Openable artificial intestinal tract device integrated with a permeable filter for evaluating drug permeation through cells.

Organs-on-chips using cultured cells have been developed and applied for evaluating in vitro biological phenomena. We previously reported an openable artificial intestinal tract system, as an in vitro model of the small intestine, for in vitro drug screening. The intestinal tract device could be transformed using an integrated artificial muscle actuator. An initial flat state was suitable for cell culture, and the transformed tubular structure was used as a fluidic channel for perfusion tests. The previously developed intestinal tract system could be used to evaluate drug absorption by cells through perfusion testing. This study presents an improved artificial intestinal tract system for analysis of drug permeation, in addition to absorption. Permeable filters were integrated into the intestinal tract device. Integration of additional filters into the design of the existing artificial muscle actuator was accomplished by considering device performance and available filter locations. Filter permeability was evaluated by perfusion testing. MDCK-II cells were cultured on the device and visually and electrically evaluated. The openable device, equipped with new functions for further pharmacokinetic analysis, could perform and evaluate drug disposition using cultured cells. We anticipate that the improved, openable organ-on-a-chip device system will contribute to advances in in vitro drug screening technology.

A pediatric case with parvovirus B19-associated uveitis without autoantibody formation.

Acute parvovirus B19 (B19) infection is often accompanied by autoantibody formation, including antinuclear antibodies and rheumatoid factor, and the symptoms of the infection are similar to those of several autoimmune diseases. Uveitis is a representative manifestation of autoimmune diseases and is rarely caused by B19. Autoantibody formation was confirmed in 2 previously reported cases with B19-associated uveitis. However, whether B19-associated uveitis is caused by the direct invasion of the virus or the induction of autoimmunity remains unclear. We herein report a pediatric case with B19-associated uveitis without autoantibody formation. We speculated that B19 might have directly invaded the eye in this patient because of the development of uveitis without antibody formation and the negative results for anti-B19-specific antibodies in the serum at the onset of the disease. Although the mechanism of invasion is unknown, B19 may have a high affinity for tissue in the eye.

[Effect of Intravitreal Bevacizumab Injection on Iris and Iridocorneal Angle Neovascularization in Neovascular Glaucoma].

Neovascular glaucoma is a serious complication associated with retinal ischemic changes, which increase the production of vascular endothelial growth factor. Vascular endothelial growth factor has been implicated as a key molecule in the development of newly formed vessels and neovascular glaucoma. Intravitreal injection of bevacizumab, a full-length humanized anti-vascular endothelial growth factor monoclonal antibody, leads to a dramatic regression of the new iris and iridocorneal angle vessels on slitlamp examination. However, anterior segment angiography reveals that bevacizumab does not cause a regression of the neovascular vessels themselves but reduces vascular permeability while newly formed vessels are still present in the iris and iridocorneal angle. This review focuses on the pathology and diagnosis of neovascula glaucoma and the effect of intravitreal bevacizumab on the iris and iridocorneal angle neovascularization.

Reconstruction of a nonfunctional trabeculectomy bleb using an amniotic membrane-wrapped silicone sponge to treat refractory glaucoma.

BACKGROUND: This study was conducted to verify the usefulness of nonfunctional trabeculectomy bleb reconstruction using a silicone sponge wrapped with amniotic membrane. Its purpose was to allow aqueous humor to flow from the flap to the posterior orbital space. METHODS: Seven consecutive patients who had undergone two or more surgeries in one eye for refractory glaucoma followed by our operation were included in this study. Conjunctival adhesion to the sclera was detached with a limbus-based conjunctival incision, followed by reopening the former trabeculectomy flap. A 1.5 × 12 mm silicone sponge used for retinal detachment surgery was wrapped three to four times with amniotic membrane, placed longitudinally on the sclera, and fixed with 10-0 nylon sutures. The anterior end of the amniotic membrane was fixed underneath the scleral flap with sutures, and the conjunctival wound was closed. We periodically checked the intraocular pressure (IOP) and for complications. Follow-up periods ranged from 15 to 30 months (average 19.4 months). Surgical success was defined as a final IOP of ≤ 21 mmHg with or without additional treatment. We defined failure as an IOP of > 21 mmHg on the second of two consecutive visits after the first 4 weeks, or the need for additional glaucoma surgery. RESULTS: Surgery was successful in five of the seven eyes, although bleb needling was performed in two eyes and amniotic membrane patch covering for early aqueous leakage was needed in one eye. In four of the five successful eyes, IOP was well controlled for longer than the period between the previous and present surgeries. One of the unsuccessful eyes, with neovascular glaucoma, had high IOP with hyphema followed by phthisis of the eyeball. The other, with aqueous leakage via the conjunctival wound, required trabeculectomy in a different area. There were no other complications. CONCLUSIONS: Reconstruction of the nonfunctional trabeculectomy bleb using a silicone sponge wrapped with amniotic membrane can be a useful strategy for treating refractory glaucoma.

A classic temporal optic disc pit showing progression in the corresponding optic nerve fiber and visual field defects.

PURPOSE: We report a rare case with a classic temporal optic disc pit (ODP) showing the progression of an associated nerve fiber layer defect (NFLD) with the corresponding visual field defect (VFD). METHODS: We describe the patient's medical records and review the pertinent literature. RESULTS: A 54-year-old woman had a temporal ODP, which was considered to be congenital, associated with both NFLD expanded to both the upper and lower sides of the horizontal line and corresponding VFD and a small ODP-like excavation at the 6.5 o'clock position on the disc edge with a narrow NFLD OD. During the 5-year follow-up period, both the NFLD and VFD associated with the temporal pit progressed without serous retinal detachment. The small ODP-like excavation located at the 6.5 o'clock position also showed progressive NFLD in the temporal lower quadrant with advanced VFD, which suggested that the excavation might be associated with glaucoma. CONCLUSION: Based on the observation that the VFD occupied the two temporal quadrants with no step, an NFLD with corresponding VFD associated with a classic temporal ODP, although not considered to be related to glaucoma, can progress.

Angiographic changes in iris and iridocorneal angle neovascularization after intravitreal bevacizumab injection.

OBJECTIVE: To evaluate the effects of the intravitreal (IV) injection of bevacizumab on anterior segment neovascularization using anterior segment angiography. METHODS: We observed 1 eye with iris and iridocorneal angle neovascularization and 3 with neovascular glaucoma from 4 patients with diabetic retinopathy in 3 eyes and central retinal vein occlusion in 1 eye. Two healthy eyes from 2 other patients served as control eyes. Three eyes, including 1 normal eye, were examined by iris angiography; the other eyes underwent iridocorneal angle angiography with fluorescein (FA) and indocyanine green (IA) using a Heidelberg Retina Angiograph 2. After angiography, 4 eyes with neovascularization were treated with IV bevacizumab (1.25 mg per 0.05 mL) and underwent angiography once more 4 to 6 days after treatment. RESULTS: Iris angiography with indocyanine green revealed many iris vessels, but not dye leaking, in both normal and glaucomatous eyes, and the angiography with fluorescein showed intensive vessel leakage in the iris as well as iridocorneal angle neovascularization, but not in normal eyes. Angle angiography revealed vessel structures with indocyanine green and intensive leakage with fluorescein in the iris and showed iridocorneal angle neovascularization and neovascular glaucoma, whereas no vessel structures appeared with IA or FA in the normal eye. After IV bevacizumab injection in eyes with neovascularization, the vascular structure did not change with IA, but dye leakage remarkably decreased with FA in the iris and angle. However, newly formed vessels in the iris and iridocorneal angle seemed to disappear on slitlamp examination. CONCLUSION: Intravitreal injection of bevacizumab effectively reduces vascular permeability, whereas newly formed vessels are still present in the iris and iridocorneal angle.

Effect of latanoprost on the diurnal variations in the intraocular and ocular perfusion pressure in normal tension glaucoma.

PURPOSE: To evaluate the effects of latanoprost on the diurnal variations in the intraocular pressure (IOP) combined with the ocular perfusion pressure (OPP) in patients with normal tension glaucoma (NTG). PATIENTS AND METHODS: Twenty-two eyes from 22 patients with NTG were used for the study. The diurnal variations in the IOP and blood pressure (BP) were measured every 3 hours without therapy, and then the patients were treated with latanoprost (0.005%) once daily for more than 12 weeks. The diurnal variations in the IOP and BP under medication were again measured every 6 hours. The diurnal variation of IOP for 24 hours, mean diurnal IOP, maximum IOP, minimum IOP, range of variation in IOP, OPP, and BP were compared between the baseline and after treatment by means of a paired t test. RESULTS: At 3 months after the start of the latanoprost treatment regimen, the IOP showed a statistically significant decrease at every assessed time point over 24 hours (P<0.001). Latanoprost significantly reduced the mean diurnal IOP, maximum IOP, minimum IOP, and mean range of variation in the IOP values from baseline (P<0.001, <0.001, <0.001, and 0.009, respectively). OPP after treatment showed no significant difference at any assessed time points from the baseline (P>0.1). Latanoprost did not significantly alter the mean diurnal OPP (P>0.1), and BP (P>0.5) from the baseline. CONCLUSIONS: Latanoprost was thus found to significantly reduce IOP over 24 hours, whereas it does not affect OPP and BP in NTG patients. Therefore, it may be a useful medication for NTG.