RDS gene and successful treatment of subfoveal CNV related to multifocal pattern type with anti-VEGF (ranibizumab) intravitreal injections. Retina 2012; 32(9): 1942-9.
[http://dx.doi.org/10.1097/IAE.0b013e31824b32e4] [PMID: 22466463]
[57]
Tiosano L, Jaouni T, Averbukh E, Grunin M, Banin E, Chowers I. Bevacizumab treatment for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Eur J Ophthalmol 2014; 24(6): 890-6.
[http://dx.doi.org/10.5301/ejo.5000486] [PMID: 24846624]
[58]
Battaglia Parodi M, Romano F, Marchese A, et al. Anti-VEGF treatment for choroidal neovascularization complicating pattern dystrophy-like deposit associated with pseudoxanthoma elasticum. Graefes Arch Clin Exp Ophthalmol 2019; 257(2): 273-8.
[http://dx.doi.org/10.1007/s00417-018-4190-7] [PMID: 30470876]
[59]
Bietti G. Ueber familiaeres vorkommen von ‘retinitis punctata albescens’ (verbunden mit ‘dystrophia marginalis cristallinea corneae’), glitzern des glaskoerpers und anderen degenerativen augenveraenderungen. Klin Monatsbl Augenheilkd 1939; 99: 737-57.
[60]
Li A, Jiao X, Munier FL, et al. Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2. Am J Hum Genet 2004; 74(5): 817-26.
[http://dx.doi.org/10.1086/383228] [PMID: 15042513]
[61]
Li Q, Li Y, Zhang X, et al. Utilization of fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging in the characterization of Bietti crystalline dystrophy in different stages. Retina 2015; 35: 2074-84.
[http://dx.doi.org/10.1097/IAE.0000000000000592]
[62]
Le Tien V, Atmani K, Querques G, Massamba N, Souied EH. Ranibizumab for subfoveal choroidal neovascularization in Bietti crystalline retinopathy. Eye (Lond) 2010; 24(11): 1728-9.
[http://dx.doi.org/10.1038/eye.2010.116] [PMID: 20798693]
[63]
Gupta B, Parvizi S, Mohamed MD. Bietti crystalline dystrophy and choroidal neovascularisation. Int Ophthalmol 2011; 31(1): 59-61.
[http://dx.doi.org/10.1007/s10792-010-9406-8] [PMID: 20972604]
[64]
Atmaca LS, Muftuoglu O, Atmaca-Sonmez P. Peripapillary choroidal neovascularization in Bietti crystalline retinopathy. Eye (Lond) 2007; 21(6): 839-42.
[http://dx.doi.org/10.1038/sj.eye.6702673] [PMID: 17173010]
[65]
Nachiappan K, Krishnan T, Madhavan J. Ranibizumab for choroidal neovascular membrane in a rare case of Bietti’s crystalline dystrophy: a case report. Indian J Ophthalmol 2012; 60(3): 207-9.
[http://dx.doi.org/10.4103/0301-4738.95873] [PMID: 22569382]
[66]
Yin X, Yang L, Chen N, et al. Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy. Exp Eye Res 2016; 146: 154-62.
[http://dx.doi.org/10.1016/j.exer.2016.03.007] [PMID: 26971461]
[67]
Mamatha G, Umashankar V, Kasinathan N, et al. Molecular screening of the CYP4V2 gene in Bietti crystalline dystrophy that is associated with choroidal neovascularization. Mol Vis 2011; 17: 1970-7.
[PMID: 21850171]
[68]
Inanc M, Tekin K, Teke MY. Bilateral choroidal neovascularization associated with gyrate atrophy managed with intravitreal bevacizumab. Int Ophthalmol 2018; 38(3): 1351-5.
[http://dx.doi.org/10.1007/s10792-017-0579-2] [PMID: 28560651]
[69]
Gulkilik G, Erdur SK, Eliacik M, et al. A case of cone dystrophy associated with choroidal neovascularization. Retin Cases Brief Rep 2018; 12(2): 111-4.
[http://dx.doi.org/10.1097/ICB.0000000000000437] [PMID: 27685498]
[70]
Chatziralli I, Theodossiadis G, Emfietzoglou I, Theodossiadis P. Intravitreal ranibizumab for choroidal neovascularization secondary to gyrate atrophy in a young patient: a multimodal imaging analysis. Eur J Ophthalmol 2015; 25(6): e119-22.
[http://dx.doi.org/10.5301/ejo.5000660] [PMID: 26419008]
[71]
Marano F, Deutman AF, Pinckers AJ, Aandekerk AL. Gyrate atrophy and choroidal neovascularization. Arch Ophthalmol 1996; 114(10): 1295.
[http://dx.doi.org/10.1001/archopht.1996.01100140495035] [PMID: 8859105]
[72]
Campos-Pavón J, Torres-Peña JL. Choroidal neovascularization secondary to choroideremia. Arch Soc Esp Oftalmol 2015; 90(6): 289-91.
[http://dx.doi.org/10.1016/j.oftal.2014.03.012] [PMID: 25433417]
[73]
Palejwala NV, Lauer AK, Weleber RG. Choroideremia associated with choroidal neovascularization treated with intravitreal bevacizumab. Clin Ophthalmol 2014; 8: 1675-9.
[http://dx.doi.org/10.2147/OPTH.S68243] [PMID: 25214760]
[74]
Endo K, Yuzawa M, Ohba N. Choroideremia associated with subretinal neovascular membrane. Acta Ophthalmol Scand 2000; 78(4): 483-6.
[http://dx.doi.org/10.1034/j.1600-0420.2000.078004483.x] [PMID: 10990059]
[75]
Robinson D, Tiedeman J. Choroideremia associated with a subretinal neovascular membrane. Case report. Retina 1987; 7(2): 70-4.
[http://dx.doi.org/10.1097/00006982-198700720-00002] [PMID: 2442805]
[76]
Bertoli F, Pignatto S, Rizzetto F, Lanzetta PA. 5-Year-Old Case of Choroidal Neovascularization in Enhanced S-Cone Syndrome Treated with Ranibizumab. Case Rep Ophthalmol 2018; 9(3): 510-5.
[http://dx.doi.org/10.1159/000495743] [PMID: 30687072]
[77]
Broadhead GK, Grigg JR, McCluskey P, Korsakova M, Chang AA. Bevacizumab for choroidal neovascularisation in enhanced S-cone syndrome. Doc Ophthalmol 2016; 133(2): 139-43.
[http://dx.doi.org/10.1007/s10633-016-9555-9] [PMID: 27424008]
[78]
Ranchod TM, Faia LJ, Drenser KA. Peripapillary choroidal neovascularization in congenital retinoschisis. Retin Cases Brief Rep 2011; 5(4): 336-8.
[http://dx.doi.org/10.1097/ICB.0b013e3181ff0960] [PMID: 25390429]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 12
Year: 2020
Published on: 18 September, 2020
Page: [1201 - 1207]
Pages: 7
DOI: 10.2174/1389450121666200428103334
Price: $65

Article Metrics

PDF: 29
HTML: 2
PRC: 1



Most Downloaded Article(s)