The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork.

Glucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by ß-catenin knockdown increased glucocorticoid-induced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.

Twenty-Four-Month Outcome of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Eyes With Prior Corneal Transplant Surgery.

PURPOSE: Glaucoma is a well-known sequelae of corneal transplant surgery and is a leading cause of visual loss in this patient group. We evaluated the performance and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in this population. DESIGN: Noncomparative retrospective case series. PARTICIPANTS: Consecutive eyes of patients receiving the GATT procedure for uncontrolled intraocular pressure (IOP) following corneal transplant surgery from 2016 to 2019. METHODS: Retrospective analysis of eyes with a history of prior corneal transplant undergoing GATT at Glaucoma Associates of Texas between 2016 and 2019 was performed. Data included IOP, patient demographics, preoperative and postoperative medications, preoperative and postoperative corneal procedures, complications, and need for reoperation for IOP control. MAIN OUTCOME MEASURES: IOP reduction and medication use following the procedure. RESULTS: Thirty-nine eyes of 32 patients with prior corneal transplant surgery underwent a GATT procedure. Prior corneal surgery included penetrating keratoplasty (59.0%), Descemet's stripping endothelial keratoplasty (35.9%), Descemet's membrane endothelial keratoplasty (2.6%), and deep anterior lamellar keratoplasty (2.6%). Patient age ranged from 24 to 94 years (mean 68.0 y) with 44% female and 81% Caucasian. The majority of patients had secondary open angle glaucoma (64.1%). There was a significant reduction in IOP and number of medications at all postoperative time points after censoring patients requiring reoperation to control IOP (P<0.001). At 24 months the pressure decreased from baseline of 30.9±11.5 to 13.9±4.7 mm Hg. Medications decreased from 4.2±1.0 medications at baseline to 0.6±1.0 at 24 months. Visual acuities decreased significantly over the first postsurgical month (all P<0.05), but these recovered at subsequent follow-up visits with 2-Snellen line improvements exceeding losses from month 3 to 36. Seven eyes required reoperation for uncontrolled glaucoma at a median of 8.5 months (range: 1.6 to 16.2 mo) after GATT. The cumulative proportion of eyes undergoing repeat cornea surgery was 2.6%, 2.6%, and 14.3% at 12, 24, and 36 months post-GATT, respectively. CONCLUSIONS: This case series describes a group of glaucoma patients, with a history of prior corneal surgery, that were safely and successfully treated with GATT. While classically traditional glaucoma surgeries are considered the standard of care for eyes following corneal transplant surgery, GATT should be considered as a reasonable, safe and effective alternative for surgically lowering IOP.

Outcomes of bleb revision with ologen following filtering glaucoma surgery.

PURPOSE: This study reports long-term outcomes of bleb revision with ologen™ Collagen Matrix (Aeon Astron Europe BV, the Netherlands) for the surgical management of various bleb-related issues including persistent bleb leaks with or without associated hypotony, bleb dysesthesia, overhanging blebs, or hypotony after filtering glaucoma surgery. MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent ologen bleb revision from 2012 to 2019 at Glaucoma Associates of Texas. RESULTS: The study included 23 eyes of 22 patients undergoing bleb revision with the ologen implant. Mean age was 74.0 ± 11.3 years, 16 (69.6%) were female, and 13 (56.5%) were White. Indications for bleb revision included bleb leak (78.3%), dysesthesia (13.0%), and hypotony from an overfiltering bleb (8.7%). Mean preoperative intraocular pressure was 6.8 ± 4.1 mmHg and the number of medications was 0.3 ± 0.9. Median follow-up was 24 months (range: 12-84 months); all patients had at least 12 months of follow-up. At 1 year, mean intraocular pressure was 10.9 ± 4.6 mmHg on 0.2 ± 0.5 medications, and at last follow-up, mean intraocular pressure was 10.4 ± 3.6 mmHg on 0.3 ± 0.7 medications. Bleb morphology remained low, diffuse, and posterior. One patient developed kissing choroidal effusions requiring surgical drainage with subsequent stabilization of intraocular pressure and bleb function, and three patients required additional surgery due to persistent leaks or bleb failure; there were no other vision-threatening complications. CONCLUSIONS: Use of the ologen implant during surgical bleb revision is a useful surgical technique that confers long-term improvements in bleb morphology and stability of function.

Clinical Outcomes of Ahmed ClearPath Implantation in Glaucomatous Eyes: A Novel Valveless Glaucoma Drainage Device.

PRCIS: Designed with novel features to facilitate implantation and improve safety, the Ahmed ClearPath (ACP) glaucoma drainage device (GDD) provided intraocular pressure (IOP) reduction comparable with other GDDs in eyes with refractory glaucoma in a multicenter retrospective study. PURPOSE: To present clinical outcomes with a novel valveless GDD (ACP, New World Medical). The 250 and 350 mm2 models feature a contoured plate for optimal globe apposition, anteriorized suture points to facilitate suturing to the globe, and a prethreaded 4-0 polypropylene ripcord suture. METHODS: This was a multicenter retrospective analysis of eyes with medically and/or surgically uncontrolled glaucoma implanted with the 250 or 350 mm2 ACP either as a standalone procedure or in combination with other procedures. Pre-, intra-, and postoperative data through 6 months were collected. RESULTS: A total of 104 eyes (100 subjects) received the ACP by 10 US surgeons, 63.5% of which had primary open-angle glaucoma and 62.5% had severe glaucoma. Mean baseline IOP was 26.3 (9.0) mm Hg and mean medication use was 3.9 (1.3). Through 6 months' follow-up, mean IOP ranged from 13.6 to 16.7 mm Hg and mean medication use from 0.9 to 1.9 medications (P<0.0001 at all timepoints for each outcome measure). At 6 months, mean IOP was 13.7 mm Hg (-13.0 mm Hg, 43.0%, P<0.0001) and mean medication use was 1.9 medications per eye (-2.1, 47.7%, P<0.0001). Common adverse events included anterior chamber inflammation (16.3%), hyphema (15.4%), and hypotony (6.7%). CONCLUSION: The new ACP appears to be safe and efficacious as a standalone procedure or in combination with other procedures for uncontrolled glaucoma, and may be considered as a GDD option for patients in whom its unique design may facilitate the implantation process.

Early Results of Goniotomy with the Kahook Dual Blade, a Novel Device for the Treatment of Glaucoma.

PURPOSE: To report the outcomes of patients who underwent goniotomy with the Kahook Dual Blade (KDB) either as a standalone procedure or in combination with cataract extraction. PATIENTS AND METHODS: This retrospective chart review included 111 eyes of 90 patients who underwent KDB goniotomy from January to November 2016 at Glaucoma Associates of Texas. KDB goniotomy was combined with cataract surgery in 100 eyes. The main outcome measures were postoperative intraocular pressure (IOP) and number of IOP lowering medications. RESULTS: Preoperatively, mean IOP was 17.1 ± 4.7 mmHg (range 8-34 mmHg) and mean number of IOP lowering medications was 2.4 ± 1.3 (range 0-6). Postoperatively, mean IOP was 14.9 mmHg, 13.9 mmHg, 14.1 mmHg, 14.4 mmHg, and 14.7 mmHg at 1, 3, 6, 9, and 12 months follow-up, respectively (all p <0.004). Mean numbers of IOP lowering medications were 0.8, 1.0, 1.0, 1.0, and 1.6 at 1, 3, 6, 9, and 12 months follow-up, respectively (all p <0.001). The cumulative reoperation rates for uncontrolled IOP after KDB were 0%, 1.0%, 2.1%, and 4.6% at 3, 6, 9, and 12 months, respectively. Eyes with a preoperative IOP >21 mmHg were significantly more likely to undergo reoperation (p = 0.038, log-rank test). There were no serious complications at any time point in the follow-up period. CONCLUSION: The Kahook Dual Blade results in a reduction in IOP and use of glaucoma medications after one year of follow-up. Further prospective studies are needed to fully characterize safety and efficacy.

Micropulse Cyclophotocoagulation: Initial Results in Refractory Glaucoma.

PURPOSE: The purpose of this study is to evaluate the use of micropulse transscleral cyclophotocoagulation (MP-TSCPC), a new and increasingly popular treatment, in patients with uncontrolled glaucoma. METHODS: A retrospective chart review was performed for all patients who underwent a MP-TSCPC at the Glaucoma Associates of Texas. RESULTS: A total of 84 eyes were treated with MP-TSCPC in this study with a mean follow-up time of 4.3 months. The mean age of treated patients was 74 years and 48 (57%) were female. Preoperatively, mean intraocular pressure (IOP) was 27.7 mm Hg and mean number of ocular antihypertensive medications used was 3.3. Mean postoperative IOP at months 1, 3, 6, and 12 were lowered to 16.3 mm Hg (41.2% reduction), 14.6, 13.0, and 11.1 mm Hg, respectively. Postoperative ocular antihypertensive medication use was also lowered to 1.9, 2.0, 2.0, and 2.3 medications at months 1, 3, 6, and 12, respectively. Five patients required further laser or surgical intervention for adequate IOP control. Complications included hypotony, IOP spike, hyphema, serous choroidal detachment, persistent inflammation, and vision loss. At 3 months, inflammation was still present in 46% of eyes and vision loss of at least 1 line was present in 41% of eyes. CONCLUSIONS: MP-TSCPC is effective at lowering IOP and decreasing the need for ocular antihypertensive medications. Eyes with limited visual potential or at high risk for incisional glaucoma surgery can successfully be treated with MP-TSCPC as a reasonable and effective alternative to traditional CPC. These results present short-term data and both longer follow-up and further studies are necessary.

Endophthalmitis Associated With Glaucoma Drainage Implants.

BACKGROUND AND OBJECTIVE: To identify the clinical features, organisms, and treatment outcomes in patients with endophthalmitis associated with glaucoma drainage implants. PATIENTS AND METHODS: A retrospective noncomparative case series. RESULTS: Of the 13 patients, exposure occurred in eight eyes, including exposure of the tube in four eyes, exposure of the patch graft in three eyes, and exposure of the plate in one eye. In the remaining five eyes, either recent implant placement or conjunctival revision occurred. The most common organism was Staphylococcus epidermidis (five eyes). Intravitreal antibiotics were administered in all eyes, with the exception of one eye (primary evisceration). Removal of the implant was performed in six eyes and evisceration or enucleation was performed in three eyes. Median pre-infection visual acuity was 20/80 (range: 20/30 to hand motion). Visual acuity at last follow-up was no light perception (five eyes), light perception (two eyes), hand motion (one eye), and better than or equal to 20/200 (five eyes). CONCLUSION: Clinical features associated with endophthalmitis include implant exposure and a history of recent surgery. Staphylococcus epidermidis was the most common isolate. Although removal of the implant was performed in many patients, successful treatment was accomplished in some patients without removal. Visual outcomes were generally poor. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:563-569.].

Gonioscopy assisted transluminal trabeculotomy: an ab interno circumferential trabeculotomy for the treatment of primary congenital glaucoma and juvenile open angle glaucoma.

BACKGROUND/AIMS: To introduce a novel ab interno 360° trabeculotomy for treating primary congenital glaucoma (PCG) and juvenile open angle glaucoma (JOAG) and report preliminary results. METHODS: A retrospective chart review of patients who underwent a gonioscopy assisted transluminal trabeculotomy (GATT) procedure by four of the authors (DSG, OS, RLF and DGG) between October 2011 and October 2013. The surgery was performed in patients ≤30 years old with a dysgenic anterior segment angle and uncontrolled PCG and JOAG. RESULTS: Fourteen eyes of 10 patients underwent GATT with follow-up >12 months (12-33 months; mean 20.4). Patients ranged in age from 17 months to 30 years (mean=18.4 years), and five (50%) were female patients. No complications occurred during or following surgery except for early postoperative hyphema in five (36%) of eyes, all cleared by 1 month. The mean intraocular pressure (IOP) decreased from 27.3 to 14.8 mm Hg and the mean number of medications required decreased from 2.6 to 0.86. Five eyes had a drop in IOP ≥15 mm Hg (range 15-39). CONCLUSIONS: The preliminary results and safety for GATT, a minimally invasive conjunctival sparing circumferential trabeculotomy, are promising and at least equivalent to previous results for ab externo trabeculotomy for the treatment of PCG and JOAG. All eyes in the study were considered a clinical success.

Topical silver nanoparticles result in improved bleb function by increasing filtration and reducing fibrosis in a rabbit model of filtration surgery.

PURPOSE: To compare the effects of silver nanoparticles (AgNPs) and mitomycin C (MMC) on intraocular pressure (IOP) and external, histologic, and immunohistochemical bleb characteristics in a rabbit model of filtration surgery. METHODS: Filtration surgery with concurrent topical application of either AgNPs or MMC was performed on 14 pigmented Dutch Belted rabbits. IOP and bleb characteristics were compared on postoperative day 1 and at weeks 1 through 6. Hematoxylin and eosin staining and smooth muscle actin (SMA) immunohistochemistry were performed at postoperative week 6. RESULTS: Average IOP across all time points was reduced 5.8 and 3.8 mm Hg in AgNP- and MMC-treated eyes, respectively. At week 6, IOP was reduced 4.1 and 0.2 mm Hg in AgNP- and MMC-treated eyes, respectively. Blebs were smaller, thicker, and less ischemic in AgNP-treated eyes. AgNP-treated eyes showed less fibrosis and more stromal edema, suggesting increased filtration, and also had fewer SMA-positive myofibroblasts, suggesting reduced bleb contraction. AgNP-treated eyes showed more lymphocytes than MMC-treated eyes. There were few complications in both groups. CONCLUSIONS: In a rabbit model of filtration surgery, AgNPs are a reasonable alternative to MMC as adjunctive therapy. Compared to MMC, AgNPs result in an improved and sustained reduction of IOP and promote blebs with decreased fibrosis and ischemia as well as increased filtration despite a smaller overall size. This combination may offer an opportunity to promote long-term surgical IOP reduction with an improved complication profile.

Ten rural women living with fibromyalgia tell it like it is.

The purpose of this qualitative study was to gain an understanding of the personal experiences of 10 rural women dealing with fibromyalgia based on the theoretical frameworks of adaptation to chronic illness and social support. The data were gathered from a nursing intervention that provided computer-based peer support and encouragement. The women described themes of pain, fatigue, depression, and sleep disturbances; expressed views on the experience of rural isolation; and shared positive philosophies of dealing with this disease. With this understanding, professionals and significant others can compassionately respond to the needs of sufferers of fibromyalgia.