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    Histological findings in experimental macular surgery with indocyanine green. Invest Ophthalmol Vis Sci.

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    PURPOSE. To analyze the effect of different concentrations and application intervals of indocyanine green (ICG) on the retina in an experimental setting of macular surgery. METHODS. Twenty-one porcine eyes were used within 5 hours after enucleation. The eyes were hemisected and the vitreous removed. Different doses of ICG (up to 1 mg) were applied over the trephined macula, and the remainder of the eyecup was filled with a balanced salt solution (BSS). Both the ICG solution and the BSS were drained after 30 or 60 seconds and the complete eyecup irrigated and filled with fresh BSS. The posterior pole was then illuminated with a standard surgical light pipe and light source at maximum power for 3 minutes. Both the ICG-treated retina and the nontreated surrounding retina were processed for histology. RESULTS. Exposure of the retina at different concentrations of ICG either for 30 or 60 seconds, followed by illumination, caused no histologically detectable damage compared with the controls. No microarchitectural disorganization or cellular disruption was detected. The vitreoretinal interface seemed unaffected. CONCLUSIONS. Previously described severe damage to the inner retina of human donor eyes could not be found with even higher doses of ICG in this porcine model. Although differences within the species may contribute to these contradictory results, it is conceivable that the postmortem time and the vitality of the tissue influence the outcome in this ex vivo system. (Invest Ophthalmol Vis Sci. 2004;45:282-286) DOI: 10.1167/iovs.03-0797 T he inner limiting membrane (ILM) is a physiological structure at the vitreoretinal interface. Though many functions have been attributed to this basal lamina, intentional removal of the ILM has become a routine procedure in macular hole surgery. Because of the poor visibility of the ILM, however, complete removal is difficult and not always obvious. Therefore, damage at the vitreoretinal interface or unsatisfactory outcomes may be the consequence of this surgical maneuver. Since the first report by Grizzard and Tornambe 1 and publications by Kadonosono et al. 14 -16 To examine whether ICG is toxic or not some laboratory studies have been performed and published. Inspired by this study, we repeated the experiments to answer the following questions: Does ICG have the same effect on fresher tissue? Is there a safe ICG dose that can be used? Is the effect based on osmolarity or pH? To answer these questions and to mimic the clinical situation better, the experimental setting had to be modified. Because our results are contradictory to the above-mentioned study, the clinical importance of both experimental settings will be discussed critically. MATERIALS AND METHODS Tissue Preparation Twenty-one adult porcine eyes were received from the local abattoir. The freshly enucleated porcine eyes were transported to the laboratory in ice and used within 5 hours after death. The eyes were processed by using a modification of the method described by Gandorfer et al. 20 After removal of the anterior segment, we additionally removed the vitreous. A trephine of 9-mm diameter was positioned over the posterior pole afterward and left in place to create a chamber that allowed a standardized application of ICG dye (Pulsion, Munich, Germany) without treating the areas outside the chamber. The eyecup itself created a second chamber surrounding the trephine. This second chamber was filled with balanced salt solution (BSS; Pharmacia, Groningen, The Netherlands) as a control A 25-mg vial of ICG dye was reconstituted with distilled water. The concentration of this ICG stock solution was 10 mg/mL. The stock solution was further diluted with BSS to attain the experimental concentrations 0.1, 1, and 2 mg/mL of ICG. Because the volume used within the trephine chamber was 0.5 mL, the absolute doses of ICG applied to the retina were 1, 0.5, and 0.05 mg, respectively. The ICG solutions were poured into the trephine and left in contact with the retina for 30 seconds or 1 minute, respectively. The removal of the dye From th
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