A. Higuchi

Choroidal Neovascularization Is Provided by Bone Marrow Cells

Choroidal neovascularization (CNV) is a known cause of age‐related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy × 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.

Retinal neovascularisation without ischaemia in the spontaneously diabetic Torii rat

Aims/hypothesisThe spontaneously diabetic Torii (SDT) rat has recently been established as a model of type 2 human diabetes mellitus. Male SDT rats develop severe diabetic ocular complications. This study investigated the nature of the ocular complications in this model and addressed the question of whether the SDT rat is a good model of human proliferative diabetic retinopathy.MethodsMale SDT rats aged 50 weeks were studied for a period of 8 months. Under deep anaesthesia, one eye of each animal was enucleated following perfusion with fluorescein dextran and a retinal flat mount was prepared to study vascular structure. The other eye was enucleated and investigated histologically by haematoxylin–eosin and azan staining and by immunohistochemistry using antibodies against vascular endothelium (Griffonia simplicifolia isolectin B4 antibody) and vascular endothelial growth factor (VEGF).ResultsFrom the vascular structure study, 17 of 32 rats (53%) showed proliferative retinopathy without vascular non-perfusion. The histological study revealed traction retinal folds in rats with proliferative retinopathy. Azan staining showed some proliferative matrix in rats with normal retinal structure and those with proliferative retinopathy compared with normoglycaemic controls. Staining with Griffonia simplicifolia isolectin B4 antibody showed no specific vascular changes in any of the rats, while VEGF staining revealed higher immunoreactivity in the retina of rats with normal retinal structure and those with proliferative retinopathy, but only low immunoreactivity in the control animals.Conclusions/interpretationThere appear to be differences between the SDT rat model of diabetic retinopathy and human proliferative diabetic retinopathy, as the SDT rat develops retinal neovascularisation without retinal ischaemia. This very unique display of ocular neovascularisation may be caused by increased expression of VEGF.

Pars Plana Vitrectomy with Removal of Posterior Hyaloid Face in Treatment of Refractory Diabetic Macular Edema Resistant to Triamcinolone Acetonide

BackgroundTriamcinolone acetonide (TA) has recently been used to treat diabetic macular edema (DME) but its effectiveness is limited.CasesThree patients (three eyes) with unresolved diffuse DME who did not respond to a posterior sub-Tenons injection of TA underwent vitrectomy.ObservationsIntraoperatively, it was found that all of the eyes had a posterior hyaloid face that was adherent to a large area of the posterior pole retina, although this had not been detected by slit-lamp biomicroscopy or optical coherence tomography. After vitrectomy and removal of the posterior hyaloid face, there was a significant reduction in the central macular thickness of all three eyes and an improvement in the visual acuity of the patients.ConclusionsWhen TA treatment is not effective for DME, vitrectomy with the complete removal of the posterior hyaloid face, including removal of the internal limiting membrane, should be considered.

Trans-Tenon's retrobulbar injection of triamcinolone acetonide for diffuse diabetic macular edema

PurposeTo determine whether a trans-Tenons retrobulbar injection of triamcinolone acetonide (TA) is a safe and effective treatment for diffuse diabetic macular edema.MethodsThirty-nine eyes of 30 diabetic patients with persistent macular edema were treated with 20 mg of TA injection. Central macular thickness (CMT) determined by optical coherence tomography (OCT) and visual acuity were evaluated before the injection and at 1, 2, 3, and 6 months, and up to 1 year in some eyes, after the injection.ResultsThe CMT decreased significantly from 478 ± 129 µm (mean ± SD) before injection to 316 ± 102 µm at 1 month, 307 ± 104 µm at 2 months, and 275 ± 89 µm at 3 months after a single injection of TA. A 20% reduction of CMT from the initial value was maintained by a single injection of TA in 27 of 39 eyes (69.2%) at 3 months, in 14 of 22 eyes (63.6%) at 6 months, and in 5 of 7 eyes at 12 months. A recurrence of macular edema was observed in 10% of the eyes at 3 months, and in 22.7% at 6 months. The 17 eyes in which vitrectomy had been carried out had a more significant improvement in CMT than the eyes without vitrectomy.ConclusionA 20-mg trans-Tenons retrobulbar TA injection is a safe and effective treatment for diabetic macular edema. Jpn J Ophthalmol 2005;49:509–515