PI3K/Akt Pathway: A Role in δ-Opioid Receptor–Mediated RGC Neuroprotection

This study examines the role of PI3K/Akt pathway in δ-opioid receptor agonist (SNC-121)-induced RGC neuroprotection in a chronic glaucoma rat model. Injecting hypertonic saline into the limbal veins of Brown Norway rats elevated IOP. Rats were treated either with 1 mg/kg SNC-121 or 3 mg/kg 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY-294002; PI3K/Akt inhibitor) plus SNC-121 once daily for 7 days. Pattern ERGs were recorded in response to contrast reversal of patterned visual stimuli. Retinal ganglion cells (RGC) were visualized by Fluorogold retrograde labeling. Optic nerve head (ONH) astrocytes were pretreated with PI3K/Akt inhibitors for 30 minutes followed by 1-μM SNC-121 treatment. Changes in matrix metalloproteinases (MMP-1, -2, and -3) production and PI3K/Akt activation in optic nerve and TNF-α treated ONH astrocytes were measured by immunohistochemistry and Western blotting. SNC-121 activates the PI3K/Akt pathway in ONH astrocytes and the retina. In ONH astrocytes, SNC-121-induced Akt activation was fully inhibited by PI3K/Akt inhibitors. A sustained decline (7-42 days post injury) in Akt activation was seen in the ocular-hypertensive retina and optic nerve. This decline is reversed to normal levels by 1-mg/kg intraperitoneally (i.p.) SNC-121 treatment. Both pattern ERG amplitudes and RGC numbers were reduced in ocular hypertensive eyes, which were significantly increased in SNC-121-treated animals. Interestingly, SNC-121-induced increase in pattern-ERG amplitudes and RGC numbers were inhibited in LY-294002 pretreated animals. Additionally, SNC-121 treatment inhibited MMP-1, -2, and -3 production from the optic nerve of ocular hypertensive rats and TNF-α-treated ONH astrocytes. PI3K/Akt pathway plays a crucial role in SNC-121-mediated RGC neuroprotection against glaucomatous injury

Efficacy of selective laser trabeculoplasty following incisional glaucoma surgery

AIM: To evaluate the efficacy of selective laser trabeculoplasty (SLT) in glaucomatous eyes with previous incisional glaucoma surgery. METHODS: A retrospective cohort of eyes that underwent SLT at a single institution from 2013-2015 were followed for 1y. Reduction in intraocular pressure (IOP) following SLT was evaluated in eyes with prior trabeculectomy with ExPress mini shunt (Alcon, Ft Worth, TX, USA), Ahmed valve (New World Medical, Cucamonga, CA, USA), or combined phacoemulsification-trabeculectomy. A control group was included with eyes without prior surgery that underwent SLT. Success was defined as >20% drop in IOP from pre-SLT baseline. RESULTS: One-hundred and six eyes were included with 53 in both the prior glaucoma surgery (PGS) and no prior glaucoma surgery (NPGS) groups. Mean pre-SLT IOP was 19.2±4.3 and 20.6±6.0 mm Hg for PGS and NPGS groups, respectively (P=0.17). Both groups produced statistically significant IOP reductions at 1 and 6mo (P<0.04). At 6mo, mean IOP reduction reached 7.3% and 10.8% for the PGS and NPGS groups, respectively (P=0.42). Overall, 27.9% and 31.7% of eyes in PGS and NPGS groups met success criteria at 1y (P=0.70). In the PGS group, eyes with baseline IOP ≥21 mm Hg had IOP reductions of 18.1% (P<0.001), 16.7% (P<0.01), and 8.4% (P=0.31) compared to eyes with baseline IOP <21 mm Hg who had IOP reductions of 2.3% (P=0.39), 3.4% (P=0.19), and 1.1% (P=0.72) at 1, 6mo, and 1y, respectively. CONCLUSION: SLT is efficacious in eyes with prior incisional glaucoma surgery and results in similar IOP reductions compared to eyes without PGS. A larger IOP reduction is observed following SLT in eyes with higher pre-SLT IOP

Iris melanoma presenting as childhood glaucoma

Purpose: To describe the natural history and management of a rare case of iris melanoma in a pediatric patient. Observations: A Caucasian female presented with left pupillary abnormalities at age 7, progressive iris changes at age 9, and markedly elevated intraocular pressure with advanced optic nerve cupping at 11 years of age. She was found to have a pigmented lesion overlying her iris and invading her angle. Trans-corneal fine needle aspirate biopsy demonstrated malignant melanoma of the iris. The patient subsequently underwent Iodine-125 plaque brachytherapy for the tumor. Conclusions: and Importance: Early identification and treatment of iris melanoma may be associated with decreased risk of local progression and metastatic disease. Treatment of glaucoma in conjunction with uveal melanoma is complicated by tumor specific considerations, including treatment of the tumor and prevention of metastasis. Keywords: Iris melanoma, Glaucoma, Pediatri