Teprotumumab-associated chronic hearing loss screening and proposed treatments.

We report a case of a woman in her 50s with chronic teprotumumab-associated sensorineural hearing loss. The patient presented with chronic thyroid eye disease with proptosis and diplopia despite systemic thyroid control and orbital decompression. She was started on teprotumumab but developed tinnitus after the third dose, followed by frank hearing loss after the fifth dose. Her audiogram showed bilateral mild to moderate-severe hearing loss, which was significantly worse compared with her baseline audiogram obtained prior to treatment. Teprotumumab was immediately stopped, however repeat audiogram 6 weeks later showed no improvement. Given potentially irreversible sensorineural hearing loss, we recommend close monitoring with regular audiometric testing before, during and after teprotumumab therapy and propose potential treatment to reverse its effects in the ear.

FAILED LASER RETINOPEXY IN A PATIENT UNDERGOING PAZOPANIB THERAPY.

PURPOSE: To report a case of failed endolaser retinopexy in patient taking pazopanib and possible association with impaired retinal remodeling. METHODS: Case report. RESULTS: A 68-year-old man with a history of radiation-induced high-grade metastatic mediastinal leiomyosarcoma, on pazopanib 600 mg daily, presented with a superior retinal tear 2 months after initiating pazopanib. The patient was treated with pars plana vitrectomy and endolaser retinopexy without any immediate complications. One month postoperatively, the patient was found to have a new superior macula-sparing rhegmatogenous retinal detachment extending through the laser barricade nasally. A large proportion of the laser lesions in this area had notably remained chalk-white. The patient underwent pars plana vitrectomy with scleral buckling, and repeat endolaser retinopexy. Pazopanib therapy was stopped 1 week later in consultation with the oncology team and was reinitiated after the retina seemed stable under silicone oil for several weeks. The scars from the patient's repeat endolaser retinopexy remained pale white at his clinic visit 2 months after the procedure, and at that time, his initial laser scars had only just begun to darken with pigment. Four and a half months after the initial vitrectomy and endolaser retinopexy, and three and a half months after his repeat vitrectomy and endolaser retinopexy, all the patient's laser scars have developed increased pigment, and his retina remains completely flat under silicone oil tamponade. CONCLUSION: Pazopanib may have had an adverse effect on retinal wound healing after vitrectomy with endolaser retinopexy, leading to persistence of pale laser lesions many weeks after laser application. It is possible that this may have impaired the typical development of chorioretinal laser scar formation and led to subsequent retinal detachment.

Comparison of surgical outcomes of trabeculectomy, Ahmed shunt, and Baerveldt shunt in uveitic glaucoma.

BACKGROUND: Uveitis is defined as a collection of syndromes involving intraocular inflammation which can lead to pain, tissue damage, and vision loss. Ophthalmic surgery in uveitis patients can be challenging due to inflammation-induced fibrosis and scarring. Trabeculectomy and implantation of glaucoma drainage devices (aqueous shunts) have been used in surgical management of uveitic glaucoma, however there is a paucity of literature examining the comparative results of these entities in this unique setting. The purpose of this retrospective comparative study is to compare clinical outcomes of trabeculectomy with MMC, Ahmed shunt, and Baerveldt shunt surgery specifically in uveitic glaucoma. RESULTS: Median IOP, IOP reduction, glaucoma medication use, and visual acuity at 6- and 12-month follow-up were similar across groups. Postoperative hypotony rate was significantly different across trabeculectomy (53%), Baerveldt (24%), and Ahmed (18%) groups (p = 0.027); other complication rates were similar. Baerveldt eyes had a lower failure rate compared to trabeculectomy (p = 0.0054) and Ahmed (p = 0.0008) eyes. CONCLUSIONS: While there was no difference in IOP reduction between trabeculectomy, Ahmed, and Baerveldt, Baerveldt eyes had the lowest failure rate.

Lactams as EP4 prostanoid receptor subtype selective agonists. Part 1: 2-Pyrrolidinones-stereochemical and lower side-chain optimization.

A series of 7-[(5R)-substituted 2-oxo-1-pyrrolidinyl]-heptanoic acids were prepared, their isomeric purity determined, and pharmacologically evaluated. Lactams with affinity for the EP(4) receptor displayed agonist behavior. The lower side-chain of the lactam template could be substituted to afford ligands (e.g., 17, 24, 30, 31, and 33) of high potency and greater than 1000-fold affinity for EP(4) versus the other EP prostanoid receptors.