Keita Yamakiri

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.

Ultrastructure of the trabecular meshwork in secondary glaucoma eyes after intravitreal triamcinolone acetonide.

PurposeTo study the histology of the trabecular meshwork of eyes with glaucoma by intravitreal injection of triamcinolone acetonide (TA). DesignTwo cases report. Participants/MethodsA 68-year-old Japanese man with branch retinal vein occlusion and a 48-year-old Japanese woman with uveitis were treated by cataract surgery, intraocular lens implantation, and TA-assisted pars plana vitrectomy. At the end of surgery, TA suspension (4 mg) was intravitreously injected. During the follow-up period, the intraocular pressure (IOP) of the patients increased over 30 mm Hg even with full medication. Trabeculectomy was performed at 4 months after TA injection in case 1 and at 6 months in case 2, and intraocular pressure returned to the normal range in both cases. Light and electron microscopic studies of the resected trabecular tissue were carried out. ResultsThe histology showed minimal deposition of extracellular matrix in the trabecular meshwork in case 1. Case 2 showed the beginnings of deposition of extracellular matrix including fingerprintlike material in the trabecular meshwork with decreased intertrabecular spaces. ConclusionsThe ultrastructural changes in the trabecular meshwork of eyes with glaucoma after treatment with intravitreal TA might resemble those with glaucoma after topical corticosteroid treatment.

Steroid-induced glaucoma in children with acute lymphoblastic leukemia: a possible complication.

PurposeTo evaluate the ocular hypertensive response to repetitive cycles of high-dose systemic corticosteroid in young patients with acute lymphoblastic leukemia (ALL). Patients and MethodsFive patients up to 6 years of age with ALL who received chemotherapy between November 2003 and March 2005 were examined. As maintenance therapy, they received oral or intravenous dexamethasone 6 to 12 mg/m2/day for 2 weeks, followed by 1-week taparing and 5 weeks break were used in 1 cycle. The duration of maintenance therapy was 15 cycles for 2.5 to 3 years. Comprehensive ophthalmic check-up, including best-corrected visual acuity, intraocular pressure (IOP), and slit-lamp and fundus examinations, were performed. ResultsAll patients were followed up until final cycle. Symmetrical IOP rise >21 mm Hg was observed in all patients. Right IOP increased to a maximum of mean 39.6±7.2 mm Hg. (range: 28 to 47). The range of cycle to reach a maximal IOP was 5th to 11th. All patients were maintained IOP control with antiglaucoma medications. However, 1 patient already had severe glaucomatous optic atrophy at the time of consultation. ConclusionsSystemic corticosteroid in childhood-ALL treatment has a risk for IOP elevation. Periodical and careful ophthalmic check-up is necessary, especially in patients with dexamethasone.

Stromal-Derived Factor-1 and Inflammatory Cytokines in Retinal Vein Occlusion

Purpose: To identify the roles of stromal-derived factor (SDF-1) and inflammatory cytokines in retinal vein occlusion (RVO). Methods: Samples were collected by vitrectomy and the levels of SDF-1, vascular endothelial growth factor, and inflammatory cytokines (interleukins [IL-1β, IL-6, IL-8, IL-10, IL-12p70]; tumor necrosis factor-α) were measured in 20 eyes with RVO, and 9 eyes with epiretinal membrane served as negative controls. Four eyes with inflammatory diseases were also investigated. Results: SDF-1 levels in active RVO (A-RVO; 4 eyes with iris neovascularization) were significantly higher than those in quiescent RVO (Q-RVO; 16 eyes without iris neovascularization) and the negative controls (p <. 01), whereas there were no significant difference between the Q-RVO and the negative controls. There were no significant correlations between the concentrations of SDF-1 and other cytokines. Conclusions: Elevation of intravitreous SDF-1 levels in A-RVO but not Q-RVO suggested a pivotal role of SDF-1 in angiogenic changes during RVO.

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 diagnosis of macular hole closure of a gas-filled eye with Watzke-Allen slit beam test and spectral domain optical coherence tomography.

Purpose: The purpose of this study was to evaluate the usefulness of the Watzke–Allen slit beam test (W/A test) and spectral domain optical coherence tomography (SD-OCT) for diagnosing macular hole closure in gas-filled eyes during the early postoperative period. Methods: A retrospective comparative study was performed on 40 consecutive eyes of 40 patients with macular hole treated with vitrectomy. Macular hole closure was initially judged within 2 days after surgery with both the W/A test and SD-OCT. Final diagnosis was confirmed with SD-OCT after the gas disappeared. The concordance rate of initial diagnosis and final diagnosis using each method was evaluated. Results: The W/A test could be done for the gas-filled eyes of all patients next day, whereas a diagnosable SD-OCT image could be obtained in 77.5% of patients. The concordance rate was 85% (34of 40 examined eyes) with the W/A test and 77.5% (31 of 40 examined eyes) with SD-OCT (P = 0.39, chi-square test). If a diagnosable result (image or response) could be obtained within 2 days after surgery, the accuracy of SD-OCT (31 of 31 eyes) was significantly better than that of the W/A test (31 of 40 eyes) (P = 0.026, chi-square test). Conclusion: The W/A test is more useful for diagnosing macular hole closure of a gas-filled eye than SD-OCT; however, SD-OCT gives more accurate information when diagnosable. Combining both methods could improve the accuracy and applicability.

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.

Individualized, spectral domain-optical coherence tomography-guided facedown posturing after macular hole surgery: minimizing treatment burden and maximizing outcome.

Purpose: To evaluate the individualized, optical coherence tomography-guided facedown posturing after macular hole (MH) surgery in minimizing the burden and maximizing outcome. Methods: A retrospective comparative study. One hundred and seven consecutive eyes with an MH (<500 &mgr;m) received vitrectomy and gas tamponade. After surgery, optical coherence tomography examination was performed from 6 hours to postoperative Day 2. In Group A, with a pro re nata posturing protocol, the duration of facedown posturing was determined from the optical coherence tomography findings. Group A was subdivided as follows: Group A1, facedown posturing required postoperatively and Group A2, no posturing required. When MH closure was confirmed, facedown posturing (if any) was discontinued. If the MH did not close, additional posturing was advised. Group B was the control group, consisted of 42 consecutive eyes with traditional 7 days of posturing. Results: After a single surgery, Group A had the MH closure rate of 96.2%, 95.8% in Group A1 and 97.1% in Group A2, whereas Group B had the MH closure rate of 95.2%. The average posturing period was 42 hours for Group A, 57 hours for Group A1 and 10 hours for Group A2 (P < 0.001). The MH size was correlated significantly with the closure time (R = 0.47, P = 0.005, Spearman correlation coefficient). Conclusion: A pro re nata posturing protocol achieves a high MH closure rate with a significant reduction of posturing time especially for pseudophakic eyes.