Yukihiko Suzuki

Expression profiles of cytokines and chemokines in vitreous fluid in diabetic retinopathy and central retinal vein occlusion

PurposeThe involvement of cytokines and chemokines in vitreous fluid is important in the development and progression of diabetic retinopathy (DR) and central retinal vein occlusion (CRVO). In this study, the concentrations of cytokines and chemokines in the vitreous fluid of eyes with DR and CRVO were measured and compared.MethodsWe studied 76 eyes with proliferative DR and diabetic macular edema (DR group), 10 eyes with CRVO (CRVO group), and 23 eyes with an epiretinal membrane and macular hole (control group), among a series of 160 eyes from which vitreous fluid samples were collected during vitrectomy. The vitreous fluid samples were collected by suction with a vitreous cutter at the initial stage of vitrectomy. Twenty-seven different cytokines and chemokines were measured simultaneously using an array system (Bio-Plex®) with beads combined with antibodies (Bio-Rad), as follows: interleukin (IL)-1β, IL-1 receptor agonist, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, basic fibroblast growth factor, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon-inducible 10-kDa protein (IP-10), monocytochemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1α), MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated upon activation, normal T cell expressed and secreted, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF).ResultsCompared to the control group, the levels of IL-6, IL-8, IL-10, IL-13, IP-10, MCP-1, MIP-1β, PDGF and VEGF in the vitreous fluid were significantly higher in the DR group, while the levels of IL-1β, IL-2, IL-5, IL-8, IL-9, IL-10, IL-12, IL-13, eotaxin, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1β, TNF-α and VEGF were significantly higher in the CRVO group. Compared to the DR group, IL-2, IL-9, IL-12, MCP-1 and IFN-γ were significantly elevated in the CRVO group. Multivariate regression analysis revealed that among 6 factors correlated to VEGF in the DR group, IL-10 and IL-13 were more positively correlated and PDGF was most inversely correlated to VEGF.ConclusionIn addition to inflammatory cytokines and neurotrophic factors such as VEGF, anti-inflammatory cytokines such as IL-10 and IL-13 may be involved more in the pathogenesis of DR and CRVO than in other diseases; cytokines and chemokines may also be correlated to VEGF in the vitreous fluid. It is also suggested that the inflammatory reaction may be more activate in CRVO than in DR.

Postoperative refractive error after simultaneous vitrectomy and cataract surgery.

PURPOSE To evaluate the effect of vitrectomy on postoperative refraction after simultaneous vitrectomy and cataract surgery. METHODS We compared the spread between predicted and actual refractions in 206 eyes after a simultaneous vitrectomy, phacoemulsification, aspiration and acrylic lens insertion (combined surgery group), and in 67 eyes after cataract surgery only (cataract surgery group) as control. A vitrectomy was performed for diabetic retinopathy in 127 eyes, macular hole in 32 eyes, rhegmatogenous retinal detachment in 16 eyes, branch retinal vein occlusion in 15 eyes, and other conditions in 26 eyes. In the combined surgery group, 79 eyes had a gas tamponade after insertion of the intraocular lens. RESULTS The spread between predicted and actual refractions was - 0.05 +/- 1.18 diopters (average +/- SD) in the combined surgery group and +0.55 +/- 1.32 D in the cataract surgery group. The actual refractive errors in the combined surgery group were found to shift toward myopia when compared with the controls. Among the combined surgery group, 127 eyes without a gas tamponade showed a postoperative refractive error of +0.14 +/- 1.11 D, while 79 eyes with a gas tamponade demonstrated an error of -0.36 +/- 1.22 D. CONCLUSIONS Use of a gas tamponade in the combined surgery group increased the myopic change and was thought to have pressed the intraocular lens forward.

Long-term results of vitrectomy for removal of submacular hard exudates in patients with diabetic maculopathy.

Purpose To investigate long-term results of vitrectomy for the removal of submacular hard exudates in patients with diabetic maculopathy. Methods Thirteen eyes of 10 patients with diabetic maculopathy underwent vitrectomy to remove submacular hard exudates from December 1993 to March 1999. The mean preoperative logMAR visual acuity ± SD was 1.54 ± 0.43. Preoperatively, the exudates ranged from 0.5 to 3 disk diameters (average, 1.25 disk diameters). Exudates were removed using subretinal forceps through a minimal paramacular retinotomy after vitrectomy. In all cases, 20% SF6 gas tamponade was added. The mean postoperative observation period was 43.2 months. Results Visual acuity was improved in 7 eyes (54%) 1 year after surgery; however, visual acuity over longer periods was improved in only 5 eyes (38%) as compared with the preoperative findings. The mean final visual acuity ± SD was 1.62 ± 0.59, which did not show statistically significant improvement over that in the control group. Although submacular hard exudates and macular edema disappeared during the postoperative period, atrophic or degenerative changes occurred in many cases. Conclusion Visual improvement could not be obtained for a long period after removing submacular hard exudates in most of the patients, suggesting that diabetic maculopathy should be treated before massive exudate deposits appear in the macula.

Postoperative Complications After Simultaneous Vitrectomy and Cataract Surgery

OBJECTIVE We reviewed postoperative complications after simultaneous vitrectomy, phacoemulsification, aspiration, and acryl lens insertion. PATIENTS AND METHODS Combined surgery was performed in 316 eyes of 279 patients between 1995 and 1997. Postoperative observation was continued in all of them for more than 6 months. The diagnoses that led to vitrectomy included diabetic retinopathy in 155 eyes, rhegmatogenous retinal detachment in 64 eyes, macular hole in 43 eyes, and other diseases in 93 eyes. The rate of postoperative complications that needed any reoperation was investigated. RESULTS Reoperations were needed for intravitreal hemorrhage in 23 eyes (7.3%), retinal detachment in 15 eyes (4.7%), rubeotic glaucoma in 6 eyes (1.9%), and other conditions in 4 eyes (1.3%). Among them, reoperations were performed on 13 eyes (4.1%) twice and more. A removal of an intraocular lens was needed in 16 eyes (5.1%) for treatment of vitreoretinal disease. In patients with diabetic retinopathy, reoperations were needed for intravitreal hemorrhage in 21 eyes (13.5%), rubeotic glaucoma in 6 eyes (3.9%), other diseases in 4 eyes (2.6%), and a removal of an intraocular lens was needed in 10 eyes (6.5%) at a higher rate than the other disease. CONCLUSION This combined surgery is considered advantageous for removing peripheral vitreous, while preventing these complications is important for preserving visual function.

Massive hemorrhagic retinal detachment during radial optic neurotomy

BackgroundWe encountered obvious arterial bleeding from the incision site during radial optic neurotomy (RON) in a 55-year-old woman with central retinal vein occlusion (CRVO) and report the findings herein.Case reportThe patient initially demonstrated a retinal hemorrhage and macular edema due to a left CRVO. Her corrected visual acuity was 0.5 OS. Since her symptoms did not improve and were aggravated, even though she received an oral anticoagulant drug orally, RON was performed 2 months after the onset of symptoms. During surgery, obvious arterial bleeding started from the RON incision site and it was not arrested although the infusion bottle was fully elevated. However, a subsequent infusion of liquid perfluoro-carbon successfully stopped the bleeding by direct pressure. Hemorrhagic retinal detachment occurred in the nasal quadrant and postoperative vitreous hemorrhage was treated surgically. The hemorrhagic retinal detachment was gradually absorbed and replaced by fibrous scar tissue. Two years after the surgery, no expansion of retinal detachment has been observed and corrected visual acuity is being maintained at 0.2 OS.ConclusionWe conclude that RON for CRVO carries a risk of arterial bleeding and that infusion of liquid perfluoro-carbon seems to be effective to arrest arterial bleeding from the RON site.

Visual improvement after removal of submacular exudates in patients with diabetic maculopathy

OBJECTIVE To improve the central visual function of eyes affected by massive hard exudates in cases of diabetic maculopathy. PATIENTS AND METHODS Six eyes of 4 patients with diabetic maculopathy were treated by pars plana vitrectomy for massive retinal exudates persisting for more than 3 months. The massive hard exudates were removed from the subretinal space with subretinal forceps. We evaluated the visual acuity of these eyes 6 months after surgery. RESULTS Following the removal of the hard exudates, visual acuity improved in all eyes. Massive hard exudates were mainly located in the subretinal space and were removable using subretinal forceps. No serious postoperative complications occurred. The removed tissues consisted of macrophages laden with many cholestrin crystals and lipid droplets, as well as fibrous tissues. CONCLUSION We concluded that central visual function can be improved by removing subretinal exudates surgically.

Effects of intravitreal injection of bevacizumab on inflammatory cytokines in the vitreous with proliferative diabetic retinopathy.

Background: To investigate the effects of preoperative intravitreal injection of bevacizumab (IVB) on the levels of 27 inflammatory cytokines, including interleukins (ILs) and vascular endothelial growth factor. Methods: From among 200 patients who had proliferative diabetic retinopathy and underwent vitrectomy in our department from September 2009 to October 2010, 8 study subjects met the enrollment criteria in which both eyes at nearly equivalent stages underwent vitrectomy. The first vitrectomy for each patient was performed without IVB (control group), whereas the second vitrectomy on the contralateral eye was performed with IVB treatment (1.25 mg/0.05 mL) 3 days before surgery (IVB group). Undiluted vitreous fluid was collected at the start of each vitrectomy. A multiplex assay was used to simultaneously determine the levels of 27 inflammatory cytokines and growth factors. Results: Mean vascular endothelial growth factor levels were significantly lower in the IVB group (519.69 pg/mL) than in the control group (11,807.44 pg/mL) (P = 0.012, Wilcoxon signed rank test). Moreover, the mean levels (IVB/control, pg/mL) of IL-1RA (38.50/62.31, P = 0.036), IL-5 (27.75/34.00, P = 0.018), IL-10 (433.63/1,995.94, P = 0.012), IL-12 (246.69/1,033.69, P = 0.012), IL-13 (707.50/1,450.38, P = 0.012), and interferon &ggr; (71.13/84.69, P = 0.036) were significantly lower in the IVB group. No other significant differences were observed in the levels of the other 20 cytokines and growth factors between the 2 groups. Conclusion: Preoperative IVB reduced not only the intravitreal vascular endothelial growth factor level but also the intravitreal levels of other inflammatory cytokines, including IL-1RA, IL-5, IL-10, IL-12, IL-13, and interferon &ggr;. These results indicate the interaction of some cytokines in the vitreous fluid of proliferative diabetic retinopathy patients and suggest the possibility that preoperative IVB may not only reduce vascular proliferation by its direct antivascular endothelial growth factor effect but also modulate the inflammatory response through putative cytokine networks. None of the other cytokines examined were elevated after IVB.

Expression Profile of Intravitreous Cytokines, Chemokines and Growth Factors in Patients with Fuchs Heterochromic Iridocyclitis

Purpose: To report the postoperative courses of 2 patients with Fuchs heterochromic iridocyclitis (FHI) and the concentrations of various cytokines, chemokines and growth factors in vitreous fluid samples to obtain insights into pathobiochemical aspects. Subjects: The patients were a 27- and a 47-year-old woman. Phacoemulsification and aspiration, intraocular lens (IOL) implantation, and pars plana vitrectomy were performed to treat their cataracts and vitreous opacities. During their early postoperative periods, inflammatory cells precipitated on the IOL and intraocular pressure was increased in both patients. Methods: At the time of surgery, undiluted vitreous fluid specimens were collected. The concentrations of multiple cytokines, chemokines and growth factors were measured by a bead array immunodetection system. Results: The levels of interleukin-1ra, -5, -6, -8, -10 and -13, interferon-inducible 10-kDa protein, monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, and regulated upon activation, normal T-cell expressed and secreted (RANTES) were significantly elevated in vitreous fluid in both patients. Conclusion: Although the postoperative course was generally favorable in patients with FHI, steroid instillation was necessary for a few months postoperatively, as precipitates easily formed on the IOL surface and elevated intraocular pressure. The profiles of intravitreal concentrations of cytokines, chemokines and growth factors may characterize postoperative inflammatory reactions.

Profiles of Inflammatory Cytokines in the Vitreous Fluid from Patients with Rhegmatogenous Retinal Detachment and Their Correlations with Clinical Features

Purpose. To characterize the profiles for inflammatory cytokines in the vitreous fluid from patients with rhegmatogenous retinal detachment (RRD) by comparing those of other vitreoretinal diseases and to analyze the correlation between intravitreal cytokines and clinical features. Materials and Methods. Vitreous fluid was obtained at the time of surgery from 28 RRD eyes. Vitreous fluid was similarly collected from patients with macular hole (MH), epiretinal membrane, proliferative diabetic retinopathy (PDR), and retinal vein occlusion as controls. Twenty-seven cytokines were measured. Intravitreal cytokine profiles in RRD were characterized by comparing these with those in other vitreoretinal diseases. We also analyzed the correlations between vitreous cytokines and clinical features. Results. There were statistical differences in the MCP-1, MIP-1β, and IP-10 between the RRD and MH, while the IL-6 and IL-8 exhibited levels that were between those for the PDR and MH. MIP-1β was significantly correlated to both the extent and duration of the RRD, while IL-8 was significantly correlated to the extent of the RRD. Conclusions. MCP-1, MIP-1β, and IP-10 may modify the pathologic features of RRD. The levels of these cytokines are related in part to the clinical features and the level of photoreceptor damage.

Predicted versus actual postoperative refractive error after simultaneous vitrectomy and cataract surgery

PURPOSE We compared the spread between predicted and postoperative actual refractive errors after simultaneous vitrectomy, phacoemulsification, aspiration, and acryl lens insertion and after cataract surgery alone. METHODS Cataract surgery and vitrectomy (combined surgery group) were performed in 185 eyes, and cataract surgery only (cataract surgery group) in 63 eyes. Vitrectomy was needed for diabetic retinopathy in 104 eyes, macular hole in 26 eyes, rhegmatogenous retinal detachment in 25 eyes, and other conditions in 30 eyes. RESULTS The spread between predicted and actual refractive errors were +0.19 +/- 1.24 D (mean +/- standard deviation) in the combined surgery group and +0.91 +/- 1.40 D in the cataract surgery group. Gas tamponade in the combined surgery group increased the myopic change more than anything else. CONCLUSION Actual refractive errors in the combined surgery group were found to shift to myopia more than in the cataract surgery group. Gas tamponade was considered to press the intraocular lens forward in the combined surgery group.