Skip to main content
Top
Published in: International Ophthalmology 4/2017

01-08-2017 | Original Paper

Effect of antibiotic prophylaxis on Coagulase-negative Staphylococcus virulence factor profiles in patients undergoing cataract surgery

Authors: Yolanda López, Margarita Samudio, Norma Fariña, Verónica Castillo, Sonia Abente, Martin M. Nentwich, Nilsa González-Britez, Florentina Laspina, Agustín Carron, Diógenes Cibils, Herminia Miño de Kaspar

Published in: International Ophthalmology | Issue 4/2017

Login to get access

Abstract

Purpose

In this prospective study, multiplex polymerase chain reaction (PCR) was used to identify genes encoding virulence factors (ica, atlE and mecA) in Coagulase-negative Staphylococcus (CNS) isolates from the ocular microbiota of patients undergoing cataract surgery and to investigate possible changes in the CNS profile due to antibiotic prophylaxis.

Methods

Between 09/2011 and 08/2013, patients undergoing cataract surgery were recruited at the Department of Ophthalmology, National University of Asuncion, Paraguay. In the eye to be operated on, patients received moxifloxacin 0.5 % eye drops four times at the day before surgery and a last drop 1 hour before surgery (T1). The other eye remained as control (T0). Conjunctival swabs were taken from both eyes 1 hour after the last drop. The presence of genes encoding biofilm formation (ica and atlE) and methicillin resistance (mecA) was detected by a multiplex PCR.

Results

Of the 162 patients (162 study eyes, 162 fellow eye as control group), 87 (53.7 %) eyes were positive for CNS at T0 yielding 96 CNS isolates; 70 eyes (43.2 %) were positive at T1 yielding 77 CNS isolates. For this study, 43 CNS isolates (44.8 %) from T0 and 45 (64.3 %) from T1 were used. Of the total isolates, 81.8 % (72/88) had at least one virulence factor gene (37/43 from T0 and 35/45 from T1) (p = 0.314). Simultaneous detection of ica and atlE genes was higher in T0 (58.0 %) than T1 (46.7 %), but the difference was not significant (p = 0.28).

Conclusion

A high frequency of genes encoding virulence factors was observed in the coagulase-negative Staphylococcus isolates. The use of moxifloxacin did not significantly modify the CNS virulence factor profiles.
Literature
1.
go back to reference Taban M, Behrens A, Newcomb RL, Nobe MY, Saedi G, Sweet PM, McDonnell PJ (2005) Acute endophthalmitis following cataract surgery: a systematic review of the literature. Arch Ophthalmol 123(5):613–620CrossRefPubMed Taban M, Behrens A, Newcomb RL, Nobe MY, Saedi G, Sweet PM, McDonnell PJ (2005) Acute endophthalmitis following cataract surgery: a systematic review of the literature. Arch Ophthalmol 123(5):613–620CrossRefPubMed
2.
go back to reference Nentwich MM, Yactayo-Miranda Y, Schwarzbach F, Wolf A, Kampik A (2014) Mino de Kaspar H. Endophthalmitis after intravitreal injection: decreasing incidence and clinical outcome-8-year results from a tertiary ophthalmic referral center. Retina 34(5):943–950CrossRefPubMed Nentwich MM, Yactayo-Miranda Y, Schwarzbach F, Wolf A, Kampik A (2014) Mino de Kaspar H. Endophthalmitis after intravitreal injection: decreasing incidence and clinical outcome-8-year results from a tertiary ophthalmic referral center. Retina 34(5):943–950CrossRefPubMed
3.
4.
go back to reference Barry P, Cordovés L, Gardner S (2013) ESCRS Guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusions. The European Society for Cataract & Refractive Surgeons, Dublin Barry P, Cordovés L, Gardner S (2013) ESCRS Guidelines for prevention and treatment of endophthalmitis following cataract surgery: data, dilemmas and conclusions. The European Society for Cataract & Refractive Surgeons, Dublin
5.
go back to reference Yoshida JU, Kim AL, Pratzer KI et al (2010) Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besi-floxacin 0.6% ophthalmic suspension in cataract surgery patients. J Cataract Refract Surg 36:1499–1502CrossRefPubMed Yoshida JU, Kim AL, Pratzer KI et al (2010) Aqueous penetration of moxifloxacin 0.5% ophthalmic solution and besi-floxacin 0.6% ophthalmic suspension in cataract surgery patients. J Cataract Refract Surg 36:1499–1502CrossRefPubMed
6.
go back to reference Donnenfeld ED, Comstock TL, Proksch JW (2011) Human aqueous humor concentrations of besifloxacin, moxifloxacin, and gatifloxacin after topical ocular application. J Cataract Refract Surg 37(6):1082–1089CrossRefPubMed Donnenfeld ED, Comstock TL, Proksch JW (2011) Human aqueous humor concentrations of besifloxacin, moxifloxacin, and gatifloxacin after topical ocular application. J Cataract Refract Surg 37(6):1082–1089CrossRefPubMed
7.
go back to reference Arbisser LB (2008) Safety of intracameral moxifloxacin for prophylaxis of endophthalmitis after cataract surgery. J Cataract Refract Surg 34(7):1114–1120CrossRefPubMed Arbisser LB (2008) Safety of intracameral moxifloxacin for prophylaxis of endophthalmitis after cataract surgery. J Cataract Refract Surg 34(7):1114–1120CrossRefPubMed
8.
go back to reference Galvis V, Tello A, Sánchez MA, Camacho PA (2014) Cohort study of intracameral moxifloxacin in postoperative endophthalmitis prophylaxis. Ophthalmol Eye Dis 16(6):1–4 Galvis V, Tello A, Sánchez MA, Camacho PA (2014) Cohort study of intracameral moxifloxacin in postoperative endophthalmitis prophylaxis. Ophthalmol Eye Dis 16(6):1–4
10.
go back to reference Van Loosdrecht M, Lyklema J, Norde W, Zehnder A (1990) Influence of interfaces on microbial activity. Microbial Rev 54:75–87 Van Loosdrecht M, Lyklema J, Norde W, Zehnder A (1990) Influence of interfaces on microbial activity. Microbial Rev 54:75–87
12.
go back to reference Thomas V, Sanford B, Moreno R, Ramsay M (1997) Enzyme-linked Iectinsorbent assay measures N-acetyl-d-glucosamine in matrix of biofilm produced by Staphyococcus epidermidis. Curr Microbiol 35:249–254CrossRefPubMed Thomas V, Sanford B, Moreno R, Ramsay M (1997) Enzyme-linked Iectinsorbent assay measures N-acetyl-d-glucosamine in matrix of biofilm produced by Staphyococcus epidermidis. Curr Microbiol 35:249–254CrossRefPubMed
13.
go back to reference Araujo G, Coelho R, Barbosa de Carvalho C, Maciel M, Zambrana Coronado A, Rozenbaum R et al (2006) Commensal isolates of methicillin-resistant Staphylococcus epidermidis are also well equipped to produce biofilm on polystyrene surfaces. J Antimicrob Chemother 57(5):855–864CrossRefPubMed Araujo G, Coelho R, Barbosa de Carvalho C, Maciel M, Zambrana Coronado A, Rozenbaum R et al (2006) Commensal isolates of methicillin-resistant Staphylococcus epidermidis are also well equipped to produce biofilm on polystyrene surfaces. J Antimicrob Chemother 57(5):855–864CrossRefPubMed
14.
go back to reference Bradford R, Abdul Manan R, Daley AJ, Pearce C, Ramalingam A, D’Mello D et al (2006) Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants. Eur J Clin Microbiol Infect Dis 25:283–290CrossRefPubMed Bradford R, Abdul Manan R, Daley AJ, Pearce C, Ramalingam A, D’Mello D et al (2006) Coagulase-negative staphylococci in very-low-birth-weight infants: inability of genetic markers to distinguish invasive strains from blood culture contaminants. Eur J Clin Microbiol Infect Dis 25:283–290CrossRefPubMed
15.
go back to reference McKenney D, Hübner J, Muller E, Wang Y, Goldmann DA, Pier GB (1998) The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect Immun 66(10):4711–4720PubMedPubMedCentral McKenney D, Hübner J, Muller E, Wang Y, Goldmann DA, Pier GB (1998) The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin. Infect Immun 66(10):4711–4720PubMedPubMedCentral
16.
go back to reference Gad G, El-Feky M, El-Rehewy M, Hassan M, Abolella H, El-Baky R (2009) Detection of icaA, icaD genes and biofilm production by Staphylococcus aureus and Staphylococcus epidermidis isolated from urinary tract catheterized patients. J Infect Dev Ctries 3(5):342–351PubMed Gad G, El-Feky M, El-Rehewy M, Hassan M, Abolella H, El-Baky R (2009) Detection of icaA, icaD genes and biofilm production by Staphylococcus aureus and Staphylococcus epidermidis isolated from urinary tract catheterized patients. J Infect Dev Ctries 3(5):342–351PubMed
17.
go back to reference Vandecasteele SJ, Peetermans WE, Merckx R, Van Eldere J (2003) Expression of biofilm-associated genes in Staphylococcus epidermidis during in vitro and in vivo foreign body infections. J Infect Dis 188(5):730–737CrossRefPubMed Vandecasteele SJ, Peetermans WE, Merckx R, Van Eldere J (2003) Expression of biofilm-associated genes in Staphylococcus epidermidis during in vitro and in vivo foreign body infections. J Infect Dis 188(5):730–737CrossRefPubMed
18.
go back to reference von Eiff C, Peters G, Heilmann C (2002) Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect Dis 2:677–685CrossRef von Eiff C, Peters G, Heilmann C (2002) Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infect Dis 2:677–685CrossRef
19.
go back to reference Sader HS, Jones RN, Gales AC, Silva JB, Pignatari AC (2004) SENTRY antimicrobial surveillance program report: Latin American and Brazilian results for 1997 through 2001. Braz J Infect Dis 8:25–79CrossRefPubMed Sader HS, Jones RN, Gales AC, Silva JB, Pignatari AC (2004) SENTRY antimicrobial surveillance program report: Latin American and Brazilian results for 1997 through 2001. Braz J Infect Dis 8:25–79CrossRefPubMed
20.
go back to reference Raad I, Alrahwan A, Rolston K (1998) Staphylococcus epidermidis: emerging resistance and the need for alternative agents. Clin Infect Dis 26:1182–1187CrossRefPubMed Raad I, Alrahwan A, Rolston K (1998) Staphylococcus epidermidis: emerging resistance and the need for alternative agents. Clin Infect Dis 26:1182–1187CrossRefPubMed
21.
go back to reference Archer G, Climo M (2006) Staphylococcus epidermidis y otros estafilococos coagulasa negativos. In: Mandell GL, Douglas RG, Bennett JE (eds) Enfermedades Infecciosas. Principios y Práctica, 6a edn. Elsevier, Madrid Archer G, Climo M (2006) Staphylococcus epidermidis y otros estafilococos coagulasa negativos. In: Mandell GL, Douglas RG, Bennett JE (eds) Enfermedades Infecciosas. Principios y Práctica, 6a edn. Elsevier, Madrid
22.
go back to reference Miño de Kaspar H, Chang R, Shriver E, et al (2011) Methicillin resistance and biofilm production in isolated Staphylococcus epidermidis from pathological specimens and from normal conjunctival flora. Available in: www.arvo.org/am Miño de Kaspar H, Chang R, Shriver E, et al (2011) Methicillin resistance and biofilm production in isolated Staphylococcus epidermidis from pathological specimens and from normal conjunctival flora. Available in: www.​arvo.​org/​am
23.
go back to reference Fariña N, Carpinelli L, Samudio M, Guillén R, Laspina F, Sanabria R et al (2013) Clinically significant coagulase-negative staphylococci: most frequent species and virulence factors. Rev Chilena Infectol 30(5):480–488CrossRefPubMed Fariña N, Carpinelli L, Samudio M, Guillén R, Laspina F, Sanabria R et al (2013) Clinically significant coagulase-negative staphylococci: most frequent species and virulence factors. Rev Chilena Infectol 30(5):480–488CrossRefPubMed
24.
go back to reference Clinical and Laboratory Standard Institutes (CLSI) (2012) Performance standards for antimicrobial susceptibility testing: approved standard M100-S20. CLSI, Wayne Clinical and Laboratory Standard Institutes (CLSI) (2012) Performance standards for antimicrobial susceptibility testing: approved standard M100-S20. CLSI, Wayne
25.
go back to reference Zhang K, Sparling J, Chow B, Elsayed S, Hussain Z, Church D et al (2004) New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol 42(11):4947–4955CrossRefPubMedPubMedCentral Zhang K, Sparling J, Chow B, Elsayed S, Hussain Z, Church D et al (2004) New quadriplex PCR assay for detection of methicillin and mupirocin resistance and simultaneous discrimination of Staphylococcus aureus from coagulase-negative staphylococci. J Clin Microbiol 42(11):4947–4955CrossRefPubMedPubMedCentral
26.
go back to reference Sharma P, Lahiri K, Kapila K (2011) Conventional and molecular characterization of coagulase-negative staphylococcus in hospital isolates. Indian J Pathol Microbiol 54:85–89CrossRefPubMed Sharma P, Lahiri K, Kapila K (2011) Conventional and molecular characterization of coagulase-negative staphylococcus in hospital isolates. Indian J Pathol Microbiol 54:85–89CrossRefPubMed
28.
go back to reference Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI (2005) Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175CrossRefPubMed Hoffman LR, D’Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI (2005) Aminoglycoside antibiotics induce bacterial biofilm formation. Nature 436:1171–1175CrossRefPubMed
29.
go back to reference Wang Q, Sun FJ, Liu Y, Xiong LR, Xie LL, Xia PY (2010) Enhancement of biofilm formation by subinhibitory concentrations of macrolides in icaADBC-positive and -negative clinical isolates of Staphylococcus epidermidis. Antimicrob Agents Chemother 54(6):2707–2711CrossRefPubMedPubMedCentral Wang Q, Sun FJ, Liu Y, Xiong LR, Xie LL, Xia PY (2010) Enhancement of biofilm formation by subinhibitory concentrations of macrolides in icaADBC-positive and -negative clinical isolates of Staphylococcus epidermidis. Antimicrob Agents Chemother 54(6):2707–2711CrossRefPubMedPubMedCentral
30.
go back to reference Ishak M, Gröschel D, Mandell G, Wenzel R (1985) Association of slime with pathogenicity of coagulase-negative staphylococci causing nosocomial septicemia. J Clin Microbiol 22:4–1025 Ishak M, Gröschel D, Mandell G, Wenzel R (1985) Association of slime with pathogenicity of coagulase-negative staphylococci causing nosocomial septicemia. J Clin Microbiol 22:4–1025
31.
go back to reference Galdbart J, Allignet J, Tung H, Rydèn C, El Solh N (2000) Screening for Staphylococcus epidermidis markers discriminating between skin-flora strains and those responsible for infections of joint prostheses. J Infect Dis 182:351–355CrossRefPubMed Galdbart J, Allignet J, Tung H, Rydèn C, El Solh N (2000) Screening for Staphylococcus epidermidis markers discriminating between skin-flora strains and those responsible for infections of joint prostheses. J Infect Dis 182:351–355CrossRefPubMed
32.
go back to reference Klingenberg C, Aarag E, Rønnestad A, Sollid JE, Abrahamsen TG, Kjeldsen G, Flaegstad T (2005) Coagulase-negative staphylococcal sepsis in neonates. Association between antibiotic resistance, biofilm formation and the host inflammatory response. Pediatr Infect Dis J 24(9):817–822CrossRefPubMed Klingenberg C, Aarag E, Rønnestad A, Sollid JE, Abrahamsen TG, Kjeldsen G, Flaegstad T (2005) Coagulase-negative staphylococcal sepsis in neonates. Association between antibiotic resistance, biofilm formation and the host inflammatory response. Pediatr Infect Dis J 24(9):817–822CrossRefPubMed
33.
go back to reference Vandecasteele SJ, Peetermans WE, R Merckx R, Rijnders BJ, Van Eldere J (2003) Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clin Microbiol Infect 9(2):114–119CrossRefPubMed Vandecasteele SJ, Peetermans WE, R Merckx R, Rijnders BJ, Van Eldere J (2003) Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clin Microbiol Infect 9(2):114–119CrossRefPubMed
34.
go back to reference Rohde H, Kalitzky M, Kröger N, Scherpe S, Horstkotte MA, Knobloch JK et al (2004) Detection of virulence-associated genes not useful for discriminating between invasive and commensal Staphylococcus epidermidis strains from a bone marrow transplant unit. J Clin Microbiol 42(12):5614–5619CrossRefPubMedPubMedCentral Rohde H, Kalitzky M, Kröger N, Scherpe S, Horstkotte MA, Knobloch JK et al (2004) Detection of virulence-associated genes not useful for discriminating between invasive and commensal Staphylococcus epidermidis strains from a bone marrow transplant unit. J Clin Microbiol 42(12):5614–5619CrossRefPubMedPubMedCentral
35.
go back to reference Chambers HF (1997) Methicillin-resistant Staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 10(4):781–791PubMedPubMedCentral Chambers HF (1997) Methicillin-resistant Staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 10(4):781–791PubMedPubMedCentral
36.
go back to reference Mather R, Karenchak LM, Romanowski EG, Kowalski RP (2002) Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 133(4):463–466CrossRefPubMed Mather R, Karenchak LM, Romanowski EG, Kowalski RP (2002) Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol 133(4):463–466CrossRefPubMed
37.
go back to reference Arantes TE, Cavalcanti RF, Diniz Mde F, Severo MS, Lins Neto J, Castro CM (2006) Conjunctival bacterial flora and antibiotic resistance pattern in patients undergoing cataract surgery. Arq Bras Oftalmol 69(1):33–36CrossRefPubMed Arantes TE, Cavalcanti RF, Diniz Mde F, Severo MS, Lins Neto J, Castro CM (2006) Conjunctival bacterial flora and antibiotic resistance pattern in patients undergoing cataract surgery. Arq Bras Oftalmol 69(1):33–36CrossRefPubMed
38.
go back to reference Pinna A, Zanetti S, Sotgiu M, Sechi LA, Fadda G, Carta F (1999) Identification and antibiotic susceptibility of coagulase negative staphylococci isolated in corneal/external infections. Br J Ophthalmol 83(7):771–773CrossRefPubMedPubMedCentral Pinna A, Zanetti S, Sotgiu M, Sechi LA, Fadda G, Carta F (1999) Identification and antibiotic susceptibility of coagulase negative staphylococci isolated in corneal/external infections. Br J Ophthalmol 83(7):771–773CrossRefPubMedPubMedCentral
39.
go back to reference Ta CN, Chang RT, Singh K, Egbert PR, Shriver EM, Blumenkranz MS et al (2003) Antibiotic resistance patterns of ocular bacterial flora. Ophthalmology 110(10):1946–1951CrossRefPubMed Ta CN, Chang RT, Singh K, Egbert PR, Shriver EM, Blumenkranz MS et al (2003) Antibiotic resistance patterns of ocular bacterial flora. Ophthalmology 110(10):1946–1951CrossRefPubMed
40.
go back to reference Li B, de Kaspar HM, Haritoglou C, Kook D, Kampik A, Sheng M, Nentwich MM (2015) Comparison of 1-day versus 1-hour application of topical neomycin/polymyxin-B before cataract surgery. J Cataract Refract Surg 41(4):724–731CrossRefPubMed Li B, de Kaspar HM, Haritoglou C, Kook D, Kampik A, Sheng M, Nentwich MM (2015) Comparison of 1-day versus 1-hour application of topical neomycin/polymyxin-B before cataract surgery. J Cataract Refract Surg 41(4):724–731CrossRefPubMed
41.
go back to reference Li B, Nentwich MM, Hoffmann LE, Haritoglou C, Kook D, Kampik A, Sheng M, de Kaspar HM (2013) Comparison of the efficacy of povidone-iodine 1.0, 5.0, and 10.0% irrigation combined with topical levofloxacin 0.3% as preoperative prophylaxis in cataract surgery. J Cataract Refract Surg 39(7):994–1001CrossRefPubMed Li B, Nentwich MM, Hoffmann LE, Haritoglou C, Kook D, Kampik A, Sheng M, de Kaspar HM (2013) Comparison of the efficacy of povidone-iodine 1.0, 5.0, and 10.0% irrigation combined with topical levofloxacin 0.3% as preoperative prophylaxis in cataract surgery. J Cataract Refract Surg 39(7):994–1001CrossRefPubMed
42.
go back to reference Nentwich MM, Rajab M, Ta CN, He L, Grueterich M, Haritoglou C, Gandorfer A, Kampik A, De Kaspar HM (2012) Application of 10% povidone iodine reduces conjunctival bacterial contamination rate in patients undergoing cataract surgery. Eur J Ophthalmol 22(4):541–546CrossRefPubMed Nentwich MM, Rajab M, Ta CN, He L, Grueterich M, Haritoglou C, Gandorfer A, Kampik A, De Kaspar HM (2012) Application of 10% povidone iodine reduces conjunctival bacterial contamination rate in patients undergoing cataract surgery. Eur J Ophthalmol 22(4):541–546CrossRefPubMed
43.
go back to reference Speaker MG, Menikoff JA (1991) Prophylaxis of endophthalmitis with topical povidone–iodine. Ophthalmology 98:1769–1775CrossRefPubMed Speaker MG, Menikoff JA (1991) Prophylaxis of endophthalmitis with topical povidone–iodine. Ophthalmology 98:1769–1775CrossRefPubMed
44.
go back to reference Nentwich MM, Ta CN, Kreutzer TC, Li B, Schwarzbach F, Yactayo-Miranda YM, Kampik A, de Kaspar HM (2015) Incidence of postoperative endophthalmitis from 1990 to 2009 using povidone-iodine but no intracameral antibiotics at a single academic institution. J Cataract Refract Surg 41(1):58–66CrossRefPubMed Nentwich MM, Ta CN, Kreutzer TC, Li B, Schwarzbach F, Yactayo-Miranda YM, Kampik A, de Kaspar HM (2015) Incidence of postoperative endophthalmitis from 1990 to 2009 using povidone-iodine but no intracameral antibiotics at a single academic institution. J Cataract Refract Surg 41(1):58–66CrossRefPubMed
45.
go back to reference Onizuka N, Uematsu M, Kusano M, Sasaki H, Suzuma K, Kitaoka T (2014) Influence of different additives and their concentrations on corneal toxicity and antimicrobial effect of benzalkonium chloride. Cornea 33(5):521–526CrossRefPubMed Onizuka N, Uematsu M, Kusano M, Sasaki H, Suzuma K, Kitaoka T (2014) Influence of different additives and their concentrations on corneal toxicity and antimicrobial effect of benzalkonium chloride. Cornea 33(5):521–526CrossRefPubMed
Metadata
Title
Effect of antibiotic prophylaxis on Coagulase-negative Staphylococcus virulence factor profiles in patients undergoing cataract surgery
Authors
Yolanda López
Margarita Samudio
Norma Fariña
Verónica Castillo
Sonia Abente
Martin M. Nentwich
Nilsa González-Britez
Florentina Laspina
Agustín Carron
Diógenes Cibils
Herminia Miño de Kaspar
Publication date
01-08-2017
Publisher
Springer Netherlands
Published in
International Ophthalmology / Issue 4/2017
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-016-0355-8

Other articles of this Issue 4/2017

International Ophthalmology 4/2017 Go to the issue