Trabeculotomy Using the Kahook Dual Blade for Exfoliation Glaucoma and Primary Open Angle Glaucoma: Comparison of Outcomes According to Incision Range.

PRCIS: Large amount of trabeculotomy with Kahook Dual Blade (KDB) confers better intraocular pressure (IOP) lowering. PURPOSE: We compared the postoperative outcomes of trabeculotomy using the KDB in patients with exfoliation glaucoma (EXG) and primary open angle glaucoma between the 120-degree incision and the 210- to 240-degree incision groups. PATIENTS AND METHODS: We retrospectively analyzed the postoperative outcomes of trabeculotomy performed using the KDB in 101 eyes with EXG and primary open angle glaucoma, who received 120- and 210- to 240-degree incisions at Kumamoto University Hospital between April 25, 2018, and August 11, 2021. Kaplan-Meyer survival curves were used to assess the outcomes. Surgical failure was defined as IOP ≥21 mm Hg (criterion A) and ≥19 mm Hg (criterion B), or an IOP ≤4 mm Hg in either criterion and the need for additional glaucoma surgery. RESULTS: In total, 64 and 37 eyes were included in the 120 and 210- to 240-degree groups, respectively. The 210- to 240-degree group had a higher 1-year success rate compared with the 120-degree group, both when considering all eyes and when considering only those with EXG (P<0.05). CONCLUSIONS: In trabeculotomy with KDB, a 210- to 240-degree incision was more effective than a 120-degree incision in lowering IOP in EXG cases.

Risk factors for Baerveldt glaucoma drainage implantation for uveitic glaucoma.

Uveitic glaucoma (UG) is sometimes intractable, including intricate interaction between intraocular pressure (IOP) elevation associated with inflammation and side effects of steroids. Based on the Tube Versus Trabeculectomy study in refractory glaucoma results in 2012, tube shunt surgeries have been performed for UG, but few reports have focused on UG. We retrospectively examined the surgical efficacy, complications, and risk factors in 62 eyes with UG that underwent Baerveldt glaucoma drainage device (BGD) implantation at Kumamoto University. The IOPs significantly dropped, and the mean number of glaucoma medications was reduced by more than two. Kaplan‒Meier survival curves were presented under 2 conditions: an IOP reduction of 20% and 6 ≤ IOP ≤ 18 mmHg (criterion A) or 6 ≤ IOP ≤ 15 mmHg (criterion B). In criterion A, the median survival times (MST) were 124 days (complete) and 997 days (qualified). In criterion B, the MST was 129 days (complete) and 867 days (qualified). The Cox hazard proportional model found that the hazard ratio was 0.170 for a history of cataract surgery (95% CI 0.0303-0.950) and 8.669 for systemic immunosuppressive therapy (95% CI 1.810-41.51). BGD implantation is effective for treating UG, but the presence of systemic treatment and the lens status should be considered.

Outcomes and risk factors for ab interno trabeculotomy with a Kahook Dual Blade.

PURPOSE: To verify the surgical results and risk factors for ab interno trabeculotomy using a Kahook Dual Blade (KDB-LOT) in patients with various glaucoma types. METHODS: This study was a retrospective case series of 205 eyes that underwent KDB-LOT. For Kaplan-Meier survival analysis, criterion A was defined as a ≤ 20% reduction in intraocular pressure (IOP) from baseline. Criteria B, C, and D were IOPs of ≤ 21, 18, and 15 mmHg, respectively. The Cox proportional hazard (CPH) model investigated prognostic factors. RESULTS: The mean (SD) IOP decreased from 24.7 (7.98) to 17.6 (4.80) mmHg in all cases, from 21.3 (6.88) to 17.8 (3.52) mmHg in primary open-angle glaucoma (POAG), from 25.4 (7.32) to 17.1 (4.65) mmHg in exfoliation glaucoma, from 30.6 (8.88) to 17.8 (8.29) mmHg in uveitic glaucoma, and from 30.8 (7.29) to 17.3 (0.83) mmHg in steroid-induced glaucoma at 1 year after KDB-LOT. The Kaplan-Meier survival analysis showed that patients with POAG had the best prognosis under criteria B and C, and the 1-year survival rate in patients under criterion D was less than 35% for any disease type. CPH analysis revealed that age and KDB-LOT with phacoemulsification were good prognostic factors. Risk factors for surgical failure were previous cataract surgery, selective laser trabeculoplasty, and postoperative peripheral anterior synechiae. CONCLUSION: KDB-LOT was effective in treating patients with several glaucoma types but showed difficulty in pushing IOP below 15 mmHg. Prognostic factors should be considered when making decisions regarding surgical indications.

Elevated soluble vascular endothelial growth factor receptor levels in aqueous humor from patients with different types of glaucoma.

We investigated the aqueous humor levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)1, and sVEGFR2 in glaucoma patients and the correlations among them. Aqueous humor was collected from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF and its receptors, sVEGFR1 and sVEGFR2, were measured using multiplex bead-based immunoassays. Aqueous humor samples were obtained from 79 participants: 21 with primary open angle glaucoma (POAG), 22 with uveitic glaucoma (UG), 19 with neovascular glaucoma (NVG), and 17 with cataracts as controls. sVEGFR1 levels were significantly higher in NVG than in the other cases (NVG, 2839.8 pg/mL, P < 0.001). The sVEGFR2 levels of glaucoma patients were significantly higher than those of the controls (POAG, 699.0 pg/mL; UG, 866.2 pg/mL; NVG, 1198.1 pg/mL; P < 0.001). In the aqueous humor of glaucoma patients, sVEGFR1 and sVEGFR2 levels were positively correlated (POAG, P = 0.0196; UG, P = 0.0047; NVG, P = 0.0050). VEGF levels were negatively correlated with both sVEGFR1 (P = 0.0197) and sVEGFR2 (P = 0.0015) in POAG patients. In UG patients, the correlation between VEGF and sVEGFR1 levels was negative (P = 0.0144). sVEGFR2 levels were increased in various glaucomatous eyes. sVEGFR levels were negatively correlated with VEGF levels in some glaucoma types, implying that sVEGFRs may modulate the effects of aqueous VEGF in glaucoma pathogenesis.

Comparing Surgical Outcomes in Neovascular Glaucoma between Tube and Trabeculectomy: A Multicenter Study.

OBJECTIVE: To compare the surgical outcomes between Baerveldt glaucoma implant (BGI) surgery and trabeculectomy with mitomycin C for patients with neovascular glaucoma (NVG). DESIGN: Retrospective clinical cohort study at 5 clinical centers in Japan. PARTICIPANTS: Patients treated with trabeculectomy or BGI for NVG between April 1, 2012, and December 31, 2019, at 5 clinical centers were recruited. METHODS: The inclusion criteria were age ≥ 20 years and having NVG. The exclusion criteria were eyes with no light perception vision and with previous tube-shunt surgery. If both eyes in the same patient satisfied the inclusion criteria, the eye that was treated first was investigated. We included 100 eyes undergoing BGI surgery and 204 eyes undergoing trabeculectomy. MAIN OUTCOME MEASURES: The primary outcome was surgical success or failure, with failure being defined according to 3 criteria: < 20% reduction of the preoperative intraocular pressure (IOP) or criterion A (IOP > 21 mmHg), criterion B (IOP > 17 mmHg), or criterion C (IOP > 14 mmHg). Cases of reoperation, a loss of light perception vision, or hypotony were also considered failures. RESULTS: The probability of success was significantly higher in patients undergoing BGI surgery than in those receiving trabeculectomy for criteria A (P < 0.01) and B (P = 0.01). Trabeculectomy was significantly associated with surgical failure in the multivariable analysis for criterion A (hazard ratio, 1.70) and criterion B (hazard ratio, 1.50). The overall incidence of postoperative complications was similar between the 2 groups. Reoperations for glaucoma were required significantly more frequently in the trabeculectomy group than in the BGI surgery group (20.1 % vs. 5.0%; P < 0.01). CONCLUSIONS: Baerveldt glaucoma implant surgery had a higher success rate compared with trabeculectomy in patients with NVG for a target IOP < 21 mmHg or < 17 mmHg. The rates of postoperative complications were similar between both surgical procedures. Additional glaucoma surgery was required more frequently after trabeculectomy than after BGI surgery.

Factors associated with the surgical outcomes of Baerveldt glaucoma implant for open-angle glaucoma, an age-related eye disease.

To identify the factors associated with the surgical outcomes of Baerveldt glaucoma implant (BGI) for open-angle glaucoma (OAG), the medical records of 51 consecutive OAG patients (age, 43-91 years) who underwent BGI were retrospectively reviewed (median follow-up, 21.7 months). Surgical success was defined as the following postoperative intraocular pressures (IOPs, mmHg): (A) 6 ≤ IOP ≤ 21; (B) 6 ≤ IOP ≤ 18; and (C) 6 ≤ IOP ≤ 15 without loss of light perception or additional glaucoma surgery. Univariate analysis showed that age (all criteria), glaucoma type (criterion C), and preoperative IOP (criteria A and B) were the candidate factors (P < 0.20). When the patients were divided into two groups according to median age (72 years), the success probability was higher in the older group for criteria B (P = 0.047) and C (P = 0.02), and the postoperative IOP was lower in the older group 1-year post-surgery (P = 0.002). Furthermore, the multivariate Cox proportional hazards model revealed that older age was independently associated with surgical success for criteria B (relative risk [RR], 0.94; P = 0.02) and C (RR, 0.94; P = 0.01). In conclusion, older age is a factor associated with the surgical success of BGI for OAG.

Early bleb parameters as long-term prognostic factors for surgical success: a retrospective observational study using three-dimensional anterior-segment optical coherence tomography.

BACKGROUND: The object of this study is to investigate the effect of early bleb parameters measured by three-dimensional anterior-segment optical coherence tomography on the surgical success of trabeculectomy. METHODS: This retrospective study included 45 patients with 19 of exfoliation glaucoma, 17 of primary open angle glaucoma, 4 of neovascular glaucoma, 4 of uveitic glaucoma and 1 of glaucoma caused from familial amyloid polyneuropathy who underwent trabeculectomy. Bleb parameters, such as total bleb height, the position and the width of filtration openings on the scleral flap, bleb wall thickness, fluid-filled cavity height, and bleb wall intensity were assessed by three-dimensional anterior-segment optical coherence tomography 0.5 months after trabeculectomy, and were subjected to a Cox proportional hazard model as potential prognostic factors. Surgical success was defined as: IOP < 21 mmHg (A), < 18 mmHg (B), < 15 mmHg (C) with (qualified success) or without medication (complete success). Complete failure was defined as hypotony and additional glaucoma surgeries required. RESULTS: The width of filtration openings was identified as a prognostic factor for all criteria. By multivariable analysis, the width of the filtration openings was a prognostic factor in all criteria tested, and the preoperative IOP were significant prognostic factors for surgical success in qualified success in criteria B and C. Separate from the median widths of filtration openings, wide filtration opening showed significant survival ratio for qualified success in criteria A and B and for complete success in all criteria, respectively. CONCLUSIONS: The width of filtration opening at an early stage is a prognostic factor for surgical success of trabeculectomy.

Interleukin-6-mediated trans-signaling inhibits transforming growth factor-ß signaling in trabecular meshwork cells.

Glaucoma is one of the major causes of blindness, and transforming growth factor-ß2 (TGF-ß2) has been found to be elevated in the aqueous humor of eyes with primary open-angle glaucoma (POAG). TGF-ß2 in aqueous humor causes the glaucoma-related fibrosis of human trabecular meshwork (HTM), suggesting an important role of TGF-ß in POAG pathogenesis. Here, we sought to elucidate the effects of IL-6 trans-signaling on TGF-ß signaling in HTM cells. Using a multiplex immunoassay, POAG patients decreased IL-6 levels and increased soluble IL-6 receptor (sIL-6R) levels compared with the controls. In in vitro experiments, we observed that the IL-6 level was increased in the conditioned medium of HTM cells after TGF-ß2 stimulation. To elucidate the relationship between TGF-ß2 and IL-6 in HTM cells, we conducted Western blotting and immunohistochemical analyses, and we noted that the combination of IL-6 and sIL-6R (IL6/sIL-6R) suppressed TGF-ß-induced up-regulation of α-smooth muscle actin in HTM cells, whereas IL-6 alone did not. This suggests that trans-signaling, not classic signaling, of IL-6 suppresses TGF-ß-induced fibrosis of HTM. IL6/sIL-6R also suppressed TGF-ß-mediated activation of myosin light chain 2 (MLC2), Smad2, and p38. Of note, these inhibitory effects of IL6/sIL-6R on TGF-ß were partly reduced by siRNA-mediated knockdown of STAT3. Moreover, IL-6/sIL-6R partly inhibited TGF-ß-induced activation of the Smad-sensitive promoter detected with luciferase reporter gene assays and up-regulation of TGFRI and TGFRII, evaluated by quantitative real-time RT-PCR. Strikingly, overexpression of TGFRI and TGFRII diminished these inhibitory effects of IL-6/sIL-6R. We conclude that of IL-6-mediated trans-signaling potently represses TGF-ß signaling in HTM cells.

Decreased MCP-1/CCR2 axis-mediated chemotactic effect of conjunctival fibroblasts after transdifferentiation into myofibroblasts.

The purpose of this study is to investigate the change in chemotactic effects of human conjunctival fibroblasts (HConFs) after transdifferentiation into myofibroblasts, and to explore related molecular mechanisms. HConFs were treated with 5 ng/mL transforming growth factor (TGF)-ß2 for 48 h to induce transdifferentiation into myofibroblasts. The cytokine concentrations in the conditioned media of HConFs were measured by multiplex bead-based immunoassays. The Boyden chamber assay was used to assess the chemotactic effects using the monocyte cell line, THP-1 cells. The concentration of monocyte chemoattractant protein (MCP)-1 in the conditioned media was decreased after transdifferentiation into myofibroblasts (P < 0.001). The conditioned media of HConFs exerted a chemotactic effect on THP-1 cells, but this effect decreased after transdifferentiation into myofibroblasts (P = 0.032). The number of migrated THP-1 cells decreased significantly upon treatment with neutralizing anti-MCP-1 antibodies (P = 0.006) and tended to decrease upon treatment with C-C chemokine receptor (CCR) 2 antagonist. The chemotactic effect of HConFs mediated by the MCP-1/CCR2 axis was decreased after transdifferentiation into myofibroblasts.

Prospective 3D Investigation of Bleb Wall after Trabeculectomy Using Anterior-Segment OCT.

PURPOSE: We used three-dimensional anterior-segment optical coherence tomography (3D AS-OCT) to evaluate time-dependent posttrabeculectomy changes in bleb wall volume and intensity. METHODS: This prospective observational study included patients with open-angle glaucoma who underwent fornix-based trabeculectomy between January 2012 and October 2012. Twenty-nine eyes met inclusion criteria, and the bleb walls of 22 were amenable to three-dimensional analysis by 3D AS-OCT for 1 year after surgery. The high-intensity volume ratio was calculated as the proportion of the high-intensity region in the total bleb wall. Changes in the high-intensity volume ratio were of high intensity, and parameters influencing the ratio were analyzed using 3D AS-OCT. RESULTS: The mean high-intensity volume ratios (±SDs) were 43.5 ± 21.4, 44.1 ± 14.8, 41.5 ± 22.6, and 43.2 ± 19.7% at 0.5, 3, 6, and 12 months after trabeculectomy, respectively. When the volume ratios obtained 0.5 and 12 months posttrabeculectomy were compared, four and five eyes exhibited decreases and increases of over 20%, respectively. The volume ratios at 12 months correlated with the intraocular pressure (IOP) at that time (t = 2.44, P = 0.024) and the bleb wall vascularity score at 12 months (t = 5.44, P < 0.001). CONCLUSIONS: The high-intensity bleb wall at 12 months posttrabeculectomy reflected the IOP and the bleb wall vascularity at that time.

Prospective observation of filtration blebs in high-risk eyes with limbal-based conjunctival flap.

OBJECTIVE: To evaluate time-dependent changes in filtering bleb parameters using 3-dimensional anterior segment optical coherence tomography (3-D AS-OCT) in high-risk eyes after a limbal-based trabeculectomy procedure. DESIGN: Prospective, observational study. PARTICIPANTS: Twenty-three patients who underwent uncombined limbal-based trabeculectomy surgery and who also had a history of prior intraocular surgery. METHODS: Of 23 eyes, 15 eyes were followed for 1 year without additional glaucoma surgeries, and their bleb parameters were measured 0.5, 3, 6, and 12 months after the trabeculectomy using 3-dimensional anterior segment optical coherence tomography. The correlations of these parameters to other clinical data were investigated. RESULTS: Statistical analysis showed significant changes in the bleb wall thickness (0.7 ± 0.4 mm vs 0.4 ± 0.2 mm; p = 0.007) and fluid cavity height (0.3 ± 0.2 mm vs 0.7 ± 0.4 mm; p = 0.005) between 0.5 and 3 months only. The width of the filtration openings at 0.5 months after trabeculectomy (2.1 ± 1.0 mm) was significantly associated with the intraocular pressure at 12 months (15.1 ± 5.7 mm Hg; R2 = 0.37, t = -2.65, and p = 0.021). CONCLUSIONS: The width of the filtration opening in the early stage may be a prognostic factor for long-term intraocular pressure control.

Visualization of Intravital Immune Cell Dynamics After Conjunctival Surgery Using Multiphoton Microscopy.

PURPOSE: To visualize intravital immune cell dynamics in the subconjunctival tissue during the wound-healing process using multiphoton microscopy. METHODS: Gene-targeted mice expressing enhanced green fluorescent protein under the control of the endogenous lysozyme M promoter (LysM-eGFP mice) were anesthetized with isoflurane, and injured by a 10-0 nylon conjunctival suture. Vessels were visualized by intravenous injection of 70 kDa rhodamine-conjugated dextran. Using a multiphoton microscope, the three-dimensional images of the subconjunctival tissue were acquired every minute for 20 minutes before and 0.5, 3, 6, and 72 hours after injury. Raw imaging data were processed for four-dimensional images and analyzed for the number and the velocity of the LysM-eGFP-positive cells using Imaris software. RESULTS: The intravital LysM-eGFP-positive cells and the red-labeled vessels were successfully visualized using a multiphoton microscope. The conjunctival and scleral collagen fibers were detected as secondary harmonic generation signals, which were colored blue. Compared with mice without injury, the number of LysM-eGFP-positive cells in the subconjunctival tissue after conjunctival surgery increased in a time-dependent manner. The cell velocities significantly increased until 3 hours after surgery (5.9 ± 3.2 µm/min; P < 0.0001) and the elevated level was sustained until 72 hours after injury (5.9 ± 3.3 µm/min). CONCLUSION: This is the first report to visualize and evaluate intravital cellular dynamics during inflammation in the subconjunctival tissue using multiphoton microscopy. This technique may be a useful tool to characterize the molecular mechanisms of the wound-healing process after various ocular injuries, such as glaucoma surgery.

Intravital imaging of the cellular dynamics of LysM-positive cells in a murine corneal suture model.

BACKGROUND: Corneal suturing is a surgical procedure used in patients with corneal trauma or transplants. It was reported that endogenous neutrophils are brightly labelled in gene-targeted mice expressing enhanced green fluorescent protein (eGFP) under the control of the endogenous lysozyme M promoter (LysM-eGFP mice). METHODS: We applied intravital imaging methods to analyse in vivo the dynamics of LysM-positive granulocytes (neutrophils) in LysM-eGFP mice with corneal sutures and examined their role in the elicitation of neutrophil infiltration. RESULTS: We found that in the presuturing state, neutrophils strongly positive for LysM were located in the periphery of the corneal stromal layer; none were present in the centre of the cornea. After introducing a corneal suture, neutrophils accumulated in limbal vessels and then migrated to the corneal side and the conjunctival side, suggesting that they derived from limbal vessels. Thereafter they accumulated towards the central corneal area, arriving at the suture about 7 h after its placement. Although corneal sutures may elicit the continuous infiltration of neutrophils, their number was markedly decreased by day 1 after suture removal and continued to decrease thereafter. CONCLUSIONS: Our results showed that corneal sutures may elicit the continuous infiltration of neutrophils.

Postoperative Changes in Aqueous Monocyte Chemotactic Protein-1 Levels and Bleb Morphology after Trabeculectomy vs. Ex-PRESS Shunt Surgery.

PURPOSE: To evaluate the postoperative changes in blebs and levels of aqueous monocyte chemotactic protein-1 (MCP-1) after trabeculectomy vs. Ex-PRESS tube shunt surgery. METHODS: Rabbits were subjected to trabeculectomy or Ex-PRESS tube shunt surgery and observed for up to 3 months. Intraocular pressure (IOP) was measured using a rebound tonometer. The MCP-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Bleb morphology was evaluated using photos and anterior-segment optical coherence tomography (OCT). RESULTS: There were no differences in bleb appearance or IOP at any time between the groups. Bleb wall density in the anterior-segment OCT image was significantly lower 1 week after surgery in the Ex-PRESS group than the trabeculectomy group. The MCP-1 level in control eyes was 304.1 ± 45.2 pg/mL. In the trabeculectomy group, the mean aqueous MCP-1 level was 1444.9, 1914.3, 1899.8, 516.4, 398.3, 427.3, 609.5, 1612.7, 386.2, and 167.9 pg/mL at 3, 6, and 12 h, and 1, 2, 5, 7, 14, 30, and 90 days after surgery, respectively. In the Ex-PRESS group, the corresponding values were 1744.0, 1372.0, 932.5, 711.7, 396.1, 487.3, 799.5, 1327.9, 293.6, and 184.0 pg/mL. There were no significant differences in the aqueous MCP-1 level between the groups at any time point. CONCLUSION: The postoperative changes were similar in the Ex-PRESS and trabeculectomy groups, except for bleb wall density in the anterior-segment OCT image. The postoperative aqueous MCP-1 level had bimodal peaks in both groups.

Filtering blebs using 3-dimensional anterior-segment optical coherence tomography: a prospective investigation.

IMPORTANCE: Posttrabeculectomy changes in bleb parameters measured using 3-dimensional (3-D) anterior-segment optical coherence tomography (OCT) remain uncharacterized and might be related to postsurgical intraocular-pressure (IOP) control. OBJECTIVE: To evaluate time-dependent posttrabeculectomy changes in filtering bleb parameters using 3-D anterior-segment OCT. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted at Kumamoto University Hospital, Kumamoto, Japan. Patients with open-angle glaucoma who underwent uncombined fornix-based trabeculectomy at Kumamoto University Hospital between January 1, 2012, and October 31, 2012, were included. Twenty-nine eyes were enrolled, 23 of which were followed up for 1 year without additional glaucoma surgical procedures; 3 required additional glaucoma surgery. INTERVENTIONS: Imaging filtering blebs using 3-D anterior-segment OCT. MAIN OUTCOMES AND MEASURES: The primary end points were changes in bleb parameters including the position and width of the filtration openings on the scleral flap, the total bleb height, fluid-filled cavity height, bleb wall thickness, and bleb wall intensity, which were measured using 3-D anterior-segment OCT. The secondary end points were postsurgical IOP measured 0.5, 3, 6, and 12 months after trabeculectomy, and the effects of aqueous cytokine levels on the bleb parameters. RESULTS: We observed increased total bleb height (0.82 to 1.25 mm; difference: 95% CI, 0.10 to 0.75; P = .01), bleb wall thickness (0.46 to 0.61 mm; difference: 95% CI, 0.02 to 0.28; P = .03), and distance from the top of the scleral flap to the filtration opening (1.69 to 2.16 mm; difference: 95% CI, 0.28 to 0.70; P < .001), as well as decreased width of the filtration opening (2.08 to 1.12 mm; difference: 95% CI, -1.75 to -0.49; P = .002) between 0.5 and 12 months posttrabeculectomy. The filtration openings tended to close from the fornix side of the scleral flap during the wound healing process. Moreover, the width of the filtration opening at 0.5 months posttrabeculectomy correlated with the IOP at 12 months (P = .02). The aqueous humor level of monocyte chemoattractant protein-1 was correlated with the width of the filtration opening at 3 and 6 months posttrabeculectomy. CONCLUSIONS AND RELEVANCE: The width of the filtration opening at 0.5 months posttrabeculectomy correlated with the IOP at 12 months. The width of the filtration opening at the early stage may be a prognostic factor for long-term IOP control. Large-scale studies with longer follow-up periods are required.

Evaluation of filtering blebs exhibiting transconjunctival oozing using anterior segment optical coherence tomography.

PURPOSE: To explore the features of filtering blebs exhibiting transconjunctival oozing via three-dimensional anterior segment optical coherence tomography (3D AS-OCT). METHODS: In this cross-sectional study, 131 eyes of 131 patients exhibiting filtering blebs were examined. Of those, 20 eyes were excluded as flat-shaped, non-functioning bleb. Transconjunctival oozing was defined as transconjunctival aqueous egress evident on the bleb surface, in the absence of any point leak observable using a slit-lamp, as confirmed by application of digital pressure. Total bleb height, the height of the fluid-filled cavity, and bleb wall thickness and density were measured using 3D AS-OCT. Patient age, the etiology of glaucoma, postoperative follow-up period, number of glaucoma medication classes prescribed, intraocular pressure (IOP), grade of bleb vascularity, and bleb parameters were compared in eyes with and without bleb oozing. RESULTS: Sixty (54.0 %) of 111 eyes excluding non-functioning flat blebs exhibited oozing; mean IOP value (11.7 ± 4.5 vs. 14.8 ± 4.0 mmHg) and bleb vascularity grade (1.5 ± 0.7 vs. 2.4 ± 1.0) were lower than those of eyes without oozing. Total bleb height (1.1 ± 0.4 vs. 0.9 ± 0.4 mm), bleb wall thickness (0.7 ± 0.4 vs. 0.5 ± 0.3 mm), and bleb wall density (131.3 ± 45.7 vs. 180.9 ± 39.8 optical density units) differed significantly between the two groups (oozing vs. non-oozing). CONCLUSION: Transconjunctival oozing after trabeculectomy with MMC was associated with a low IOP, low-level bleb vascularity, an elevated total bleb height, a thicker bleb wall, and low bleb wall density.

Fornix-based versus limbal-based conjunctival flaps in trabeculectomy with mitomycin C in high-risk patients.

PURPOSE: To compare the surgical outcomes of limbal-based and fornix-based trabeculectomy in eyes with a history of ocular incisional surgery. METHODS: Twenty-six eyes underwent limbal-based trabeculectomy (group LB), and were condition matched with 26 eyes that received fornix-based trabeculectomy (group FB). Surgical failure was recorded retrospectively if the intraocular pressure value was either ≥21, ≥18, and ≥15 mmHg (conditions A, B, and C, respectively) or <4 mmHg or if the patient required additional glaucoma surgery. Kaplan-Meier survival curve analysis was used to assess surgical failure. RESULTS: For condition A, the 2 year surgical success probabilities were 75.0% and 63.9% in groups FB and LB, respectively (P=0.124). The corresponding values were 55.0% and 61.7% (P=0.638) in condition B, and 55.0% and 57.0% (P=0.454) in condition C. The rates of bleb leakage, hypotony, choroidal detachment, and bleb-related infection were 11.5%, 26.9%, 50.0%, and 7.7% in group LB, respectively. The corresponding values in group FB were 30.8%, 23.1%, 46.2%, and 0.0%, which were not statistically different between the two groups. CONCLUSION: No significant differences in surgical outcomes were observed between limbal-based and fornix-based trabeculectomy for patients with a history of incisional ocular surgeries.

Tear fluid signs associated with filtration blebs, as demonstrated by three-dimensional anterior segment optical coherence tomography.

PURPOSE: To determine the clinical features of tear fluid signs associated with filtration blebs via three-dimensional anterior segment optical coherence tomography (3D AS-OCT). METHODS: In total, 152 eyes (130 patients) with glaucoma that underwent trabeculectomy with mitomycin C were evaluated retrospectively. We investigated tear fluid signs associated with filtration blebs, using 3D AS-OCT with custom software, and compared the findings of lower tear meniscus. We also analyzed postoperative intraocular pressure and the bleb parameters of filtration blebs between eyes with and without tear fluid signs. RESULTS: We found tear fluid signs associated with filtration blebs in 45 (30%) of 152 eyes. The mean postoperative intraocular pressure of the eyes with the tear fluid sign in a filtration bleb was significantly lower than that in eyes without the tear fluid sign (P<0.001). Blebs with tear fluid signs have more frequent identifiable filtration openings, greater total height, increased fluid-filled cavity height, and less wall intensity compared with blebs without these signs. CONCLUSION: We identified tear fluid signs in AS-OCT images on or along filtration blebs that depended on bleb morphology. The occurrence of these signs may be related to the presence of functional blebs, which may thereby control postoperative intraocular pressure.

Epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells.

The trabecular meshwork (TM) is a major component of the conventional outflow pathway and the excess extracellular matrix (ECM), and fibrosis in the TM causes increased outflow resistance. In this study, we first investigated the effects of several ECM components in the induction of an epithelial mesenchymal transition (EMT)-like phenomenon in TM cells. TM cells were isolated from cynomolgus monkeys (Macaca fascicularis). The cells were cultured in ECM-coated dishes and then subjected to both western blot analysis and immunocytochemistry to measure the levels of EMT-associated markers. Cell motility was assessed using wound healing and chemotaxis assays. We found that type I collagen, fibronectin and laminin induced the dissociation of cell-cell contact and elongation of actin stress fibers in the cultured monkey TM cells. In addition, following the same stimulation of the ECM, the expression of mesenchymal markers, such as fibronectin and α-smooth muscle actin, and the phosphorylation of Smad2 increased in the TM cells. Our results showed the significant acceleration of TM cellular motility following stimulation with type I collagen, fibronectin and laminin. These phenomena were inhibited by the c-Jun N-terminal kinase (JNK) inhibitor SP600125. In addition, siRNA against paxillin was transfected to evaluate the association between paxillin and the EMT-like phenomenon. The knockdown of paxillin expression by transfection with siRNA blocked the EMT-like alteration of the cellular characteristics and chemotaxis toward transforming growth factor-ß2 in the cultured TM cells. Our results showed that the ECM-JNK-paxillin pathway induced an EMT-like phenomenon in TM cells, resulting in the abundant expression of fibronectin and activation of motility in TM cells. This EMT-like phenomenon could result in aberrant conditions in the aqueous outflow pathway in glaucomatous eyes.

Filtration bleb revision guided by 3-dimensional anterior segment optical coherence tomography.

OBJECTIVE: To elucidate the usefulness of 3-dimensional anterior segment optical coherence tomography (3D AS-OCT) for bleb revision after trabeculectomy. DESIGN: Case series. PARTICIPANTS: Two patients who underwent trabeculectomy and subsequent bleb revision. METHODS: Three-dimensional AS-OCT and intraoperative observation. MAIN OUTCOME MEASURES: AS-OCT and intraoperative observation were analyzed to identify the filtration openings on the scleral flap margin and leaking points. RESULTS: In 1 case with a leaking bleb, 3D AS-OCT examinations suggested the presence of numerous internal ostia (filtration openings). With 3D AS-OCT guidance, we carefully removed the leaking bleb with peripheral scar tissue. Histopathologic findings showed the presence of a thin bleb wall in the limbal conjunctiva corresponding to the point of aqueous leakage. In another case of an overhanging bleb, 3D AS-OCT examination revealed a thin bleb wall and multiloculated cystic structures. Histopathologic findings showed the presence of a thin region in the conjunctival epithelium in which connective tissue did not support the conjunctival epithelium, which seemed to correspond to the point at which oozing occurred. CONCLUSIONS: Three-dimensional AS-OCT enables evaluation of the internal morphology of filtration blebs and is useful for preoperative guidance for bleb revision.