Aims: To compare the anatomical and visual outcomes of macular hole repair surgery using indocyanine green (ICG) or trypan blue (TB) staining of the internal limiting membrane (ILM).
Method: Retrospective analysis of 37 eyes from 37 consecutive patients with stage 2, 3, and 4 idiopathic macular holes who underwent macular hole repair by one surgeon using the same technique but utilising different dyes for ILM peeling. In 19 patients ICG was used while 18 patients had TB. The anatomical and visual results in these two groups were compared.
Results: There were no significant differences in the demographic and macular hole characteristics of the ICG and TB groups. Macular hole closure was achieved in 91.9% of all patients of which the ICG group had an 89.5% hole closure rate and the TB group had a 94.4% hole closure rate. After excluding cases with failed hole closure and other vision affecting complications, there was no significant difference between the preoperative visual acuities in the TB and ICG groups but the postoperative visual acuities were better in the TB than the ICG group (p = 0.036). The TB group also had more Snellen lines of improvement than the ICG group (2.94 v 1.79 lines; p = 0.046).
Conclusion: TB appears to be less toxic than ICG when used in dye assisted peeling of ILM during macular hole repair as reflected by the better visual results in the TB group of patients.
macular hole; indocyanine green; trypan blue
Internal limiting membrane (ILM) peeling with indocyanine green (ICG) staining is a commonly used procedure to treat idiopathic macular holes (MH).
To report changes in the patterns of residual ICG fluorescence over time after vitrectomy using the Heidelberg Retina Angiograph 2 (HRA2, Heidelberg Engineering, Heidelberg, Germany).
10 patients (10 eyes) who had undergone vitrectomy for MH with ILM peeling were included. 9 (90%) patients underwent ILM peeling with ICG, and 1 (10%) patient had it with triamcinolone acetonide (TA). We observed residual ICG using HRA2, postoperatively. Autofluorescence, optical coherence tomography images and best‐corrected visual acuity (BCVA) measurements were also obtained. The minimal follow‐up was 3 months.
The MHs were closed postoperatively in all patients (100%). In eyes that underwent ILM peeling with ICG, the BCVA improved significantly (p<0.001) in 8 (89%) eyes and was unchanged in 1 (11%) eye. HRA2 showed the ICG fluorescence patterns but not TA postoperatively. The ICG hyperfluorescent signal was typically diffuse at the posterior retina and was hypofluorescent around the fovea. The hyperfluorescence then migrated towards the optic nerve disc presumably along the nerve fibre, and the area of ILM peeling was clearly identified. A large number of hyperfluorescent dots were observed instead of diffuse hyperfluorescence that was observed just after surgery.
Patterns of residual ICG fluorescence were sequentially observed with HRA2 after vitrectomy for MH with ICG‐assisted ILM peeling.
Aims: To determine the surgical outcome of indocyanine green (ICG) assisted retinal internal limiting membrane (ILM) peeling in macular hole surgery for severely myopic eyes and compare the visual and anatomical outcomes with an emmetropic control group.
Methods: 10 severely myopic eyes (−6.0 D or greater) of 10 patients with macular holes without retinal detachment were recruited prospectively. All eyes received ICG assisted ILM removal of 3–4 disc diameters around the macular holes. Cases were matched with a prospective control group of 10 emmetropic macular hole patients who underwent identical ICG assisted ILM peeling surgery in the same period.
Results: The mean refractive error in the myopic and control group was −11.8 D and +0.3 D, respectively (two tailed t test, p < 0.001). The mean follow up duration for the myopic and control group was 12.1 and 13.3 months, respectively (two tailed t test, p = 0.63). The primary anatomical closure rate in both groups was 90% (Fisher’s exact test, p = 1.0). For both the myopic and control groups, there were significant improvement in the mean log MAR visual acuity after the surgery with improvements from 0.86 to 0.57 for the myopic group (two tailed t test, p = 0.015) and 0.89 to 0.44 for the control group (two tailed t test, p = 0.002). The mean preoperative and postoperative visual acuity, rates of final visual acuity of 20/50 or better, and improvement of two or more lines were not statistically different between the two groups.
Conclusion: ICG assisted ILM peeling in macular hole surgery for severely myopic eyes without retinal detachment gives promising anatomical and visual outcomes, which are comparable to that of non-severely myopic eyes.
severe myopia; indocyanine green; internal limiting membrane; macular hole
Aims: To determine surgical outcome in primary idiopathic stage 3 or 4 macular holes with indocyanine green (ICG) assisted retinal internal limiting membrane (ILM) peeling.
Methods: A prospective, consecutive, interventional case series with 41 eyes of 40 patients was included. No patient defaulted follow up. Besides a standard macular hole surgery, all eyes received ICG assisted ILM removal of 3–4 disc diameters around macular holes. At the end of the surgery, 12% perfluoropropane gas was used. A face down posture for 2 weeks was required postoperatively.
Results: The mean follow up period was 15.1 months (range 6–24 months). Twenty (48.8%) eyes had stage 3 macular holes and 21 (51.2%) had stage 4 macular holes. The overall median duration of holes was 11 months. 19 (46.3%) were chronic macular holes of more than 12 months’ duration. The anatomical success rates after one surgery was 87.8% (36 eyes), while that of chronic and non-chronic ones was 78.9% and 95.5%, respectively. The median preoperative and postoperative visual acuity was 20/200 (range 20/60 to counting fingers) and 20/100 (range 20/20 to 20/400), respectively. 24 (58.5%) eyes had improvement of two or more Snellen lines. The mean was 3.2 lines (range two to nine lines), with 3.6 lines and 2.7 lines for non-chronic and chronic holes, respectively. For all the 41 eyes, 16 (39%) eyes had a final visual acuity of 20/50 or better.
Conclusion: ICG assisted retinal ILM removal, in idiopathic primary chronic and non-chronic stage 3 or 4 macular hole surgery, appears to give a promising anatomical closure rate without compromising the visual result.
indocyanine green; internal limiting membrane; macular hole
To assess the clinical outcomes in idiopathic epiretinal membrane (ERM) patients after vitrectomy and ERM removal with or without additional indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling.
The medical records of 43 patients with an idiopathic ERM that underwent vitrectomy and ERM removal between July 2007 and April 2010 were reviewed. The patients were divided into two groups: triamcinolone-assisted simple ERM peeling only (group A, n = 23) and triamcinolone-assisted ERM peeling followed by ICG staining and peeling of the remaining internal ILM (group B, n = 20).
No difference was found between the two groups in terms of visual acuity, macular thickness, P1 amplitude or implicit time on multifocal-electroretinogram (mfERG) at six and 12 months postoperatively. In group B, ICG staining after ERM peeling demonstrated that the ILM had been removed together with the ERM in 12 eyes (60%), and all 12 eyes showed punctate retinal hemorrhages during ERM peeling. There was no recurrence of an ERM in either group.
Additional procedures involving ICG staining and ILM peeling during ERM surgery do not appear to have an additive effect on the clinical outcomes in terms of visual acuity, retinal function based on mfERG, or recurrence rate.
Double staining; Epiretinal membrane; Internal limiting membrane
To compare the anatomic and functional results of 3 different epimacular dissection techniques on macular hole surgery.
Vitrectomy was performed in 123 eyes for macular hole in a retrospective, consecutive case series by one surgeon. The surgical technique was identical except for the method of epimacular dissection, which was performed using 1 of 3 techniques sequentially. The first group of 29 eyes had abrasion of the macula with a sharp pick (epiretinal dissection [ERD]), the second group of 32 eyes had partial or complete removal of the internal limiting membrane (ILM), without ILM staining. The third group of 62 eyes had complete removal of the ILM using indocyanine green (ICG) to stain the ILM.
The mean preoperative visual acuity was 20/125 -2 in the ERD and ILM groups and 20/160 -2 in the ICG groups (P = .167). Long-term successful closure of the macular hole was achieved with one operation in 22 of 29 ERD eyes (75.9%), 31 of 32 ILM eyes (96.7%), and 62 of 62 ICG eyes (100%). The mean visual acuity at 3 months was 20/63 +2 (ERD), 20/80 (ILM), and 20/125 (ICG) (P < .001), with significantly poorer visual acuity in the ICG group. The final visual acuity (mean, 2.27 years) was 20/63 +1 (ERD), 20/50 -2 (ILM), and 20/80 -1 (ICG, P = .073), with no significant differences in mean visual acuity, visual acuity gain, gain of ≥3 lines, or percentage ≥20/40.
Removal of the ILM decreases persistent and recurrent macular holes. ICG staining and complete removal of the ILM slows the rate of visual recovery but does not appear to have any long-term deleterious effect on the results of macular hole surgery.
Aim: To investigate macular function and morphology after surgical removal of idiopathic epiretinal membrane (IEM) with and without assistance of indocyanine green (ICG).
Methods: A retrospective study as a consecutive case series, of 39 patients with IEM. 39 patients, 23 female, 16 male, mean age 67 years, underwent standard three port pars plana vitrectomy with removal of epiretinal membrane. Two groups of patients were consecutively operated: in 20 patients ICG 0.1% in glucose 5% was used to stain the epiretinal membrane. 19 patients underwent the identical procedure but without use of ICG. Postoperative follow up was 1–92 months (mean 15.5 months). Functional outcome was assessed with subjective improvement, best corrected visual acuity (BCVA), Amsler grid test, 10° and 30° automated perimetry (Heidelberg visual field analyser) (HFA), and Goldmann kinetic perimetry. Macular morphology was assessed with stereoscopic biomicroscopy and optical coherence tomography (OCT). The main outcome measures were macular function as determined by BCVA, presence of visual field defects, and metamorphopsia as determined by Amsler grid test, macular morphology as determined by slit lamp biomicroscopy, and OCT.
Results: BCVA improved in 28 patients, remained unchanged in eight patients, and decreased in three patients. Improvement of BCVA was statistically significant in both groups (p = 0.003). Mean BCVA in patients operated with ICG improved from 0.33 preoperatively to 0.53 postoperatively. Mean BCVA in patients operated without ICG improved from 0.32 preoperatively to 0.54 postoperatively. Reduction of macular oedema as measured by OCT was statistically significant in both groups (p<0.01). There was no statistically significant difference in postoperative BCVA, macular oedema as measured by OCT, postoperative Amsler grid test, and subjective improvement between the two groups. The incidence of residual or recurrent epiretinal membrane was greater in the group operated without ICG (p = 0.014). Visual field defects were detected in one patient operated with ICG and in three patients operated without ICG.
Conclusions: Removal of epiretinal tissue with or without assistance of ICG improved visual function and reduced macular oedema in most patients. Adverse effects clearly attributable to the use of ICG were not observed but further investigation is warranted.
indocyanine green; toxicity; epiretinal membrane; visual field
To report micro- and ultrastructural features of internal limiting membranes (ILMs) in various maculopathies and to evaluate the effects of indocyanine green (ICG) and triamcinolone acetonide (TA) on epiretinal proliferations associated with ILM and on retinal cleavage plane.
ILMs from various maculopathies were evaluated regarding presence or absence of membrane-associated cells, type of cells and ILM thickness based on routine histopathology, immunohistochemistry and transmission electron microscopy (TEM).
Thirty ILM specimens were enrolled; 25 of which were evaluated by histopathology and immunohistochemistry and 5 by TEM. ICG only had been used in 17 specimens, TA in 4, and both agents in one specimen. The majority of specimens were immunoreactive for glial fibrillary acidic protein and neuron specific enolase. No significant difference in specimen cellularity and alteration of cleavage plane was noted between ICG-stained and non-ICG-stained ILMs or between TA-assisted and non-TA-assisted ones. Excluding central retinal vein occlusion (CRVO) cases, acellularity was not observed in any of ILMs from diabetic macular edema (DME), cystoid macular edema (CME), and traumatic macular hole (TMH) eyes. TEM disclosed ILM thickening and cellularity in DME as compared to CRVO.
Acellular membranes from CRVO maculopathy may be a sequel of acute retinal ischemia. Thickened diabetic ILMs with high cellularity may be related to chronic activation of Muller cells. No obvious influence of ICG or TA on epiretinal cellularity was detected and the dyes seem to have no significant effect on cleavage plane.
Interanl Limiting Membrane; Maculopathy; Central Retinal Vein Occlusion: Transmission Electron Microscopy
Purpose. To compare the postoperative changes of the retinal nerve fiber layer (RNFL) thickness in patients with macular holes (MHs) treated with vitrectomy with indocyanine green- (ICG-), brilliant blue G- (BBG-), or triamcinolone acetonide- (TA-)assisted internal limiting membrane (ILM) peeling. Methods. Sixty-one eyes of 61 consecutive patients with MHs were studied. Each eye was randomly selected to undergo either ICG- (n = 18), BBG- (n = 21), or TA-assisted (n = 22) ILM peeling. The circumferential retinal nerve fiber layer (RNFL) thickness was determined by spectral-domain optical coherence tomography (SD-OCT) before and 1, 3, 6, 9, and 12 months postoperatively. The mean overall and the sectoral thicknesses of the RNFL were obtained for each group. Results. A transient increase of the RNFL thickness was seen in the mean overall and sectoral thicknesses except for the nasal/inferior sector at 1 month after surgery for the three groups. Then, the thickness gradually decreased and returned to the baseline level in all sectors except for the nasal/inferior sector. The differences in the RNFL thickness among the groups were not significant for at least 12 months postoperatively. Conclusions. The degree of change of the RNFL thickness was not significantly related to the type of vital stain used during MH surgery.
Backgrounds/aims: Staining of internal limiting membrane with indocyanine green (ICG) has been reported to be associated with postoperative atrophic retinal pigment epithelium (RPE) change. Here the authors examined whether removing sodium from the solvent reduces ICG induced RPE cytotoxicity.
Methods: Human RPE cells were exposed to ICG (0.25 and 0.025 mg/ml) reconstituted with balanced salt solution (BSS) or Na+ free BSS. Light microscopy, trypan blue dye exclusion, acridine orange/ethidium bromide staining, and DNA electrophoresis were used to evaluate the cytotoxic effects of ICG. ICG uptake was measured by optical absorption at 790 nm.
Results: Sodium removal reduced the ICG induced changes in cell morphology and improved the RPE cell viability. When RPE cells were incubated for 4 hours in 0.25 mg/ml ICG dissolved in BSS and sodium free BSS, 86.3% (SD 6.7%) and 2.4% (1.1%) of the cells were stained with trypan blue, respectively. After ICG treatment, RPE dies mainly through a necrotic mechanism. ICG uptake by RPE was also reduced with sodium removal.
Conclusions: ICG induced cytotoxicity in cultured human RPE was reduced with removal of sodium from the solvent. This reconstitution method may provide a safer intravitreal use of ICG in macular hole surgery.
indocyanine green; retinal pigment epithelium; cytotoxicity; macular hole surgery
Near-infrared fluorescence imaging using indocyanine green (ICG) has recently been introduced as a novel technique for sentinel lymph node (SLN) mapping in early-stage cervical cancer. Although preclinical research has shown that ICG adsorbed to human serum albumin (ICG:HSA) improves its performance, the need for HSA has not yet been confirmed in cervical cancer patients. The current randomized study aims to determine whether ICG:HSA offers advantages over using ICG alone.
Eighteen consecutive early-stage cervical cancer patients scheduled to undergo pelvic lymphadenectomy were included. Prior to surgery, 1.6 mL of 500 μM ICG:HSA or 500 μM ICG alone was injected transvaginally in 4 quadrants around the tumor. The Mini-FLARE imaging system was used for intraoperative NIR fluorescence detection and quantitation.
SLNs were identified intraoperatively in 78% of the patients. Patient and tumor characteristics were equally distributed over both treatment groups. No significant difference in signal-to-background ratio (9.3 vs. 10.1, P = .72) or average number of detected SLNs (2.9 vs 2.7, P = .84) was found between the ICG:HSA group and the ICG alone group, respectively.
In conclusion, this double-blind, randomized trial showed no advantage of ICG:HSA over ICG alone for the SLN procedure in early-stage cervical cancer. Further optimization is required to improve the intraoperative detection rate.
Near-Infrared Fluorescence Imaging; Image-Guided Surgery; Cervical Cancer; Sentinel Lymph Node Mapping; Indocyanine Green; Albumin
Aims: To evaluate the effect of pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peeling on the closure and configuration of idiopathic macular holes (IMH).
Methods: PPV was performed for IMH on 44 eyes with ILM peeling (ILM peeled group) and on 42 eyes without ILM removal (ILM preserved group). Optical coherence tomography (OCT) was performed on 34 ILM peeled eyes and 14 ILM preserved eyes after successful surgery. The repaired macular holes were classified by the OCT images as being of “good shape” (nearly normal foveal contour) or “poor shape” (abnormal foveal contour with flat fovea and steep edge, or with a thick retina without a foveal pit).
Results: The anatomical closure rate was significantly higher in the ILM peeled group (93.2%) than in the ILM preserved group (76.2%) (p = 0.028). In the ILM peeled group, 31 eyes had a fovea of good shape and three eyes had a fovea with a poor shape, while in the ILM preserved group, six eyes had a fovea of good shape and eight eyes had a fovea of poor shape. The percentage of eyes with good macular configuration in the ILM peeled group was significantly higher than in the ILM preserved group (p = 0.0003). No significant difference was found in the postoperative visual acuity and the increase of visual acuity between the ILM peeled group and the ILM preserved group (p = 0.26, and p = 0.91 respectively). There was also no significant difference in the postoperative visual acuity and improvement in visual acuity between eyes with a fovea of good shape and those with fovea of poor shape fovea (p = 0.99 and p = 0.66, respectively).
Conclusions: ILM peeling may provide better anatomical success and recovery of the macular shape, but the postoperative visual acuity and improvement of visual acuity were not related to the morphological results.
optical coherence tomography; macular hole surgery; internal limiting membrane
To evaluate the usefulness and limitations of the intraoperative near-infrared (NIR) indocyanine green videoangiography (ICG-VA) and analysis of fluorescence intensity in cerebrovascular surgery.
Forty-eight patients received ICG-VA during various surgical procedures from May 2010 to August 2010. Included among them were 45 cases of cerebral aneurysms and 3 cases of cerebral arteriovenous malformations (AVMs). The infrared fluorescence module integrated into the surgical microscope was used to visualize fluorescent areas in the surgical field. An integrated analytical visualization tool constantly analyzed the fluorescence video sequence and generated it in the form of an intensity diagram for objective interpretation.
Overall, the procedure of ICG VA was done 158 times in 48 patients. There was no adverse effect of ICG dye. In cerebral aneurysm cases, the images obtained were of high resolution. In 4 cases, incomplete clipping was detected by ICG-VA and allowed suitable adjustment to completely obliterate the aneurysm. In 3 aneurysm cases, the intensity diagram of ICG VA provided valuable information. ICG-VA identiﬁed the feeding arteries, the draining veins, and nidus in all 3 AVM cases, which was conﬁrmed by an immediate analysis of fluorescence intensity.
ICG-VA provides high resolution images allowing real-time assessment of the blood flow in surgical field. The intensity analysis function, in addition, is a useful adjunct to improve the accuracy of the clipping and decrease the complication rates in cerebral aneurysm cases. In cerebral AVM cases, with the help of color map and intensity diagram function, the superficial feeders, drainers, and nidus can be identified easily.
Cerebral aneurysm; cerebral arteriovenous malformation; indocyanine green videoangiography
Phototoxic maculopathy caused by endoillumination during macular surgery is uncommon. Previously identified risk factors have included intensity of the light source, proximity to the retinal surface, and length of exposure. In the era of indocyanine green (ICG)-assisted internal limiting membrane (ILM) peeling, the use of ICG, and the technique of ILM peeling may both contribute to subsequent phototoxic maculopathy. We present cases of routine chromovitrectomy who developed phototoxic maculopathy in the precise discrete distribution of the ILM rhexes, and discuss potential mechanisms and implications.
ILM peeling; indocyanine green; vitrectomy; ERM
To evaluate the anatomical and functional outcome in eyes with indocyanine green (ICG)-assisted idiopathic epiretinal membrane (ERM) peeling by optical coherence tomography (OCT) and multifocal electroretinogram (MFERG).
Prospective, interventional, noncomparative case series.
Twenty eyes of 20 patients with idiopathic ERM underwent pars plana vitrectomy and ICG-assisted ERM and internal limiting membrane (ILM) removal. Visual acuity (VA), OCT, and MFERG measurements were performed preoperatively and postoperatively at 1, 3, 6, and 12 months.
Best-corrected VA (BCVA) improved ≥2 Snellen lines in 70% of our patients at the 12th postoperative month. Mean VA increased from 20/100 preoperatively to 20/40 at 12 months. VA increased significantly at all postoperative examinations, compared to preoperative VA. Foveal thickness measured by OCT decreased significantly at all postoperative examinations. OCT mean values dropped from 472.3 μm preoperatively, to 249.2 μm at 12 months. Preoperative MFERG values significantly improved only at 12 months. OCT measurements and MFERG values did not correlate at any time. OCT values correlated with VA values only preoperatively while MFERG measurements correlated with VA at 12 months.
In our series of eyes with ERM surgery, OCT measurements and VA improved gradually throughout the first postoperative year, while MFERG values showed significant improvement at 12 months.
A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery.
Patients with stage 2–3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity ≤ 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events.
FILMS will provide high quality evidence on the role of ILM peeling in FTMH surgery.
This trial is registered with Current Controlled Trials ISRCTN number 33175422 and Clinical Trials.gov identifier NCT00286507.
Near-infrared (NIR) fluorescence imaging has the potential to improve sentinel lymph node (SLN) mapping in breast cancer. Indocyanine green (ICG) is currently the only clinically available fluorophore that can be used for SLN mapping. Preclinically, ICG adsorbed to human serum albumin (ICG:HSA) improves its performance as a lymphatic tracer in some anatomical sites. The benefit of ICG:HSA for SLN mapping of breast cancer has not yet been assessed in a clinical trial. We performed a double-blind, randomized study to determine if ICG:HSA has advantages over ICG alone. The primary endpoint was the fluorescence brightness, defined as the signal-to-background ratio (SBR), of identified SLNs. Clinical trial subjects were 18 consecutive breast cancer patients scheduled to undergo SLN biopsy. All patients received standard of care using 99mTechnetium-nanocolloid and patent blue. Patients were randomly assigned to receive 1.6 mL of 500 μM ICG:HSA or ICG that was injected periareolarly directly after patent blue. The Mini-Fluorescence-Assisted Resection and Exploration (Mini-FLARE) imaging system was used for NIR fluorescence detection and quantitation. SLN mapping was successful in all patients. Patient, tumor and treatment characteristics were equally distributed over the treatment groups. No significant difference was found in SBR between the ICG:HSA group and the ICG alone group (8.4 vs. 11.3, respectively, P = 0.18). In both groups, the average number of detected SLNs was 1.4 ± 0.5 SLNs per patient (P = 0.74). This study shows that there is no direct benefit of premixing ICG with HSA prior to injection for SLN mapping in breast cancer patients, thereby reducing the cost and complexity of the procedure. With these optimized parameters that eliminate the necessity of HSA, larger trials can now be performed to determine patient benefit.
Near-Infrared Fluorescence Imaging; Image-Guided Surgery; Breast Cancer; Sentinel Lymph Node Mapping; Indocyanine Green; Albumin
During cardiac surgery with cardiopulmonary bypass (CPB) haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious, complication. Clinical data have validated the plasma-disappearance rate of indocyanine green (PDR ICG) as a marker of hepatic function and perfusion. Primary objective of this analysis was to investigate the impact of haemodilutional anaemia on hepatic function and perfusion by the time course of PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to define predictors of prolonged ICU treatment like decreased PDR ICG after surgery.
60 Patients were subjected to normothermic CPB with predefined levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB). Hepatic function and perfusion was assessed by PDR ICG, plasma levels of aspartate aminotransferase (ASAT) and α-GST. Prolonged ICU treatment was defined as treatment ≥ 48 hours.
Logistic regression analysis showed that all postoperative measurements of PDR ICG (P < 0.01), and the late postoperative ASAT (P < 0.01) measurement were independent risk factors for prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was best of the PDR ICG one hour after admission to the ICU. Furthermore, the time course of PDR ICG as well as ASAT and α-GST did not differ between groups of haemodilutional anaemia.
Our study provides evidence that impaired PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid marker of prolonged ICU treatment. Additionally this study provides evidence that haemodilutional anaemia to a Hct of 20% does not impair hepatic function and perfusion.
The purpose of this study was to describe and evaluate a surgical approach, known as internal limiting membrane (ILM) peeling, as an adjunct to repair of recurrent retinal detachment due to proliferative vitreoretinopathy (PVR).
This was a retrospective case series. All eyes underwent repair of recurrent PVR-related rhegmatogenous retinal detachment incorporating macular indocyanine green-assisted ILM peeling. Patients with primary detachments, diabetes, staphyloma, or macular holes were excluded. The main outcome measure was the anatomic success of single surgery. The characteristics of the group were studied, including the number and types of previous detachment repair attempts, as well as the subsequent surgeries.
Fourteen eyes from 14 patients were included. Anatomic success with single surgery was achieved in 11 of 14 (79%) of the operated eyes using this technique, and eventual success was achieved in all eyes (100%). Among the failed repairs prior to ILM peeling, 8/14 eyes had scleral buckles, 7/14 had silicone oil tamponade, and two had inferior retinectomies. There was no subsequent development of epiretinal membranes after ILM peeling.
ILM peeling in conjunction with vitrectomy and peeling of peripheral membranes is an effective technique with a high anatomic success rate in the challenging scenario of PVR-related recurrent detachments. We describe the technique as an alternative to the traditional retinectomy.
internal limiting membrane; retinal detachment; proliferative vitreoretinopathy; retinectomy; surgical technique
To investigate the relationship between the size of macular holes and the possible benefit of internal limiting membrane (ILM) peeling.
84 consecutive cases of idiopathic macular hole followed up for at least 3 months were included in this retrospective study. Surgery comprised pars plana vitrectomy, peeling of any epiretinal membrane, 17% C2F6 (hexafluoroethane) gas filling and 10 days of positioning. 36 eyes had ILM peeling. The main outcome measure was the macular hole closure rate checked by optical coherence tomography.
The overall postoperative closure rate was 90.5%. For macular holes ⩾400 μm in diameter, the rate was 100% with ILM peeling versus 73.3% without (p = 0.015). For smaller macular holes, the rates were 100% in both groups. Postoperative gain in visual acuity was not significantly different in eyes with ILM peeling and those without.
ILM peeling does not seem to be useful for macular hole <400 μm in diameter. Its likely benefit has to be investigated for larger macular hole sizes, for which the failure rate is higher.
We analyzed the anatomical and visual outcomes after surgical treatment of idiopathic macular holes with pars plana vitrectomy, internal limiting membrane (ILM) peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing.
This was a retrospective interventional study of 10 eyes in eight patients who underwent surgical treatment of idiopathic macular holes using pars plana vitrectomy, ILM peeling using Brilliant Blue dye, and silicone oil tamponade without postoperative posturing. The preoperative staging of macular holes and postoperative anatomic outcomes were assessed using spectral-domain optical coherence tomography.
All patients were women with a mean age of 66.86 ± 4.8 years. In two patients, bilateral macular holes were present and both eyes were operated on. Stage 2 macular hole was diagnosed in three eyes, three eyes had stage 3, and four eyes had stage 4 macular holes. Anatomical success and closure of the macular hole was achieved in nine eyes (90%) after one operation. In one eye, the macular hole was closed after reoperation. The preoperative mean best-corrected visual acuity (BCVA) was 0.15 decimal units (0.8 logMAR units). Until the end of the follow-up period, BCVA was 0.25 decimal units (0.6 logMAR units). Visual acuity was improved in seven patients (70%). In two patients (20%), visual acuity remained at the same level, and in one eye (10%), visual acuity decreased. Postoperatively, all patients reported a significant reduction of metamorphopsia.
Initial results after 20G pars plana vitrectomy with peeling of the ILM, use of dye (Brilliant Blue), and tamponade with silicone oil without postoperative posturing gave good anatomical and functional outcome in terms of visual acuity and reduction of metamorphopsia. Taking into account the age of the patients, this method, which does not require prolonged postoperative face-down posturing, was well tolerated by the patients. Because the anatomical and visual outcome as well as the rate of postoperative complications are comparable to those when gas is used as a tamponading agent, silicone oil tamponade can also be safely used as a first option in surgery of macular holes. However, a longer period of follow-up of the operated eyes, as well as a larger group of operated eyes, will be required to identify long-term outcomes of this surgical treatment.
macular hole; silicone oil; ILM peeling; pars plana vitrectomy
The ability to switch optical imaging probes from the quenched (off) to the active state (on) has greatly improved target to background ratios. The optimal activation efficiency of an optical probe depends on complete quenching before activation and complete de-quenching after activation. For instance, monoclonal antibody-indocyanine green (mAb-ICG) conjugates, which are promising agents for clinical translation, are normally quenched but can be activated, when bound to a cell surface receptor and internalized. However, the small fraction of commonly used ICG derivative (ICG-Sulfo-OSu) can bind noncovalently to its mAb and is thus, gradually released from the mAb leading to relatively high background signal especially in the liver and the abdomen. In this study, we re-engineered a mAb-ICG conjugate, (Panitumumab-ICG) using bifunctional ICG derivatives (ICG-PEG4-Sulfo-OSu and ICG-PEG8-Sulfo-OSu) with short polyethylene glycol (PEG) linkers. Higher covalent binding (70–86%) was observed using the bifunctional ICG with short PEG linkers resulting in less in vivo non-covalent dissociation. Panitumumab-ICG conjugates with short PEG linkers were able to detect human epidermal growth factor receptor 1 (EGFR)-positive tumors with high tumor-to-background ratios (15.8 and 6.9 for EGFR positive tumor-to-negative tumor and tumor-to-liver ratios, respectively, at 3 d postinjection).
indocyanine green; PEG linker; fluorescence imaging; activatable; monoclonal antibody
To investigate the effects of indocyanine green (ICG) with or without illumination on rat retinal ganglion cells (RGC) and retinal morphology.
Intravitreal injections of 1.0 mg/ml ICG solution were performed in rat eyes with or without subsequent illumination for 5 minutes. Eyes in the control group had intravitreal injections of balanced salt solution with illumination. Retrograde labelling of RGC with 6% Fluoro‐Gold was performed 1 month later and RGC densities were compared between the three groups. Light microscopy with measurements of outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were also performed and compared.
Eyes with ICG without illumination showed insignificant reduction in RGC density compared with the control group (p = 0.28), whereas a significant decrease in RGC density was found in eyes that had ICG injection with illumination (p = 0.036). A significant increase in ONL thickness was also observed in the ICG with illumination treated eyes compared with the ICG without illumination and the control groups (p<0.001). No significant difference in INL thickness was observed between the three groups.
Intravitreal injection of 0.1 mg/ml ICG in rat eyes followed by illumination resulted in photosensitising toxicity to RGC. Lower ICG concentration or illumination level should be considered when performing ICG assisted macular surgery.
indocyanine green; retinal ganglion cell; photosensitising toxicity; rat
AIM: To establish a reliable definition of postoperative liver failure (PLF) and allow the prediction of outcomes after hepatectomy.
METHODS: The clinical data of 478 consecutive patients who underwent hepatectomy were retrospectively analyzed. The examined prognostic factors included the ratio of total bilirubin (TBIL) on postoperative day (POD) X to TBIL on POD 1 (TBIL-r1) and the ratio of the international normalized ratio (INR) on POD X to the INR on POD 1 (INR-r1) for PODs 3, 5 and 7. Student’s t test, the χ2 test, logistic regression, survival analysis and receiver operating curve analysis were used to evaluate risk factors and establish the definition of postoperative liver failure (PLF).
RESULTS: Fourteen patients (2.9%) died of liver failure within 3 mo of surgery. Significant differences were found between patients who died of liver failure and the remaining patients in terms of TBIL-r1 and INR-r1 on PODs 3, 5 and 7. The combination of TBIL-r1 and INR-r1 on POD 5 showed strong predictive power for liver failure-related death (sensitivity 92.9% and specificity 90.1%). The hepatic damage score (HDs), which was derived from TBIL-r1 and INR-r1, was used to define the degree of metabolic functional impairment after resection as mild (HDs = 0), reversible hepatic “dysfunction” (HDs = 1) or fatal hepatic failure (HDs = 2). Furthermore, the indocyanine green retention rate at 15 min (ICG-R15) and the number of resected segments (RSs) were identified as independent predictors of the HDs. A linear relationship was found between ICG-R15 and RSs in the HDs = 2 group. The regression equation was: RSs = -0.168 × ICG-R15 + 5.625 (r2 = 0.613, F = 14.257, P = 0.004).
CONCLUSION: PLF can be defined by the HDs, which accurately predicts liver failure-related death after liver resection. Furthermore, the ICG-R15 and RSs can be used as selection criteria for hepatectomy.
Liver failure; Hepatectomy; Mortality; Morbidity; Hepatic dysfunction
Recently, microscope-integrated near infrared indocyanine green videoangiography (ICG-VA) has been widely used in cerebrovascular surgery because it provides real-time high resolution images. In our study, we evaluate the efficacy of intraoperative ICG-VA during cerebrovascular surgery.
Between August 2011 and April 2012, 188 patients with cerebrovascular disease were surgically treated in our institution. We used ICG-VA in that operations with half of recommended dose (0.2 to 0.3 mg/kg). Postoperative digital subtraction angiography and computed tomography angiography was used to confirm anatomical results.
Intraoperative ICG-VA demonstrated fully occluded aneurysm sack, no neck remnant, and without vessel compromise in 119 cases (93.7%) of 127 aneurysms. Eight clipping (6.3%) of 127 operations were identified as an incomplete aneurysm occlusion or compromising vessel after ICG-VA. In 41 (97.6%) of 42 patients after carotid endarterectomy, the results were the same as that of postoperative angiography with good patency. One case (5.9%) of 17 bypass surgeries was identified as a nonfunctioning anastomosis after ICG-VA, which could be revised successfully. In the two patients of arteriovenous malformation, ICG-VA was useful for find the superficial nature of the feeding arteries and draining veins.
ICG-VA is simple and provides real-time information of the patency of vessels including very small perforators within the field of the microscope and has a lower rate of adverse reactions. However, ICG-VA is not a perfect method, and so a combination of monitoring tools assures the quality of cerebrovascular surgery.
Cerebrovascular surgery; Indocyanine green videoangiography; Intraoperative angiography; Patency of graft; Complete obliteration of aneurysm