Mina B. Pantcheva

Activation of caspase 9 in a rat model of experimental glaucoma

Purpose. We investigated retinal ganglion cell (RGC) death and activation of caspase 9 in rats with experimental glaucoma. Methods. Elevated intraocular pressure (IOP) was induced in rats using the Morrison model. Surviving backlabeled RGC were counted and TUNEL staining detected apoptosis. Procaspase 9 expression and activated caspase 9 were studied by immunoblot and immunohistochemistry. Results. IOP correlated with surviving RGC. TUNELpositive RGC were observed in animals with elevated IOP. Procaspase 9 levels increased with IOP intensity. Cleaved caspase 9 was detected by immunoblot only in rats with peak IOP above 35mmHg for =6 days. Cleaved caspase 9 staining was seen only in the ganglion cell layer of retinas from rats with peak IOP =32mmHg. Conclusions. RGC loss is correlated with IOP in experimental glaucoma. These results support activation of caspase 9, the intrinsic caspase cascade, in RGC death in experimental glaucoma.

Comparison of acute structural and histopathological changes in human autopsy eyes after endoscopic cyclophotocoagulation and trans-scleral cyclophotocoagulation

Aim: To study the histological effects of trans-scleral cyclophotocoagulation (TCP) and endoscopic cyclophotocoagulation (ECP) on the ciliary body and other structures collected at autopsy and to compare with untreated controls. Materials and methods: TCP and ECP were performed on human eyes at autopsy. Detailed histological evaluations were perfomed using light microscopy and scanning electron microscopy on treated eyes and compared with untreated controls. Results: Histological changes were observed with both light microscopy and scanning electron microscopy for all treated tissues. Tissue treated with TCP showed pronounced tissue disruption of the ciliary body muscle and stroma, ciliary processes, and both pigmented and non-pigmented ciliary epithelium. ECP-treated tissue exhibited pronounced contraction of the ciliary processes with disruption of the ciliary body epithelium, sparing of the ciliary body muscle and less architectural disorganisation. The sclera was not affected by either laser treatment. Conclusions: ECP treatment caused less damage to the ciliary body compared with TCP when evaluated by light microscopy and scanning electron microscopy. Compared with TCP, ECP seems to be a more selective form of cyclophotocoagulation, resulting in less tissue disruption while achieving the goal of destroying ciliary body epithelium.

Tafluprost: a novel prostaglandin analog for treatment of glaucoma.

ObjectiveThe objective of this review is to evaluate the safety and efficacy of tafluprost, a fluoroprostaglandin receptor analog, for reduction of intraocular pressure in open angle glaucoma and ocular hypertension.MethodsA search of published literature was performed on the PubMed database using the search term “tafluprost.” The literature search identified 48 publications, including clinical and preclinical studies, from 2003 to 2011. From these ressults, articles available in the English language and in full text were selected and systematically reviewed by the authors.ResultsRecent studies have shown that tafluprost is an effective IOP-lowering medication. Evidence based medicine also reveals that tafluprost is safe and well-tolerated. Preservative-free tafluprost is as potent as the preserved formulation, but with fewer and milder ocular surface side effects.ConclusionSince its introduction in 2008, initial studies have demonstrated that preserved and preservative-free tafluprost formulations have proven efficacy and safety in the treatment of glaucoma and ocular hypertension. Larger studies with longer follow-up are needed to assess long-term safety, efficacy, and tolerability compared with other prostaglandin analogs used for treating glaucoma.

Ab interno trabeculectomy.

Anterior chamber drainage angle surgery, namely trabeculotomy and goniotomy, has been commonly utilized in children for many years. Its’ reported success has ranged between 68% and 100% in infants and young children with congenital glaucoma. However, the long-term success of these procedures has been limited in adults presumably due to the formation of anterior synechiae (AS) in the postoperative phase. Recently, ab interno trabeculectomy with the Trabectome™ has emerged as a novel surgical approach to effectively and selectively remove and ablate the trabecular meshwork and the inner wall of the Schlemm’s canal in an attempt to avoid AS formation or other forms of wound healing with resultant closure of the cleft. This procedure seems to have an appealing safety profile with respect to early hypotony or infection if compared to trabeculectomy or glaucoma drainage device implantation. This might be advantageous in some of the impoverish regions of the Middle East and Africa where patients experience difficulties keeping up with their postoperative visits. It is important to note that no randomized trial comparing the Trabectome to other glaucoma procedures appears to have been published to date. Trabectome surgery is not a panacea, however, and it is associated with early postoperative intraocular pressure spikes that may require additional glaucoma surgery as well as a high incidence of hyphema. Reported results show that postoperative intraocular pressure (IOP) remains, at best, in the mid-teen range making it undesirable in patients with low-target IOP goals. A major advantage of Trabectome surgery is that it does not preclude further glaucoma surgery involving the conjunctiva, such as a trabeculectomy or drainage device implantation. As prospective randomized long-term clinical data become available, we will be better positioned to elucidate the exact role of this technique in the glaucoma surgical armamentarium.

αB-crystallin is essential for the TGF-β2-mediated epithelial to mesenchymal transition of lens epithelial cells

Transforming growth factor (TGF)-β2-mediated pathways play a major role in the epithelial to mesenchymal transition (EMT) of lens epithelial cells (LECs) during secondary cataract formation, which is also known as posterior capsule opacification (PCO). Although αB-crystallin is a major protein in LEC, its role in the EMT remains unknown. In a human LEC line (FHL124), TGF-β2 treatment resulted in changes in the EMT-associated proteins at the mRNA and protein levels. This was associated with nuclear localization of αB-crystallin, phosphorylated Smad2 (pSmad2) (S245/250/255), pSmad3 (S423/425), Smad4 and Snail and the binding of αB-crystallin to these transcription factors, all of which were reduced by the down-regulation of αB-crystallin. Expression of the functionally defective R120G mutant of αB-crystallin reduced TGF-β2-induced EMT in LECs of αB-crystallin knockout (KO) mice. Treatment of bovine lens epithelial explants and mouse LEC with TGF-β2 resulted in changes in the EMT-associated proteins at the mRNA and protein levels. This was accompanied by increase in phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) (T202/Y204), p38 MAPK (T180/Y182), protein kinase B (Akt) (S473) and Smad2 when compared with untreated cells. These changes were significantly reduced in αB-crystallin depleted or knocked out LEC. The removal of the fibre cell mass from the lens of wild-type (WT) mice resulted in the up-regulation of EMT-associated genes in the capsule-adherent epithelial cells, which was reduced in the αB-crystallin KO mice. Together, our data show that αB-crystallin plays a central role in the TGF-β2-induced EMT of LEC. αB-Crystallin could be targeted to prevent PCO and pathological fibrosis in other tissues.

Collagen and collagen-chondroitin sulfate scaffolds with uniaxially aligned pores for the biomimetic, three dimensional culture of trabecular meshwork cells.

Glaucoma is a disease in which damage to the optic nerve leads to progressive, irreversible vision loss. The intraocular pressure (IOP) is the only modifiable risk factor for glaucoma and its lowering is considered a useful strategy for preventing or slowing down the progression of glaucomatous neuropathy. Elevated intraocular pressure associated with glaucoma is due to increased aqueous humor outflow resistance, primarily through the trabecular meshwork (TM) of the eye. Current in vitro models of the trabecular meshwork are oversimplified and do not capture the organized and complex three‐dimensional nature of this tissue that consists primarily of collagen and glycoasaminoglycans. In this work, collagen and collagen‐chondroitin sulfate (CS) scaffolds were fabricated via unidirectional freezing and lyophilization to induce the formation of aligned pores. Scaffolds were characterized by scanning electron microscopy, dynamic mechanical analysis, and a chondroitin sulfate quantification assay. Scaffold characterization confirmed the formation of aligned pores, and also that the CS was leaching out of the scaffolds over time. Primary porcine trabecular meshwork (TM) cells were seeded onto the surface of scaffolds and their gene expression, proliferation, viability, migration into the scaffolds, and morphology were examined. The TM cells were viable and proliferated 2 weeks after seeding. The cells migrated down into the internal scaffold structure and their morphology reflected the topography and alignment of the scaffold structure. This work is a promising step toward the development of a three dimensional in vitro model of the TM that can be used for testing of glaucoma pharmacological agents in future experimentation and to better our understanding of the trabecular meshwork and its complex physiology. Biotechnol. Bioeng. 2017;114: 915–923.

Outcomes after combined phacoemulsification and trabecular microbypass stent implantation in controlled open-angle glaucoma

Purpose To study the effect of combined phacoemulsification cataract surgery and iStent (trabecular microbypass stent) implantation on intraocular pressure (IOP) and medication use in open‐angle glaucoma (OAG) patients with a low mean preoperative IOP. Setting University of Colorado Health Eye Center, Aurora, Colorado, USA. Design Retrospective case series. Methods Treatment outcomes analyzed included IOP, medication use, and corrected distance visual acuity (CDVA). Treatment success was defined as a 20% or more IOP reduction or discontinuation of at least 1 medication. Results Sixty‐four eyes of 45 patients were included in the analysis. At 1 year, the mean IOP was significantly reduced from 14.7 ± 3.2 mm Hg (SD) to 13.2 ± 2.8 mm Hg (P < .01) and the mean medication use decreased from 1.81 ± 1.13 to 1.41 ± 1.48 (P = .0001). The estimated IOP reduction at 1, 3, 6, and 12 months was 3.5% (P = .23), 7.9% (P = .04), 9.7% (P = .01), and 12.2% (P = .002), respectively. Treatment success at 1 year was achieved in 76.1% of patients, and 41% of patients were medication free at 1 year. The CDVA was significantly improved from 0.4 ± 0.38 logMAR at baseline to 0.17 ± 0.35 at 1 year (P < .0001). Conclusions Combined cataract surgery and trabecular microbypass stent implantation was statistically effective in reducing IOP and/or medication burden in OAG patients with a low preoperative IOP. During the informed surgical consent process, the physician and patient should consider the clinical benefit of modest IOP lowering and/or a decrease in medication use. Financial Disclosure Drs. Seibold, SooHoo, Pantcheva, and Kahook have received grant support from Glaukos Corp. No other author has a financial or proprietary interest in any material or method mentioned.

Efficacy of combined cataract extraction and endoscopic cyclophotocoagulation for the reduction of intraocular pressure and medication burden

AIM To report on the efficacy of combined endoscopic cyclophotocoagulation (ECP) and phacoemulsification cataract extraction (PCE) with intraocular lens placement for reduction of intraocular pressure (IOP) and medication burden in glaucoma. METHODS A retrospective case review of 91 eyes (73 patients) with glaucoma and cataract that underwent combined PCE/ECP surgery was performed. Baseline demographic and ocular characteristics were recorded, as well as intraocular pressure, number of glaucoma medications, and visual acuity postoperatively with 12-month follow-up. Treatment failure was defined as less than 20% reduction in IOP from baseline on two consecutive visits (at 1, 3, 6, or 12mo postoperatively), IOP ≥21 mm Hg or ≤5 mm Hg on two consecutive visits, or additional glaucoma surgery performed within 12mo after PCE/ECP. RESULTS Overall, mean medicated IOP was reduced from 16.65 mm Hg at baseline to 13.38 mm Hg at 12mo (P<0.0001). Mean number of glaucoma medications was reduced from 1.88 medications at baseline to 1.48 medications at 12mo (P=0.0003). At 3mo postoperatively, the success rate was 73.6% (95%CI: 63.3, 81.5), 57.1% at 6mo (95% CI: 46.3, 66.6), and 49.7% at 12mo (95%CI: 38.9, 59.6). Patient demographic characteristics were not associated with treatment success. The only ocular characteristic associated with treatment success was a higher baseline IOP. CONCLUSION Combined PCE/ECP surgery is an effective surgical option for the reduction of IOP and medication burden in glaucoma patients. Patients with higher baseline IOP levels are most likely to benefit from this procedure.

Aflibercept for the treatment of neovascular glaucoma

Neovascular glaucoma (NVG) is a potentially blinding disease associated with ocular ischaemia. Use of an anti‐vascular endothelial growth factor agent has been reported as a treatment option for NVG. The purpose of this study was to investigate initial results regarding the treatment of NVG with intravitreal aflibercept.

Delayed presentation of retained acrylic intraocular lens (IOL) fragment after uncomplicated cataract surgery

Purpose To report a case of delayed presentation of a severed acrylic single-piece intraocular lens (IOL) haptic fragment causing corneal edema after uneventful phacoemulsification surgery. Observations An 85-year-old male presented with inferior corneal decompensation six months after a reportedly uneventful phacoemulsification in his left eye. A distal haptic fragment of an acrylic single-piece posterior chamber intraocular lens was found in the inferior anterior chamber angle. Intraoperative examination revealed that the dislocated fragment originated from the temporal haptic, the remainder of which was adherent to the anterior surface of the capsular bag. The clipped edge of the haptic fragment showed a clean, flat surface, suggesting it was severed by a sharp object. The findings were considered consistent with cutting of the fragment during implantation presumably from improper lens loading, improper implantation technique, or defective implantation devices. Conclusions and Importance This is the first case report of a foldable acrylic intraocular lens severed during routine uncomplicated cataract surgery that was not noted at the time of the surgery or in the immediate postoperative period. Delayed presentation of severed IOL fragments should be considered in cases of late onset corneal edema post-operatively, when other causes have been ruled out. Careful implantation technique and thorough examination of the intraocular lens after implantation to assess for lens damage intraoperatively is essential to avoid such rare complications.