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 intraocular pressure elevation in a six-month period after ab interno trabeculotomy using a Kahook Dual Blade.

BACKGROUND: To examine the risk factors for an early postoperative intraocular pressure (IOP) increase after ab interno trabeculotomy using a Kahook Dual Blade (KDB trabeculotomy). METHODS: A retrospective study was performed in 76 exfoliation glaucoma (EXG) eyes and 56 primary open angle glaucoma (POAG) eyes that underwent KDB trabeculotomy, with or without cataract surgery at Kumamoto University Hospital. Postoperative high IOP was classified as IOP≥20 mmHg (within three months after surgery, whether persistent or temporary), transient IOP≥20 mmHg (IOP≥20 mmHg after surgery, then dropped below 20 mmHg), and the presence of IOP spikes (≥ 10 mmHg from baseline). Risk factors were examined using logistic regression analysis. RESULTS: The preoperative mean IOP (SD) was 24.98 (7.23) mmHg in patients with EXG and 21.28 (6.58) mmHg in patients with POAG. IOP was reduced by 32.1% in patients with EXG and by 17.7% in patients with POAG at 6 months after surgery. Postoperative IOP≥20 mmHg was observed in 56.6% of EXG patients and in 51.8% of POAG patients. IOP spikes occurred in 15.8% of EXG patients and in 14.3% of POAG patients. Logistic regression analysis showed that factors with significant odds ratios (ORs) were age (OR = 0.866, 95% CI = 0.793-0.945), preoperative medication use (OR = 2.02, 95% CI = 1.17-3.49), trabeculotomy in combination with cataract surgery (OR = 0.0674, 95% CI = 0.015-0.303), and IOP at day 1 (OR = 1.41, 95% CI = 1.18-1.68) for postoperative IOP≥20 mmHg, the IOP at day 1 (OR = 1.1, 95% CI = 1.03-1.17) for transient IOP≥20 mmHg, and age (OR = 0.948, 95% CI = 0.901-0.997) and preoperative IOP (OR = 0.83, 95% CI = 0.736-0.936) for IOP spikes. CONCLUSION: Although KDB trabeculotomy is an effective treatment for patients with EXG and POAG, patients who take multiple preoperative medications and have a high IOP on day 1 require careful follow-up to prevent postoperative IOP elevation.

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.

Intraocular Pressure-Lowering Effects of Trabeculectomy Versus MicroShunt Insertion in Rabbit Eyes.

Purpose: To compare the surgical results of PRESERFLO MicroShunt (MicroShunt) insertion and trabeculectomy in rabbit eyes. Methods: Trabeculectomy or MicroShunt insertion was performed on the eyes of Japanese white rabbits. Intraocular pressure (IOP) was measured on conscious rabbits using a rebound tonometer for up to 12 weeks after surgery. Filtering bleb appearance was evaluated. Scarring in the filtering bleb was assessed by immunohistochemical analyses. The change in mRNA expression in the conjunctiva was evaluated using RNA sequence analyses. Results: The preoperative IOP of the operative eye did not differ significantly between trabeculectomy (11.6 ± 1.0 mmHg, n = 10) and MicroShunt insertion (12.6 ± 1.3 mmHg, n = 10). In both groups, the IOP of the operative eye was significantly lower than that of the contralateral eye at one day postoperatively, which continued until 12 weeks after surgery. The peak differences in IOP were -8.4 ± 3.0 (trabeculectomy) and -8.1 ± 2.1 mmHg (MicroShunt) at two weeks after surgery; no significant differences were observed in IOP reduction between the groups. Appearance and immunohistochemical analyses of the filtering bleb showed no significant difference between the groups. Moreover, RNA sequence analysis results showed no difference between the groups in mRNA expression fluctuations. Conclusions: Postoperative IOP, bleb appearance, and immunohistochemical analysis results were similar in the trabeculectomy and MicroShunt groups, indicating that MicroShunt insertion is as effective as trabeculectomy in lowering IOP. Translational Relevance: Comparison of surgical procedures using animal models has made it possible to predict clinical efficacy and safety.

Correlation between intraocular pressure reduction and anterior chamber aqueous flare after micropulse transscleral cyclophotocoagulation.

BACKGROUND: Micropulse transscleral cyclophotocoagulation (MP-CPC) is a technique that has been approved in recent years to treat glaucoma. MP-CPC causes anterior chamber inflammation; a relationship with reduced intraocular pressure (IOP) has not been reported. Therefore, we analyzed the correlation between IOP and anterior chamber aqueous flare after MP-CPC. METHODS: This retrospective study included 37 eyes of 37 patients who underwent MP-CPC between November 2018 and October 2020. IOP and flare values were measured at 1, 4, and 12 weeks after MP-CPC. Correlations were assessed between the percentage IOP reduction and flare elevation by calculating Spearman's rank correlation coefficient. RESULTS: The percentage IOP reduction at 1 week after surgery was correlated with the flare elevation at 1 week after surgery (ρ = 0.47, P = 0.006). The percentage IOP reduction at 12 weeks after surgery was correlated with the flare elevation at 4 weeks after surgery (ρ = 0.53, P = 0.006). CONCLUSIONS: A short-term correlation was implied between reduced IOP and flare elevation after MP-CPC.

A Case of Primary Open-angle Glaucoma With Conjunctival Laceration After Micropulse Transscleral Cyclophotocoagulation.

PURPOSE: We report a case of primary open-angle glaucoma with conjunctival laceration after micropulse transscleral cyclophotocoagulation (MP-CPC). PATIENTS AND METHODS: A 74-year-old man with primary open-angle glaucoma underwent MP-CPC using a Cyclo G6 device (IRIDEX) due to an increase in intraocular pressure (IOP) to 25 mm Hg in his left eye. At 1 week after surgery, IOP had decreased to 12 mm Hg. However, at 2 months after surgery, IOP had increased again to 25 mm Hg. MP-CPC was performed again at 3 months after the first surgery using a Cyclo G6 device, in accordance with treatment guidelines outlined by the manufacturer. Before the MP-CPC treatment, the patient received anesthesia with 2% lidocaine in the sub-Tenon space. A large amount of subconjunctival hemorrhage was observed in the sub-Tenon space. RESULTS: At 1 day after the second MP-CPC treatment, an arc-shaped conjunctival erosion and a brown lesion were observed in the MP-CPC-irradiated area in the lower hemisphere. The possibility of scleral laceration was considered. The IOP was 25 mm Hg and no aqueous humor leakage was observed. The wound had become enlarged. At 20 days after the second MP-CPC, the patient was hospitalized to close the wound. During the repair surgery, the brown lesion was easily detached from the sclera. There was conjunctival laceration, but no scleral laceration. Pathologic examination revealed that the exfoliated tissue contained abundant clots, connective tissue, and elastic fibers. CONCLUSION: Special care and consideration are required when performing MP-CPC in cases of severe subconjunctival hemorrhage.

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.

Stimulation of the adenosine A3 receptor, not the A1 or A2 receptors, promote neurite outgrowth of retinal ganglion cells.

Among candidate neuroprotective agents, adenosine is thought to be a possible treatment for central nervous system disorders. Adenosine elicits biological effects through four G protein-coupled receptors (A1, A2A, A2B, and A3). The A2A and A2B receptors stimulate adenylyl cyclase (AC) and increase cyclic adenosine monophosphate (cAMP) levels, whereas A1 and A3 receptors inhibit AC and decrease cAMP levels. Several studies have investigated the effects of adenosine receptors (AdoRs) in glaucoma, because modulation of A1, A2A, or A3 receptor regulates intraocular pressure. In addition, AdoR-related phenomena may induce neuroprotective effects in retinal neurons. Notably, A1, A2A, and A3 receptor agonists reportedly inhibit retinal ganglion cell (RGC) death in in vitro and in vivo glaucoma models. However, there is limited knowledge of the effects of AdoR activation on neurite outgrowth or the regeneration of RGCs. In this report, we described the role of an AdoR subtype in neurite outgrowth and RGC axonal regeneration. The distribution of AdoRs in the retina was evaluated by immunohistochemical analysis. Using primary cultured rat RGCs in vitro and an optic nerve crush model in vivo, neurite elongation was evaluated after stimulation by the following AdoR agonists: CHA, an A1 receptor agonist; CGS21680, an A2A receptor agonist; BAY60-6583, an A2B receptor agonist; and 2-Cl-IB-MECA, an A3 receptor agonist. To determine the mechanism of neurite promotion, the candidate molecules of signal transduction associated with the neurite elongation of AdoRs were evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. All four AdoRs (A1, A2A, A2B, and A3) were present in the inner retinal layers. Among the agonists for AdoR, only 2-Cl-IB-MECA significantly promoted neurite outgrowth in primary cultured RGCs. Signaling pathway analyses showed that 2-Cl-IB-MECA caused upregulated phosphorylation of Akt in cultured RGCs. Additionally, LY294002, an inhibitor of Akt, suppressed the neurite-promoting effects of the A3 receptor agonist in RGCs. Moreover, 2-Cl-IB-MECA increased the number of regenerating axons in the optic nerve crush model. Taken together, these data indicate that activation of the A3 receptor, not the A1 or A2 receptors, promotes in vitro and in vivo neurite outgrowth during the regeneration of rat RGCs, which is caused by the activation of an Akt-dependent signaling pathway. Therefore, AdoR activation may be a promising candidate for the development of novel regenerative modalities for glaucoma and other optic neuropathies.

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.

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.

Precise identification of filtration openings on the scleral flap by three-dimensional anterior segment optical coherence tomography.

PURPOSE: To elucidate the potential of three-dimensional anterior segment optical coherence tomography (3D AS-OCT) for identifying filtration openings where aqueous humor flows from the sclera into the subconjunctival space. METHODS: We used 3D AS-OCT and custom software to identify filtration openings, which were defined by pits and/or troughs in fluid-filled cavities in both horizontal and vertical rasters and corresponding C-scan images of scleral flap margin in the blebs. We measured bleb parameters, and at least three different reviewers surveyed the complete 3D images of the internal structure of the filtration blebs and associated findings. RESULTS: We identified filtration openings in 118 (95%) of 124 eyes. Among these 118 eyes, we found only a single filtration opening in 90 eyes (76%) and two or more filtration openings in the remaining 28 eyes (24%). Filtration openings were located in the middle third of the scleral flap margins in 57 eyes (63%) of the 90 eyes. The pattern of incision and sutures used for closure of the conjunctival flap affected the location of the openings, but additional laser suture lysis did not. In 6 (5%) of the 124 eyes, filtration openings could not be identified because of high reflectivity and/or elevated bleb wall (2 eyes), and no fluid-filled cavities because a sponge-like structure masked the filtration openings just above the scleral flap (4 eyes). CONCLUSIONS: 3D AS-OCT allows, in most cases, detailed evaluation of internal morphology of filtration blebs and precise identification of filtration openings on the scleral flap margins after trabeculectomy.