Administration of novel dyes for intraocular surgery: an in vivo toxicity animal study.
OBJECTIVE
To investigate the effect of intravitreal injections of new vital dyes on the retina, the retinal pigment epithelium (RPE) and the choroid in an in vivo rat model.


METHODS
Rats were injected intravitreally with four dyes: light-green SF yellowish (LGSF), copper(II)phthalocyanine-tetrasulfonic acid (E68), bromphenol blue (BPB), and Chicago blue (CB) dissolved in physiologic saline solution (PSS) at concentrations of 0.5% and 0.02%. PSS served as the control. Additional animals were treated with single injections of 0.5%, 0.02%, 0.002%, and 0.0002% ICG or 0.002% E68 into one eye. Adverse effects on anterior and posterior segments were evaluated by slit lamp biomicroscopy and ophthalmoscopy. Retinal toxicity was assessed by histology and retinal ganglion cell (RGC) quantification 7 days after dye administration.


RESULTS
Eyes treated with 0.5% E68, 0.5% ICG, or 0.5% CB showed discrete staining of both cornea and lens not seen at lower concentrations or with other dyes. Histology revealed dose-dependent reactions after E68 administration. ICG 0.5% induced significant thinning of inner retinal layers compared with PSS. ICG 0.02% caused focal degenerative changes of the outer retina in three of seven eyes, whereas 0.002% and 0.0002% ICG did not. CB led to heterogeneous morphologic alterations. BPB- or LGSF-treated eyes showed normal retinal morphology. ICG at all tested concentrations induced significant RGC loss, as did E68 at 0.5% but not at lower concentrations.


CONCLUSIONS
BPB or LGSF produced no significantly detectable toxic effects on the retina in vivo. The safety of these new dyes must be established in other models and/or in preclinical studies before the clinical use of any of these dyes.
Schuettauf
Frank
F
Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Tübingen, Germany. fschuettauf@uni-tuebingen.de
Haritoglou
Christos
C
May
Christian A
CA
Rejdak
Robert
R
Mankowska
Anna
A
Freyer
Wolfgang
W
Eibl
Kirsten
K
Zrenner
Eberhart
E
Kampik
Anselm
A
Thaler
Sebastian
S
D000818:Animals; D001391:Azo Compounds / Q000633:toxicity; D001485:Basement Membrane / Q000601:surgery; D001978:Bromphenol Blue / Q000633:toxicity; D002452:Cell Count; D002829:Choroid / Q000187:drug effects* / Q000473:pathology; D004396:Coloring Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D019773:Epiretinal Membrane / Q000601:surgery; D007211:Indoles / Q000633:toxicity; D007267:Injections; D008086:Lissamine Green Dyes / Q000633:toxicity; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology; D012167:Retinal Perforations / Q000601:surgery; D014343:Trypan Blue; D014822:Vitreous Body
D001391:Azo Compounds; D004396:Coloring Agents; D007211:Indoles; D008086:Lissamine Green Dyes; D009942:Organometallic Compounds; D001978:Bromphenol Blue; C009000:pontamine sky blue; C056110:copper phthalocyanine tetrasulfonic acid; C016537:Light green SF; D014343:Trypan Blue