Effect of peripheral iridectomy on VEGF-A and TGF-β levels in rabbit aqueous humour

Background Peripheral iridectomy (PI), routinely performed during glaucoma filtration surgery, may contribute to scarring. This study aims to determine whether PI alters the concentrations of VEGF-A and TGF-β isoforms in the rabbit aqueous humour. Methods Anterior chamber paracentesis (ACP) was performed in both eyes of six New Zealand white rabbits, with additional surgical PI performed in the right eyes. Eyes were examined on postoperative days (PODs) 1, 7, 30 and 60 by means of the tonopen, slit-lamp biomicroscopy, and bead-based cytokine assays for TGF-β and VEGF-A concentrations in the aqueous humor. Results ACP caused a significant reduction in intraocular pressure (IOP) from mean preoperative 11.47 ± 1.01 mmHg to 5.67 ± 1.63 mmHg on POD 1 while PI did not cause further IOP reduction. Limbal conjunctival vasculature appeared slightly increased on POD 1 in both ACP and PI eyes with PI also causing mild bleeding from damaged iris vessels. Two PI eyes developed fibrinous anterior chamber reaction and/ or peripheral anterior synechiae. Aqueous VEGF-A levels were not significantly different between eyes treated with ACP and PI. Aqueous TGF-β concentrations distributed in the ratio of 4:800:1 for TGF-β1:TGF-β2:TGF-β3 respectively. While aqueous TGF-β2 was not significantly induced by either procedure at any time point, TGF-β1 and TGF-β3 were significantly induced above baseline levels by PI on POD 1. Conclusion PI increases the risk of inflammation. The combined induction of aqueous TGF-β1 and TGF-β3 by PI in glaucoma surgery may impact surgery success in glaucoma subtypes sensitive to these isoforms.

Effect of SMILE-derived decellularized lenticules as an adhesion barrier in a rabbit model of glaucoma filtration surgery

Background To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticules on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery. Methods Trabeculectomy was performed on both eyes of New Zealand rabbits. A decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (the decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (the control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery. Results Decellularized lenticules significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. The histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. Conclusions Decellularized lenticules can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and they may represent a novel antifibrotic agent for trabeculectomy.

Ocular Manifestations of the Sturge–Weber Syndrome

Sturge–Weber syndrome (SWS) or encephalotrigeminal angiomatosis is a non-inherited congenital disorder characterized by neurologic, skin, and ocular abnormalities. A somatic activating mutation (R183Q) in the GNAQ gene during early embryogenesis has been recently recognized as the etiology of vascular abnormalities in SWS. Approximately, half of the patients with SWS manifest ocular involvement including glaucoma as the most common ocular abnormality followed by choroidal hemangioma (CH). The underlying pathophysiology of glaucoma in SWS has not been completely understood yet. Early onset glaucoma comprising 60% of SWS glaucoma have lower success rates after medical and surgical treatments compared with primary congenital glaucoma. Primary angle surgery is associated with modest success in the early onset SWS glaucoma while the success rate significantly decreases in late onset glaucoma. Filtration surgery is associated with a higher risk of intraoperative and postoperative choroidal effusion and suprachoroidal hemorrhage. CH is reported in 40–50% of SWS patients. The goal of treatment in patients with CH is to induce involution of the hemangioma, with reduction of subretinal and intraretinal fluid and minimal damage to the neurosensory retina. The decision for treating diffuse CHs highly depends on the patient’s visual acuity, the need for glaucoma surgery, the presence of subretinal fluid (SRF), its chronicity, and the potential for visual recovery.

The Effect of a Triple Combination of Bevacizumab, Sodium Hyaluronate and a Collagen Matrix Implant in a Trabeculectomy Animal Model

Currently available anti-scarring treatments for glaucoma filtration surgery (GFS) have potentially blinding complications, so there is a need for alternative and safer agents. The effects of the intrableb administration of a new combination of the anti-VEGF bevacizumab, sodium hyaluronate and a collagen matrix implant were investigated in a rabbit model of GFS, with the purpose of modulating inflammation, angiogenesis, fibroblast migration and fibrogenesis in the wound healing process. A comparative-effectiveness study was performed with twenty-four rabbits, randomly assigned to the following treatments: (a) biodegradable collagen matrix implant (Olo), (b) bevacizumab-loaded collagen matrix implant (Olo-BVZ), (c) bevacizumab-loaded collagen matrix implant combined with sodium hyaluronate (Olo-BVZ-H5) and (d) sham-operated animals (control). Rabbits underwent a conventional trabeculectomy and were studied over 30 days in terms of intraocular pressure and bleb characterization (height, area and vascularity in central, peripheral and non-bleb zones). Histologic differences among groups were further evaluated at day 30 (inflammation, total cellularity and degree of fibrosis in the area of surgery). Local delivery of bevacizumab (Olo-BVZ and Olo-BVZ-H5) increased the survival of the filtering bleb by 21% and 31%, respectively, and generated a significant decrease in inflammation and cell infiltration histologically 30 days after surgery, without exhibiting any local toxic effects. Olo-BVZ-H5 showed less lymphocyte infiltration and inflammation than the rest of the treatments. Intraoperative intrableb implantation of bevacizumab, sodium hyaluronate and a collagen matrix may provide an improved trabeculectomy outcome in this model of intense wound healing. This study showed an effective procedure with few surgical complications and a novel combination of active compounds that offer new possibilities to improve the efficacy of filtration surgery.

Comparison of phaco time parameters in eyes with and without glaucoma filtration surgery due to pseudoexfoliation glaucoma

Purpose: To compare the phaco time parameters including ultrasound time (UST), effective phaco time (EPT), and average phaco power (APP) in eyes with pseudoexfoliation glaucoma (PEG) and had or had not glaucoma filtration surgery. Methods: In this retrospective comparative study, Group 1 was constructed with 84 PEG patients who had not operated previously, and Group 2 was constructed with 49 PEG patients who had glaucoma filtration surgery. The mean values of UST, EPT, and APP were compared. The preoperative clinical characteristics and surgical manipulations were also compared. Results: The mean ages and male-to-female ratios of the groups were similar ( p > 0.05, for both). There was no difference in the preoperative clinical characteristics, including biometric values between the groups ( p > 0.05, for all). Some surgical manipulations, including pupillary stretching ( p = 0.004), pupillary membrane peeling ( p = 0.021), iris hook using ( p = 0.041), and capsular tension ring implantation ( p = 0.041), were significantly performed more commonly in Group 2. Although the mean UST and EPT values were similar ( p > 0.05, for both), the mean APP value was significantly lower in Group 2 ( p = 0.011). Conclusion: The lower APP parameter was observed in PEG patients having had glaucoma filtration surgery. Needing more surgical manipulation to overcome poor pupillary dilation and weak zonular instability can be a reason for this result.

Effects Of SMILE-Derived Decellularized Lenticule As An Adhesion Barrier In A Rabbit Model of Glaucoma Filtration Surgery

Background: To investigate the effects of small incision lenticule extraction (SMILE)-derived decellularized lenticule on intraocular pressure (IOP) and conjunctival scarring in a rabbit model of glaucoma filtration surgery. Methods: Trabeculectomy was performed on both eyes of New Zealand rabbits. Decellularized lenticule was placed in the subconjunctival space in one eye of the rabbits (decellularized lenticule group), and no adjunctive treatment was performed in the fellow eye (control group). The filtering bleb features and IOP were evaluated 0, 3, 7, 14, 21, and 28 days after surgery, and histopathologic examination was performed 28 days after surgery. Results: Decellularized lenticule significantly increased bleb survival and decreased IOP postoperatively in the rabbit model with no adverse side effects. Histopathologic results showed a larger subconjunctival space and less subconjunctival fibrosis in the decellularized lenticule group. Conclusions: Decellularized lenticule can prevent postoperative conjunctiva-sclera adhesion and fibrosis, and it may represent a novel antifibrotic agent for trabeculectomy.

Surgical treatment of neovascular glaucoma with Ex-PRESS glaucoma shunt

Purpose To compare the efficacy and safety profile of deep sclerectomy combined with Ex-PRESS shunt versus Ex-PRESS shunt surgery in eyes with neovascular glaucoma. Methods Twenty eyes with neovascular glaucoma secondery to proliferative diabetic retinopathy were included in our study. Panretinal photocoagulation and intravitreal bevacizumab injection were applied to these eyes. Despite full antiglaucomatous treatment and iris, angle neovascularization regression whose intraocular pressures were 21mm Hg and above were taken to surgery. Patients were randomly divided into two groups. Group A (10 patients) underwent deep sclerectomy combined with insertion of Ex-PRESS drainage device, group B (10 patients) underwent only Ex-PRESS glaucoma filtration surgery. Primary outcome measures were the intraocular pressure (IOP) and the number of antiglaucomatous medications at the first year follow-up visit. Results There was no difference in IOP between the groups at the first 2 month postoperatively (p>0.05). In the first 2 months, there was no need for antiglaucomatous medication in either group. In the third month, an antiglaucomatous drug was administered to 2 patients in group A and to 4 patients in group B. IOP values were lower in group A than group B at the third and sixth months (p<0.05). At the end of the first year, ≤18 mm Hg IOP rate was found 80% in group A and 60 in group B without medication. Conclusion Ex-PRESS shunt surgey demonstrated to be an effective treatment in eyes with neovascular glaucoma at the first year follow-up period. Ex-PRESS drainage device implantation with deep sclerectomy increased surgical success.

Novel PEGylated Lipid Nanoparticles Have a High Encapsulation Efficiency and Effectively Deliver MRTF-B siRNA in Conjunctival Fibroblasts

The master regulator of the fibrosis cascade is the myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway, making it a key target for anti-fibrotic therapeutics. In the past, inhibitors and small interfering RNAs (siRNAs) targeting the MRTF-B gene have been deployed to counter fibrosis in the eye, with the latter showing promising results. However, the biggest challenge in implementing siRNA therapeutics is the method of delivery. In this study, we utilised the novel, pH-sensitive, cationic lipid CL4H6, which has previously demonstrated potent targeting of hepatocytes and endosomal escape, to safely and efficiently deliver an MRTF-B siRNA into human conjunctival fibroblasts. We prepared two lipid nanoparticle (LNP) formulations, incorporating targeting cleavable peptide cY in one of them, and measured their physicochemical properties and silencing effect in human conjunctival fibroblasts. Both proved to be non-cytotoxic at a concentration of 50 nM and effectively silenced the MRTF-B gene in vitro, with the targeting cleavable peptide not affecting the silencing efficiency [LNP with cY: 62.1% and 81.5% versus LNP without cY: 77.7% and 80.2%, at siRNA concentrations of 50 nM (p = 0.06) and 100 nM (p = 0.09), respectively]. On the other hand, the addition of the targeting cleavable peptide significantly increased the encapsulation efficiency of the LNPs from 92.5% to 99.3% (p = 0.0005). In a 3D fibroblast-populated collagen matrix model, both LNP formulations significantly decreased fibroblast contraction after a single transfection. We conclude that the novel PEGylated CL4H6-MRTF-B siRNA-loaded LNPs represent a promising therapeutic approach to prevent conjunctival fibrosis after glaucoma filtration surgery.