Additive Intraocular Pressure-Lowering Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, Combined with Existing Antiglaucoma Agents in Conscious Ocular Normotensive Monkeys.

Purpose: To investigate the intraocular pressure (IOP)-lowering effects of omidenepag isopropyl (OMDI), a potent and highly selective prostanoid EP2 receptor agonist, as a potential first-line ocular hypotensive agent when combined with existing antiglaucoma agents in conscious ocular normotensive monkeys. Methods: Male cynomolgus monkeys were examined under conscious conditions. OMDI ophthalmic solution alone was topically applied to an eye or combined with other ophthalmic solutions at 5-min intervals. The contralateral eye was left untreated. IOP was measured before and at 2, 4, 6, and 8 h after instillation. Results: Topical application of OMDI to the eye resulted in statistically significant IOP reduction, which lasted for at least 6 h. The IOP-lowering effects of OMDI concomitantly administered with any of the tested antiglaucoma agents (timolol, brinzolamide, netarsudil, ripasudil, and brimonidine) were greater than those of OMDI alone. Furthermore, these enhanced IOP responses to their concomitant use were statistically significant compared with those of the tested antiglaucoma agents alone. Any combination of OMDI with the tested agents did not lead to serious abnormalities either systemically or locally in the eye. Conclusions: We demonstrated that OMDI has additive IOP-lowering effects when administered in combination with various antiglaucoma agents, namely, ß-adrenergic antagonist, carbonic anhydrase inhibitor, Rho-associated coiled-coil containing protein kinase inhibitors, and α2-adrenergic agonist. These results suggest that OMDI provides additional clinical benefits because of its unique mechanisms of action when combination therapy is required.

The Antiglaucoma Agent and EP2 Receptor Agonist Omidenepag Does Not Affect Eyelash Growth in Mice.

Purpose: The present study investigated the effects of the antiglaucoma agent and selective E2 receptor agonist omidenepag isopropyl (OMDI) on eyelash growth in comparison with a prostaglandin analog (prostamide receptor agonist) in mice. Methods: Four-week-old female mice (C57BL/6J) were divided into 3 groups of n = 10 each. The groups were administered 3 µL of 0.003% OMDI solution, the vehicle (negative control), or a 0.03% bimatoprost solution (positive control) on the upper eyelids of the right eyes once daily for 14 days. On the 15th day, all animals were euthanized, and the upper eyelids with eyelashes were fixed with 10% neutral formalin. Eyelashes were evaluated for number, length, and thickness using a stereomicroscope. Specimens were then paraffin-embedded and stained with hematoxylin and eosin, followed by microscopic examination to assess eyelash morphology and growth cycle. Results: Eyelash number (143.5 ± 6.7/eyelid), thickness, and percentage of dermal papilla in the anagen phase in the OMDI group were similar to those observed in the vehicle group (eyelash number, 144.2 ± 5.7/eyelid). In contrast, eyelash number (166.7 ± 7.0/eyelid), thickness, and the percentage of dermal papilla in the anagen phase were significantly greater in the bimatoprost group compared with those of the vehicle group. Conclusions: Unlike existing prostaglandin analogs, our findings indicate that OMDI has no effect on eyelash growth in mice, suggesting that it may be a promising antiglaucoma agent with a reduced number of adverse effects.

Real-time viewing of video capsule endoscopy for on-going mid GI bleeding.

RAPID Access Real-Time (RT) has the ability to provide an endoscopist with the presence of bleeding and its location for cases with on-going mid GI bleeding. However, to date, the clinical benefits of this device remain unknown as studies on it have not yet been published. We present a case of recurrent GI bleeding where video capsule endoscopy (VCE) with real time viewing helped them decide on the route of double-balloon enteroscopy (DBE). Since the bleeding image of RT had not been obtained over 150 minutes after passing the pylorus, the patient underwent retrograde DBE. In the middle of the ileum, active bleeding from Dieulafoy's lesion was found and we treated it successfully. It was suggested the effectiveness of VCE in reference to the determination of RT for on-going mid GI bleeding.

Management of small-bowel polyps in Peutz-Jeghers syndrome by using enteroclysis, double-balloon enteroscopy, and videocapsule endoscopy.

BACKGROUND: Management of small-bowel polyps in Peutz-Jeghers syndrome (PJS) by using fluoroscopic enteroclysis (FE), double-balloon enteroscopy (DBE), and videocapsule enteroscopy (VCE) remains incompletely determined. OBJECTIVE: To evaluate the usefulness of FE, VCE, and DBE and compute the polyp growth rate. DESIGN: Single-center retrospective study. SETTING: Tertiary referral hospital. PATIENTS: Between June 2003 and January 2010, 18 consecutive patients with PJS were enrolled. MAIN OUTCOME MEASUREMENTS: Polyp detection rates among FE, VCE, and DBE, histology of resected polyps, and the polyp growth rate. RESULTS: Total enteroscopy rate was higher at VCE (89%) than at DBE (52%; 27% in patients with ≥2 previous laparotomies and 90% in patients with ≤1 [P = .001]). FE demonstrated fewer polyps than DBE, whereas VCE had detection rates similar to those of DBE. Of 387 DBE-resected and 22 surgically resected polyps, histologic analysis of 110 retrieved polyps showed adenoma or adenocarcinoma in 30.0% of polyps >20 mm and in only 1.3% of polyps ≤20 mm (P < .0001). Multiple linear regression analysis showed that the number of small-bowel polyps >10 mm (X1; P = .0366) and colorectal polyps >5 mm (X2; P = .002) were independent predictors of the growth rate of small-bowel polyps (Y), and a forward stepwise selection model was constructed: Y = 0.136 × X1 + 0.289 × X2 - 0.589 (R(2) = 0.665). LIMITATIONS: Small sample size. CONCLUSIONS: DBE and VCE were useful for the management of small-bowel polyps in PJS. VCE may replace barium examinations for surveillance after polyp resection at intervals depending on the polyp growth rate.

Route selection for double-balloon endoscopy, based on capsule transit time, in obscure gastrointestinal bleeding.

BACKGROUND: Double-balloon endoscopy (DBE) utilizes both oral and anal routes. The proper selection of the initial route is important for more rapid management of obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to clarify the accuracy of the transit time of video capsule endoscopy (VCE) to the lesion as a predictive indicator for the decision on the initial DBE route. METHODS: Of 172 patients who underwent both DBE and VCE, 65 who were diagnosed with small-intestinal hemorrhagic lesions by both means were enrolled. The relation between VCE transit time to the lesion and the DBE route by which the lesion was discovered was analyzed, distinguishing between 46 complete and 19 incomplete VCEs. RESULTS: Among the 46 patients with a complete VCE, the transit time and position of the lesion were strongly correlated. The best cutoff values for route selection by the VCE transit time from capsule intake and from the duodenal bulb to the lesion, determined using a receiver operating characteristic (ROC) curve, were 60% and 50%, respectively, of the transit time to the cecum. At that point, the accuracy of route selection was 90% and 94%, respectively. Positions shown by VCE for ileal lesions tended to be more proximal than those shown by surgery. In the 19 patients with incomplete VCEs, the best cutoff for transit time was 180 min from the duodenal bulb. CONCLUSIONS: The VCE transit time was useful for determining the route for DBE in OGIB. This parameter was most accurate when the cutoff value for the selection was half of the small-bowel transit time in the complete VCE examination.