Kayako Matsuyama

Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab

Aims To determine the level of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the plasma of patients with proliferative diabetic retinopathy before and after an intravitreal injection of bevacizumab. Methods Eleven patients with type 2 diabetes and control of 30 non-diabetic patients were studied. The 11 eyes of 11 patients received an injection of bevacizumab (1.25 mg). Samples of blood were collected just before the injection, and after 1 day, 7 days and 1 month. The concentrations of VEGF and PEDF in the plasma were measured by ELISA. Results The VEGF concentration before the injection was 114.0 pg/ml. It was significantly reduced to 9.7 pg/ml after 1 day, to 11.7 pg/ml after 7 days and to 25.9 pg/ml even after 1 month (p<0.001, p<0.001, p<0.001, respectively). The PEDF concentration before the injection was 7.2 μg/ml. It was significantly reduced to 5.8 μg/ml after 1 day, to 5.8 μg/ml after 7 days and to 6.3 μg/ml after 1 month (p<0.001, p<0.001, p>0.05, respectively). Conclusions The decreased levels of blood VEGF after an intravitreal injection of bevacizumab indicate that bevacizumab enters the general circulation and may also affect the PEDF levels. Thus, we should carefully examine patients for systemic changes and the fellow eye after an intravitreal injection of bevacizumab.

Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab.

PurposeBevacizumab is a human monoclonal IgG1 antibody that blocks the action of vascular endothelial growth factor (VEGF). The purpose of this study was to determine the level of VEGF and pigment epithelium-derived factor (PEDF) in eyes with proliferative diabetic retinopathy (PDR) before and after an intravitreal injection of bevacizumab.MethodsEleven eyes of ten patients were studied. Patients were included if they had neovascular glaucoma, rubeosis of the iris with PDR, or aggressive PDR. Samples of aqueous humor were collected just before the injection of bevacizumab and the vitrectomy. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay, and the effects of bevacizumab on PDR were evaluated.ResultsThe free VEGF concentration before the injection was 676.5 ± 186.7 pg/ml (mean ± SEM, n = 11). Seven days later, it was significantly reduced to 7.1 ± 7.1 pg/ml (P < 0.005, n = 9). The PEDF concentration before the injection was 2.32 ± 0.49 μg/ml (n = 11), and 7 days later, it was 3.23 ± 0.76 μg/ml (P = 0.33). During the vitrectomy, patients had less intraoperative bleeding when the neovascular tissues were cut.ConclusionsAn intravitreal injection of bevacizumab significantly decreased the free VEGF in the aqueous humor by 7 days, indicating that the clinical effects of bevacizumab appear rapidly. However, intravitreal bevacizumab did not affect the level of intraocular PEDF.

Effects of Intravitreally Injected Bevacizumab on Vascular Endothelial Growth Factor in Fellow Eyes

PURPOSE Whether an intravitreal injection of bevacizumab in 1 eye will have any effect on the fellow eye has been discussed. The aim of this study was to determine the level of vascular endothelial growth factor (VEGF) in the fellow eyes after an intravitreal injection of bevacizumab in 1 eye with proliferative diabetic retinopathy. METHODS Eight patients who had similar findings of proliferative diabetic retinopathy in both eyes were studied. Four patients had rubeosis (rubeosis group), and 4 patients did not have rubeosis (no-rubeosis group) in the anterior chamber. All patients received an intravitreal injection of bevacizumab (1.25 mg) in 1 eye. Samples of aqueous humor were collected from the injected eyes just before the injection of bevacizumab and 1 day after the first injection just before vitrectomy. Samples of aqueous humor from the fellow eyes were collected just before a second injection of bevacizumab in the fellow eye at 7 days after the first injection. The concentration of VEGF in the aqueous humor was measured by enzyme-linked immunosorbent assay. RESULTS After 1 day, the concentration of VEGF in injected eyes was significantly reduced from 3,230.3±2,136.8 to 3.1±3.6 pg/mL (P<0.05) in eyes with rubeosis and 465.0±78.8 to 0 pg/mL (P<0.05) in those without rubeosis. After 7 days, the VEGF level of the fellow eyes was still significantly lower than that in the injected eye just before the injection of bevacizumab (688.5±443.1 pg/mL) in the rubeosis group, and it was 7.8±13.2 pg/mL in the no-rubeosis group (P<0.05). CONCLUSIONS A single intravitreal injection of bevacizumab significantly reduced the VEGF concentrations in the aqueous humor of the fellow untreated eye. Thus, we need to be observant of the fellow eyes after a unilateral injection and also examine the patients for systemic changes.

Early-onset endophthalmitis caused by methicillin-resistant Staphylococcus epidermidis after 25-gauge transconjunctival sutureless vitrectomy.

culture studies were negative. A diagnostic biopsy was performed, and the white mass from the anterior chamber was examined. Although the smear staining showed no fungal elements, systemic and topical fl uconazole eight times/day and topical pimaricin eight times/day were given on the assumption that the endophthalmitis was fungal in origin. After 5 days, the culture revealed a growth of Penicillium sp. (Fig. 2A) and the white exudative tissue stained positively with Grocott stain (Fig. 2B). Because an earlier study had shown that Penicillium is controlled by topical administration of amphotericin B, the treatment was changed to amphotericin B (50 μg/ml) topically every 2 h, the anterior chamber was irrigated with amphotericin B (10 μg/ml) once, and an intracameral injection of amphotericin B (10 μg/0.1 ml) was given twice. In addition, intravenous amphotericin B was given, and the topical corticosteroid and cyclosporin A were stopped. This treatment was continued for 1 month with assessments of heart and kidney functions. Slit-lamp examination showed that the soft exudative mass in the anterior chamber had disappeared before the patient discharged. The follow-up examination at 6 months revealed a persistent corneal clouding with total synechia and shallow angle (Fig. 1D). The visual acuity was light perception.

Dampening of diurnal intraocular pressure fluctuation by combined trabeculotomy and sinusotomy in eyes with open-angle glaucoma.

Purpose:Large diurnal intraocular pressure (IOP) fluctuation ([INCREMENT]IOP) is believed to be one of the causes of progression in glaucomatous changes. Some fully medicated glaucoma patients whose IOPs are controlled during the regular office hours (10:00 to 16:00 h) still have progression in glaucomatous changes and IOP elevation during off-office hours. The purpose of this study was to determine whether [INCREMENT]IOP is dampened after combined trabeculotomy and sinusotomy (LOT+SIN) in glaucoma patients with low IOPs during the regular office hours. Patients and Methods:Fourteen eyes of 8 open-angle glaucoma patients who had large [INCREMENT]IOP despite low IOPs during the office hours were studied. The IOP was measured every 3 hours for 24 hours before and >3 months after the operation. The IOPs were measured in the sitting position with a Goldmann applanation tonometer. All patients underwent LOT+SIN. Results:All patients had IOP elevations >20 mm Hg between 0:00 and 3:00 hours before the operation, and none had an IOP peak after the operation. The postoperative mean IOP (16.5±1.7 to 13.9±2.0 mm Hg, P=0.00064), the maximum IOP (21.9±2.4 to 16.1±2.5 mm Hg, P=0.0020), and [INCREMENT]IOP (8.9±2.7 to 4.3±1.2 mm Hg, P=0.0032) were significantly lower than the preoperative values. However, the minimum IOP was not reduced significantly (13.0±1.9 to 11.7±1.7 mm Hg). Conclusions:The diurnal [INCREMENT]IOPs are dampened by LOT+SIN in glaucoma patients with controlled IOPs during regular office hours. These results indicate that these surgical procedures can be used for the treatment of open-angle glaucoma patients.

Favorable anatomic and visual outcomes with 25-gauge vitrectomy for myopic foveoschisis.

Purpose To report the surgical outcomes of 25-gauge vitrectomy in eyes with myopic foveoschisis (MF). Methods The medical records of 40 eyes of 36 patients that had undergone 25-gauge vitrectomy with internal limiting membrane peeling for MF were studied. The main outcome measures were the best-corrected visual acuity (BCVA) and the optical coherence tomography (OCT) findings. The eyes were divided into two groups: 1) those with a foveal detachment (FD; FD group); and 2) those without a FD (no-FD group). Results The postoperative OCT images showed a resolution of the MF with a significant reduction in the central foveal thickness from the preoperative values in both the FD group (479±150 μm to 196±56 μm; P=0.002, mean ± standard deviation) and in the no-FD group (369±116 μm to 245±50 μm; P=0.001). The final mean BCVA significantly improved from the preoperative values in the FD group (0.96±0.53 logarithm of the minimum angle of resolution [logMAR] units to 0.70±0.56 logMAR units; P=0.009) and in the no-FD group (0.46±0.38 logMAR units to 0.34±0.36 logMAR units; P=0.007). The final BCVA in the FD group improved in 63%, remained unchanged in 31%, and worsened in 6%. In the no-FD group, the final BCVA improved in 21%, remained unchanged in 71%, and worsened in 8% of the eyes. A better final BCVA was significantly correlated with a better preoperative BCVA in both groups (P<0.001). Conclusion Twenty five-gauge vitrectomy results in favorable visual and anatomic outcomes for MF. We recommend that 25-gauge vitrectomy be used to treat eyes with MF.

Intraocular pressure in Japanese diabetic patients.

Background To determine whether the intraocular pressure (IOP) in diabetic patients is significantly different from that in nondiabetic patients. Methods The medical records of all patients who were initially examined in the Department of Ophthalmology, Kansai Medical University, Takii Hospital were reviewed. At the initial examination, patients had a detailed interview and underwent a comprehensive ophthalmic examinations. All patients were over 20 years of age and did not have glaucoma. Results A total of 703 patients were evaluated. The mean (±standard error) IOP of the diabetic patients was 15.5 ± 0.2 mmHg (n = 206), and was significantly higher than the 14.0 ± 0.1 mmHg (n = 497) in the nondiabetic patients (P < 0.0001). The IOP was negatively correlated with age (r = −0.202; P = 0.024) in the diabetic patients and was weakly but significantly correlated with the glycosylated hemoglobin (HbA1c) level (r = 0.240; P = 0.015) in the group with diabetic retinopathy. Conclusion The significantly higher IOP in diabetic patients and positive correlation of IOP with HbA1c levels in patients with diabetic retinopathy indicate that IOP in diabetic patients is higher, especially in those with poor control of diabetes.

Intraocular Pressure (IOP) Reduction by Latanoprost in Japanese Normal Tension Glaucoma Patients Over a Five-Year Period Stratified by Presenting IOP

PURPOSE We examined the effectiveness of latanoprost for reducing intraocular pressure (IOP) in Japanese patients with normal tension glaucoma (NTG) over a 5-year period. DESIGN Prospective interventional case series. The patients were classified into 2 groups based on mean IOP. METHODS A total of 38 patients with NTG were studied after being classified into the high-tension (mean IOP 16 mmHg or greater, n = 27) and low-tension (mean IOP lower than 15 mmHg, n = 11) groups. IOP was measured and Humphrey Field Analyzer (HFA) examinations were conducted at 6, 12, 24, 36, 48, and 60 months after beginning a daily administration of latanoprost. RESULTS Mean IOP before administration was 17.6 mmHg in the high-tension group, which was reduced to 13.9, 14.6, 14.4, 14.1, 13.6, and 14.6 mmHg at 6, 12, 24, 36, 48, and 60 months, respectively, after beginning administration. That in the low-tension group was 13.6 mmHg before administration, and then was reduced to 12.2, 11.4, 11.5, 12.5, 10.5, and 11.5 mmHg, respectively, after beginning administration was noted. Mean deviation (MD) values in the HFA examinations were reduced by -4.27 and -1.49 dB after 5 years in the high- and low-tension groups, respectively. CONCLUSIONS Latanoprost administration was effective in reducing IOP over a 5-year period in a range of 3.1-4.1 and 1.3-3.6 mmHg in NTG patients with high- and low-tension levels, respectively. In addition, our results indicate that latanoprost helped to prevent a decrease in MD values in both groups, as shown by the results of HFA examinations.

Posterior sub-Tenon injection of triamcinolone acetonide as pretreatment for focal laser photocoagulation in diabetic macular edema patients

PurposeTo determine whether a posterior sub-Tenon injection of triamcinolone acetonide (TA) before focal photocoagulation is safe and effective in patients with diabetic macular edema.MethodsSixteen eyes of 11 diabetic patients with unresolved diffuse macular edema were treated with a 20-mg sub-Tenon injection of TA 1 to 2 months before focal photocoagulation. Focal photocoagulation was applied only to microaneurysms, and grid laser photocoagulation was not performed. The main outcome measures used were visual acuity (VA), central macular thickness (CMT) determined by optical coherence tomography (OCT), and the fluorescein angiographic appearance of the retina. Patients were followed for at least 6 months.ResultsOne month after the sub-Tenon injection of TA, the macular edema was resolved with a significant reduction of the CMT on OCT. VA improved slightly. Subsequent focal photocoagulation of the microaneurysms maintained the significant reduction of CMT for up to 6 months. A significant improvement of VA was observed in 37.5% patients at 6 months, and there was no decrease in VA in any of the patients.ConclusionsA 20-mg sub-Tenon TA injection prior to focal laser photocoagulation is a safe and beneficial treatment in patients with diabetic macular edema.

Case of Primary Intraocular Lymphoma with Extraocular Extension

Purpose: To describe a case of primary intraocular lymphoma (PIOL) with an extension through the sclera that was confirmed to be part of the PIOL by histopathological examinations. Case: An 89-year-old woman was referred to a local clinic with a 1-year history of persistent blurred vision in her left eye. After 2 years without aggressive treatments, she had a marked reduction of vision and pain in her left eye. The clinical diagnosis was panophthalmitis, and the eye was enucleated and submitted for histopathological study. Results: Light microscope examination showed that atypical lymphocytic cells had infiltrated into both the intraocular and extraocular areas. The anterior chamber angle was blocked by infiltrating tumor cells, which were also detected around the optic nerve. The tumor cells destroyed Bruchs membrane and infiltrated around the perineural and perivascular areas within the sclera. Immunohistochemistry showed that the tumor cells were positive for B-lymphocyte surface antigen (CD20), B-cell antigen receptor complex-associated protein alpha chain (CD79-alpha), and had a high positive rate for anti-Ki-67 antibody. Conclusion: The finding in our case indicates that early diagnosis and treatment are important for eyes with PIOL because the tumor can spread and penetrate the sclera and invade extraocular tissues.