Yasushi Sonoda

Vitreous Mediators after Intravitreal Bevacizumab or Triamcinolone Acetonide in Eyes with Proliferative Diabetic Retinopathy

PURPOSE To evaluate vitreous vascular endothelial growth factor (VEGF), stromal cell-derived factor 1alpha (SDF-1alpha), interleukins (ILs), and tumor necrosis factor-alpha (TNF-alpha) after intravitreal bevacizumab or triamcinolone acetonide (TA) in eyes with proliferative diabetic retinopathy (PDR). DESIGN Interventional, consecutive, retrospective, comparative study with a historical control. PARTICIPANTS Forty-seven eyes of 47 patients affected by active PDR were investigated. Bevacizumab (1.25 mg; 19 eyes; bevacizumab group) or TA (4 mg; 10 eyes; TA group) was injected into the vitreous cavity as preoperative adjunctive therapy 7 days before vitrectomy. Eighteen eyes without injection served as controls (control group). METHODS The vitreous samples were obtained at vitrectomy and were analyzed for concentrations of total protein, VEGF, SDF-1alpha, IL-1beta, IL-6, IL-8, IL-10, IL-12p70, and TNF-alpha. MAIN OUTCOME MEASURES Vitreous concentrations of VEGF, SDF-1alpha, ILs, and TNF-alpha were compared among bevacizumab, TA, and control groups. RESULTS Vitreous concentrations of VEGF and SDF-1alpha were lower in bevacizumab and TA groups compared with the control group. The median VEGF level was 0 pg/ml (range, 0-79.2 pg/ml) in the bevacizumab group, 343.5 pg/ml (range, 0-1683.3 pg/ml) in the TA group, and 1202.5 pg/ml (range, 76-4213.9 pg/ml) in the control group. The median SDF-1alpha level was 149.2 pg/ml (range, 0-519.4 pg/ml) in the bevacizumab group, 87.5 pg/ml (range, 0-252.5 pg/ml) in the TA group, and 245.7 pg/ml (range, 0-856.8 pg/ml) in the control group. The differences in both vitreous VEGF and SDF-1alpha concentrations among 3 groups were statistically significant (P<0.001 and P = 0.010, respectively). The eyes with intravitreal bevacizumab demonstrated the lowest vitreous level of VEGF, and the level was statistically significant compared with the eyes with intravitreal TA and control eyes (P<0.001 and P<0.001, respectively). The control eyes had the highest vitreous level of SDF-1alpha, and the level was statistically significant compared with the eyes with intravitreal bevacizumab and TA (P = 0.015 and P = 0.009, respectively). There was no significant difference regarding ILs and TNF-alpha. CONCLUSIONS Intravitreal injection of bevacizumab potentially diminishes not only VEGF but also SDF-1alpha. These findings suggest that intravitreal bevacizumab may influence intraocular mediators beyond VEGF. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Posturing time after macular hole surgery modified by optical coherence tomography images: a pilot study.

PURPOSE To see the early postoperative stage of macular hole (MH) surgery and to distinguish eyes needing prolonged posturing from those that do not use Fourier-domain optical coherence tomography (FD-OCT). DESIGN Interventional case series. METHODS Sixteen eyes of 15 patients with MH underwent the protocol at Kagoshima University Hospital. After the pars plana vitrectomy with 16% SF(6) gas tamponade followed by posturing, the eyes were examined by FD OCT from 3 hours to the day after surgery. After MH closure was confirmed, posturing was stopped. Follow-up was performed for 4 months or longer. The main outcome measures included time and OCT finding of MH closure after surgery. RESULTS On the day after surgery, the macula could be examined by FD-OCT in 13 of 16 eyes; 10 eyes had a closed MH and 3 had an unclosed MH. At day 2, 2 of the 3 eyes with unclosed MHs on day 1 demonstrated a closed MH. Posturing continued for 8 days in 4 eyes whose MH closure was not confirmed. The MH was closed in all eyes within 1 month. FD-OCT showed bridge formation of the neural retina in 9 eyes and simple closure in 3 eyes within 7 days. At 1 month, 12 eyes showed simple closure and 4 eyes showed bridge formation. Among 9 eyes with bridge formation within 7 days, 6 eyes had changed to simple closure at 1 month. CONCLUSIONS FD-OCT enabled confirmation of MH closure the day after surgery even in gas-filled eyes. This imaging method may be a good indicator to determine when to stop posturing for each patient.

Intraocular expression and release of high-mobility group box 1 protein in retinal detachment

High-mobility group box 1 (HMGB1) protein is a multifunctional protein, which is mainly present in the nucleus and is released extracellularly by dying cells and/or activated immune cells. Although extracellular HMGB1 is thought to be a typical danger signal of tissue damage and is implicated in diverse diseases, its relevance to ocular diseases is mostly unknown. To determine whether HMGB1 contributes to the pathogenesis of retinal detachment (RD), which involves photoreceptor degeneration, we investigated the expression and release of HMGB1 both in a retinal cell death induced by excessive oxidative stress in vitro and in a rat model of RD-induced photoreceptor degeneration in vivo. In addition, we assessed the vitreous concentrations of HMGB1 and monocyte chemoattractant protein 1 (MCP-1) in human eyes with RD. We also explored the chemotactic activity of recombinant HMGB1 in a human retinal pigment epithelial (RPE) cell line. The results show that the nuclear HMGB1 in the retinal cell is augmented by death stress and upregulation appears to be required for cell survival, whereas extracellular release of HMGB1 is evident not only in retinal cell death in vitro but also in the rat model of RD in vivo. Furthermore, the vitreous level of HMGB1 is significantly increased and is correlated with that of MCP-1 in human eyes with RD. Recombinant HMGB1 induced RPE cell migration through an extracellular signal-regulated kinase-dependent mechanism in vitro. Our findings suggest that HMGB1 is a crucial nuclear protein and is released as a danger signal of retinal tissue damage. Extracellular HMGB1 might be an important mediator in RD, potentially acting as a chemotactic factor for RPE cell migration that would lead to an ocular pathological wound-healing response.

Retinal morphologic changes and concentrations of cytokines in eyes with diabetic macular edema.

Purpose: To determine the relationship between the retinal morphologic changes and concentrations of intravitreal cytokines in eyes with diabetic macular edema. Methods: A retrospective comparative study was performed. The preoperative optical coherence tomography images were evaluated to determine the presence of serous retinal detachments (SRDs), retinal cystic changes, and retinal swelling. The concentrations of vascular endothelial growth factor, interleukin (IL)-6, and IL-8 in vitreous samples collected during vitrectomy were determined. The correlations between optical coherence tomography parameters, other clinical factors, and the concentration of cytokines were calculated. Results: Fifty-two eyes (52 patients) were investigated. An SRD was found in 19 of the 52 eyes (36.5%). Multivariate regression analysis showed that IL-6 was the only factor significantly associated with the presence of an SRD (P = 0.001; odds ratio, 1.268; 95% confidence interval, 1.105–1.452). The other morphologic changes, such as retinal cystic changes and retinal swellings, were not significantly associated with the concentrations of intravitreal cytokines. Conclusion: The significant association of SRD with intravitreal IL-6 indicates that inflammation may play an important role in the development of SRD in diabetic macular edema.

Early imaging of macular hole closure: a diagnostic technique and its quality for gas-filled eyes with spectral domain optical coherence tomography.

Background/Aims: This study was conducted to establish a reliable method to determine macular hole (MH) closure of gas-filled eyes. Method: 21 consecutive eyes with MH underwent vitrectomy with gas tamponade, and spectral domain optical coherence tomography (SD-OCT) was performed using our diagnostic technique. The quality of OCT images was rated as signal strength (SS) and evaluated by masked observers. Results: The quality to determine MH closure (SS ≥4) was sufficient in all eyes. In addition, SD-OCT images (SS ≥6) obtained from 16/21 eyes showed detailed retinal structures including the inner segment/outer segment line. The next day after surgery, MH closure was confirmed in 12/21 eyes, and residual MH was observed in 9/21 eyes. Among these 9 eyes, 7 eyes were closed within 2 weeks. Conclusion: The present method provided clear SD-OCT images from gas-filled eyes, which is not only essential for the diagnosis of MH closure but also for establishing proper protocols and for studying the pathology of gas-filled eyes.

Early change of central macular thickness after intravitreous triamcinolone or bevacizumab in diabetic macular edema or retinal vein occlusion.

Purpose: To evaluate the immediate changes after intravitreous triamcinolone acetonide or intravitreous bevacizumab in diabetic macular edema (DME). Methods: A nonrandomized interventional study. Type 2 diabetic patients were included. Intravitreous triamcinolone acetonide (4 mg) was injected for 22 eyes with DME and IVB (1.25 mg) for 18 eyes with DME. The early time-dependent changes of central macular thickness were evaluated by optical coherence tomography before and from 1 hour to 1 month after intervention. Intravitreous bevacizumab was also tested in patients with retinal vein occlusion as a control of non-DME. Visual acuity was also examined. Results: Compared with the baseline, central macular thickness of eyes with DME decreased significantly 1 hour after intravitreous triamcinolone acetonide (P < 0.05, Wilcoxon signed rank test), while it did not significantly until 24 hours after IVB. The decrease in central macular thickness was observed significantly from 3 hours after IVB in retinal vein occlusion (P < 0.05, Wilcoxon signed rank test), and it was more evident in retinal vein occlusion than DME after IVB. Visual acuity improved significantly in DME with intravitreous triamcinolone acetonide or IVB at 1 month (P < 0.01 and P < 0.05, respectively, Wilcoxon signed rank test). Conclusion: Factors responsive to triamcinolone acetonide, other than vascular endothelial growth factor, might play an important role in pathogenesis of DME compared with retinal vein occlusion. Although no conclusion can be drawn, immediate decrease in central macular thickness after intravitreous triamcinolone acetonide might indicate the possible involvement of a nongenomic pathway of triamcinolone acetonide action.

Intravitreal Triamcinolone Acetonide for Exudative Age-Related Macular Degeneration among Japanese Patients

Aim: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. Methods: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. Results: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. Conclusions: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.

Endoscopy-Guided Subretinal Fluid Drainage in Vitrectomy for Retinal Detachment

Purpose: To study the usefulness of endoscopy-guided subretinal fluid drainage in pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Participants/Methods: A prospective non-comparative study of a small number of RRD cases. The study involved examining 10 eyes of 10 patients with RRD that received PPV. Two eyes had hazy corneas, which hindered the observation by surgical microscopy. Fluid-gas exchange was performed and then subretinal fluid was drained through a primary retinal break guided by an endoscope. No drainage retinotomy was made. Each clinical feature was studied and the surgical outcome and complications were evaluated. Results: All eyes had retinal reattachment by a single operation. No serious complication related to surgery was experienced. Conclusions: Endoscopy-guided subretinal fluid drainage is the safe and effective procedure in PPV for RRD.