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Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3',4'-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery ( n = 5) or a single intraoperative treatment of MMC ( n = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon's layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS.

Purpose: To assess the risk factors for suprachoroidal hemorrhage (SCH) following glaucoma surgery in pediatric patients at a tertiary eye center., Methods: The medical records of 326 patients (326 eyes) who underwent glaucoma surgery between January 2014, and September 2017 were reviewed retrospectively. Seventeen cases with SCH were compared with 309 controls who underwent uneventful glaucoma surgery during the same period. We documented age, sex, baseline intraocular pressure, glaucoma diagnosis, previous surgery, preoperative axial length, pachymetry, lens status and type of glaucoma surgery performed (whether combined with cataract or other glaucoma procedure or being standalone)., Results: Of the 17 cases of SCH, only a single case occurred intraoperatively; the remainder occurred in the early postoperative period. The most frequent diagnosis was primary congenital glaucoma (PCG), accounting for 10 patients (59%) in cases and 247 (80%) in controls, followed by glaucoma associated with nonacquired ocular anomalies, which accounted for 3 cases (18%) and 22 controls (7%). Aphakia and combined surgeries (in the univariate analysis) were found to be possible risk factors for the development of SCH, with none achieving significance in the multivariable analysis., Conclusions: In our study cohort, combined surgeries as well aphakia were possible risk factors for SCH., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: The success of XEN Gel Stent (XEN) and Preserflo MicroShunt (Preserflo) implantation depends mainly on the development of bleb fibrosis. This study aimed to describe the histological findings of bleb fibrosis after XEN and Preserflo surgery., Methods: This retrospective study included patients with different types of glaucoma who underwent revision surgery after XEN or Preserflo implantation. The available clinical information and histological samples of removed fibrotic tissue were analyzed., Results: Thirty-six patients were included. Revision surgery was performed at a median of 195 (range = 31-1264) days after primary surgery. The mean intraocular pressure changed from 29.1 (± 10.3) mmHg at baseline to 18.3 (± 8.7) mmHg (- 37%; p < 0.0001) and 16.2 (± 4.2) mmHg (- 45%; p < 0.0001) after 6 and 12 months, respectively. Histological analysis revealed an increase in activated fibroblasts and macrophages in all specimens and a parallel orientation of fibroblasts in a minor part of the probe in 60% of the specimens. No pronounced inflammatory reaction in the form of lymphocytic or granulocytic infiltration was observed. The comparison of specimens from uveitic glaucoma and primary open-angle glaucoma patients revealed no significant differences., Conclusions: The histological analysis of fibrotic blebs from the XEN and Preserflo implants did not show any pronounced immune or foreign-body reaction and revealed a similar histological pattern of failed blebs after trabeculectomy., (© 2024. The Author(s).)

Prcis: Bleb revision procedures for hypotony maculopathy (HM) following glaucoma filtering surgery show promising outcomes, including notable improvements in visual acuity and IOP., Purpose: This study assesses morphologic characteristics using SD-OCT in patients with HM following glaucoma filtering surgery and evaluates the results of its treatment., Materials and Methods: A retrospective analysis of all HM patients between January 2019 and March 2023. Inclusion criteria consisted of both preoperative and postrevision SD-OCT images of the macula and the presence of HM as observed on OCT images preoperatively. HM was graded according to its appearance in OCT both prerevision and postrevision surgery. Changes in visual acuity and IOP were assessed., Results: A total of 45 eyes of 45 patients were included. In all, 21 eyes had HM limited to retinal pigment epithelium (RPE), 18 eyes had involvement of RPE and photoreceptor layers, and 6 eyes had additional intraretinal or subretinal edema. After revision surgery with IOP elevation, 64% of eyes had complete HM regression with no HM signs in OCT imaging. Overall, 80% of patients achieved at least 1 grade improvement in HM. Preoperative visual acuity increased from 0.7±0.4 (logMAR) to 0.4±0.4 at 2 weeks postoperatively, over the course of an increase of IOP from 3.5±1.8 to 17.1±10.6 mm Hg at day 1. Eyes with complete HM regression had higher IOP at day 1 compared with those without improvement ( P =0.04). The median time between HM onset and revision was 10.0 days for those with complete regression and 27 days for those without improvement ( P =0.04)., Conclusions: Bleb revision procedures for HM following glaucoma filtering surgery show promising outcomes, including notable improvements in visual acuity and IOP. The timing of revision surgery appears to influence the outcome. In our study, earlier intervention was associated with better results. Even delayed surgeries can lead to an improvement, although complete morphologic restoration may not be achieved in advanced grades of HM., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Trabeculectomy and non-penetrating trabecular surgery are common operations for glaucoma. This meta-analysis aims to compare the effect of trabeculectomy and non-penetrating trabecular surgery in postoperative astigmatism of patients with glaucoma., Methods: A systematic literature search was performed for studies comparing trabeculectomy and non-penetrating trabecular surgery in patients with glaucoma. The time frame for the search was from the time of construction to April 2024. There were no restrictions regarding study type or type of glaucoma. The endpoint was the surgically induced astigmatism assessed 6 months after operation. We conducted this meta-analysis following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)., Results: Five eligible studies were included in this meta-analysis and presented data for 359 eyes with various types of glaucoma at different stages. The results revealed an increase in astigmatism in patients with glaucoma after trabeculectomy and non-penetrating trabecular surgery. Trabeculectomy had a higher incidence of astigmatism than in the non-penetrating trabecular surgery group at or around 6 months postoperatively, and the difference was statistically significant. (SMD = 0.40, 95% CI = 0.19 to 0.61, P = 0.02)., Conclusion: Our results demonstrated that both trabeculectomy and non-penetrating trabecular surgery could increase astigmatism until 6 months after operation. Moreover, non-penetrating trabecular surgery group seems to have less influence on astigmatism., Trial Registration Number: CRD42024517708., (© 2024. The Author(s).)

Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon's ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon's ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon's ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon's ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon's ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon's ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Roodnat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-β1 in rat Tenon's capsule fibroblasts., Methods: Cultured rat Tenon's capsule fibroblasts were treated with TGF-β1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-β1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms., Results: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-β1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1β, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis., Conclusions: MiR-146a effectively reduced TGF-β1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS., (© 2024. The Author(s).)

Aims: To investigate the rate and risk factors of undergoing glaucoma filtration surgery (GFS) in patients with newly diagnosed open-angle glaucoma (OAG)., Methods: This is a population-based historic cohort study, consisting of 9420 patients older than 45 years diagnosed with OAG during 1997-2010. Follow-up spanned from 1997 to 2017. We obtained data for trabeculectomy (TRE), deep sclerectomy (DS), and glaucoma drainage implant (GDI) surgeries from national administrative healthcare registers by hospital billing data. We plotted the cumulative incidence of GFS and carried out a multivariate Poisson regression analysis adjusted for age, sex, hospital district, systemic comorbidities, and the number of IOP-lowering drugs. We reported incidence rate ratios (IRR) with 95% confidence intervals (CI) for GFS after the onset of OAG., Results: The cumulative incidence of GFS at 5 years from OAG onset was 3.1% and at 10 years 5.4%. Age over 80 years at baseline was associated with lower GFS incidence (IRR 0.51, CI 0.31-0.84). The number of IOP-lowering drugs in the first 2 years of treatment correlated with the risk of GFS increasing from (IRR 3.23, CI 2.32-4.50) for two drugs, (IRR 7.44, CI 5.28-10.47) for three and to (IRR 14.95, CI 10.38-21.52) for four drugs., Conclusion: This study characterized the treatment path of OAG from diagnosis to surgical intervention refining the role of GFS among glaucoma therapies., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To investigate the function and mechanism of tumor protein p53 in pathological scarring after glaucoma filtration surgery (GFS) using human Tenon's fibroblasts (HTFs) and a rabbit GFS model., Methods: The expression of p53 in bleb scarring after GFS and transforming growth factor-β (TGF-β)-induced HTFs (myofibroblasts [MFs]) was examined by western blot and immunochemical analysis. The interaction between p53 and specificity protein 1 (Sp1) was investigated by immunoprecipitation. The role of p53 and Sp1 in the accumulation of collagen type I alpha 1 chain (COL1A1) and the migration of MFs was evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound healing, and Transwell assay. The regulatory mechanisms among p53/Sp1 and miR-29b were detected via qRT-PCR, western blot, luciferase reporter assay, and chromatin immunoprecipitation assay. The therapeutic effect of mithramycin A, a specific inhibitor of Sp1, on scarring formation was evaluated in a rabbit GFS model., Results: p53 was upregulated in bleb scar tissue and MFs. p53 and Sp1 form a transcription factor complex that induces the accumulation of COL1A1 and promotes the migration of MFs through downregulation of miR-29b, a known suppressor of COL1A1. The p53/Sp1 axis inhibits miR-29b expression by the direct binding promoter of the miR-29b gene. Mithramycin A treatment attenuated bleb scar formation in vivo., Conclusions: The p53/Sp1/miR-29b signaling pathway plays a critical role in bleb scar formation after GFS. This pathway could be targeted for therapeutic intervention of pathological scarring after GFS., Translational Relevance: Our research indicates that inhibition of p53/Sp1/miR-29b is a promising therapeutic strategy for preventing post-GFS pathological scarring.

Rationale: Angle-closure glaucoma secondary to iridocorneal endothelial syndrome (ICE) is challenging to treat, especially in patients who have already undergone multiple surgical procedures. Long-term success is difficult to achieve with traditional filtration surgery again. This case report describes a novel nonbleb-dependent surgery for managing such a young patient., Patient Concerns: A 30-year-old male with glaucoma secondary to ICE was referred to West China Hospital, Sichuan University for uncontrolled intraocular pressure following multiple failed filtering surgeries under maximum topical antiglaucoma medications in his right eye., Diagnoses: The patient was diagnosed with angle-closure glaucoma secondary to ICE in the right eye based on a series of ophthalmic examinations., Interventions: Penetrating canaloplasty was performed to manage glaucoma secondary to ICE in the right eye., Outcomes: The patient's visual acuity improved, the intraocular pressure was reduced to 11 to 15 mm Hg through 30 months of follow-up, and no antiglaucoma medication or additional surgical procedures were needed., Lessons: Penetrating canaloplasty could be considered as an option for the treatment of refractory angle-closure glaucoma secondary to ICE with extensive angle adhesion., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: While ptosis is a well-known consequence of glaucoma surgery, some isolated case reports point to the possibility of upper eyelid retraction occurring after glaucoma surgery. This study aims to analyze the occurrence of ptosis and eyelid retraction after glaucoma surgery and to evaluate factors contributing to these palpebral fissure changes., Methods: Cross-sectional study including 100 eyes of 100 patients that had undergone unilateral glaucoma surgery. Upper eyelid height in the operated eye was measured by digital photography and compared with the fellow, non-operated eye. The main outcome was to determine if ptosis or retraction occurred in the operated eye in comparison with the fellow eye. The secondary outcome was to determine if any variable was associated with ptosis or retraction. A clinically significant difference (either toward ptosis or retraction) was defined as a difference ≥1 mm between both eyes., Results: Of 100 eyes included 81 (81%) showed no change in eyelid height (-0.133 mm ± 0.496), 11 (11%) showed ptosis (-1.348 mm ± 0.387) and 8 eyes (8%) showed retraction (1.705 ± 0.634). A statistically significant relation was found between ptosis and pseudoexfoliation glaucoma (p = 0.003). A trend toward lower postoperative IOP and higher conjunctival blebs was found in eyes with postoperative eyelid retraction., Conclusions: Eyelid retraction was present in 8% of patients and ptosis in 11%. Patients with eyelid retraction showed around a 3 mmHg lower postoperative IOP than eyes without retraction . The presence of pseudoexfoliation may be a risk factor for this complication. A prospective study with a large number of patients would be required to confirm these results.

Purpose: To report the clinical profile and effectiveness of oral doxycycline as a non-invasive treatment for glaucoma filtering surgery complications., Method: Prospective case series., Results: Doxycycline is widely used in treating corneal melts, ocular surface diseases, meibomian gland disease, recurrent epithelial cell erosion, rosacea, and keratitis sicca. This prospective case series highlights the successful treatment of five patients with leaking blebs and conjunctiva erosion from glaucoma filtration surgery with the use of oral doxycycline. There was no adverse event reported in our cases., Conclusions: This study suggests that oral doxycycline may be a feasible non-surgical treatment modality due to its ability to inhibit collagenolysis, restore the Meibomian gland function, thereby stopping breakdown and promote conjunctival tissue healing.

Purpose: To conduct a narrative review of research articles on the potential anti- and pro-fibrotic mechanisms of noncoding RNAs following glaucoma filtration surgery., Methods: Keyword searches of PubMed, and Medline databases were conducted for articles discussing post-glaucoma filtration surgeries and noncoding RNA. Additional manual searches of reference lists of primary articles were performed., Results: Fifteen primary research articles were identified. Four of the included papers used microarrays and qRT-PCR to identify up- or down-regulated microRNA (miRNA, miR) profiles and direct further study, with the remainder focusing on miRNAs or long noncoding RNAs (lncRNAs) based on previous work in other organs or disease processes. The results of the reviewed papers identified miR-26a, -29b, -139, -155, and -200a as having anti-fibrotic effects. In contrast, miRs-200b and -216b may play pro-fibrotic roles in filtration surgery fibrosis. lncRNAs including H19, NR003923, and 00028 have demonstrated pro-fibrotic effects., Conclusions: Noncoding RNAs including miRNAs and lncRNAs are emerging and promising therapeutic targets in the prevention of post-glaucoma filtration surgery fibrosis.

Despite the well-known effectiveness of pharmacological glaucoma therapy, surgical approach remains one of the main treatment options for some forms and stages of the disease. The long-term success of glaucoma surgery depends on the intensity of local wound healing processes at the surgical site. The most common way to influence healing processes in surgical treatment of glaucoma is the use of antimetabolites. However, given the high risk of serious complications associated with their use, the search for new drugs devoid of these disadvantages continues. The aim of this review is to describe the efficacy and safety of both currently used and upcoming pharmacological ways to influence the wound healing process after glaucoma surgery in order to improve the stability of hypotensive effect.

Purpose: To investigate the effect of two surgical techniques in primary Baerveldt glaucoma implant (BGI) surgery, that is the sutured technique and the unsutured (free) plate technique, on the ocular motility and prevalence of diplopia. We hypothesize that the free plate technique results in a lower diplopia prevalence., Methods: We performed a prospective study of patients who underwent BGI surgery with the free plate technique and compared them with patients from a previous study who had undergone BGI surgery with the sutured technique. Their ductions, ocular alignment and fusion range and the prevalence of diplopia were measured before surgery and at 3 months, 6 months and 1 year postoperatively., Results: We analysed 57 free plate and 51 sutured plate patients. One year postoperatively, we found no statistically significant difference in the prevalence of diplopia between the two techniques. All duction changes between baseline and 1-year follow-up were restrictions and occurred statistically significantly more frequently in the free plate than in the sutured plate group (p = 0.03; 60% versus 34%). About the ocular alignment, in the horizontal direction, a change in exodirection was more common in both groups, while in the vertical direction, a hyperdeviation of the operated eye was more common. The vertical ocular alignment change was smaller in the free plate group than in the sutured plate group (p = 0.04 at near and p = 0.02 at distance)., Conclusions: One year postoperatively, the prevalence of diplopia was not significantly different between patients with the sutured plate and patients with the free plate technique. Both surgical techniques induce diplopia and changes in ocular motility and/or in ocular alignment., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To compare the optical coherence tomography (OCT) findings on the condition of filtering bleb (FB) in patients with primary open-angle glaucoma (POAG) who used different local therapy before glaucoma surgery., Material and Methods: The study included a total of 82 patients (82 eyes) followed up after glaucoma surgery: 50 patients (50 eyes) who received preservatives-containing drugs before glaucoma surgery; 32 patients (32 eyes) - who were on preservative-free drug treatment before glaucoma surgery. The examinations were carried out 7 days, 1 and 3 months after micro-invasive sinus trabeculectomy. The condition of filtering bleb was studied using the Visante AS-OCT device, as well as with a slit lamp for clinical observation. Corneal-compensated intraocular pressure (IOPcc) was determined by bi-directional pneumatic applanation of the cornea using the Ocular Response Analyzer (ORA)., Results: After 3 months post-op, a functioning FB and intraocular pressure below 15.0 mm Hg were observed in 38 eyes out of 50 (76%) in group 1, in 12 eyes (24%) the FB was nonfuncitonal. In Group 2, 25 eyes out of 32 (78%) had functioning FB and intraocular pressure lower than 15.0 mm Hg; in 7 eyes (22%) the FB was nonfuncitonal. Needling was needed 3 months after the operation in 7 eyes out of 32 (22%) in group 2. The need for needling according to OCT findings in patients of group 1 occurred already one week after surgery for 4 eyes out of 50 (8%), after one month - for 14 eyes (28%)., Conclusion: In patients on pre-operative drug therapy with preservative-containing medications, the process of scarring in the FB is faster. The OCT method allows early detection of the initial signs of scarring, as well as determining the need for needling.

Inhibition of fibrosis is indispensable for maintaining filtering blebs after glaucoma filtration surgery (GFS). The purpose of this study was to investigate the ability of a pluripotent epigenetic regulator OBP-801 (OBP) to ameliorate extracellular matrix formation in a rabbit model of GFS. Rabbits that underwent GFS were treated with OBP. The gene expression profiles and intraocular pressure (IOP) were monitored until 30 postoperative days. The bleb tissues were evaluated for tissue fibrosis at 30 postoperative days. In in vitro models, OBP interfered the functions of diverse genes during the wound-healing process. In in vivo GFS models, the expressions of TGF-β3, MMP-2, TIMP-2 and 3, LOX, COL1A and SERPINH1 were significantly inhibited at 30 postoperative days in the OBP group compared with those in the vehicle control group. OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.

Purpose: To present the case of a patient who developed bleb-related endophthalmitis after an intravitreal injection using the InVitria injection guide, alongside a review of the literature on bleb-related endophthalmitis., Methods: Our case is presented in context of the current literature on bleb-related endophthalmitis., Results: Bleb-related endophthalmitis occurs in up to 2% of eyes within 5 years of filtering glaucoma surgery. Risk factors include bleb leakage, use of anti-fibrinolytic agents, blepharitis, hypotony, and nasolacrimal duct obstruction. Our patient presented with a bleb leak and bleb-related endophthalmitis 2 weeks after an intravitreal injection using the InVitria injection guide., Conclusion: Injection guides can cause bleb trauma and resulting bleb leakage. They should be avoided in patients with filtering glaucoma surgery.

Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo., Competing Interests: The authors have declared that no competing interests exist.

To clarify the early alterations of gene expression using a mouse model of glaucoma filtration surgery, we carried out microarray expression analysis. Using BALB/c mice, a filtration surgery model was made by incision of the limbal conjunctiva, followed by the insertion of a 33G needle tip into the anterior chamber, and 11-0 nylon sutures. Subgroups of mice were treated intraoperatively with 0.4 mg/ml mitomycin-C (MMC). At day 3 after surgery the bleb was maintained. The bleb region tissue was sampled 3 days after the filtration surgery, and gene expression analysis was carried out using a mouse Agilent 8 × 60 K array. We found 755 hyperexpressed transcripts in the bleb region compared to control conjunctiva. The hyperexpressed transcripts included epithelial cell metaplasia-related (Il1b, Krt16, Sprr1b), inflammation-related (Ccl2, Il6) and wound healing-related (Lox, Timp1) genes. We also found downregulation of a goblet cell marker gene (Gp2) in the bleb conjunctiva. MMC treatment suppressed elastin (Eln) gene expression and enhanced keratinization-related gene expression (Krt1, Lor) in the bleb region. Our results suggest the importance of epithelial wound healing after filtration surgery, and this filtration surgery model will be a useful tool for further pathophysiological analysis.

Background: Canaloplasty has been reported to manage primary open-angle glaucoma (POAG) effectively. However, no study has specifically and systematically investigated the efficacy and safety of canaloplasty for the treatment of POAG. Thus, this study will systematically and comprehensively appraise the efficacy and safety of canaloplasty for the treatment of POAG., Methods: MEDLINE, EMBASE, Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be sought from the construction to the February 29, 2020. Only randomized controlled trials (RCTs) focusing on canaloplasty for the treatment of POAG will be included. Two reviewers will independently undertake selection of study, data extraction, and risk of bias assessment. Any doubts between 2 reviewers will be resolved through discussion with another experienced reviewer. RevMan 5.3 software will be employed for data analysis., Results: This study will summarize high-quality RCTs on investigating efficacy and safety of canaloplasty for the treatment of POAG., Conclusion: The findings of this study will help to determine whether canaloplasty is effective and safety for the treatment of POAG.Systematic review registration: INPLASY202040119.

Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.

Purpose: The purpose of this study was to evaluate the outcome of pericardium patch graft (Tutoplast) as an adjuvant to either bleb repair or bleb reduction after nonpenetrating filtering surgery., Methods: Retrospective study, at a tertiary glaucoma center. Bleb revision with Tutoplast positioning was performed either for bleb repair to treat early leaks or hypotony with maculopathy, either for bleb reduction to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. Intraocular pressure (IOP), best corrected visual acuity, number of antiglaucoma medications, and postoperative complications were analyzed postoperatively at 1 week, 1, 3, 6 months, and compared with the preoperative baseline. Surgical success was defined as achieving an IOP between 8 and 16 mm Hg., Results: Six-month data were available from 15 eyes of 15 patients; mean patient age was 69.6±11.7 (66.7% male). Bleb revision was necessary for 10 patients due to bleb dysesthesia (bleb reduction), and in 5 patients due to leaking filtering bleb (bleb repair). The success rate was 73.3% at 6 months, with a significant IOP increase from 4.9±2.2 mm Hg preoperatively to 12.7±3.5 mm Hg at 6 months (P=0.0001), and a concomitant rise of best corrected visual acuity from 0.5±0.3 to 0.6±0.3 (P=0.2871). To control IOP, antiglaucoma medications were needed for 3 patients (20%) at 6 months. Overall, 3 patients (20%) required additional bleb revision for persistent hypotony, and 1 patient underwent a subsequent glaucoma surgery (transscleral cyclodestruction)., Conclusion: Pericardium patch graft (Tutoplast) is a safe and effective adjuvant for bleb revision due to bleb dysesthesia of leaking filtering bleb after nonpenetrating filtering surgery.

Purpose: To characterize the clinical presentation of limbal stem cell deficiency (LSCD) associated with glaucoma surgeries., Methods: This is a retrospective cross-sectional study of patients with LSCD and glaucoma who presented to the Stein Eye Institute at the University of California, Los Angeles, between 2009 and 2018. Patients who underwent trabeculectomy and/or aqueous shunt surgery were included. The severity of LSCD was staged using global consensus guidelines and a clinical scoring system, and basal epithelial cell density was measured by in vivo confocal microscopy. Anatomic locations of glaucoma and non-glaucoma surgeries, locations of LSCD, and severity of LSCD were compared., Results: Fifty-one eyes of 41 patients with LSCD associated with glaucoma surgery were included in this study. LSCD in these patients uniquely featured sectoral replacement of corneal epithelium by conjunctival epithelium, without corneal neovascularization or pannus. The sites of glaucoma surgery strongly correlated with the locations of LSCD (P = 0.002). There was a trend toward increased severity of LSCD in eyes with 2 or more glaucoma surgeries as compared to eyes with 1 glaucoma surgery, although the difference did not reach statistical significance (P = 0.3). Use of topical glaucoma medications correlated with LSCD severity, while the impact of antimetabolites did not reach statistical significance. The location of glaucoma drainage surgery is correlated with the location of LSCD., Conclusions: LSCD associated with glaucoma surgery has clinical features distinct from LSCD resulting from other etiologies. Further study is required to delineate the full impact of glaucoma surgery on limbal stem cell function and survival.

Purpose: To report the incidence and outcomes of suprachoroidal hemorrhage (SCH) associated with pediatric glaucoma surgery., Method: The medical records of pediatric patients (<18 years of age) who had undergone glaucoma surgery and developed SCH from June 2014 to September 2017 were reviewed retrospectively. In all cases, the SCH was suspected clinically and was confirmed by B-scan ultrasound. Baseline characteristics, intraoperative details (including surgery type), and subsequent and final outcomes were extracted from the records., Results: Of 2,656 glaucoma surgeries during the study period, 17 cases of SCH were documented, for an overall incidence of 0.64%. Of the 17 cases, 16 occurred postoperatively, and 1 was noted intraoperatively. By surgery type, the incidence of SCH was highest for trabeculectomy (4/121), followed by glaucoma drainage device surgery (6/463), deep sclerectomy (6/851), and transcleral cyclophotocoagulation (1/542). Four children had received prior transcleral cyclophotocoagulation, and 5 of the children were aphakic at the time of the glaucoma surgery. At a mean final follow-up of 1.71 ± 1.08 years), visual acuity in the affected eye was 20/50 or better in 3 children, between 20/50 and 20/200 in 5 children, and counting fingers or worse in 9 children., Conclusions: In our study cohort, the overall incidence of SCH associated with glaucoma surgery was 0.64%. Further study of risk factors for SCH associated with glaucoma surgery in children is needed., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Introduction: This article compares and evaluates the safety and clinical results of 3techniques for the management of hyper-filtrating ischaemic bleb in glaucoma, such as collagen crosslinking (CXL) with riboflavin versus conjunctival sliding and conjunctival autologous graft., Methods: A total of 24 eyes were selected from 18 patients with ischemic blebs that underwent filtering glaucoma surgery between 2012 and 2017 and subjected them to crosslinking using riboflavin (n=4), conjunctival autologous graft (n=5), and conjunctival sliding (n=15). The results of the intraocular pressure (IOP) prior to the procedure and at 12 months were compared, as well as visual acuity and previous anti-glaucoma medication at 12 months., Results: The 4eyes that underwent CXL, went from a previous mean IOP of 12.11 ± 3.14 to an IOP of 12.32 ±5.29 at one year (P=.655). Five eyes were treated by conjunctival autologous graft, had a previous mean IOP of 11.65 ± 5.76 and an IOP at one year of 14.68 ± 7.21 (P=.273). Fifteen eyes subjected to conjunctival sliding had a previous IOP of 9.32 ±5.34 and at one year it was 15.16 ± 9.24 (P=.021). There were no adverse effects or complications associated with any of the 3techniques., Conclusions: The management of the hyper-filtrating ischaemic bleb is difficult. Surgical procedures are associated with increased IOP and need for medication, while CXL using riboflavin and UV radiation does not seem to have an effect on the revitalisation of the bleb., (Copyright © 2019 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The placement of a XEN gel stent is an ab-interno, minimally invasive glaucoma surgery which provides a subconjunctival drainage pathway and decreases intraocular pressure (IOP)., Case Presentation: A 75-year-old male patient who had undergone XEN45 gel implantation after phacoemulsification and intraocular lens implantation appealed to the clinic. A filtration bleb was seen that extended through the nasal 180 degrees of the eye which caused ectropion of the lower eyelid. The value of the IOP was 12 mm Hg (mmHg). By the "Drainage Channel with Sutures" method this complication was effectively treated. As with every new method, there is a lack of knowledge about long-term outcomes in terms of effectiveness, technique and complications., Conclusion: The "Drainage Channel with Sutures" method has not been described in the literature yet. By this minimal invasive method, hypertrophic bleb complication of XEN gel implant has been successfully treated.

Purpose: To report a patient with retinal and choroidal vascular occlusion as a presenting sign of sickle cell trait following the development of aqueous misdirection syndrome., Methods: Retrospective chart review., Results: A patient treated for bilateral chronic angle-closure glaucoma with sequential EX-PRESS glaucoma filtration device surgery developed sequential bilateral aqueous misdirection syndrome. The left eye developed retinal arterial and localized choroidal vascular occlusions subsequent to an acute elevation in intraocular pressure and possibly the use of oral acetazolamide. The patient was subsequently found to have sickle cell trait. The right eye developed aqueous misdirection with acute elevation of intraocular pressure as well, but the patient was not treated with oral acetazolamide and did not develop vascular occlusion., Conclusion: Retinal and choroidal vascular occlusions can be the presenting sign of a patient with sickle cell trait. Sickle cell screening may be beneficial in African American or Middle Eastern patients after an acute rise in intraocular pressure, particularly before initiation of treatment with oral carbonic anhydrase inhibitors.

Importance: Management of cystic bleb leak is difficult. It would be essential to look for a method to strengthen the original pathological conjunctiva and reverse bleb leak., Background: To evaluate the long-term efficacy and safety of collagen crosslinking in patients with leaking cystic bleb., Design: Prospective interventional case series at a university-based hospital., Participants: Twelve eyes in 12 subjects with late-onset bleb leak from cystic bleb, without indications for prompt surgical interventions were included., Methods: The subjects underwent crosslinking with 0.1% riboflavin application to bleb surface, followed by ultraviolet irradiation for 30 minutes. The subjects were followed up at baseline and at 1 week, 1 month, 3 months, 6 months post-treatment and then every 6 months afterwards., Main Outcome Measures: Interval from treatment to cessation of bleb leak, recurrence rate of bleb leak and side effects of treatment., Results: The mean follow-up after crosslinking was 29.33 ± 12.45 months. Bleb leak subsided in 11 (92%) of 12 patients after a single session of crosslinking, after 1 to 8 weeks (median 3 weeks). Time to leak cessation was significantly correlated with the number of prior glaucoma interventions (R = .71, P = .014). Bleb wall at 3 months was significantly thicker than at baseline (0.70 ± 0.67 vs 0.81 ± 0.62 mm, P = .008). None of the patients experienced any complications., Conclusions and Relevance: Crosslinking achieves resolution of cystic bleb leak which lasts for at least 12 months, without the need of subsequent surgical interventions. Crosslinking is a simple, non-invasive treatment for bleb leak. It aims to restore the integrity of conjunctiva., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Precis: Wider area bleb revision using bleb knife with adjunctive mitomycin C (MMC) had a good success rate, according to strict success criteria, except in patients with neovascular glaucoma (NVG)., Purpose: We determined the efficacy of wider area bleb revision after filtering surgery using bleb knife with adjunctive MMC., Patients and Methods: In this retrospective single-center study, we analyzed 86 patients with glaucoma (46 primary open-angle, 18 exfoliations, 13 secondary, and 9 neovascular) after bleb revision using bleb knife with adjunctive MMC after a minimum follow-up of 6 months. A Kaplan-Meier survival analysis with log-rank tests and Cox proportional hazards regression analyses were performed. The main outcome measure was a successful initial bleb revision using bleb knife with adjunctive MMC, arbitrarily defined as intraocular pressure (IOP) control <15 mm Hg without any IOP-lowering medication, additional bleb revision, or glaucoma surgery., Results: The mean time since the initial filtering surgery was 243.8 days, and the mean prebleb revision IOP was 22.0±4.8 mm Hg. The total cumulative success rate of the bleb revision using bleb knife with MMC was 49% at 6 months and 30% at 1 year. Patients with primary open-angle glaucoma had the best success rate (64% at 6 mo and 40% at 1 y). Log-rank tests revealed that patients with NVG had the worst prognosis (P<0.01). NVG was the only significant risk factor identified for short survival time (odds ratio, 167.10; 95% confidence interval, 1.78-15620.44; P=0.027)., Conclusion: Wider area bleb revision using bleb knife with adjunctive MMC had a good success rate, according to strict success criteria, except in patients with NVG.

Purpose: We report a case of progressive high hypermetropia following glaucoma filtration surgery in a child with Axenfeld-Rieger syndrome and congenital glaucoma., Methods/results: We report a case of a 4-day-old female child presented as a case of Axenfeld-Rieger anomaly with secondary glaucoma in both eyes (OU), who underwent combined trabeculotomy with trabeculectomy in OU at the age of 3 weeks. On postoperative third month, cornea cleared and posterior embryotoxon was noted in OU with Habb's striae in OS. Intraocular pressure (IOP) was controlled and fundus was normal in OU. Refraction was +2.00 D sph. in OD and 3.00D sph. in OS and was observed. On postoperative eighth month, IOP was controlled in OU, whereas retinoscopy showed refraction of +4.00D sph./-2.00D cyl at 30 degrees in OD and +10.00 D sph/-3.00 cyl at 120 degrees in OS, glasses were prescribed and was asked to review. After 4 years, the patient presented with blurring of vision, the best-corrected visual acuity noted was 20/100 in OD and 20/320 in OS. IOP was 28 and 14 mm Hg in OD and OS, respectively, but with healthy optic disc in OU. Refractive error had increased and was +5.50D sph in OD and +14.00D sph/-5.00 D cyl at 90 degrees in OS. Corneal topography showed cornea plana in OU, which was more in OS (K1: 32.6D and K2: 38.9D) compared with OD (K1: 38.7D and K2: 40.1D). The patient was started on glaucoma medications in OD. Four months later, IOP was controlled and refraction was stable in OU., Conclusions: Present case is the first to describe the unusual presentation of progressive high hypermetropia in a child with Axenfeld- Rieger anomaly with congenital glaucoma after surgical intervention for glaucoma. Childhood glaucoma is classically associated with myopic shift in refraction and refraction is one of the most important clinical parameter measured at every follow-up visit. Although progressive hypermetropic shift is a rare occurrence, clinicians should be aware of this possibility. Keratomerty should be performed when such refractive surprises arise, which may help detect the clinical condition and the etiology for such presentation.

Purpose: To report a new approach for the treatment of severe ocular hypotony secondary to glaucoma filtering surgery with mitomycin C by injecting autologous eye platelet-rich plasma (E-PRP) in the anterior chamber to block excessive diffuse filtration through an abnormally thinned sclera., Methods: A 49-year-old patient with the Axenfeld-Rieger syndrome and severe chronic hypotony and corneal edema following filtering glaucoma surgery with mitomycin C received an isolated injection of 0.3 mL of autologous platelet-rich plasma in the anterior chamber., Results: Intraocular pressure measured by Goldman's applanation tonometry 6 h after the procedure improved to 18 mmHg. Intraocular pressure remained stable along the full follow-up period of 6 month. No filtration or hypotony or any other complications were observed., Conclusion: Intracameral platelet-rich plasma (E-PRP) injection was an effective, rapidly effective, and safe procedure for treatment of severe chronic ocular hypotony following glaucoma filtrating surgery.

PRéCIS:: Anterior chamber depth, IOP, and thickness confounded the assessment of corneal biomechanical properties with noncontact applanation in glaucoma eyes. Compared with normal eyes, glaucoma eyes, which underwent long-term treatment or filtration surgery, had similar properties., Purpose: The purpose of this study was to evaluate corneal stiffness in primary angle-closure (PACG) and primary open-angle (POAG) glaucoma eyes that were subgrouped on the basis of the type of topical medication and filtration surgery using noncontact applanation., Methods: All eyes were retrospectively reviewed for intraocular pressure (IOP) with Corvis-ST (OCULUS Optikgerate Gmbh, Germany). Nonglaucoma (n=140), PACG (n=102 under medication), and POAG (n=154 under medication) eyes were included. Corneal stiffness was calculated using deformation amplitude and a biomechanical model. Multivariate analyses were performed, which evaluated the effect of systemic conditions (diabetes and hypertension), the effect of medication (prostaglandins or beta blockers or combined), and the effect of filtration surgery (PACG: n=23; POAG: n=26). Age, IOP, central corneal thickness (CCT), refractive error, and anterior chamber depth (ACD) were covariates., Results: Diabetes and hypertension did not alter corneal stiffness of glaucoma eyes compared with nonglaucoma eyes (P>0.05). Corneal stiffness of POAG and nonglaucoma eyes was similar but significantly different from the stiffness of PACG eyes (P=0.002), irrespective of the type of topical medication. This difference was strongly correlated with ACD (P=0.003) in addition to IOP and CCT. In eyes treated with filtration surgery, ACD (P=0.04) again impacted the trends between nonglaucoma and glaucoma eyes., Conclusions: Medication or filtration surgery did not affect the corneal biomechanical parameters differentially from nonglaucoma eyes. However, IOP, CCT, and ACD strongly affected corneal biomechanical parameters in the same glaucoma eyes.

Precis: Rabbit model studies suggested better morphology blebs with equal intraocular pressure (IOP) efficacy as a standard mitomycin C (MMC) trabeculectomy using a novel slow-release drug delivery antifibrotic system delivering small quantities of MMC and 5-fluorouracil (5-FU)., Purpose: To evaluate 2 different concentrations of biodegradable poly(lactic-co-glycolic acid) (PLGA) system with 5-FU and MMC (ElutiGLASS) for their ability to reduce fibrosis and compare the results with standard trabeculectomy with MMC in a rabbit model., Materials and Methods: New Zealand albino rabbits (19) were divided into 3 groups (A, B, C) and standard trabeculectomy operation was performed in the right eye of each rabbit.Group (A) had trabeculectomy with MMC (0.4 mg/mL) applied using a Weck cell sponge; (B) trabeculectomy with slow-release ElutiGLASS (0.23 mg, 5-FU/0.33 μg MMC released over 23 to 30 d); (C) trabeculectomy with rapid release ElutiGLASS (0.45 mg of 5-FU/0.65 μg MMC, released over 5 to 7 d). The rabbits were followed for 3 months before euthanasia., Results: Bleb morphology, vascularity, and fibrosis were less pronounced in groups B and C when compared with group A at 3 months. Group B appears to have a lower and more diffuse bleb appearance compared with the other 2 groups with honeycomb appearance on both clinical examination and ultrasound biomicroscopy imaging with higher percentage of maintained bleb space (83%), less fibrosis than group A while maintaining the same low inflammation score as the other 2 groups on histology. At 3 months, the PLGA polymer had completely disappeared in all rabbits. There were no statistical differences in the degree of IOP reduction or histologic inflammation, among the 3 groups., Conclusions: We successfully created a sustained-release antifibrotic drug delivery system that delivered known dosage of the drugs at doses that are significantly lower than the current standard, and resulted in less fibrosis while maintaining a healthy bleb and equal reduction of IOP., Translational Relevance: These results are supportive of the antifibrotic effect of the slow-release drug delivery system used in conjunction with trabeculectomy, thus paving the way for human pilot studies to improve and simplify existing surgical techniques for filtering surgeries in glaucoma.

Purpose: The purpose of this study was to evaluate the efficacy and safety of subliminal cyclophotocoagulation using a 25% duty cycle diode laser (Supra 810, SubCyclo, Quantel Medical)., Methods: This was a pilot study of patients who underwent a SubCyclo photocoagulation procedure with a 25% duty cycle, between April 2016 and April 2017 at the Glaucoma Institute of Saint Joseph Hospital of Paris. All patients presented with an evolving moderate to severe glaucoma that were resistant to previous surgical treatments or with a contraindication for filtration surgery. Laser settings were programmed as follows: power 2000 mW, "on" time 0.63 ms, "off" time 1.9 ms, and 25% duty cycle per 100 seconds to each eye., Results: A total of 44 eyes of 34 patients were treated with subliminal cyclophotocoagulation, with a mean follow-up time of 12 months. Surgical success was defined as IOP ranging 6 to 21 mm Hg or a 20% IOP reduction at the last 12 months follow-up visit. The mean age of patients was 63.83±16.2 years. The mean preoperative IOP was 32.8±11.8 mm Hg which then decreased postoperatively to 24.02±7.03 mm Hg after 1 day, 18.34±8.31 mm Hg after 1 week, 18.26±8.53 mm Hg after 1 month, 20.5±8.53 mm Hg after 3 months, 18.9±9.2 mm Hg after 6 months and 18.8±9.3 mm Hg after 12 months. Our preliminary study using Subcyclo transscleral cyclophotocoagulation with a 25% duty cycle showed a 37% IOP reduction from the baseline after 3 months with a single laser session and a 45% reduction at the last 12 months follow-up, after more than one laser session. The mean number of ocular antihypertensive medications used was 3.4±1.7 before treatment which decreased to 3.0±1.6 after treatment. No significant complications or anatomic modifications were found after subliminal cyclophotocoagulation., Conclusions: Subliminal cyclophotocoagulation with a 25% duty cycle is a safe and effective procedure for reducing IOP in cases of refractory glaucoma and seems to be safer than conventional transscleral cyclophotocoagulation.

PRéCIS:: In this study, we report clinical results after implantation of an adjustable glaucoma drainage device. The intraocular pressure (IOP) profile was efficiently controlled postoperatively as the resistance to aqueous humor outflow was finely adjusted., Purpose: The main purpose of this study was to evaluate the safety and efficacy of the new adjustable glaucoma drainage device eyeWatch used in conjunction with a Baerveldt glaucoma implant in refractory glaucoma., Patients and Methods: This was a multicentric, prospective, noncomparative clinical trial. Patients older than 18 years of age suffering from refractory glaucoma after failed surgeries, with IOP of ≥20 mm Hg, in whom a further glaucoma procedure using an aqueous shunt was planned, were enrolled in this study. The primary outcome was the success rate, defined as an IOP≤18 mm Hg and reduction of >20% from baseline, IOP≥6 mm Hg. Secondary outcomes were mean IOP, visual acuity, number of antiglaucoma medications, number, and type of complications., Results: Fifteen patients were included. The mean follow-up time was 15.6±3.5 months. The mean baseline IOP decreased from 26.2±6.8 mm Hg before surgery to 11.9±2.8 mm Hg at 12 months (P<0.001). The mean number of glaucoma medications decreased from 3.0±0.7 before surgery to 0.8±0.9 at last visit (P<0.001). The success rate was 40% for complete success and 93% for overall success at last follow-up. Complication rate was 7%., Conclusions: The novel glaucoma device allows for perioperative and postoperative noninvasive adjustments of the resistance to aqueous humor outflow. This leads to better management of IOP during the early postoperative period, preventing ocular hypotony and eliminating the need for obstructive elements and reinterventions. The rate of complications was low, IOP was adequately controlled and lowered, with a substantial reduction in the number of antiglaucoma medication.

Introduction:: To report the case of a high hyperopic refractive shift associated with significant shortening of the ocular axial length following glaucoma filtering surgery., Methods:: Case report. Patient's records were consulted retrospectively., Results:: A 57-year-old woman, highly myopic, with a history of bilateral intraocular refractive surgery in 1998 (phakic lens ZB5M) and bilensectomy in 2011 (phakic intraocular lens extraction plus cataract surgery with pseudophakic intraocular lens implantation), presented with consistently high intraocular pressure. Despite the treatment with different topical antiglaucomatous medications and good compliance, her intraocular pressure values remained consistently above 20 mmHg. In 2016, the patient was submitted for glaucoma filtering surgery and the mini shunt Ex-Press was implanted in both the eyes (3 months between surgeries). On the first postoperative day, the eyes were hypotonic (intraocular pressure of 5 mmHg) and bilateral macular edema was observed. Three days later, the intraocular pressure in both the eyes reached values higher than 6 mmHg (between 6 and 14 mmHg). Five months after the surgery the macular edema resolved and a significant shortening of the axial length and an important hyperopic refractive shift was observed. When comparing the preoperative and postoperative (18 months) measurements, the variation of the axial length was 2.49 mm in the right eye and 2.19 mm in the left eye; the patient refraction (spherical equivalent) shifted 2.50 diopters in the right eye and 1.75 diopters in the left eye., Conclusion:: To the best of our knowledge, we report herein the first documented case of an axial length change of this magnitude after glaucoma filtering surgery.

Purpose : To determine the clinical manifestations and risk factors of developing strabismus in primary congenital glaucoma (PCG) patients who underwent glaucoma surgery. Methods : A retrospective case-series study of 54 PCG patients who were followed for at least 3 years after glaucoma surgery. The subjects were divided into 2 groups based on the occurrence of strabismus. Age at glaucoma diagnosis and surgery, visual acuity, intraocular pressure, amblyopia, cup-disc ratio, and orthoptic status were compared between the 2 groups. Results : Twenty of 54 patients (37.0%) developed strabismus after glaucoma surgery. The mean ages at the time of glaucoma diagnosis and surgery were 3.2 ± 2.7 months and 3.4 ± 2.8 months in the strabismus group and 24.3 ± 19.1 months and 26.4 ± 18.9 months in the non-strabismus group, respectively ( p < .05). In addition, the mean logMAR visual acuities were 0.87 ± 0.38 in the strabismus group and 0.24 ± 0.21 in the non-strabismus group ( p < .05). The proportion of patients experiencing amblyopia was 90.0% in the strabismus group. Low visual acuity and young age at glaucoma surgery were significant predictors of developing strabismus. Kaplan-Meier survival analysis demonstrated that the probability of developing strabismus after glaucoma surgery was 50.6% at 10 years post-surgery. Conclusions : PCG patients who developed strabismus after glaucoma surgery were diagnosed with glaucoma and underwent surgery at a younger age, exhibited a worse mean best corrected visual acuity, and exhibited a higher amblyopia incidence than did patients in the non-strabismus group.

RNAi induced by double-stranded small interfering RNA (siRNA) molecules has attracted great attention as a naturally occurring approach to silence gene expression with high specificity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and, thus, represents a promising target to prevent fibrosis. A major hurdle to implementing siRNA therapies is the method of delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) nanoparticles containing MRTF-B siRNAs as a targeted approach to prevent conjunctival fibrosis. We tested 15 LPR nanoparticle formulations with different lipid compositions, surface charges, and targeting or non-targeting peptides in human conjunctival fibroblasts. In vitro, the LPR formulation of the DOTMA/DOPE lipid with the targeting peptide Y (LYR) was the most efficient in MRTF-B gene silencing and non-cytotoxic compared to the non-targeting formulation. In vivo, subconjunctival administration of LYR nanoparticles containing MRTF-B siRNAs doubled bleb survival in a pre-clinical rabbit model of glaucoma filtration surgery. Furthermore, MRTF-B LYR nanoparticles reduced the MRTF-B mRNA by 29.6% in rabbit conjunctival tissues, which led to significantly decreased conjunctival scarring with no adverse side effects. LYR-mediated delivery of siRNA shows promising results to increase bleb survival and to prevent conjunctival fibrosis after glaucoma filtration surgery., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To describe conjunctival epithelial overgrowth of the cornea after surgery for glaucoma., Methods: This is a retrospective case series (setting: Moorfields Eye Hospital). Fourteen eyes of 13 patients with suspected limbal stem cell deficiency (LSCD) and corneal conjunctivalization after glaucoma drainage surgery. Conjunctivalization was defined as corneal epithelium that demonstrated late stain after topical application of fluorescein. Patient demographics, clinical features, potential risk factors, treatment, and final visual acuity were recorded. Main outcome measures were potential risk factors for conjunctivalization, complications, and response to treatment., Results: Eleven eyes had multiple procedures involving the limbus, and in 11 eyes mitomycin C (MMC) or 5 fluorouracil had been used as an adjunct to reduce fibrosis. Affected eyes typically had a segment of late stain with fluorescein based at the site of previous glaucoma surgery, but in one eye there was total loss of the corneal epithelial phenotype. All eyes previously had topical treatment for their glaucoma but only 2 had an ocular surface disease associated with LSCD. Most cases were asymptomatic, but in 3 eyes there was visual loss when the abnormal phenotype crossed the visual axis. In these 3 eyes there was recurrent epithelial breakdown, often at the interface between the 2 epithelial phenotypes. In one individual, these symptoms resolved after limbal epithelial transfer from the unaffected contralateral eye., Conclusions: Glaucoma drainage surgery can damage the adjacent corneal limbal epithelial stem cell population. This can be associated with recurrent epithelial breakdown and reduced vision. If there is visual loss, limbal epithelial transplantation is a potential treatment option., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To study the anti- scarring effect of rapamycin in rabbits receiving glaucoma filtering surgery., Methods: Ninety-six Chinchilla rabbits were randomized equally into 3 rapamycin treatment groups and one control group. All the rabbits underwent trabeculectomy, after which the rabbits in the 3 rapamycin groups were treated with eye drops containing 1%, 3%, or 5% rapamycin in the operated eyes, and those in the control groups were given castor oil 4 times a day. The intraocular pressure (IOP) and inflammatory reaction in the treated eyes were observed, and the PCNA-positive cells in the filtering bleb were detected using immunohistochemistry. RTFs isolated from the Tenon's capsule of the rabbits were cultured in vitro , and the expressions of caspase-3, caspase-8, and caspase-9 in the fibroblasts were detected after treatment with different concentrations of rapamycin., Results: The IOP was significantly lower in rapamycin-treated group than in the control group after the surgery ( P &lt; 0.05). The counts of the PCNA-positive cells were significantly lower in rapamycin-treated rabbits than in the control group ( P &lt; 0.05). Rapamycin treatment dose-dependently increased the expressions of caspase-3 and caspase- 9 at both the mRNA ( P &lt; 0.001) and protein ( P &lt; 0.001) levels without causing significant changes in the expressions of caspase-8., Conclusions: Rapamycin can inhibit excessive proliferation of the fibroblasts in the filtering bleb to reduce scar formation after glaucoma filtration surgery in rabbits. Rapamycin also increases the expressions of caspase-3 and caspase-9 to induce apoptosis of the RTFs.

Background: To develop targeted antifibrotic therapy for glaucoma filtration surgery; this study determines the effectiveness of small interfering RNA (siRNA) to reduce in vivo secreted protein acidic and rich in cysteine (SPARC) expression using the mouse model of conjunctival scarring., Methods: Experimental surgery was performed as described for the mouse model of conjunctival scarring. Scrambled (siScram) or Sparc (siSparc) siRNAs, loaded on layer-by-layer (LbL) nanoparticles, were injected into the conjunctiva immediately after surgery. Expression of Sparc , Col1a1 , Fn1 and Mmp14 was measured by real-time PCR and immunoblotting on days 7 and 14 postsurgery. Live imaging of the operated eyes was performed using slit lamp, anterior segment-optical coherence tomography and confocal microscopy. Tissue pathology was evaluated by histochemical and immunofluorescent analyses of operated conjunctival cryosections. Tissue apoptosis was quantitated by annexin V assay. RESULTS : siSparc, delivered via expanded LbL nanoparticles, significantly inhibited Sparc transcription in both day 7 (2.04-fold) and day 14 (1.39-fold) treated tissues. Sparc suppression on day 7 was associated with a significant reduction of Col1a1 (2.52-fold), Fn1 (2.89-fold) and Mmp14 (2.23-fold) mRNAs. At the protein level, both SPARC and collagen 1A1 (COL1A1) were significantly reduced at both time points with siSparc treatment. Nanoparticles were visualised within cell-like structures by confocal microscopy, while overt tissue response or apoptosis was not observed. CONCLUSIONS : SPARC targeted therapy effectively reduced both SPARC and collagen production in the operated mouse conjunctiva. This proof-of-concept study suggests that targeted treatment of fibrosis in glaucoma surgery is safe and feasible, with the potential to extend to a range of potential genes associated with fibrosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To compare the efficacy of two cyclodestructive treatments for refractory glaucoma: High Intensity Focused Ultrasound (HIFU) cyclocoagulation and transscleral diode laser cyclophotocoagulation (cyclodiode)., Methods: A retrospective comparative single centre study including all patients who underwent cyclodestruction for refractory glaucoma by either HIFU cyclocoagulation or cyclodiode. "Refractory glaucoma" was defined as an uncontrolled high IOP despite medical treatment and at least one filtering surgery. Uncontrolled high IOP was defined as an IOP≥16mm Hg. The diagnosis of glaucoma was confirmed by automated visual field (VF) testing and peripapillary RNFL scans using a time-domain ocular coherence tomography device. Treatment success was defined as: postoperative IOP between 5mm Hg and 21mm Hg and IOP reduction greater than or equal to 20% as compared to preoperative values., Results: Among the 99 eyes of 86 patients included in this study, 29 eyes were treated by cyclodiode and 70 eyes by HIFU. Median follow-up was 3 months (IQR 3-6) for the cyclodiode group and 6 months (IQR 3-8) for the HIFU group. Average preoperative intraocular pressure (IOP) was 34.3±11.1mm Hg (cyclodiode group) and 23±6.8mm Hg (HIFU group). The treatment success rate at last follow-up was 52% [34-70] for the cyclodiode group and 25% [15-35] for the HIFU group (P value=0.01). Kaplan-Meier survival analysis showed that the mean estimated time to failure was 5.9 months (4.4-7.5) for the cyclodiode group and 3.7 months (2.8-4.7) for the HIFU group (log-Rank test, P=0.02). A 2-line visual acuity loss was observed for 31% of the patients treated by cyclodiode and 17% for those treated by HIFU. In the cyclodiode group 4 cases of hypotony were reported vs. none in the HIFU group., Conclusions: The success rate was significantly higher for cyclodiode treatment as compared to HIFU cyclodestruction when treating refractory glaucoma. However, significantly fewer complications were observed with HIFU cyclocoagulation as compared to cyclodiode., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

We report a case of Descemet's membrane detachment after inadvertent intrastromal injection of hyaluronic acid. Surgical removal was attempted with minimal but slow improvement. Near-complete resolution occurred with subsequent conservative management within 6 weeks.